scholarly journals Associations of rs4244285 in the CYP2C19 gene with multifactorial diseases

2022 ◽  
Vol 36 (4) ◽  
pp. 125-131
Author(s):  
N. P. Babushkina ◽  
A. E. Postrigan ◽  
A. N. Kucher ◽  
V. M. Shipulin
Keyword(s):  
Population Control ◽  
Population Sample ◽  
Xenobiotic Metabolism ◽  
Comorbid Conditions ◽  
Multifactorial Diseases ◽  
Organ Systems ◽  
Wide Range ◽  
Cyp2c19 Gene ◽  
Endogenous Substrates ◽  
Artery Disease

Xenobiotic metabolism system in the current populations is involved in the biotransformation of a wide range of endogenous substrates and various xenobiotics, which can contribute to developing the diseases of various organ systems, and, in some cases, comorbid conditions where increased biotransformation system activity is observed. In this regard, it is of great interest to study the involvement of polymorphism in xenobiotic metabolism genes in the development of both isolated pathology and various comorbid conditions.Aim. The goal of study was to investigate the involvement of rs4244285 in the CYP2C19 gene in the development of isolated pathology and comorbidities.Material and Methods. The frequencies of alleles and genotypes were studied in groups of patients with comorbid conditions including groups of coronary artery disease (CAD) with hypertension (HTN) (CAD_HTN, n = 133) and bronchial asthma (BA) with HTN (BA_HTN, n = 178), in group of isolated BA (n = 135), and in the population sample of the city of Tomsk (n = 377). Association analysis covered three initial groups of patients (CAD, BA, and BA_HTN) and subgroups assigned based on the presence of absence of HTN diagnosis taking into account comorbid conditions both in patient samples and in population control.Results and Discussion. The study demonstrated the predisposing eff ect of GA genotype on the development of comorbid BA and HTN (OR = 1.94, p = 0.038) and comorbid CAD and HTN (OR = 2.26, p = 0.009) compared to isolated BA. The AA genotype was observed 3.98 times less often in HTN patients than in normotensive individuals. However, the diff erences did not reach the level of statistical signifi cance due to the low occurrence of this genotype.Conclusion. The obtained results may be explained by the involvement of CYP2C19-metabolites of arachidonic acid in the regulation of vascular tone, which requires further study.

scholarly journals Fixed-dose combinations in the treatment of hypertension to increase adherence

2020 ◽  
Vol 25 (11) ◽  
pp. 4184
Author(s):  
T. E. Morozova ◽  
E. O. Samokhina
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Drugs ◽  
Fixed Dose ◽  
Optimal Solutions ◽  
Comorbid Conditions ◽  
Treatment Regimens ◽  
Wide Range ◽  
Treatment Of Hypertension ◽  
Artery Disease ◽  
Initiation Of Therapy

Despite a wide range of antihypertensive drugs, blood pressure (BP) control often remains unsatisfactory, and every year the number of people with uncontrolled high BP increases. One of the strategies aimed at improving medical adherence is the use of fixed-dose combinations of 2 antihypertensive drugs for starting therapy, and, if necessary, 3 drugs. Initiation of therapy with 2 drugs in one tablet is recommended for most patients. A review of algorithms for choosing combinations of antihypertensive drugs in different clinical situations, including in patients with various comorbid conditions, is presented. Simplification of treatment regimens makes it possible to choose the most optimal solutions in various clinical situations, in particular, with stage I-II hypertension, with a combination of hypertension with chronic kidney disease, as well as with a combination of hypertension with coronary artery disease and a number of other diseases.

Could Thyroid Disorders Be Better Understood and Dealt as a Thyroid Syndrome

2020 ◽  
Vol 5 (08) ◽  
pp. 326-328
Author(s):  
Dr. Sushma Patil ◽  
Dr. Vikrant Patil
Keyword(s):  
Reference Range ◽  
Well Being ◽  
Thyroid Disorders ◽  
Thyroid Function Tests ◽  
Thyroid Disorder ◽  
Serum Concentrations ◽  
Comorbid Conditions ◽  
Free T4 ◽  
Research Perspective ◽  
Wide Range

Thyroid disorders are common worldwide. Thyroid dysfunction, both hypo- and hyperthyroidism may increase the risk of cardiovascular disorders. Current thyroid function tests may have limitations since they only measure the total or free T4 and/or T3 and TSH serum concentrations in peripheral blood and not the effect of T4 or T3 serum on different specific target tissues. Several comorbid conditions can interfere with the absorption or increase the clearance of levothyroxine. Among patients treated with thyroid replacement, under or overmedicated may-be at risk for adverse health consequences. A wide range of drugs may interfere with levothyroxine absorption, metabolism, and action. Patients report a lack of well-being, despite reaching euthyroid reference range of TSH, with psychological distress. If we will consider Thyroid related conditions as a syndrome then research perspective at the pathophysiology, interrelation between symptoms and comorbidities will be much broader that can lead researchers to get insights of different pathways in which thyroid gland functioning can be perceived and dealt therapeutically. The deliberation of thyroid disorder as a syndrome can affluence our knowledge of correlating cofounders, action of thyroid hormones on target tissues, underlying cause and thyroid health.

scholarly journals Unusual case of amyloidosis presenting as a jejunal mass

2021 ◽  
Vol 14 (5) ◽  
pp. e240226
Author(s):  
Sachin Mohan ◽  
Elliot Graziano ◽  
James Campbell ◽  
Irshad H Jafri
Keyword(s):  
Small Intestine ◽  
Light Chain ◽  
Protein Misfolding ◽  
Unusual Case ◽  
Gi Tract ◽  
Organ Systems ◽  
Light Chain Disease ◽  
Wide Range ◽  
Amyloid Light Chain ◽  
Possible Cause

Amyloidosis constitutes a heterogeneous group of disorders of protein misfolding that can involve different organ systems. The disease can occur either in a systemic or localised manner that is well known to involve the gastrointestinal (GI) tract. GI amyloidosis can present with a wide range of symptoms including diarrhoea, bleeding and obstruction. This case illustrates a patient with localised jejunal amyloid light chain disease that was diagnosed serendipitously during a workup for haematuria. Our patient was otherwise asymptomatic, but this case underscores the importance of considering amyloidosis as a possible cause of isolated masses of the small intestine.

scholarly journals Glossary and tutorial of xenobiotic metabolism terms used during small molecule drug discovery and development (IUPAC Technical Report)

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Paul Erhardt ◽  
Kenneth Bachmann ◽  
Donald Birkett ◽  
Michael Boberg ◽  
Nicholas Bodor ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecule ◽  
Chemical Structure ◽  
Early Stage ◽  
Xenobiotic Metabolism ◽  
Drug Discovery And Development ◽  
Small Molecule Drug ◽  
Technical Report ◽  
Wide Range ◽  
Draft Version

Abstract This project originated more than 15 years ago with the intent to produce a glossary of drug metabolism terms having definitions especially applicable for use by practicing medicinal chemists. A first-draft version underwent extensive beta-testing that, fortuitously, engaged international audiences in a wide range of disciplines involved in drug discovery and development. It became clear that the inclusion of information to enhance discussions among this mix of participants would be even more valuable. The present version retains a chemical structure theme while expanding tutorial comments that aim to bridge the various perspectives that may arise during interdisciplinary communications about a given term. This glossary is intended to be educational for early stage researchers, as well as useful for investigators at various levels who participate on today’s highly multidisciplinary, collaborative small molecule drug discovery teams.

scholarly journals SGLT2 inhibitors: a narrative review of efficacy and safety

2021 ◽  
Vol 121 (2) ◽  
pp. 229-239
Author(s):  
Donald S. Nelinson ◽  
Jose M. Sosa ◽  
Robert J. Chilton
Keyword(s):  
Adverse Events ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Narrative Review ◽  
Atherosclerotic Cardiovascular Disease ◽  
Comorbid Conditions ◽  
Postprandial Plasma Glucose ◽  
Renal Outcomes ◽  
Glucose Levels ◽  
Wide Range

Abstract Type 2 diabetes mellitus (T2DM) is a cardio-renal-metabolic condition that is frequently associated with multiple comorbidities, including atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). The sodium-glucose co-transporter-2 (SGLT2) inhibitors, which lower glycated hemoglobin, fasting and postprandial plasma glucose levels, body weight, and blood pressure, as well as reduce the risk of a range of cardiovascular and renal outcomes without increasing hypoglycaemic risk, have heralded a paradigm shift in the management of T2DM. These drugs are compatible with most other glucose-lowering agents and can be used in patients with a wide range of comorbid conditions, including ASCVD, HF, and CKD, and in those with estimated glomerular filtration rates as low as 30 mL/min/1.73 m2. However, there are misunderstandings surrounding the clinical implications of SGLT2 inhibitors’ mechanism of action and concerns about the key adverse events with which this class of drugs has been associated. This narrative review summarizes the data that support the efficacy of SGLT2 inhibitors in reducing the risks of cardiovascular and renal outcomes in patients with T2DM and comorbid conditions and clarifies information relating to SGLT2 inhibitor-related adverse events.

scholarly journals Effects of lowered serotonin transmission on cocaine-induced striatal dopamine response: PET [11C]raclopride study in humans

2011 ◽  
Vol 199 (5) ◽  
pp. 391-397 ◽  
Author(s):  
Sylvia M. L. Cox ◽  
Chawki Benkelfat ◽  
Alain Dagher ◽  
J. Scott Delaney ◽  
France Durand ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Striatal Dopamine ◽  
Emission Tomography ◽  
Acute Tryptophan Depletion ◽  
Tryptophan Depletion ◽  
Comorbid Conditions ◽  
Drug Craving ◽  
Positron Emission ◽  
Wide Range

BackgroundLow serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits.AimsTo investigate the effects of lowered serotonin on cocaine-induced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving.MethodIn non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [11C]raclopride.ResultsAcute tryptophan depletion increased drug craving and striatal dopamine responses to cocaine. These acute tryptophan depletion-induced increases did not occur in the absence of cocaine.ConclusionsThe results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions.

Comorbid conditions - a reason to strengthen antianginai therapy in patients with stable coronary artery disease

2021 ◽  
pp. 49-52
Author(s):  
O. L. Barbarash ◽  
V. V. Kashtalap
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Stable Angina ◽  
Clinical Case ◽  
Stable Coronary Artery Disease ◽  
Mechanisms Of Action ◽  
Functional Class ◽  
Second Line ◽  
Comorbid Conditions ◽  
Artery Disease

In the article on the example of a clinical case approaches to enhancing antianginal therapy of coronary artery disease were discussed. Arguments were given for prescribing preparations of the second line of antianginal agents (thymetazidine) in the patient with stable angina with high functional class and concomitant hypotonia after a complicated COVID-19. The main mechanisms of action of trimetazidine and results of clinical studies were discussed.

Current state-of-the-art antiplatelet and anticoagulation therapy in diabetic patients with coronary artery disease

2021 ◽  
Author(s):  
Johny Nicolas ◽  
Victor Razuk ◽  
Gennaro Giustino ◽  
Roxana Mehran
Keyword(s):  
Diabetes Mellitus ◽  
Complex Disease ◽  
Anticoagulation Therapy ◽  
Treatment Strategies ◽  
Diabetic Patients ◽  
Current State ◽  
Organ Systems ◽  
Patients With Diabetes ◽  
The Status ◽  
Artery Disease

Diabetes mellitus is a complex disease that leads to long-term damage to various organ systems. Among the numerous cardiovascular disease-related complications, thrombotic events frequently occur in patients with diabetes. Although guidelines exist for treating and preventing most diabetes-related co-morbidities, the evidence on antithrombotic therapy in primary and secondary prevention is limited due to the scarcity of randomized trials dedicated to patients with diabetes mellitus. Most of the available data are derived from studies that only included a small proportion of patients with diabetes. The present review provides an overview of the status of knowledge on antiplatelet and anticoagulation therapy in patients with diabetes, focusing on the risk–benefit balance of these therapies and future treatment strategies.

scholarly journals Prevalence and Clinical Correlates of Coronary Artery Disease among New Dialysis Patients in the United States: A Cross-Sectional Study

2001 ◽  
Vol 12 (7) ◽  
pp. 1516-1523 ◽  
Author(s):  
AUSTIN G. STACK ◽  
WENDY E. BLOEMBERGEN
Keyword(s):  
United States ◽  
Risk Factors ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
The United States ◽  
Comorbid Conditions ◽  
Clinical Correlates ◽  
History Of ◽  
Artery Disease

Abstract. Despite the high prevalence of coronary artery disease (CAD) among patients with end-stage renal disease (ESRD), few studies have identified clinical correlates using national data. The purpose of this study was to determine the prevalence and clinical associations of CAD in a national random sample of new ESRD in the United States in 1996/1997 (n = 4025). Data on demographic characteristics and comorbidities were obtained from the Dialysis Morbidity and Mortality Study, Wave 2. The principal outcome was CAD, defined as the presence of a previous history of CAD, myocardial infarction, or angina, coronary artery bypass surgery, coronary angioplasty, or abnormal coronary angiographic findings. Multivariate logistic regression analysis was used to assess the relationship of conventional factors and proposed uremic factors to the presence of CAD. CAD was present in 38% of patients. Of the total cohort, 17% had a history of myocardial infarction and 23% had angina. Several conventional risk factors, including advancing age, male gender, diabetes mellitus, and smoking, were significantly associated with CAD. Of the proposed uremic factors, lower serum albumin levels but higher residual renal function and higher hematocrit values were significantly associated with the presence of CAD. Vascular comorbid conditions, structural cardiac abnormalities, white race, and geographic location were also strongly correlated with the presence of CAD. This national study suggests that several conventional CAD risk factors may also be risk factors for CAD among the ESRD population. This study identifies nonconventional factors such as serum albumin levels, vascular comorbid conditions, and structural cardiac abnormalities as important disease correlates. Future logitudinal studies are required to explore the relative importance of the relationships observed here.

scholarly journals Thyroid Gland Disease as a Comorbid Condition in COPD

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Aziz Gumus ◽  
Neslihan Ozcelik ◽  
Bilge Yilmaz Kara ◽  
Songul Ozyurt ◽  
Unal Sahin
Keyword(s):  
Thyroid Gland ◽  
Multinodular Goiter ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Comorbid Condition ◽  
Thyroid Function Tests ◽  
Comorbid Conditions ◽  
Obstructive Pulmonary Disease ◽  
Euthyroid Sick Syndrome ◽  
Artery Disease

Introduction. Chronic obstructive pulmonary disease (COPD) is one of the most common causes of morbidity and mortality worldwide. The disease is characterized by progressive airway inflammation, which not only affects the airways but also has systemic effects that are associated with comorbidities. Although comorbid conditions such as hypertension and coronary artery disease are very well-known in COPD patients, diseases of the thyroid gland have not been sufficiently studied. Therefore, thyroid diseases are not considered among the comorbid conditions of COPD. The purpose of this study was to determine the thyroid gland disease (TGD) prevalence in COPD and associated factors. Materials and Method. The study included 309 (297 (96%) male) patients. The patients were subjected to spirometry and thyroid function tests (TFT) in the stable period. The thyroid gland disease they were diagnosed with was recorded after face-to-face meetings and examining their files. Results. The mean age of the patients who were included in the study was 65.9 ± 9.8 (40-90). Thyroid disease was determined in 68 (22%) individuals. There were hypothyroidism in 7 (2%), euthyroidism in 45 (15%), and hyperthyroidism in 16 (%5) patients. No relationship was found between the severity of airflow limitation and the prevalence of TGD. Conclusion. Thyroid abnormalities are commonly observed in COPD. The most frequently encountered TGDs are euthyroid multinodular goiter, euthyroid sick syndrome (ESS), and toxic multinodular goiter.

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