Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corticotropin-releasing factor (CRF) is an important neuropeptide hormone which controls the body's overall response to stress. It plays a crucial role in regulating the behavioral, cardiovascular, immune and gastrointestinal systems. Over-activation of the CRF system has been implicated in many disorders including anxiety, depression, drug addiction, hypertension, Irritable Bowel Syndrome (IBS), peptic ulcers, inflammation and others. Thus, binding of CRF to its receptors is an attractive target to develop new medications which aim at treating ailments associated with chronic stress. Numerous small-molecule non-peptide CRF receptor antagonists were developed and many are in various stages in clinical trials. Many showed great promise in treatment of anxiety, depression, peptic ulcers, inflammation, IBS and drug addiction. In our recent previous work, the development of two series of pyrimidine and fused pyrimidine CRF antagonists were described. In continuation of our efforts in this direction, in the current manuscript, the synthesis of a third series of CRF receptor antagonists is described. The binding affinities of select compounds for the type 1 receptor of CRF (CRF1R) were determined and compared to a standard CRF antagonist drug antalarmin. A lead compound was identified and further evaluated by measuring its effect on the inhibition of the agonist-stimulated accumulation of second messengers.
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PMID:Synthesis of 2-imino and 2-hydrazono thiazolo[4,5-d]pyrimidines as corticotropin releasing factor (CRF) antagonists. 2875 Mar 12

The proportional incidence of intravenous drug use (IVDU)-associated infective endocarditis (IE) cases requiring surgery has increased significantly, mirroring the national opioid crisis. Recidivism is common but its impact on postoperative outcomes is unclear. We aimed to evaluate short- and mid-term postoperative outcomes associated with recidivism in this population. We retrospectively reviewed 180 consecutive patients (54 IVDU and 126 non-IVDU) surgically treated for IE from 2011 to 2016. The institutional database was linked to the Connecticut Department of Public Health Death Index to capture statewide long-term mortality and causes of death. Regression models were fitted to evaluate the association between IVDU status and perioperative adverse events, mid-term survival, and causes of death. IVDU patients were younger and had fewer comorbidities. Diabetes, hypertension, peripheral vascular disease, and previous coronary artery bypass graft were less frequently present in IVDU patients compared to non-IVDU patients (P < 0.05 for all). The Society of Thoracic Surgeons mortality prediction score for IE was lower in IVDU patients (22.9 vs 33.6, P < 0.001). IVDU was associated with a significantly increased risk of perioperative adverse events (odds ratio 2.88, 95% confidence interval 1.02-8.12) and increased risk of mid-term mortality (hazard ratio 2.2, 95% confidence interval 1.04-4.78, P = 0.04). The leading cause of death in IVDU patients was related to recidivism whereas that of non-IVDU patients was related to chronic conditions. IVDU patients who underwent cardiac surgery for IE experienced higher risks of perioperative adverse events and inferior mid-term survival compared to non-IVDU, despite being younger and having less comorbidities. Deaths in IVDU cohort were predominantly due to recidivism. Efforts to improve long-term outcome of patients presenting with IVDU IE should include drug addiction intervention and other strategies to reduce recidivism.
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PMID:Recidivism Is the Leading Cause of Death Among Intravenous Drug Users Who Underwent Cardiac Surgery for Infective Endocarditis. 3118 87

The abuse of psychotropic substances is a well-known phenomenon, and many of them are usually associated with ancestral traditions and home remedies. This is the case of Mitragyna speciosa (kratom), a tropical tree used to improve work performance and to withstand great heat. According to several published studies, the main reasons for kratom consumption involve improving sexual performance and endurance, but also social and recreational uses for the feeling of happiness and euphoria; it is also used for medical purposes as a pain reliever, and in the treatment of diarrhea, fever, diabetes, and hypertension. However, this plant has gained more popularity amongst young people over the last years. Since it is available on the internet for purchase, its use is now widely as a drug of abuse, namely as a new psychoactive substance, being a cheaper alternative to opioids that does not require medical prescription in most countries. According to internet surveys by the European Monitoring Centre for Drugs and Drug Addiction in 2008 and 2011, kratom was one of the most widely supplied new psychoactive substances. The composition of kratom is complex; in fact, more than 40 different alkaloids have been identified in Mitragyna speciosa so far, the major constituent being mitragynine, which is exclusive to this plant. Besides mitragynine, alkaloids such as corynantheidine and 7-hydroxamitragynine also present pharmacological effects, a feature that may be attributed to the remaining constituents as well. The main goal of this review is not only to understand the origin, chemistry, consumption, and analytical methodologies for analysis and mechanism of action, but also the use of secondary metabolites of kratom as therapeutic drugs and the assessment of potential risks associated with its consumption, in order to aid health professionals, toxicologists, and police authorities in cases where this plant is present.
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PMID:Mitragyna speciosa: Clinical, Toxicological Aspects and Analysis in Biological and Non-Biological Samples. 3083 9


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