scholarly journals TGF-β type 2 receptor–mediated modulation of the IL-36 family can be therapeutically targeted in osteoarthritis

2019 ◽  
Vol 11 (491) ◽  
pp. eaan2585 ◽  
Author(s):  
Tieshi Li ◽  
Susan Chubinskaya ◽  
Alessandra Esposito ◽  
Xin Jin ◽  
Lidia Tagliafierro ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Therapeutic Agent ◽  
Human Tissues ◽  
Human Cartilage ◽  
Joint Development ◽  
Naturally Occurring ◽  
Oa Chondrocytes ◽  
Disease Modifying ◽  
Surgical Conditions

Mechanisms that govern the shift from joint homeostasis to osteoarthritis (OA) remain unknown. Here, we identify a pathway used for joint development and homeostasis, and its role in OA. Using a combination of transgenic, pharmacological, and surgical conditions in mouse and human tissues, we found that TGF-β signaling promotes joint homeostasis through regulation of the IL-36 family. We identified IL-36 receptor antagonist (IL-36 in mice and IL-36RN in humans) as a potential disease-modifying OA drug. Specifically, OA development was associated with IL-36α up-regulation and IL-36Ra down-regulation in mice with tissue-specific postnatally induced ablation of Tgfbr2, mice treated with a TGF-β signaling inhibitor, mice with posttraumatic OA, and aging mice with naturally occurring OA. In human cartilage, OA severity was associated with decreased TGFBR2 and IL-36RN, whereas IL-36α increased. Functionally, intra-articular treatment with IL-36Ra attenuated OA development in mice, and IL-36RN reduced MMP13 in human OA chondrocytes. These findings highlight the relevance of TGFBR2–IL-36 interplay in joint homeostasis and IL-36RN as a potential therapeutic agent for OA.

scholarly journals Hypomagnesemia Induced by Long-Term Treatment with Proton-Pump Inhibitors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Simone Janett ◽  
Pietro Camozzi ◽  
Gabriëlla G. A. M. Peeters ◽  
Sebastiano A. G. Lava ◽  
Giacomo D. Simonetti ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Term Treatment ◽  
Cross Sectional ◽  
Magnesium Metabolism ◽  
Poor Renal Function ◽  
Long Term Treatment

In 2006, hypomagnesemia was first described as a complication of proton-pump inhibitors. To address this issue, we systematically reviewed the literature. Hypomagnesemia, mostly associated with hypocalcemic hypoparathyroidism and hypokalemia, was reported in 64 individuals on long-term proton-pump inhibitors. Hypomagnesemia recurred following replacement of one proton-pump inhibitor with another but not with a histamine type-2 receptor antagonist. The association between proton-pump inhibitors and magnesium metabolism was addressed in 14 case-control, cross-sectional studies. An association was found in 11 of them: 6 reports found that the use of proton-pump inhibitors is associated per se with a tendency towards hypomagnesemia, 2 found that this tendency is more pronounced in patients concurrently treated with diuretics, carboplatin, or cisplatin, and 2 found a relevant tendency to hypomagnesemia in patients with poor renal function. Finally, findings likely reflecting decreased intestinal magnesium uptake were observed on treatment with proton-pump inhibitors. Three studies did not disclose any relationship between magnesium metabolism and treatment with histamine type-2 receptor antagonists. In conclusion, proton-pump inhibitors may cause hypomagnesemia. In these cases, switching to a histamine type-2 receptor antagonist is advised.

scholarly journals Expression analysis of loci associated with type 2 diabetes in human tissues

Diabetologia ◽  
2010 ◽  
Vol 53 (11) ◽  
pp. 2334-2339 ◽  
Author(s):  
C. Cotsapas ◽  
L. Prokunina-Olsson ◽  
C. Welch ◽  
R. Saxena ◽  
C. Weaver ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Expression Analysis ◽  
Human Tissues

Phytoconstituents in the Management of Covid-19: Demystifying the Fact

Drug Research ◽  
2022 ◽  
Author(s):  
Md. Abul Barkat ◽  
Pawan Kaushik ◽  
Harshita Abul Barkat ◽  
Mohammad Idreesh Khan ◽  
Hazrina Ab Hadi
Keyword(s):  
Therapeutic Agent ◽  
Clinical Development ◽  
World Health ◽  
Therapeutic Drug ◽  
Scientific Communities ◽  
Synthetic Drugs ◽  
Naturally Occurring ◽  
Deadly Disease ◽  
Novel Coronavirus ◽  
Health Organization

AbstractThe 2019-nCoV (COVID-19; novel coronavirus disease-2019) outbreak is caused by the coronavirus, and its continued spread is responsible for increasing deaths, social and economic burden. COVID-19 created a chaotic situation worldwide and claimed the lives of over 5,027,183 and 248,467,363 confirmed cases have been reported so far as per the data published by WHO (World Health Organization) till 5th November 2021. Scientific communities all over the world are toiling to find a suitable therapeutic drug for this deadly disease. Although till date no promising drug has been discovered for this COVID-19. However, as per the WHO, over 102 COVID-19 vaccines are in clinical development and 185 in pre-clinical development. Naturally occurring phytoconstituents possess considerable chemical richness in the form of anti-viral and anti-parasitic potential and have been extensively exploited for the same globally. Still, phytomedicine-based therapies are considered as the best available treatment option to minimize and treat the symptoms of COVID-19 because of the least possible side effects compared to synthetic drugs recommended by the physicians/clinicians. In this review, the use of plant chemicals as a possible therapeutic agent for severe acute respiratory syndrome coronavirus 2 (SARS CoV2) is highlighted with their proposed mechanism of action, which will prove fruitful and effective in finding a cure for this deadly disease.

Catabolism of intracerebroventricularly injected 5-hydroxytryptamine in mouse: effect of coinjection of tryptamine and several pretreatments

1993 ◽  
Vol 71 (3-4) ◽  
pp. 201-204 ◽  
Author(s):  
B. Duff Sloley ◽  
Shuzo Orikasa ◽  
Alan A. Boulton
Keyword(s):  
Monoamine Oxidase ◽  
Receptor Antagonist ◽  
Mouse Brain ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Nerve Terminals ◽  
Intracerebroventricular Injection ◽  
Hydroxyindoleacetic Acid

The catabolism of intracerebroventricularly injected 5-hydroxytryptamine in mouse brain was investigated. Pretreatment of animals with the 5-hydroxytryptamine type 1 receptor antagonist metergoline, the 5-hydroxytryptamine type 2 receptor antagonist ketanserin, the 5-hydroxytryptamine reuptake inhibitor fluoxetine, or the selective 5-hydroxytryptamine neurotoxin 5,7-dihydroxytryptamine failed to alter the rate of catabolism of intracerebroventricularly administered 5-hydroxytryptamine. The monoamine oxidase inhibitor tranylcypromine effectively blocked degradation of injected 5-hydroxytryptamine and accumulation of 5-hydroxyindoleacetic acid. Coinjection of tryptamine with 5-hydroxytryptamine reduced the rate of conversion of 5-hydroxytryptamine to 5-hydroxyindoleacetic acid. These results indicate that intracerebroventricularly administered 5-hydroxytryptamine is removed by a monoamine oxidase dependent system. This catabolism is not affected by inhibition of presynaptic uptake, 5-hydroxytryptamine receptor type 1 or type 2 blockade, or destruction of serotonergic nerve terminals. The coadministration of tryptamine may prolong the residence period of 5-hydroxytryptamine through competition for monoamine oxidase.Key words: 5-hydroxytryptamine, tryptamine, monoamine oxidase, intracerebroventricular injection, catabolism.

scholarly journals Renal Effects of S18886 (Terutroban), a TP Receptor Antagonist, in an Experimental Model of Type 2 Diabetes

Diabetes ◽  
2007 ◽  
Vol 56 (4) ◽  
pp. 968-974 ◽  
Author(s):  
K. Sebekova ◽  
T. Eifert ◽  
A. Klassen ◽  
A. Heidland ◽  
K. Amann
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Antagonist ◽  
Experimental Model ◽  
Renal Effects ◽  
Tp Receptor

scholarly journals The Glucosamine Controversy; A Pharmacokinetic Issue

2011 ◽  
Vol 14 (2) ◽  
pp. 264 ◽  
Author(s):  
Ali Aghazadeh-Habashi ◽  
Fakhreddin Jamali
Keyword(s):  
Clinical Trial ◽  
Animal Studies ◽  
The Other ◽  
Naturally Occurring ◽  
Assessment Metrics ◽  
Disease Modifying ◽  
Clinical Trial Results ◽  
Higher Doses ◽  
Positive Results ◽  
Rule Out

Glucosamine (GlcN) is a naturally occurring aminosugar that is widely used to treat osteoarthritis despite controversial clinical trial results. Animal studies, on the other hand, unequivocally suggest anti-inflammatory and disease modifying effects for GlcN. Many explanations have been offered as to the root of the controversy. They include superiority of a crystalline sulphate salt over HCl, industry bias, insensitive assessment metrics and poor methodology. Herein, we rule out a difference in bioequivalence between GlcN salts and that of chemically equivalent doses and suggest additional factors; i.e., inconsistency in the chemical potency of some products used, under-dosing of patients as well as variable and erratic bioavailability indices for the lack of GlcN efficacy observed in some studies. Clinical trials using higher doses of pharmaceutical grade GlcN or formulations with greater bioavailability should yield positive results. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Surface Modification of Bacterial Cellulose for Biomedical Applications

2022 ◽  
Vol 23 (2) ◽  
pp. 610
Author(s):  
Teresa Aditya ◽  
Jean Paul Allain ◽  
Camilo Jaramillo ◽  
Andrea Mesa Restrepo
Keyword(s):  
Mechanical Properties ◽  
Drug Delivery ◽  
Tissue Engineering ◽  
Surface Modification ◽  
Bacterial Cellulose ◽  
Biomedical Applications ◽  
Human Tissues ◽  
Naturally Occurring ◽  
Microstructure And Mechanical Properties

Bacterial cellulose is a naturally occurring polysaccharide with numerous biomedical applications that range from drug delivery platforms to tissue engineering strategies. BC possesses remarkable biocompatibility, microstructure, and mechanical properties that resemble native human tissues, making it suitable for the replacement of damaged or injured tissues. In this review, we will discuss the structure and mechanical properties of the BC and summarize the techniques used to characterize these properties. We will also discuss the functionalization of BC to yield nanocomposites and the surface modification of BC by plasma and irradiation-based methods to fabricate materials with improved functionalities such as bactericidal capabilities.

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