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1
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Majumder N, Bhattacharjee M, Spagnoli GC, Ghosh S. Immune response profiles induced by silk-based biomaterials: a journey from 'immunogenicity' towards 'immuno-compatibility. J Mater Chem B 2024; 12:9508-9523. [PMID: 39225012 DOI: 10.1039/d4tb01231c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Silk is a widely accepted biomaterial for tissue regeneration owing to its tunable biomechanical properties and ease of chemical modification. However, a number of aspects associated with its clinical use are still debated. Indeed, to achieve clinical success, a biomaterial must favorably interact with host tissues without evoking local or systemic immuno-inflammatory responses. The analysis of immune responses associated with silk under in vitro and in vivo conditions provides useful insights, improving the understanding of the functional characteristics of silk biomaterials and further promoting their clinical application. Silk evokes moderate immune responses upon implantation in vivo, depending on the material structure, fabrication method, degradation time, and implantation in soft or hard tissue sites, which rapidly subside within a few days/weeks. In vitro studies indicate that its immune-stimulatory properties are largely due to inherent protein conformation and differential processing parameters. Strategically controlled levels of immune responses in vivo with marginal immunogenicity of silk-based biomaterials may contribute to matrix remodeling and replacement by native tissue matrix around the implanted site. Therefore, immunomodulatory strategies should be developed to promote the use of silk-based biomaterials as promising candidates for numerous clinical applications.
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Affiliation(s)
- Nilotpal Majumder
- Regenerative Engineering Laboratory, Department of Textile and Fibre Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi-110016, India.
| | - Maumita Bhattacharjee
- Regenerative Engineering Laboratory, Department of Textile and Fibre Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi-110016, India.
| | - Giulio C Spagnoli
- National Research Council Institute of Translational Pharmacology, Rome, Italy
| | - Sourabh Ghosh
- Regenerative Engineering Laboratory, Department of Textile and Fibre Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi-110016, India.
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2
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Zhou X, Wang Y, Ji J, Zhang P. Materials Strategies to Overcome the Foreign Body Response. Adv Healthc Mater 2024; 13:e2304478. [PMID: 38666550 DOI: 10.1002/adhm.202304478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 04/20/2024] [Indexed: 05/03/2024]
Abstract
The foreign body response (FBR) is an immune-mediated reaction that can occur with most biomaterials and biomedical devices. The FBR initiates a deterioration in the performance of implantable devices, representing a longstanding challenge that consistently hampers their optimal utilization. Over the last decade, significant strides are achieved based on either hydrogel design or surface modifications to mitigate the FBR. This review delves into recent material strategies aimed at mitigating the FBR. Further, the authors look forward to future novel anti-FBR materials from the perspective of clinical translation needs. Such prospective materials hold the potential to attenuate local immune responses, thereby significantly enhancing the overall performance of implantable devices.
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Affiliation(s)
- Xianchi Zhou
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Youxiang Wang
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Jian Ji
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, P. R. China
- State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou, 311202, P. R. China
| | - Peng Zhang
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, P. R. China
- State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou, 311202, P. R. China
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3
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Jophlin LL, Singal AK, Bataller R, Wong RJ, Sauer BG, Terrault NA, Shah VH. ACG Clinical Guideline: Alcohol-Associated Liver Disease. Am J Gastroenterol 2024; 119:30-54. [PMID: 38174913 PMCID: PMC11040545 DOI: 10.14309/ajg.0000000000002572] [Citation(s) in RCA: 54] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 10/04/2023] [Indexed: 01/05/2024]
Abstract
ABSTRACT Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide. With harmful alcohol use as the primary risk factor, increasing alcohol use over the past decade has resulted in rapid growth of the ALD-related healthcare burden. The spectrum of ALD ranges from early asymptomatic liver injury to advanced disease with decompensation and portal hypertension. Compared with those with other etiologies of liver disease, patients with ALD progress faster and more often present at an advanced stage. A unique phenotype of advanced disease is alcohol-associated hepatitis (AH) presenting with rapid onset or worsening of jaundice, and acute on chronic liver failure in severe forms conveying a 1-month mortality risk of 20%-50%. The model for end stage disease score is the most accurate score to stratify AH severity (>20 defined as severe disease). Corticosteroids are currently the only available therapeutic with proven efficacy for patients with severe AH, providing survival benefit at 1 month in 50%-60% of patients. Abstinence of alcohol use, a crucial determinant of long-term outcomes, is challenging to achieve in ALD patients with concurrent alcohol use disorder (AUD). As patients with ALD are rarely treated for AUD, strategies are needed to overcome barriers to AUD treatment in patients with ALD and to promote a multidisciplinary integrated care model with hepatology, addiction medicine providers, and social workers to comprehensively manage the dual pathologies of liver disease and of AUD. Liver transplantation, a definitive treatment option in patients with advanced cirrhosis, should be considered in selected patients with AH, who are unresponsive to medical therapy and have a low risk of relapse to posttransplant alcohol use. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the American College of Gastroenterology Practice Parameters Committee.
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Affiliation(s)
- Loretta L. Jophlin
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville Health, Louisville, Kentucky, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of South Dakota, Sioux Falls, South Dakota, USA
| | - Ramon Bataller
- Liver Unit, Department of Digestive and Metabolic Diseases, Hospital Clinic, Barcelona, Spain
| | - Robert J. Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
| | - Bryan G. Sauer
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Norah A. Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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4
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van Zyl E, Leisewitz AL, Atkinson BK, Goddard A, Rautenbach Y, Thompson PN, Schoeman JP. Serial changes in the concentrations of cortisol and thyroid hormones in Beagle dogs infected with Babesia rossi. Ticks Tick Borne Dis 2023; 14:102107. [PMID: 36535203 DOI: 10.1016/j.ttbdis.2022.102107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 11/13/2022] [Accepted: 11/13/2022] [Indexed: 12/14/2022]
Abstract
An experimental infection using Babesia (B.) rossi was performed in healthy male Beagle dogs to assess the changes in endocrine variables during disease. Two dogs were infected with a low dose (LD) of parasite inoculum (104 parasites) and three dogs were infected with a high dose (HD) (108 parasites). Basal serum cortisol, thyroxine (T4), and thyrotropin (TSH) concentrations were measured every second day. Samples were analyzed using a solid- phase, competitive chemiluminescent enzyme immunoassay (Immulyte® 2000, Siemens). Variables were compared between groups and timepoints using linear mixed models. In both groups, the median cortisol concentration increased, whilst the median T4 concentration decreased after infection, with a return towards baseline concentration post treatment. The highest cortisol and the lowest T4 concentrations were reached at 96 h and 108 h post infection, respectively, in the HD group and slightly later at 108 and 144 h post-infection, respectively, in the LD group. A higher cortisol concentration with a more rapid increase, and a lower T4 concentration with a more rapid decline, were associated with disease severity and a higher dose of parasite inoculum. The TSH concentration remained within the reference interval throughout the study period. This study illustrated the temporal changes in endocrine parameters during experimental B. rossi infection and demonstrated that cortisol and T4 tracked the severity of disease, albeit in opposite directions.
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Affiliation(s)
- E van Zyl
- Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, 175 Bryanston drive, Bryanston, Onderstepoort, Johannesburg 2021, South Africa.
| | - A L Leisewitz
- Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, 175 Bryanston drive, Bryanston, Onderstepoort, Johannesburg 2021, South Africa
| | - B K Atkinson
- Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, 175 Bryanston drive, Bryanston, Onderstepoort, Johannesburg 2021, South Africa
| | - A Goddard
- Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, 175 Bryanston drive, Bryanston, Onderstepoort, Johannesburg 2021, South Africa
| | - Y Rautenbach
- Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, 175 Bryanston drive, Bryanston, Onderstepoort, Johannesburg 2021, South Africa
| | - P N Thompson
- Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa
| | - J P Schoeman
- Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, 175 Bryanston drive, Bryanston, Onderstepoort, Johannesburg 2021, South Africa
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Li H, Sahu KK, Maughan BL. Mechanism and Management of Checkpoint Inhibitor-Related Toxicities in Genitourinary Cancers. Cancers (Basel) 2022; 14:2460. [PMID: 35626064 PMCID: PMC9139183 DOI: 10.3390/cancers14102460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 05/06/2022] [Accepted: 05/11/2022] [Indexed: 12/10/2022] Open
Abstract
The use of immune checkpoint inhibitors (ICIs) is rapidly increasing as more combinations and clinical indications are approved in the field of genitourinary malignancies. Most immunotherapeutic agents being approved are for the treatment of renal cell carcinoma and bladder cancer, which mainly involve PD-1/PD-L1 and CTLA-4 pathways. There is an ongoing need for recognizing and treating immunotherapy-related autoimmune adverse effects (irAEs). This review aims to critically appraise the recent literature on the mechanism, common patterns, and treatment recommendations of irAEs in genitourinary malignancies. We review the epidemiology of these adverse effects as well as general treatment strategies. The underlying mechanisms will also be discussed. Diagnostic considerations including differential diagnosis are also included in this review.
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Affiliation(s)
| | | | - Benjamin L. Maughan
- Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84108, USA; (H.L.); (K.K.S.)
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6
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Craig CF, Filippone RT, Stavely R, Bornstein JC, Apostolopoulos V, Nurgali K. Neuroinflammation as an etiological trigger for depression comorbid with inflammatory bowel disease. J Neuroinflammation 2022; 19:4. [PMID: 34983592 PMCID: PMC8729103 DOI: 10.1186/s12974-021-02354-1] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 12/14/2021] [Indexed: 02/06/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) suffer from depression at higher rates than the general population. An etiological trigger of depressive symptoms is theorised to be inflammation within the central nervous system. It is believed that heightened intestinal inflammation and dysfunction of the enteric nervous system (ENS) contribute to impaired intestinal permeability, which facilitates the translocation of intestinal enterotoxins into the blood circulation. Consequently, these may compromise the immunological and physiological functioning of distant non-intestinal tissues such as the brain. In vivo models of colitis provide evidence of increased blood–brain barrier permeability and enhanced central nervous system (CNS) immune activity triggered by intestinal enterotoxins and blood-borne inflammatory mediators. Understanding the immunological, physiological, and structural changes associated with IBD and neuroinflammation may aid in the development of more tailored and suitable pharmaceutical treatment for IBD-associated depression.
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Affiliation(s)
- Colin F Craig
- Institute for Heath and Sport, Victoria University, Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia
| | - Rhiannon T Filippone
- Institute for Heath and Sport, Victoria University, Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia
| | - Rhian Stavely
- Institute for Heath and Sport, Victoria University, Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia.,Department of Pediatric Surgery, Pediatric Surgery Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Joel C Bornstein
- Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Australia
| | - Vasso Apostolopoulos
- Institute for Heath and Sport, Victoria University, Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia.,Immunology Program, Australian Institute of Musculoskeletal Science (AIMSS), Melbourne, VIC, Australia
| | - Kulmira Nurgali
- Institute for Heath and Sport, Victoria University, Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia. .,Department of Medicine Western Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC, Australia. .,Regenerative Medicine and Stem Cells Program, Australian Institute of Musculoskeletal Science (AIMSS), Melbourne, VIC, Australia. .,Institute for Health and Sport, Victoria University, Level 4 Research Labs, Western Centre for Health Research and Education, Sunshine Hospital, 176 Furlong Road, St Albans, VIC, 3021, Australia.
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7
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Janssen JBE, Leow TYS, Herbschleb KH, Gijtenbeek JMM, Boers-Sonderen MJ, Gerritsen WR, Westdorp H. Immune Checkpoint Inhibitor-related Guillain-Barré Syndrome: A Case Series and Review of the Literature. J Immunother 2021; 44:276-282. [PMID: 33758147 DOI: 10.1097/cji.0000000000000364] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 02/02/2021] [Indexed: 12/26/2022]
Abstract
Immune checkpoint inhibitors (ICIs) have been approved for the treatment of various malignancies with promising clinical outcomes. Treatment can, however, be accompanied by serious immune-related adverse events. Neurological adverse events like Guillain-Barré syndrome (GBS) are rare but potentially life-threatening. We present 3 cases of ICI-related GBS; review cases described in current literature, and discuss treatment strategies. Three patients developed GBS after ICI treatment. The first case with pembrolizumab had a fatal outcome despite treatment with multiple regimens, including steroids and intravenous immunoglobulin (IVIg). The other 2 cases with nivolumab-induced and pembrolizumab-induced GBS, respectively, responded well to treatment with IVIg and steroids. In the current literature, a total of 31 other cases were found. Treatment for ICI-related GBS mostly consisted of concurrent IVIg and steroids (44%), which led to clinical improvement in 73%. Most patients recovered with remaining symptoms (68%), while 10 patients developed respiratory failure (29%) and 6 patients (18%) died. ICI-related GBS should be suspected in patients on ICI treatment who develop subacute progressive weakness of the limbs, sensory loss, and areflexia. On the basis of the guidelines recommendations and our review of the literature, we advise first-line therapy with concurrent IVIg 0.4 g/kg/d for 5 days and prednisolone 1-2 mg/kg/d. Discontinuation of immunotherapy after ICI-related GBS is advised.
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Affiliation(s)
| | | | - Karin H Herbschleb
- Department of Internal Medicine, St. Antonius Ziekenhuis, Nieuwegein, The Netherlands
| | | | | | - Winald R Gerritsen
- Departments of Medical Oncology
- Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen
| | - Harm Westdorp
- Departments of Medical Oncology
- Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen
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8
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Dickman KD, Thomas MC, Anderson B, Manuck SB, Kamarck TW. Social Integration and Diurnal Cortisol Decline: The Role of Psychosocial and Behavioral Pathways. Psychosom Med 2021; 82:568-576. [PMID: 32427757 PMCID: PMC7367491 DOI: 10.1097/psy.0000000000000825] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE A growing number of studies have associated various measures of social integration, the diversity of social roles in which one participates, with alterations in hypothalamic-pituitary-adrenocortical (HPA) functioning. The pathways through which social integration may be linked to HPA functioning, however, are as yet unknown. The present study examined whether daily social interactions, affective responses, health behaviors, and personality help explain the association between social integration and diurnal cortisol slope. METHODS A sample of 456 healthy, employed adults (53.9% female, 82.0% white, 72.2% bachelor's degree or greater, mean age of 42.86 years) completed a 4-day ecological momentary assessment protocol that measured cortisol, social interactions, affect, sleep, and physical activity at frequent intervals throughout the day. Social integration was measured at baseline. RESULTS Regression results controlling for age, sex, race, and education indicated that more socially integrated individuals showed steeper cortisol slopes (B = -0.00253, p = .006). Exploratory analyses suggested that the consistency (i.e., reduced variability) in nightly sleep midpoint partially explained this association (B = -0.00042, 95% confidence interval = -0.00095 to -0.00001). Personality, mood, social interaction patterns, and nonsleep health behavior differences did not account for the association between social integration and HPA activity. CONCLUSION This study replicates previous findings linking social integration and HPA functioning, and it examines patterns of nightly sleep as possible pathways through which the association may operate. Results have implications for understanding mechanisms for health risk and for development of future interventions.
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Meriggi F, Zaniboni A. Antibiotics and steroids, the double enemies of anticancer immunotherapy: a review of the literature. Cancer Immunol Immunother 2021; 70:1511-1517. [PMID: 33165628 PMCID: PMC10991597 DOI: 10.1007/s00262-020-02786-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 10/27/2020] [Indexed: 02/06/2023]
Abstract
The advent of immunotherapy in onco-haematology has represented a kind of revolution that has been able to modify the prognosis of numerous tumours that until recently would have been rapidly lethal. While much is known about the mechanism of action of these drugs, relatively little is known about the factors that represent potential predictors of response and toxicity. Among these factors, the simultaneous administration of antibiotics and/or steroids seems to have a negative impact. Furthermore, several retrospective studies have highlighted the strong link between cancer and gut microbiota, regardless of the tumour site, and how microbiota, playing a key role in the prevention of systemic inflammation at various levels and in the intestinal homeostasis, can be negatively influenced by the dysbiosis caused by antibiotic therapy administered during or in the weeks immediately preceding the start of immunotherapy. Moreover, we assume that the concurrent administration of steroids, which is often necessary in cancer patients, likely results in a deleterious effect on the therapeutic outcomes of immunotherapy. In this review, we will try to clarify the evidence on the possible detrimental effects of antibiotics and steroids, which are currently considered the double enemies of anticancer immunotherapy.
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Affiliation(s)
- Fausto Meriggi
- Oncology Department, Poliambulanza Foundation, Via Leonida Bissolati 57, 25124, Brescia, Italy.
| | - Alberto Zaniboni
- Oncology Department, Poliambulanza Foundation, Via Leonida Bissolati 57, 25124, Brescia, Italy
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Passiglia F, Cetoretta V, De Filippis M, Napoli V, Novello S. Exploring the immune-checkpoint inhibitors' efficacy/tolerability in special non-small cell lung cancer (NSCLC) populations: focus on steroids and autoimmune disease. Transl Lung Cancer Res 2021; 10:2876-2889. [PMID: 34295686 PMCID: PMC8264339 DOI: 10.21037/tlcr-20-635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 10/09/2020] [Indexed: 11/18/2022]
Abstract
The advent of immune-checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis, both as monotherapy and in combination strategies, produced a paradigm change of the treatment algorithm for metastatic, non-oncogene addicted, non-small cell lung cancer (NSCLC) patients. Although the great efficacy and the optimal tolerability emerging from clinical studies has been confirmed for the majority of patients treated in the real-word scenario, however the potential activity and safety profile of these agents in uncommon NSCLC populations remains still controversial. Particularly, patients with previously diagnosed autoimmune disease or concomitant steroids treatment at the time of immunotherapy initiation represent two special subgroups of patients not unusual in the real-word practice, to whom the clinical implication of immune-checkpoint inhibitors administration is largely unknown. In this review we provided an updated literature overview, summarizing available evidence and reporting practical suggestions, which may guide physicians in their clinical management of these NSCLC sub-populations.
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Affiliation(s)
- Francesco Passiglia
- Department of Oncology, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy
| | - Valeria Cetoretta
- Department of Oncology, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy
| | - Marco De Filippis
- Department of Oncology, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy
| | - Valerio Napoli
- Department of Oncology, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy
| | - Silvia Novello
- Department of Oncology, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy
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Kim SB, Ryoo S, Huh K, Joo EJ, Kim YJ, Choi WS, Kim YJ, Yoon YK, Heo JY, Seo YB, Jeong SJ, Park DA, Yu SY, Lee HJ, Kim J, Jin Y, Park J, Peck KR, Choi M, Yeom JS. Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency Guidelines on the Treatment of Patients with COVID-19. Infect Chemother 2021; 53:166-219. [PMID: 34409790 PMCID: PMC8032920 DOI: 10.3947/ic.2021.0303] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Indexed: 02/06/2023] Open
Abstract
Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.
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Affiliation(s)
- Sun Bean Kim
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Seungeun Ryoo
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Kyungmin Huh
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun Jeong Joo
- Division of Infectious Diseases, Department of Internal Medicine, Sungkyunkwan University School of Medicine, Kangbuk Samsung hospital, Seoul, Korea
| | - Youn Jeong Kim
- Division of Infectious Diseases, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Won Suk Choi
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yae Jean Kim
- Division of Infectious Diseases and Immunodeficiency. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Kyung Yoon
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jung Yeon Heo
- Department of Infectious Diseases, Ajou University school of Medicine, Suwon, Korea
| | - Yu Bin Seo
- Division of Infectious Diseases, Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Su Jin Jeong
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Ah Park
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Su Yeon Yu
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Hyeon Jeong Lee
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Jimin Kim
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Yan Jin
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Jungeun Park
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Kyong Ran Peck
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Miyoung Choi
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea.
| | - Joon Sup Yeom
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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12
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Hasegawa M, Iwasaki J, Sugiyama S, Ishihara T, Yamamoto Y, Asada H, Koide S, Hayashi H, Takahashi K, Inaguma D, Yuzawa Y, Tsuboi N. Development of aortic valve stenosis in myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement. PLoS One 2021; 16:e0245869. [PMID: 33481903 PMCID: PMC7822555 DOI: 10.1371/journal.pone.0245869] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 01/10/2021] [Indexed: 11/18/2022] Open
Abstract
Introduction Degenerative aortic valve stenosis (AS) is a chronic progressive disease that resembles atherosclerosis development. Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is reportedly associated with accelerated atherosclerosis. This study aimed to examine the development of AS in patients with myeloperoxidase-AAV (MPO-AAV) with renal involvement at more than 1 year after the onset of vasculitis. Methods We performed a retrospective review of clinical records of MPO-AAV patients with renal involvement without AS at the onset of vasculitis who were treated in three hospitals and three dialysis clinics. Results The study included 97 MPO-AAV patients with renal involvement and 230 control patients with chronic kidney disease (CKD). Among them, 64 patients had AS. The prevalence rates of AS were 28.9% and 15.7% in MPO-AAV and control patients, respectively (p = 0.006). The multivariable logistic regression analysis showed that MPO-AAV, dialysis dependence, and hypertension were independently associated factors for AS. In MPO-AAV patients, systolic blood pressure was positively significantly associated with AS, whereas glucocorticoid dose of induction therapy was negatively significantly associated. The use of cyclophosphamide tended to be negatively associated with AS. The survival rate was significantly lower for patients with AS than for those without AS. Conclusions The AS prevalence rate was significantly higher in MPO-AAV patients at more than 1 year after the onset of vasculitis than in control CKD patients. Therefore, regular monitoring of echocardiography during MPO-AAV treatment is suggested.
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Affiliation(s)
- Midori Hasegawa
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
- * E-mail:
| | - Jin Iwasaki
- Tokoname City Hospital, Tokoname, Aichi, Japan
| | | | - Takuma Ishihara
- Gifu University Hospital Innovative and Clinical Research Promotion Center, Gifu City, Gifu, Japan
| | | | | | - Shigehisa Koide
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Hiroki Hayashi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Kazuo Takahashi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
- Department of Biomedical Molecular Sciences, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Daijo Inaguma
- Department of Internal Medicine, Fujita Health University Bantane Hospital, Nagoya, Japan
| | - Yukio Yuzawa
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Naotake Tsuboi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
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13
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Gross JJ, Schwinn AC, Bruckmaier RM. Free and bound cortisol, corticosterone, and metabolic adaptations during the early inflammatory response to an intramammary lipopolysaccharide challenge in dairy cows. Domest Anim Endocrinol 2021; 74:106554. [PMID: 32920446 DOI: 10.1016/j.domaniend.2020.106554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 07/29/2020] [Accepted: 08/14/2020] [Indexed: 11/24/2022]
Abstract
Glucocorticoids, particularly cortisol and corticosterone, are key homeostatic regulators during metabolic and endocrine adaptations including inflammatory responses. Besides the established response of total cortisol (TC) concentrations during inflammatory processes in dairy cows, we investigated changes of corticosterone, free cortisol (FC), and serum albumin as the main protein of unspecific cortisol binding, in response to an intramammary lipopolysaccharide (LPS) challenge. Furthermore, we evaluated relationships of glucocorticoid responses with concomitant alterations of metabolites and their endocrine regulators, insulin and glucagon. Blood samples of 10 multiparous Holstein dairy cows (26.8 ± 3.4 d in milk, previous lactation yield: 7,601 ± 938 kg; mean ± SD) were obtained every 30 min up to 5 h after the LPS instillation, and rectal temperature and heart rate were measured in parallel. Corticosterone was measured by enzyme immunoassay, TC by radioimmunoassay, and the proportion of FC by ultrafiltration. A mixed model was used to evaluate differences within the investigated parameters among selected time points (0, 3.5, and 5 h relative to the intramammary LPS administration). Rectal temperature increased up to 41.6 ± 0.1°C at 5 h after the LPS application. Concentrations of TC and corticosterone increased until 3.5 h, and the proportion of FC relative to TC more than doubled until 3.5 h after LPS administration. Serum albumin concentration was reduced at 5 h compared with initial values, whereas concentrations of insulin, glucagon, and glucose were increased after 5 h compared with 0 h. In conclusion, the stimulation of the immune system by the intramammary LPS administration is accompanied by distinct metabolic and endocrine changes. Corticosterone and TC concentrations react similarly in response to the LPS challenge and earlier compared with metabolic adaptations. The increased need of active cortisol is covered by both increased secretion and a higher percentage of FC.
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Affiliation(s)
- J J Gross
- Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, CH-3012 Bern, Switzerland
| | - A-C Schwinn
- Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, CH-3012 Bern, Switzerland
| | - R M Bruckmaier
- Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, CH-3012 Bern, Switzerland.
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14
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Parveen RS, Hegde S, Nayak V. Investigational Drugs for the COVID 19 Pandemic – A Concise Review. PHARMACEUTICAL SCIENCES 2020. [DOI: 10.34172/ps.2020.80] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Reena Sherin Parveen
- Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal , Karnataka, -576104, India
| | - Sherya Hegde
- Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal , Karnataka, -576104, India
| | - Veena Nayak
- Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal , Karnataka, -576104, India
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15
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Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN. Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs 2020; 80:1267-1292. [PMID: 32696108 PMCID: PMC7372203 DOI: 10.1007/s40265-020-01367-z] [Citation(s) in RCA: 182] [Impact Index Per Article: 36.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms ‘coronavirus’, ‘immunology’, ‘cytokine storm’, ‘immunomodulators’, ‘pharmacology’, ‘severe acute respiratory syndrome 2’, ‘SARS-CoV-2’, and ‘COVID-19’. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte–macrophage colony-stimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms.
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Affiliation(s)
- John G Rizk
- Edson College, Arizona State University, Phoenix, AZ, USA.
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension and Kidney Transplantation, University of California, Irvine, School of Medicine, Irvine, CA, USA.,Department of Epidemiology, University of California, Los Angeles, UCLA Fielding School of Public Health, Los Angeles, CA, USA.,Tibor Rubin VA Long Beach Healthcare System, Long Beach, CA, USA
| | - Mandeep R Mehra
- Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Carl J Lavie
- John Ochsner Heart and Vascular Institute, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, LA, USA
| | - Youssef Rizk
- Department of Family Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Donald N Forthal
- Division of Infectious Diseases, Department of Medicine, University of California, Irvine, School of Medicine, Irvine, CA, USA.,Department of Molecular Biology and Biochemistry, University of California, Irvine, School of Medicine, Irvine, CA, USA
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16
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Hipp S, Voynov V, Drobits-Handl B, Giragossian C, Trapani F, Nixon AE, Scheer JM, Adam PJ. A Bispecific DLL3/CD3 IgG-Like T-Cell Engaging Antibody Induces Antitumor Responses in Small Cell Lung Cancer. Clin Cancer Res 2020; 26:5258-5268. [PMID: 32554516 DOI: 10.1158/1078-0432.ccr-20-0926] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 05/12/2020] [Accepted: 06/15/2020] [Indexed: 11/16/2022]
Abstract
PURPOSE Small cell lung cancer (SCLC) is the most lethal and aggressive subtype of lung carcinoma characterized by highly chemotherapy-resistant recurrence in the majority of patients. To effectively treat SCLC, we have developed a unique and novel IgG-like T-cell engaging bispecific antibody (ITE) that potently redirects T-cells to specifically lyse SCLC cells expressing Delta-like ligand 3 (DLL3), an antigen that is frequently expressed on the cell surface of SCLC cells, with no to very little detectable expression in normal tissues. EXPERIMENTAL DESIGN The antitumor activity and mode of action of DLL3/CD3 ITE was evaluated in vitro using SCLC cell lines and primary human effector cells and in vivo in an SCLC xenograft model reconstituted with human CD3+ T-cells. RESULTS Selective binding of DLL3/CD3 ITE to DLL3-positive tumor cells and T-cells induces formation of an immunological synapse resulting in tumor cell lysis and activation of T-cells. In a human T-cell engrafted xenograft model, the DLL3/CD3 ITE leads to an increase in infiltration of T-cells into the tumor tissue resulting in apoptosis of the tumor cells and tumor regression. Consistent with the mode of action, the DLL3/CD3 ITE treatment led to upregulation of PD-1, PD-L1, and LAG-3. CONCLUSIONS This study highlights the ability of the DLL3/CD3 ITE to induce strictly DLL3-dependent T-cell redirected lysis of tumor cells and recruitment of T-cells into noninflamed tumor tissues leading to tumor regression in a preclinical in vivo model. These data support clinical testing of the DLL3/CD3 ITE in patients with SCLC.
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Affiliation(s)
- Susanne Hipp
- Boehringer Ingelheim Pharmaceuticals, Inc., Cancer Immunology & Immune Modulation, Ridgefield, Connecticut.
| | - Vladimir Voynov
- Boehringer Ingelheim Pharmaceuticals, Inc., Biotherapeutics Discovery, Ridgefield, Connecticut
| | - Barbara Drobits-Handl
- Boehringer Ingelheim RCV, GmbH & Co KG., Cancer Pharmacology and Disease Positioning, Vienna, Austria
| | - Craig Giragossian
- Boehringer Ingelheim Pharmaceuticals, Inc., Biotherapeutics Discovery, Ridgefield, Connecticut
| | - Francesca Trapani
- Boehringer Ingelheim RCV, GmbH & Co KG., Oncology Translational Science, Vienna, Austria
| | - Andrew E Nixon
- Boehringer Ingelheim Pharmaceuticals, Inc., Biotherapeutics Discovery, Ridgefield, Connecticut
| | - Justin M Scheer
- Boehringer Ingelheim Pharmaceuticals, Inc., Biotherapeutics Discovery, Ridgefield, Connecticut
| | - Paul J Adam
- Boehringer Ingelheim RCV, GmbH & Co KG., Cancer Immunology & Immune Modulation, Vienna, Austria
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He J, Chen G, Liu M, Xu Z, Chen H, Yang L, Lv Y. Scaffold strategies for modulating immune microenvironment during bone regeneration. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 108:110411. [PMID: 31923946 DOI: 10.1016/j.msec.2019.110411] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 10/21/2019] [Accepted: 11/07/2019] [Indexed: 12/18/2022]
Abstract
Implanted bone scaffolds often fail to successfully integrate with the host tissue because they do not elicit a favorable immune reaction. Properties of bone scaffold not only provide mechanical and chemical signals to support cell adhesion, migration, proliferation and differentiation, but also play a pivotal role in determining the extent of immune response during bone regeneration. Appropriate design parameters of bone scaffold are of great significance in the process of developing a new generation of bone implants. Herein, this article addresses the recent advances in the field of bone scaffolds for immune response, particularly focusing on the physical and chemical properties of bone scaffold in manipulating the host response. Furthermore, incorporation of bioactive molecules and cells with immunoregulatory function in bone scaffolds are also presented. Finally, continuing challenges and future directions of scaffold-based strategies for modulating immune microenvironment are discussed.
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Affiliation(s)
- Jianhua He
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China.
| | - Guobao Chen
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China
| | - Mengying Liu
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China
| | - Zhiling Xu
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China.
| | - Hua Chen
- College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, PR China.
| | - Li Yang
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China.
| | - Yonggang Lv
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China.
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18
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Scherholz ML, Schlesinger N, Androulakis IP. Chronopharmacology of glucocorticoids. Adv Drug Deliv Rev 2019; 151-152:245-261. [PMID: 30797955 DOI: 10.1016/j.addr.2019.02.004] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 12/24/2018] [Accepted: 02/13/2019] [Indexed: 12/30/2022]
Abstract
Glucocorticoids influence a wide array of metabolic, anti-inflammatory, immunosuppressive, and cognitive signaling processes, playing an important role in homeostasis and preservation of normal organ function. Synthesis is regulated by the hypothalamic-pituitary-adrenal (HPA) axis of which cortisol is the primary glucocorticoid in humans. Synthetic glucocorticoids are important pharmacological agents that augment the anti-inflammatory and immunosuppressive properties of endogenous cortisol and are widely used for the treatment of asthma, Crohn's disease, and rheumatoid arthritis, amongst other chronic conditions. The homeostatic activity of cortisol is disrupted by the administration of synthetic glucocorticoids and so there is interest in developing treatment options that minimize HPA axis disturbance while maintaining the pharmacological effects. Studies suggest that optimizing drug administration time can achieve this goal. The present review provides an overview of endogenous glucocorticoid activity and recent advances in treatment options that have further improved patient safety and efficacy with an emphasis on chronopharmacology.
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Chalmers S, Khawaja A, Wieruszewski PM, Gajic O, Odeyemi Y. Diagnosis and treatment of acute pulmonary inflammation in critically ill patients: The role of inflammatory biomarkers. World J Crit Care Med 2019. [DOI: 10.5492/wjccm.v8.i5.74] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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20
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Chalmers S, Khawaja A, Wieruszewski PM, Gajic O, Odeyemi Y. Diagnosis and treatment of acute pulmonary inflammation in critically ill patients: The role of inflammatory biomarkers. World J Crit Care Med 2019; 8:59-71. [PMID: 31559145 PMCID: PMC6753396 DOI: 10.5492/wjccm.v8.i5.59] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 07/02/2019] [Accepted: 08/06/2019] [Indexed: 02/06/2023] Open
Abstract
Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite early antimicrobial therapy and lung protective mechanical ventilation. Both clinical entities are characterized by acute pulmonary inflammation in response to direct or indirect lung injury. Adjunct anti-inflammatory treatment with corticosteroids is increasingly used, although the evidence for benefit is limited. The treatment decisions are based on radiographic, clinical and physiological variables without regards to inflammatory state. Current evidence suggests a role of biomarkers for the assessment of severity, and distinguishing sub-phenotypes (hyper-inflammatory versus hypo-inflammatory) with important prognostic and therapeutic implications. Although many inflammatory biomarkers have been studied the most common and of interest are C-reactive protein, procalcitonin, and pro-inflammatory cytokines including interleukin 6. While extensively studied as prognostic tools (prognostic enrichment), limited data are available for the role of biomarkers in determining appropriate initiation, timing and dosing of adjunct anti-inflammatory treatment (predictive enrichment).
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Affiliation(s)
- Sarah Chalmers
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Ali Khawaja
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Patrick M Wieruszewski
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, United States
| | - Ognjen Gajic
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Yewande Odeyemi
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
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21
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Roxo AC, Del Pino Roxo C, Marques RG, Rodrigues NCP, Carneiro DV, Souto FMDC, Nahas FX. Endocrine-Metabolic Response in Patients Undergoing Multiple Body Contouring Surgeries After Massive Weight Loss. Aesthet Surg J 2019; 39:756-764. [PMID: 30107469 DOI: 10.1093/asj/sjy195] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The endocrine-metabolic response to trauma is directly related to its magnitude, but little is known about the adverse effects of combined surgical procedures on morbidity. OBJECTIVES The authors sought to evaluate risk factors by measuring the endocrine-metabolic response in patients who underwent multiple body-contouring surgeries after massive weight loss. METHODS This prospective, randomized, interventional study included 46 massive weight loss patients who experienced a weight loss >30% of their body mass index (BMI) and were referred for body contouring surgery. Patients were randomly allocated to the control group (n = 10) or intervention group (n = 36), which in turn was divided into 3 subgroups (n = 12, each) according to BMI, surgical time, and scar length values. Blood samples were collected from all patients at different time points to assess biological stress markers. RESULTS Levels of IL-6 in patients in the higher ranges of BMI and operating time and with more extensive scar length were significantly higher in the immediate postoperative period compared with baseline. Concentrations of noradrenaline were significantly higher 24 hours after surgery compared with baseline only in patients in the higher range of operating time. A higher level of IL-6 at 72 hours after surgery compared with baseline was associated with more extensive scar length. Levels of other biological stress markers did not significantly differ. CONCLUSIONS The combination of surgical procedures did not significantly affect the concentrations of most biological stress markers. The variable of operating time most influenced increase in plasma concentrations of stress markers. LEVEL OF EVIDENCE: 1
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Affiliation(s)
- Ana Claudia Roxo
- Division of Plastic and Reconstructive Surgery, Pedro Ernesto University Hospital, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Carlos Del Pino Roxo
- Chief of Plastic and Reconstructive Surgery Department at Andarai Federal Hospital, Rio de Janeiro, Brazil
| | - Ruy Garcia Marques
- Graduate Program in Physiopathology and Surgical Sciences, Department of General Surgery, UERJ, Rio de Janeiro, Brazil
| | | | - Diego Vigna Carneiro
- Division of Plastic and Reconstructive Surgery, Federal Hospital at Andaraí, Rio de Janeiro, Brazil
| | | | - Fabio Xerfan Nahas
- Division of Plastic Surgery, Federal University of São Paulo, São Paulo, Brazil
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22
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Ji J, Dai X, Yeung SCJ, He X. The role of long non-coding RNA GAS5 in cancers. Cancer Manag Res 2019; 11:2729-2737. [PMID: 31114330 PMCID: PMC6497482 DOI: 10.2147/cmar.s189052] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 02/15/2019] [Indexed: 12/31/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) have shown potential as a biomarker in the diagnosis and prognosis in multiple cancers. LncRNAs are dysregulated in various cancers, playing either oncogenic or tumor suppressive roles. Emerging evidences have proved that the growth arrest-specific 5 (GAS5) lncRNA can function as a tumor suppressor in several cancers. LncRNA GAS5 is downregulated in many types of cancer, regulating cellular processes such as cell proliferation, apoptosis and invasion. The low level of GAS5 expression often elevates capacity of proliferation and predicts poorer prognosis in some cancers. This review aims to summarize the recent published literature on the biogenesis, regulation mechanism and function of GAS5 in different types of cancers and explore its potential for cancer diagnosis, prognosis and treatment.
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Affiliation(s)
- Jiali Ji
- Department of Medical Oncology, The 2nd Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
| | - Xiaolan Dai
- Department of Pharmacy, School of Medicine, Shantou University, Shantou, Guangdong, People’s Republic of China
| | - Sai-Ching Jim Yeung
- Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xuexin He
- Department of Medical Oncology, The 2nd Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China
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23
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Biomaterials: Foreign Bodies or Tuners for the Immune Response? Int J Mol Sci 2019; 20:ijms20030636. [PMID: 30717232 PMCID: PMC6386828 DOI: 10.3390/ijms20030636] [Citation(s) in RCA: 363] [Impact Index Per Article: 60.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 01/22/2019] [Accepted: 01/28/2019] [Indexed: 12/11/2022] Open
Abstract
The perspectives of regenerative medicine are still severely hampered by the host response to biomaterial implantation, despite the robustness of technologies that hold the promise to recover the functionality of damaged organs and tissues. In this scenario, the cellular and molecular events that decide on implant success and tissue regeneration are played at the interface between the foreign body and the host inflammation, determined by innate and adaptive immune responses. To avoid adverse events, rather than the use of inert scaffolds, current state of the art points to the use of immunomodulatory biomaterials and their knowledge-based use to reduce neutrophil activation, and optimize M1 to M2 macrophage polarization, Th1 to Th2 lymphocyte switch, and Treg induction. Despite the fact that the field is still evolving and much remains to be accomplished, recent research breakthroughs have provided a broader insight on the correct choice of biomaterial physicochemical modifications to tune the reaction of the host immune system to implanted biomaterial and to favor integration and healing.
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24
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Lamontagne F, Rochwerg B, Lytvyn L, Guyatt GH, Møller MH, Annane D, Kho ME, Adhikari NKJ, Machado F, Vandvik PO, Dodek P, Leboeuf R, Briel M, Hashmi M, Camsooksai J, Shankar-Hari M, Baraki MK, Fugate K, Chua S, Marti C, Cohen D, Botton E, Agoritsas T, Siemieniuk RAC. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ 2018; 362:k3284. [PMID: 30097460 PMCID: PMC6083439 DOI: 10.1136/bmj.k3284] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Francois Lamontagne
- Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada
- Centre de recherche du CHU de Sherbrooke, Centre intégré universitaire de santé et de services sociaux - Estrie, Sherbrooke, Canada
| | - Bram Rochwerg
- Department of Medicine, McMaster University, Hamilton, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Lyubov Lytvyn
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Gordon H Guyatt
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Morten Hylander Møller
- Department of Intensive Care, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Djillali Annane
- Service de Médecine Intensive et Réanimation, Hôpital Raymond Poincaré, Garches, France
| | - Michelle E Kho
- School of Rehabilitation Science, McMaster University, Hamilton, Canada
| | - Neill K J Adhikari
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto Canada
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
| | - Flavia Machado
- Federal University of Sao Paulo, Sao Paulo, Brazil
- Latin America Sepsis Institute, Sao Paulo, Brazil
| | - Per O Vandvik
- Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Medicine, Innlandet Hospital Trust-division, Gjøvik, Norway
| | - Peter Dodek
- Center for Health Evaluation and Outcome Sciences and Division of Critical Care Medicine, St Paul's Hospital and University of British Columbia, Vancouver, Canada
| | - Rebecca Leboeuf
- Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
| | - Matthias Briel
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Madiha Hashmi
- Department of Anaesthesiology, Aga Khan University, Karachi, Pakistan
| | | | - Manu Shankar-Hari
- Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
- NIHR Clinician Scientist, School of Immunology & Microbial Sciences, Kings College London, United Kingdom
| | | | | | | | - Christophe Marti
- Division of General Internal Medicine, Rehabilitation and Geriatrics, University Hospitals of Geneva, Geneva, Switzerland
| | - Dian Cohen
- Centre de santé de la vallée Massawippi, Ayer's Cliff, Canada
| | - Edouard Botton
- Comité stratégique patient-partenaire, Centre de recherche du CHU de Sherbrooke, Centre intégré universitaire de santé et de services sociaux - Estrie, Sherbrooke, Canada
| | - Thomas Agoritsas
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Division General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland
| | - Reed A C Siemieniuk
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
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Penz M, Kirschbaum C, Buske-Kirschbaum A, Wekenborg MK, Miller R. Stressful life events predict one-year change of leukocyte composition in peripheral blood. Psychoneuroendocrinology 2018; 94:17-24. [PMID: 29751249 DOI: 10.1016/j.psyneuen.2018.05.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 04/25/2018] [Accepted: 05/03/2018] [Indexed: 01/13/2023]
Abstract
A plethora of cross-sectional studies suggest that psychological stress resulting from experiencing stressful life events (SLE) can result in an altered immune response. Potential maladaptive immune changes may outlast the event and affect the organism long after stress cessation. As a consequence, an increased vulnerability for immune-mediated pathologies (e.g. arthritis, diabetes) may develop over the life span. The objective of the present study was to monitor the longitudinal kinetics of peripheral white blood cells (WBCs; neutrophils, lymphocytes, and monocytes) in response to SLE. Here we present blood, hair, and behavioural measures obtained in the Dresden Burnout Study, at first visit (T1; N = 446) and one year later (T2; N = 173). Cumulative impact of SLE was assessed at T1 with the Life Stressor Checklist (LSC-R). Results indicate a significant increase in neutrophils (+2.8% per each 10 LSC-R points) between T1 and T2 in association with reported SLE. The change in neutrophils tended to correlate with the change in hair cortisol (Coheńs f = 0.6). We propose that SLE trigger immunological alterations that persist across time and thereby promote a continuous effect on WBC distribution. Such an effect might advance subclinical inflammatory processes, reduce an individualś immune defence, and promote a link between psychological stress and physical disease.
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Affiliation(s)
- Marlene Penz
- Faculty of Psychology, Technische Universität Dresden, Dresden, Germany.
| | | | | | | | - Robert Miller
- Faculty of Psychology, Technische Universität Dresden, Dresden, Germany
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Suzuki S, Iben JR, Coon SL, Kino T. SIRT1 is a transcriptional enhancer of the glucocorticoid receptor acting independently to its deacetylase activity. Mol Cell Endocrinol 2018; 461:178-187. [PMID: 28923345 PMCID: PMC5756502 DOI: 10.1016/j.mce.2017.09.012] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 09/10/2017] [Accepted: 09/13/2017] [Indexed: 12/21/2022]
Abstract
Glucocorticoids have strong effects on diverse human activities through the glucocorticoid receptor (GR). Sirtuin 1 (SIRT1) is a NAD+-dependent histone deacetylase and promotes longevity by influencing intermediary metabolism and other regulatory activities including mitochondrial function. In this study, we examined the effects of SIRT1 on GR-mediated transcriptional activity. We found that SIRT1 enhanced GR-induced transcriptional activity on endogenous and exogenous glucocorticoid-responsive genes, whereas knockdown of SIRT1 attenuated it. This effect of SIRT1 was independent to its deacetylase activity, as the SIRT1 mutant defective in this activity (H363Y) enhanced GR transcriptional activity, and the compounds inhibiting or activating the SIRT1 deacetylase activity did not influence it. RNA-seq analysis revealed that SIRT1 knockdown influenced ∼30% of the glucocorticoid-responsive transcriptome for most of which it acted as an enhancer for positive/negative effects of this hormone. SIRT1 physically interacted with GR, and was attracted to GR-bound glucocorticoid response elements in a glucocorticoid-dependent fashion. SIRT1 cooperatively activated GR transcriptional activity with the PPARγ coactivator-1α also in its deacetylase activity-independent fashion. Thus, SIRT1 is a novel transcriptional enhancer of GR-induced transcriptional activity possibly by functioning as a scaffold for the transcriptional complex formed on GR.
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Affiliation(s)
- Shigeru Suzuki
- Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA; Department of Pediatrics, Asahikawa Medical University, Asahikawa 078-8510, Japan.
| | - James R Iben
- Molecular Genomics Core, Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
| | - Steven L Coon
- Molecular Genomics Core, Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
| | - Tomoshige Kino
- Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA; Division of Translational Medicine, Sidra Medical and Research Center, Doha 26999, Qatar.
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Sylvia KE, Demas GE. Overcoming neonatal sickness: Sex-specific effects of sickness on physiology and social behavior. Physiol Behav 2017; 179:324-332. [PMID: 28689742 DOI: 10.1016/j.physbeh.2017.07.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 06/11/2017] [Accepted: 07/01/2017] [Indexed: 12/13/2022]
Abstract
Early-life environmental stressors, including sickness, have the potential to disrupt development in ways that could severely impact fitness. Despite what is known about the effects of sickness on reproduction, the precise physiological mechanisms have not yet been determined. The goal of this study was to investigate the effects of a neonatal immune challenge on adult reproductive physiology and opposite-sex social behavior. Male and female Siberian hamster (Phodopus sungorus) pups were administered lipopolysaccharide ([LPS]; a cell wall component of gram-negative bacteria) or saline injections on postnatal days 3 and 5 and body mass, food intake, and measures of reproductive maturity were taken throughout development. In adulthood, hamsters were placed in staged mating pairs with reproductively mature individuals of the opposite sex, during which a series of behaviors were scored. We found that although males and females showed no change in food intake, body mass, or reproductive behaviors, LPS-treated females had abnormal estrous cycles and smaller ovaries. Females also showed increased investigation of and increased aggression towards males in a reproductive context. In contrast, LPS-treated males showed no change in any physiological measures, nor did they show any changes in behavior. The present findings demonstrate that females may be more robustly affected by neonatal sickness than males and that these effects could have potential impacts on reproductive success. Collectively, the results of this study can be used to expand upon what is already known about sickness and reproduction, specifically the importance of social behaviors involved in pre-copulation and information necessary to choose the appropriate mate.
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Affiliation(s)
- Kristyn E Sylvia
- Department of Biology, Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, IN 47405, USA.
| | - Gregory E Demas
- Department of Biology, Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, IN 47405, USA; Program in Neuroscience, Indiana University, Bloomington, IN 47405, USA
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Kafrouni L, Savadogo O. Recent progress on magnetic nanoparticles for magnetic hyperthermia. Prog Biomater 2016; 5:147-160. [PMID: 27995583 PMCID: PMC5304434 DOI: 10.1007/s40204-016-0054-6] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Accepted: 08/19/2016] [Indexed: 01/06/2023] Open
Abstract
Recent advances in nanomaterials science contributed to develop new micro- and nano-devices as potential diagnostic and therapeutic tools in the field of oncology. The synthesis of superparamagnetic nanoparticles (SPMNPs) has been intensively studied, and the use of these particles in magnetic hyperthermia therapy has demonstrated successes in treatment of cancer. However, some physical limitations have been found to impact the heating efficiency required to kill cancer cells. Moreover, the bio-safety of NPs remains largely unexplored. The primary goals of this review are to summarize the recent progress in the development of magnetic nanoparticles (MNPs) for hyperthermia, and discuss the limitations and advances in the synthesis of these particles. Based on this knowledge, new perspectives on development of new biocompatible and biofunctional nanomaterials for magnetic hyperthermia are discussed.
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Affiliation(s)
- Lina Kafrouni
- Department of Chemical Engineering, Polytechnique Montréal, C.P. 6079, Succursale Centre-ville, Montreal, QC, H3C 3A7, Canada
- Laboratory of New Materials for Energy and Electrochemistry Systems (LaNoMat), Montreal, Canada
| | - Oumarou Savadogo
- Department of Chemical Engineering, Polytechnique Montréal, C.P. 6079, Succursale Centre-ville, Montreal, QC, H3C 3A7, Canada.
- Laboratory of New Materials for Energy and Electrochemistry Systems (LaNoMat), Montreal, Canada.
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29
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Molinaro R, Corbo C, Martinez JO, Taraballi F, Evangelopoulos M, Minardi S, Yazdi I, Zhao P, De Rosa E, Sherman M, De Vita A, Furman NT, Wang X, Parodi A, Tasciotti E. Biomimetic proteolipid vesicles for targeting inflamed tissues. NATURE MATERIALS 2016; 15:1037-46. [PMID: 27213956 PMCID: PMC5127392 DOI: 10.1038/nmat4644] [Citation(s) in RCA: 315] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 04/13/2016] [Indexed: 05/13/2023]
Abstract
A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles-which we refer to as leukosomes-retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.
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Affiliation(s)
- R. Molinaro
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
| | - C. Corbo
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
- EINGE–Biotecnologie Avanzate s.c.a.r.l., Via G. Salvatore 486, 80145 Naples, Italy
- IRCCS SDN, Via Gianturco 113, 80143 Naples, Italy
| | - J. O. Martinez
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
| | - F. Taraballi
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
- Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
| | - M. Evangelopoulos
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
| | - S. Minardi
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
| | - I.K. Yazdi
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
| | - P. Zhao
- Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
| | - E. De Rosa
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
| | - M. Sherman
- Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555
| | - A. De Vita
- Osteoncology and Rare Tumors Center, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy
| | - N.E. Toledano Furman
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
| | - X. Wang
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
| | - A. Parodi
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
- IRCCS SDN, Via Gianturco 113, 80143 Naples, Italy
| | - E. Tasciotti
- Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, Texas 77030, USA
- To whom correspondence should be addressed: Dr. Ennio Tasciotti, Department of Regenerative Medicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030,
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Chatzopoulou A, Heijmans JPM, Burgerhout E, Oskam N, Spaink HP, Meijer AH, Schaaf MJM. Glucocorticoid-Induced Attenuation of the Inflammatory Response in Zebrafish. Endocrinology 2016; 157:2772-84. [PMID: 27219276 DOI: 10.1210/en.2015-2050] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Glucocorticoids are steroid hormones that are secreted upon stress. Their effects are mediated by the glucocorticoid receptor, which acts as a transcription factor. Because the antiinflammatory activity of glucocorticoids has been well established, they are widely used clinically to treat many inflammatory and immune-related diseases. However, the exact specificity, mechanisms, and level of regulation of different inflammatory pathways have not been fully elucidated. In the present study, a tail fin amputation assay was used in 3-day-old zebrafish larvae to study the immunomodulatory effects of the synthetic glucocorticoid beclomethasone. First, a transcriptome analysis was performed, which showed that upon amputation mainly immune-related genes are regulated. This regulation was inhibited by beclomethasone for 86% of regulated genes. For two immune-related genes, tlr4bb and alox5ap, the amputation-induced increase was not attenuated by beclomethasone. Alox5ap is involved in eicosanoid biosynthesis, but the increase in leukotriene B4 concentration upon amputation was abolished, and lipoxin A4 levels were unaffected by beclomethasone. Furthermore, we studied the migration of neutrophils and macrophages toward the wound site. Our results show that amputation induced migration of both types of leukocytes and that this migration was dependent on de novo protein synthesis. Beclomethasone treatment attenuated the migratory behavior of neutrophils in a glucocorticoid receptor-dependent manner but left the migration of macrophages unaffected. In conclusion, beclomethasone has a dramatic inhibitory effect on the amputation-induced proinflammatory gene regulation, and this is reflected in an inhibition of the neutrophil migration but not the migration of macrophages, which are likely to be involved in inflammation resolution.
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Affiliation(s)
| | | | - Erik Burgerhout
- Institute of Biology, Leiden University, 2333CC Leiden, The Netherlands
| | - Nienke Oskam
- Institute of Biology, Leiden University, 2333CC Leiden, The Netherlands
| | - Herman P Spaink
- Institute of Biology, Leiden University, 2333CC Leiden, The Netherlands
| | | | - Marcel J M Schaaf
- Institute of Biology, Leiden University, 2333CC Leiden, The Netherlands
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31
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Lai W, Tian X, Xiang Q, Chu K, Wei Y, Deng J, Zhang S, Brown J, Hong G. 11β-HSD1 modulates LPS-induced innate immune responses in adipocytes by altering expression of PTEN. Mol Endocrinol 2015; 29:558-70. [PMID: 25734515 DOI: 10.1210/me.2014-1287] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) represents a therapeutic target for treating hyperglycemia in type 2 diabetes. Here, we investigate the effects of 11β-HSD1 on the innate immune response of adipocytes to produce proinflammatory cytokines. The 11β-HSD1 inhibitor emodin, or 11β-HSD1-targeted small interfering RNA, dose dependently suppressed IL-6, IL-1β, and TNF-α expression in lipopolysaccharide-treated 3T3-L1 adipocytes. Inhibiting 11β-HSD1 also reduced phosphatase and tensin homologue (PTEN) expression, a negative regulator of phosphatidylinositol 3-kinase effects, whereas 1pM cortisone or dexamethasone induced IL-6 and PTEN levels. PTEN-targeted small interfering RNA decreased IL-6, IL-1β, and TNF-α without affecting 11β-HSD1 levels. Correspondingly, emodin increased phosphorylated protein kinase B (p-PKB) (Ser473) to PKB ratio but not p-PKB (Thr308) to PKB ratio. Emodin did not increase the p-PKB (Ser473) to PKB ratio when the rapamycin-insensitive companion of mTOR was depleted, further supporting the involvement of mammalian target of rapamycin complex 2 in PKB phosphorylation. Moreover, emodin suppressed phosphorylated inhibitor of κB α (p-IκBα) to IκBα ratio and reduced nuclear factor κ B subunit p50 in the nuclear fraction. In contrast, 1pM cortisone or dexamethasone decreased p-PKB (Ser473) to PKB ratio, increased p-IκBα to IκBα ratio, and increased nuclear NF-κB subunit p50. Additionally, wortmannin had similar effects on IL-6, p-PKB (Ser473) to PKB ratio, and p-IκBα to IκBα ratio as 1pM cortisone or dexamethasone. Finally, emodin treatment of streptozotocin diabetic rats on a high-fat diet reduced levels of IL-6, PTEN, Cluster of Differentiation 68, and the ratio of p-IκBα to IκBα in visceral fat, indicating that our findings in vitro may also apply to visceral fat in vivo. Together, these results suggest that inhibiting 11β-HSD1 reduces lipopolysaccharide-induced proinflammatory innate immune responses in adipocytes by down-regulating PTEN expression, leading to activation of the PI3K/PKB pathway.
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Affiliation(s)
- Wenfang Lai
- Centre of Biomedical Research and Development (W.L., X.T., Q.X., K.C., Y.W., J.D., S.Z., J.B., G.H.), Fujian University of Traditional Chinese Medicine, Minhou Shangjie, Fuzhou, 350108, China; and School of Biological Sciences (S.Z.), Faculty of Science, University of Auckland, 1142, Auckland, New Zealand
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Swartz J, Lindblad F, Arinell H, Theorell T, Alm J. Anthroposophic lifestyle and salivary cortisol are associated with a lower risk of sensitization during childhood. Pediatr Allergy Immunol 2015; 26:153-60. [PMID: 25620268 DOI: 10.1111/pai.12342] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/05/2015] [Indexed: 11/30/2022]
Abstract
BACKGROUND Infants from anthroposophic families have low cortisol levels and low risk of IgE-sensitization during first 2 years of life. Our aim was to study the impact of an anthroposophic lifestyle and cortisol levels at 6 months on allergy sensitization up to age 5 years. METHODS A total of 507 families participated from maternal healthcare centers. Parental lifestyle was categorized as anthroposophic, partly anthroposophic, or non-anthroposophic. Blood samples for analyzes of sensitization were obtained from parents at inclusion and from children at 6, 12, 24, and 60 months. Salivary samples were collected at home at 6 months. RESULTS Sensitization increased from 2.9% to 26.0% in the anthroposophic group, from 8.4% to 26.8% in the partly anthroposophic group, and from 19.1% to 44.1% in the non-anthroposophic group. Children from anthroposophic families had lower cortisol levels in the morning, afternoon, and evening. The odds ratio (OR) for anthroposophic lifestyle was always <1 and lowest at 12 months (OR, 0.10; 95% CI, 0.03-0.36). Adjusting for cortisol levels at 6 months increased these ORs at 12 and 24 months. At the same ages, ORs for sensitization were elevated also for cortisol levels at 6 months. Analyzes in children not sensitized at 6 months confirmed the cortisol-related risk of sensitization. CONCLUSIONS Children from families with an anthroposophic lifestyle have lower risk than comparisons of developing sensitization up to 5 years. This risk is partially explained by low cortisol levels during infancy. High cortisol levels at 6 months predict sensitization up to 24 months.
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Affiliation(s)
- Jackie Swartz
- Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden; Vidarkliniken and Integrative Care Science Centre, Järna, Sweden
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Bitsika V, Sharpley CF, Andronicos NM, Agnew LL. Hypothalamus–pituitary–adrenal axis daily fluctuation, anxiety and age interact to predict cortisol concentrations in boys with an autism spectrum disorder. Physiol Behav 2015; 138:200-7. [DOI: 10.1016/j.physbeh.2014.11.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/01/2014] [Accepted: 11/03/2014] [Indexed: 12/20/2022]
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Satheeshkumar PS, Mohan MP. Tachykinin peptide, substance P, and its receptor NK-1R play an important role in alimentary tract mucosal inflammation during cytotoxic therapy. Dig Dis Sci 2014; 59:2864-73. [PMID: 24981415 DOI: 10.1007/s10620-014-3263-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2014] [Accepted: 06/19/2014] [Indexed: 12/13/2022]
Abstract
The alimentary tract mucosal inflammation has been a topic of concern in oncology; though many modalities of treatment have been proposed for mucosal inflammation, the contributing adverse effects have severely affected the quality of life of patients. This review focuses on the importance of neurogenic peptide, Substance P and its receptor NK-1R in modulating the cascades of events in mucosal inflammation during cytotoxic therapy. There are various preclinical and clinical models showing increased expression of Substance P/NK-1R in ionizing radiation and chemotherapy, but only very few preclinical studies to our knowledge have highlighted or examined its role in mucosal inflammation. Hence, the importance of neuropeptide involved in the inflammatory events in mucosal inflammation in cytotoxic therapy could be a major breakthrough for future research purposes and treatment. The factors contributing to the severity of tissue reactions have been multietiogenic; thus, resultant treatment also has to be directed toward multiple contributing factors. This review also focuses on the significance of care strategy to be adopted in alimentary tract mucositis when multietiogenic factors are taken into consideration.
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Affiliation(s)
- P S Satheeshkumar
- Department of Oncology and Palliative Medicine, Velindre Hospital, Cardiff University, Wales, CF 14 2TL, UK,
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35
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The role of H3K4me3 and H3K9/14ac in the induction by dexamethasone of Per1 and Sgk1, two glucococorticoid early response genes that mediate the effects of acute stress in mammals. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 2014; 1839:866-72. [DOI: 10.1016/j.bbagrm.2014.07.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Revised: 06/16/2014] [Accepted: 07/14/2014] [Indexed: 12/21/2022]
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Ratnayake U, Quinn T, Walker DW, Dickinson H. Cytokines and the neurodevelopmental basis of mental illness. Front Neurosci 2013; 7:180. [PMID: 24146637 PMCID: PMC3797953 DOI: 10.3389/fnins.2013.00180] [Citation(s) in RCA: 88] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2013] [Accepted: 09/19/2013] [Indexed: 11/21/2022] Open
Abstract
Epidemiological studies suggest that prenatal exposure to different types of viral or bacterial infections may be associated with similar outcomes; i.e., an increased risk of mental illness disorders in the offspring. Infections arising from various causes have similar debilitating effects in later life, suggesting that the exact pathogen may not be the critical factor in determining the neurological and cognitive outcome in the offspring. Instead, it is thought that response of the innate immune system, specifically the increased production of inflammatory cytokines, may be the critical mediator in altering fetal brain development pre-disposing the offspring to mental illness disorders later in life. Inflammatory cytokines are essential for normal brain development. Factors such as the site of cytokine production, a change in balance between anti- and pro- inflammatory cytokines, placental transfer of cytokines, the effects of cytokines on glial cells, and the effects of glucocorticoids are important when evaluating the impact of maternal infection on fetal brain development. Although it is clear that cytokines are altered in the fetal brain following maternal infection, further evidence is required to determine if cytokines are the critical factor that alters the trajectory of brain development, subsequently leading to postnatal behavioral and neurological abnormalities.
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Affiliation(s)
- Udani Ratnayake
- Ritchie Centre, Monash Institute of Medical Research, Monash University Clayton, Australia
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37
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Rose'meyer R. A review of the serotonin transporter and prenatal cortisol in the development of autism spectrum disorders. Mol Autism 2013; 4:37. [PMID: 24103554 PMCID: PMC3852299 DOI: 10.1186/2040-2392-4-37] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Accepted: 09/13/2013] [Indexed: 01/28/2023] Open
Abstract
The diagnosis of autism spectrum disorder (ASD) during early childhood has a profound effect not only on young children but on their families. Aside from the physical and behavioural issues that need to be dealt with, there are significant emotional and financial costs associated with living with someone diagnosed with ASD. Understanding how autism occurs will assist in preparing families to deal with ASD, if not preventing or lessening its occurrence. Serotonin plays a vital role in the development of the brain during the prenatal and postnatal periods, yet very little is known about the serotonergic systems that affect children with ASD. This review seeks to provide an understanding of the biochemistry and physiological actions of serotonin and its termination of action through the serotonin reuptake transporter (SERT). Epidemiological studies investigating prenatal conditions that can increase the risk of ASD describe a number of factors which elevate plasma cortisol levels causing such symptoms during pregnancy such as hypertension, gestational diabetes and depression. Because cortisol plays an important role in driving dysregulation of serotonergic signalling through elevating SERT production in the developing brain, it is also necessary to investigate the physiological functions of cortisol, its action during gestation and metabolic syndromes.
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Affiliation(s)
- Roselyn Rose'meyer
- School of Medical Sciences, Griffith University, Gold Coast Campus, Parklands Drive, Southport, Queensland 4222, Australia.
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Brooks K, Caruthers RL, Schumacher KR, Stringer KA. Pharmacotherapy challenges of Fontan-associated plastic bronchitis: a rare pediatric disease. Pharmacotherapy 2013; 33:922-34. [PMID: 23686915 DOI: 10.1002/phar.1290] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Pediatric pharmacotherapy is often challenging due to the paucity of available clinical data on the safety and efficacy of drugs that are commonly used in children. This quandary is even more prevalent in children with rare diseases. Although extrapolations for dosing and administration are often made from available adult data with similar disease states, this translation becomes even more problematic in rare pediatric diseases. Understanding of rare disease pathophysiology is typically poor, and few, if any, effective therapies have been studied and identified. One condition that illustrates these issues is plastic bronchitis, a rare, most often pediatric disease that is characterized by the production of obstructive bronchial airway casts. This illness primarily occurs in children with congenital heart disease, often after palliative surgery. Plastic bronchitis is a highly clinically relevant and therapeutically challenging problem with a high mortality rate, and, a generally accepted effective pharmacotherapy regimen has yet to be identified. Furthermore, the disease is ill defined, which makes timely identification and treatment of children with plastic bronchitis difficult. The pharmacotherapies currently used to manage this disease are largely anecdotal and vary between the use of macrolide antibiotics, mucolytics, bronchodilators, and inhaled fibrinolytics in a myriad of combinations. The purpose of this review is 2-fold: first, to highlight the dilemma of treating plastic bronchitis, and second, to bring attention to the continuing need for studies of drug therapies used in children so safe and effective drug regimens can be established, particularly for rare diseases.
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Affiliation(s)
- Kristina Brooks
- Department of Clinical, Social and Administrative Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan
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Luo MJ, Thieringer R, Springer MS, Wright SD, Hermanowski-Vosatka A, Plump A, Balkovec JM, Cheng K, Ding GJ, Kawka DW, Koo GC, Grand CBL, Luo Q, Maletic MM, Malkowitz L, Shah K, Singer I, Waddell ST, Wu KK, Yuan J, Zhu J, Stepaniants S, Yang X, Lum PY, Wang IM. 11β-HSD1 inhibition reduces atherosclerosis in mice by altering proinflammatory gene expression in the vasculature. Physiol Genomics 2012; 45:47-57. [PMID: 23170035 DOI: 10.1152/physiolgenomics.00109.2012] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is implicated in the etiology of metabolic syndrome. We previously showed that pharmacological inhibition of 11β-HSD1 ameliorated multiple facets of metabolic syndrome and attenuated atherosclerosis in ApoE-/- mice. However, the molecular mechanism underlying the atheroprotective effect was not clear. In this study, we tested whether and how 11β-HSD1 inhibition affects vascular inflammation, a major culprit for atherosclerosis and its associated complications. ApoE-/- mice were treated with an 11β-HSD1 inhibitor for various periods of time. Plasma lipids and aortic cholesterol accumulation were quantified. Several microarray studies were carried out to examine the effect of 11β-HSD1 inhibition on gene expression in atherosclerotic tissues. Our data suggest 11β-HSD1 inhibition can directly modulate atherosclerotic plaques and attenuate atherosclerosis independently of lipid lowering effects. We identified immune response genes as the category of mRNA most significantly suppressed by 11β-HSD1 inhibition. This anti-inflammatory effect was further confirmed in plaque macrophages and smooth muscle cells procured by laser capture microdissection. These findings in the vascular wall were corroborated by reduction in circulating MCP1 levels after 11β-HSD1 inhibition. Taken together, our data suggest 11β-HSD1 inhibition regulates proinflammatory gene expression in atherosclerotic tissues of ApoE-/- mice, and this effect may contribute to the attenuation of atherosclerosis in these animals.
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Affiliation(s)
- Mingjuan J Luo
- Cardiovascular Disease Department, Merck Research Laboratories, Rahway, NJ, USA
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Activity-guided screening of bioactive natural compounds implementing a new glucocorticoid-receptor-translocation assay and detection of new anti-inflammatory steroids from bacteria. Biotechnol Lett 2012; 35:11-20. [DOI: 10.1007/s10529-012-1042-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Accepted: 08/24/2012] [Indexed: 12/23/2022]
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Martin C, Steinke T, Bucher M, Raspé C. [Perioperative Addisonian crisis]. Anaesthesist 2012; 61:503-11. [PMID: 22695777 DOI: 10.1007/s00101-012-2033-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2011] [Revised: 04/02/2012] [Accepted: 04/19/2012] [Indexed: 10/28/2022]
Abstract
An Addisonian crisis marks an acute adrenocortical failure which can be caused by decompensation of a chronic insufficiency due to stress, an infarct or bleeding of the adrenal cortex and also abrupt termination of a long-term glucocorticoid medication. This article reports the case of a 25-year-old patient with Crohn's disease who suffered an Addisonian crisis with hypotension, hyponatriemia and hypoglycemia during an emergency laparotomy after he had terminated prednisolone medication on his own authority. This necessitated an aggressive volume therapy in addition to an initial therapy with 100 mg hydrocortisone, 8 g glucose and a continuous administration of catecholamines. Under this treatment regimen hemodynamic stabilization was achieved. Reduction of the administration of hydrocortisone after 3 days resulted in cardiovascular insufficiency which required an escalation of the hydrocortisone substitution.
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Affiliation(s)
- C Martin
- Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle, Deutschland.
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Saban KL, Mathews HL, Bryant FB, O'Brien TE, Janusek LW. Depressive symptoms and diurnal salivary cortisol patterns among female caregivers of stroke survivors. Biol Res Nurs 2012; 14:396-404. [PMID: 22531368 DOI: 10.1177/1099800412439458] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Informal caregivers of stroke survivors experience elevated chronic stress and are at risk of developing depressive symptoms. The cumulative effects of chronic stress can increase allostatic load and dysregulate biological processes, thus increasing risk of stress-related disease. Stress-induced alterations in the pattern of cortisol secretion vary with respect to stressor onset, intensity, and chronicity. Little is known about the psychoendocrine response to stress in female caregivers of stroke survivors. The purpose of this study was to examine perceived stress, caregiver burden, and the association between caregiver depressive symptoms and diurnal cortisol in 45 females caring for a significant other who experienced a stroke within the past year. Women completed the Center for Epidemiologic Studies Depression Scale (CES-D) and collected saliva for cortisol upon awakening, 30 min postawakening, noon, and bedtime for 2 consecutive days. Results revealed that women had high levels of perceived stress and caregiver burden. In women with CES-D scores ≥ 16, salivary cortisol levels were significantly lower across the day relative to women with CES-D scores < 16. This difference persisted after adjusting for age, number of caregiving hours per week, perceived social support, and quality of sleep. Younger age was associated with more depressive symptoms as well as lower levels of cortisol at awakening and 30 min postawakening. Results demonstrate that the burden of caregiving increases risk of depressive symptoms and hypocortisolism across the day. Hypocortisolism may contribute to increased risk of depressive symptoms as a result of the loss of glucocorticoid attenuation of stress-induced inflammation.
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Affiliation(s)
- Karen L Saban
- Loyola University Chicago, Marcella Niehoff School of Nursing, Maywood, IL 60153, USA.
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43
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Gump BB, MacKenzie JA, Dumas AK, Palmer CD, Parsons PJ, Segu ZM, Mechref YS, Bendinskas KG. Fish consumption, low-level mercury, lipids, and inflammatory markers in children. ENVIRONMENTAL RESEARCH 2012; 112:204-211. [PMID: 22030286 PMCID: PMC3267839 DOI: 10.1016/j.envres.2011.10.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2011] [Revised: 10/01/2011] [Accepted: 10/05/2011] [Indexed: 05/29/2023]
Abstract
There is considerable evidence that consuming fish has numerous health benefits, including a reduced risk of cardiovascular disease. However, fish is also the primary source of human exposure to mercury (Hg). In a cross-sectional study of 9-11 year old children (N=100), we measured fish consumption, blood lipids, total blood Hg, diurnal salivary cortisol (4 samples collected throughout the day), and performed a proteomic analysis of serum proteins using spectral count shotgun proteomics. Children who consumed fish had a significantly more atheroprotective lipid profile but higher levels of blood Hg relative to children that did not consume fish. Although the levels of blood Hg were very low in these children (M=0.77 μg/L; all but 1 participant had levels below 3.27 μg/L), increasing blood Hg was significantly associated with blunted diurnal cortisol levels. Blood Hg was also significantly associated with acute-phase proteins suggesting systemic inflammation, and several of these proteins were found to significantly reduce the association between Hg and diminished cortisol when included in the model. This study of a pediatric population is the first to document an association between blood Hg, systemic inflammation, and endocrine disruption in humans. Without a better understanding of the long-term consequences of an atheroprotective lipid profile relative to blunted diurnal cortisol and systemic inflammation, a determination of the risk-benefit ratio for fish consumption by children is not possible.
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Affiliation(s)
- Brooks B Gump
- Department of Public Health, Food Studies, and Nutrition, Syracuse University, Syracuse, NY 13244, USA.
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Keh D, Feldheiser A, Ahlers O. Current state of corticosteroid therapy in patients with septic shock. ACTA ACUST UNITED AC 2011. [DOI: 10.3109/09563070512331391309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Goodin BR, Quinn NB, King CD, Page GG, Haythornthwaite JA, Edwards RR, Stapleton L, McGuire L. Salivary cortisol and soluble tumor necrosis factor-α receptor II responses to multiple experimental modalities of acute pain. Psychophysiology 2011; 49:118-27. [PMID: 21895688 DOI: 10.1111/j.1469-8986.2011.01280.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The present study compared cortisol and soluble tumor necrosis factor-α receptor II (sTNFαRII) responses provoked by cold pressor, hot water, ischemic, and neutral water (i.e., room temperature) modalities. Oral fluid samples were collected before, immediately after, and during recovery to assess physiological responses. From baseline, the cold pressor, but not hot water or ischemic modalities, produced a significant time-dependent elevation in cortisol, whereas cortisol significantly decreased for the neutral water task. When compared to baseline, the cold pressor, hot water, and ischemic modalities were associated with decreased sTNFαRII responses over time. The sTNFαRII response to neutral water initially decreased but returned to approximate baseline levels. Pain ratings were positively associated with cortisol increase from baseline and the overall cortisol response was negatively associated with the overall sTNFαRII response.
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Affiliation(s)
- Burel R Goodin
- University of Florida College of Dentistry, Gainesville, Florida 32610, USA.
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Franz S, Rammelt S, Scharnweber D, Simon JC. Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials. Biomaterials 2011; 32:6692-709. [PMID: 21715002 DOI: 10.1016/j.biomaterials.2011.05.078] [Citation(s) in RCA: 939] [Impact Index Per Article: 67.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2011] [Accepted: 05/26/2011] [Indexed: 12/11/2022]
Abstract
A key for long-term survival and function of biomaterials is that they do not elicit a detrimental immune response. As biomaterials can have profound impacts on the host immune response the concept emerged to design biomaterials that are able to trigger desired immunological outcomes and thus support the healing process. However, engineering such biomaterials requires an in-depth understanding of the host inflammatory and wound healing response to implanted materials. One focus of this review is to outline the up-to-date knowledge on immune responses to biomaterials. Understanding the complex interactions of host response and material implants reveals the need for and also the potential of "immunomodulating" biomaterials. Based on this knowledge, we discuss strategies of triggering appropriate immune responses by functional biomaterials and highlight recent approaches of biomaterials that mimic the physiological extracellular matrix and modify cellular immune responses.
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Affiliation(s)
- Sandra Franz
- Department of Dermatology, Venerology and Allergology, University Leipzig, 04103 Leipzig, Germany.
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Vogelzangs N, Beekman ATF, Milaneschi Y, Bandinelli S, Ferrucci L, Penninx BWJH. Urinary cortisol and six-year risk of all-cause and cardiovascular mortality. J Clin Endocrinol Metab 2010; 95:4959-64. [PMID: 20739384 PMCID: PMC2968721 DOI: 10.1210/jc.2010-0192] [Citation(s) in RCA: 106] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
CONTEXT The stress hormone cortisol has been linked with unfavorable cardiovascular risk factors, but longitudinal studies examining whether high levels of cortisol predict cardiovascular mortality are largely absent. OBJECTIVE The aim of this study was to examine whether urinary cortisol levels predict all-cause and cardiovascular mortality over 6 yr of follow-up in a general population of older persons. DESIGN AND SETTING Participants were part of the InCHIANTI study, a prospective cohort study in the older general population with 6 yr of follow-up. PARTICIPANTS We studied 861 participants aged 65 yr and older. MAIN OUTCOME MEASURE Twenty-four-hour urinary cortisol levels were assessed at baseline. In the following 6 yr, all-cause and cardiovascular mortality was ascertained from death certificates. Cardiovascular mortality included deaths due to ischemic heart disease and cerebrovascular disease. RESULTS During a mean follow-up of 5.7 (sd = 1.2) yr, 183 persons died, of whom 41 died from cardiovascular disease. After adjustment for sociodemographics, health indicators, and baseline cardiovascular disease, urinary cortisol did not increase the risk of noncardiovascular mortality, but it did increase cardiovascular mortality risk. Persons in the highest tertile of urinary cortisol had a five times increased risk of dying of cardiovascular disease (hazard ratio = 5.00; 95% confidence interval = 2.02-12.37). This effect was found to be consistent across persons with and without cardiovascular disease at baseline (p interaction = 0.78). CONCLUSIONS High cortisol levels strongly predict cardiovascular death among persons both with and without preexisting cardiovascular disease. The specific link with cardiovascular mortality, and not other causes of mortality, suggests that high cortisol levels might be particularly damaging to the cardiovascular system.
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Affiliation(s)
- Nicole Vogelzangs
- Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
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Hong-wei G, Jun D, Xi-chuan Y, Bai-yu Z, Zhu S, Shao-yan Y, Bao-heng L, Fei H. Melanocortin receptor type 2 (MC2R, ACTH receptor) expression in patients with alopecia areata. Exp Dermatol 2010; 19:1020-2. [DOI: 10.1111/j.1600-0625.2010.01125.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Reduced stress fever is accompanied by increased glucocorticoids and reduced PGE2 in adult rats exposed to endotoxin as neonates. J Neuroimmunol 2010; 225:77-81. [PMID: 20546941 DOI: 10.1016/j.jneuroim.2010.04.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2010] [Revised: 04/26/2010] [Accepted: 04/27/2010] [Indexed: 11/22/2022]
Abstract
Immune challenges during neonatal period may permanently program immune responses later in life, including endotoxin fever. We tested the hypothesis that neonatal endotoxin exposure affects stress fever in adult rats. In control rats (treated with saline as neonates; nSal) body temperature peaked approximately 1.5 degrees C during open-field stress, whereas in rats exposed to endotoxin (lipopolysaccharide, LPS) as neonates (nLPS) stress fever was significantly attenuated. Following stress, plasma corticosterone levels significantly increased from 74.29+/-7.05 ng ml(-1) to 226.29+/-9.87 ng ml(-1) in nSal rats, and from 83.43+/-10.31 ng ml(-1) to 324.7+/-36.87 ng ml(-1) in nLPS rats. Animals treated with LPS as neonates and adrenalectomized one week before experimentation no longer displayed the attenuated febrile response to stress. This attenuated stress fever caused by an increased corticosterone secretion is likely to be linked to an inhibitory effect of glucocorticoids on cyclooxygenase activity/PGE(2) production in preoptic/anteroventral third ventricular region (AV3V) since stress failed to cause a significant increase in PGE(2) in nLPS rats, and this effect was reverted by adrenalectomy. Altogether, the present results indicate that endogenous glucocorticoids are key modulators of the attenuated stress fever in adult rats treated with LPS as neonates, and they act downregulating PGE(2) production in AV3V. Moreover, our findings also support the notion that neonatal immune stimulus affects programming of stress responses during adulthood, despite the fact that inflammation and stress are two distinct processes mediated largely by different neurobiological mechanisms.
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