Mechanisms of Immune-Related Complications in Cancer Patients Treated with Immune Checkpoint Inhibitors
Immune checkpoint inhibitors (ICIs) have changed the prognosis of many cancer patients. Blocking antibodies targeting inhibitory cytotoxic T-lymphocyte-associated antigen 4 or programmed cell death protein-1 receptors or the programmed cell death ligand-1 have led to long-lasting remissions in patients with even advanced cancers. Main side effects induced by ICIs are inflammatory complications with sometimes severe sequelae for patients. Recent studies have improved our understanding how such immune-related adverse events (irAEs) develop. Here, we summarize the current knowledge of pathomechanisms involved in the de velo...
Source: Pharmacology - July 28, 2020 Category: Drugs & Pharmacology Source Type: research
Role of Nitric Oxide in the Change of 5-Hydroxytryptamine Synthesis in the Intestine by a Consecutive Administration of Methotrexate to Rats
This study aimed to investigate whether the consecutive administration of methotrexate affects 5-hydroxytryptamine (5-HT) synthesis in the rat small intestine. Rats received methotrexate at a dose of 12.5 mg/kg intraperitoneally on 4 consecutive days.NG-nitro-L-arginine methyl ester (L-NAME) was given subcutaneously to inhibit nitric oxide (NO) synthase. Methotrexate moderately altered 5-HT synthesis, whereas the combined administration of methotrexate and L-NAME significantly changed 5-HT synthesis in the rat ileal tissue. These results suggest that endogenous NO has an antagonistic role in the induction of 5-HT synthesis...
Source: Pharmacology - July 21, 2020 Category: Drugs & Pharmacology Source Type: research
An Integrated TK-TD Model for Evaluation of < b > < i > Radix Aconitikusnezoffii < /i > < /b > (RAK)
Conclusions: The integrated TK-TD model with linear atrioventricular first-order elimination kinetics and indirect response represents a novel mathematical method to evaluate drug-induced changes in HR and QT.Pharmacology (Source: Pharmacology)
Source: Pharmacology - July 21, 2020 Category: Drugs & Pharmacology Source Type: research
Direct Interaction of Daxx and Androgen Receptor Is Required for Their Regulatory Activity in Cholesterol Biosynthesis
Conclusions: The Daxx-mediated antagonism of AR depicts a more complete picture as to how Daxx regulates intracellular cholesterol level and provides a new target for treatment of atherosclerosis.Pharmacology (Source: Pharmacology)
Source: Pharmacology - July 21, 2020 Category: Drugs & Pharmacology Source Type: research
Berberine Promotes the Proliferation and Osteogenic Differentiation of Alveolar Osteoblasts through Regulating the Expression of miR-214
Conclusion: BBR could promote the proliferation and osteogenic differentiation of HAOBs through downregulating the expression of miR-214.Pharmacology (Source: Pharmacology)
Source: Pharmacology - July 20, 2020 Category: Drugs & Pharmacology Source Type: research
Protective Effect of Colchicine on LPS-Induced Lung Injury in Rats via Inhibition of P-38, ERK1/2, and JNK Activation
Conclusion: In summary, colchicine treatment prevents LPS-induced lung damage in rats through targeting activation of P-38, ERK1/2, and JNK. Therefore, colchicine may be used for the development of treatment for ALI.Pharmacology (Source: Pharmacology)
Source: Pharmacology - July 20, 2020 Category: Drugs & Pharmacology Source Type: research
Combination of LMT-28 and Metformin Improves Beneficial Anti-Inflammatory Effect in Collagen-Induced Arthritis
Conclusion: Combination treatment with LMT-28 and metformin significantly ameliorates arthritic symptoms in CIA by suppressing Th17 differentiation and IL-6 signaling.Pharmacology (Source: Pharmacology)
Source: Pharmacology - July 16, 2020 Category: Drugs & Pharmacology Source Type: research
Triphala Ameliorates Nephropathy via Inhibition of TGF- β1 and Oxidative Stress in Diabetic Rats
Conclusion: From the results, it can be concluded that Triphala churna has a significant nephroprotective effect because of its capability of inhibiting oxidative stress and TGF- β in diabetes.Pharmacology (Source: Pharmacology)
Source: Pharmacology - July 16, 2020 Category: Drugs & Pharmacology Source Type: research
Molecular Study on the Potential Protective Effects of Bee Venom against Fructose-Induced Nonalcoholic Steatohepatitis in Rats
Conclusion: These findings support the therapeutic usefulness of BV, a remedy with a favorable safety profile, in the prevention of fructose-induced NASH.Pharmacology (Source: Pharmacology)
Source: Pharmacology - July 8, 2020 Category: Drugs & Pharmacology Source Type: research
Different Effects of Cannabis Abuse on Adolescent and Adult Brain
Cannabis abuse is a common phenomenon among adolescents. The dominant psychoactive substance inCannabis sativa is tetrahydrocannabinol (THC). However, in the past 40 years the content of the psychoactive ingredient THC in most of the preparations is not constant but has increased due to other breeding and culturing conditions. THC acts as the endocannabinoids at CB1 and CB2 receptors but pharmacologically can be described as a partial (not a pure) agonist. Recent evidence shows that activation of the CB1 receptor by THC can diminish the production of neuronal growth factor in neurons and affect other signalling cascades in...
Source: Pharmacology - July 6, 2020 Category: Drugs & Pharmacology Source Type: research
Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Fc Receptor-Targeting Biologics
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation, swelling, and pain in the joints and involves systemic complications. Mouse models of RA have been extensively used to model the pathogenesis of RA and to develop effective therapies. Although many components of the immune system have been studied in these models, the role of crystallizable fragment (Fc) gamma receptors (Fc γRs) in RA has been sorely neglected. The aim of this review was to introduce the different mouse models of RA and to describe the different drug development strategies that have been tested in these models ...
Source: Pharmacology - June 22, 2020 Category: Drugs & Pharmacology Source Type: research
Autoimmune Hemolytic Anemia in Chronic Myeloid Leukemia
Background: Autoimmune hemolytic anemia (AIHA) might be associated with underlying hematological malignancies such as chronic lymphocytic leukemia. However, the association between AIHA and chronic myelogenous leukemia is extremely unusual.Summary: We reviewed case reports and series of 54 patients with chronic myeloid leukemia (CML) who developed autoimmune hemolysis between 1952 and 2018. Almost all the patients were in the chronic phase and were classified into transplant and non-transplant groups. The onset of autoimmune hemolysis was earlier in the transplant group and required second- and third-line therapy to contro...
Source: Pharmacology - June 2, 2020 Category: Drugs & Pharmacology Source Type: research
Does Crizotinib Auto-Inhibit CYP3A in vivo?
Crizotinib is a tyrosine kinase inhibitor used to treat anaplastic lymphoma kinase-positive lung cancer. There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics. In order to test whether crizotinib treatment alters CYP3A activity in vivo, mice were treated with 5 and 25 mg/kg crizotinib (p.o.) daily for 14 days. Results showed that crizotinib treatment did not alter CYP3A activity as determined by erythromycinN-demethylation. In addition, CYP3A polypeptide expression as measured by Western blot was unchanged. Therefore, our...
Source: Pharmacology - May 27, 2020 Category: Drugs & Pharmacology Source Type: research
Comparison of Adrenaline and Dexmedetomidine in Improving the Cutaneous Analgesia of Mexiletine in Response to Skin Pinpricks in Rats
Conclusions: Both Dex and Adr improve the sensory block and enhance the nociceptive block duration of Mex. But in most cases, Adr is superior to Dex. It may be that different mechanisms of action of the 2 adjuvants lead to the differences.Pharmacology (Source: Pharmacology)
Source: Pharmacology - May 27, 2020 Category: Drugs & Pharmacology Source Type: research
Inhibition of p38mapk Reduces Adipose Tissue Inflammation in Aging Mediated by Arginase-II
Conclusions: Arg-II promotes IL-6 production in aging adipose tissues through p38mapk. The results suggest that targeting Arg-II or inhibiting p38mapk could be beneficial in reducing age-associated adipose tissue inflammation.Pharmacology (Source: Pharmacology)
Source: Pharmacology - May 26, 2020 Category: Drugs & Pharmacology Source Type: research
