scholarly journals Application of ELISA Technique and Human Microsomes in the Search for 11β-Hydroxysteroid Dehydrogenase Inhibitors

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Daria Kupczyk ◽  
Renata Studzińska ◽  
Rafał Bilski ◽  
Alina Woźniak
Keyword(s):  
Metabolic Syndrome ◽  
Visceral Obesity ◽  
Hydroxysteroid Dehydrogenase ◽  
Pyrimidine Ring ◽  
Target Cells ◽  
Fast Method ◽  
Inhibition Activity ◽  
The Metabolic Syndrome ◽  
Elisa Technique ◽  
Thiouracil Derivatives

The metabolic syndrome is defined by impaired carbohydrate metabolism and lipid disorders and often accompanied by hypertension, all of which will lead to obesity and insulin resistance. Glucocorticoids play a regulatory role in the metabolism of proteins, lipids, and carbohydrates. There is growing evidence for a role of glucocorticoids in the development of the metabolic syndrome. The most important factor that regulates the access of endogenous glucocorticoids to receptors after release of glucocorticoids and their diffusion into the cytoplasm of target cells is the steroid metabolism involving a microsomal enzyme, 11β-hydroxysteroid dehydrogenase (11β-HSD). The changes in intracellular glucocorticoid metabolism in the pathogenesis of obesity indicate the participation of modulation by 11β-HSD1, which may represent a new therapeutic target for the treatment of diseases such as type 2 diabetes, visceral obesity, or atherosclerosis. The aim of our study was to determine the fast and effective method to assess inhibition activity of compounds in relation with 11β-hydroxysteroid dehydrogenase. The material for this study was human liver and kidney microsomes. In this study we used ELISA technique using 96-well microplates coated with antibodies which were specific for analyzed enzymes. The method can quickly and efficiently measure the inhibition of both 11β-HSD1 and 11β-HSD2. This method can be used to search for and determine inhibitors of this enzyme. Cortisone and cortisol were used as the substrates for corresponding enzyme assays. Furthermore, 3-N-allyl-2-thiouracil derivatives were used by us for comparison purposes in developing the method, although, due to their structure, those derivatives have not previously been considered as potential inhibitors of 11β-HSD1. 3-N-Allyl-2-thiouracil derivatives are a group worth considering, because by modifying their structure (e.g., by introducing other substituents into the pyrimidine ring) it will be possible to obtain an increase in the activity of compounds in this regard. In conclusion, this study shows an efficient and fast method of determining inhibition activity of compounds in relation with 11β-hydroxysteroid dehydrogenase.

Prevalence of metabolic syndrome in never treated mood disordered patientss

2007 ◽  
Vol 30 (4) ◽  
pp. 95
Author(s):  
Valerie Taylor ◽  
Glenda M. MacQueen
Keyword(s):  
Metabolic Syndrome ◽  
Mood Disorders ◽  
Population Attributable Risk ◽  
Disease Process ◽  
Visceral Obesity ◽  
Premature Mortality ◽  
Overweight And Obesity ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Bipolar Patients

Bipolar disorder and major depression are life-shortening illnesses. Unnatural causes such as suicide and accidents account for only a portion of this premature mortality1 Research is beginning to identify that mood disordered patients have a higher incidence of metabolic syndrome, an illness characterized by dyslipidemia, impaired glucose tolerance, hypertension and obesity.2 Metabolic syndrome is associated with an increased risk for a variety of physical illnesses. Hypothesis: Never treated patients with mood disorders have preexisting elevations in the prevalence of the component variables of metabolic syndrome. Central obesity will be especially elevated, predicting increased premature mortality. Methods: We assessed never treated patients with mood disorders for metabolic syndrome and its component variables. Patients were assessed at baseline and followed up at 6-month intervals. All psychiatric pharmacotherapy was documented. Body mass index (BMI) was also obtained and the percentage of deaths attributable to overweight and obesity was calculated using the population attributable risk (PAR). [PAR= ∑[P (RR-1)/RR] Results: Prior to the initiation of treatment, patients did not differ from population norms with respect to metabolic syndrome or BMI. At 2-year follow-up, BMI had increased for unipolar patients 2.02 points and 1.92 points for bipolar patients. (p < .001) This increase in BMI predicted an increase in mortality of 19.4%. Conclusion: An increase in visceral obesity is often the first component of metabolic syndrome to appear and may indicate the initiation of this disease process prematurely in this group. The increase in BMI places patients with mood disorders at risk for premature mortality and indicates a need for early intervention. References 1.Osby U, Brandt L, Correia N, Ekbom A & Sparen P. Excess mortability in bipolar and Unipolar disorder rin Sweden. Archives of General Psychiatry, 2001;58: 844-850 2.Toalson P, Saeeduddin A, Hardy T & Kabinoff G. The metabolic syndrome in patients with severe mental illness. Journal of Clinical Psychiatry, 2004; 6(4): 152-158

scholarly journals Effect of menopausal hormone therapy on components of the metabolic syndrome

2016 ◽  
Vol 11 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Dragana Lovre ◽  
Sarah H. Lindsey ◽  
Franck Mauvais-Jarvis
Keyword(s):  
Metabolic Syndrome ◽  
Hormone Therapy ◽  
Visceral Obesity ◽  
Menopausal Hormone Therapy ◽  
World Population ◽  
Metabolic Function ◽  
Metabolic Dysfunction ◽  
The Metabolic Syndrome ◽  
The World

The world population is aging, and women will spend an increasing share of their lives in a postmenopausal state that predisposes to metabolic dysfunction. Thus, the prevalence of metabolic syndrome (MetS) in women is likely to increase dramatically. This article summarizes the effects of menopause in predisposing to components of MetS including visceral obesity, dyslipidemia, type 2 diabetes (T2D) and hypertension (HTN). We also summarize the effects of menopausal hormone therapy (MHT) in reversing these metabolic alterations and discuss therapeutic advances of novel menopausal treatment on metabolic function.

The Metabolic SYNDROME and the RISK of Venous Thrombosis: RESULTS of AN Individual LEVEL Patient Meta-ANALYSIS

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3177-3177
Author(s):  
Francesco Dentali ◽  
Cihan Ay ◽  
Moon Jang ◽  
Matteo di Minno ◽  
Ingrid Pabinger ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Multivariate Analysis ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Visceral Obesity ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Individual Features ◽  
The Individual ◽  
The Impact

Abstract Abstract 3177 Background: The metabolic syndrome (MS) is a cluster of interrelated risk factors that identify patients at increased risk of cardiovascular events. Recent studies also suggested an association between MS and venous thromboembolism (VTE). However, the role of the individual features of MS and whether MS and its features are more important than obesity alone to predict VTE remain to be established. Methods: We performed an individual patient level meta-analysis of case-control studies comparing the prevalence of MS in patients with unprovoked VTE and in controls. MEDLINE, EMBASE databases, and abstract books were searched up to January 2010. Odds ratios (OR) and 95% confidence intervals of pooled results were calculated. The influence of individual variables (age, sex, BMI and MS) on the likelihood of VTE was compared using logistic regression analysis. Multivariate analysis was subsequently performed including the individual components of MS in the place of MS. The impact of increasing number of individual components of MS on the risk of VTE was investigated. Results: Four studies were identified and analyzed, for a total of 1332 patients (479 cases and 833 controls). Mean age was 53.3 and 52.7, respectively (p=n.s.), 49.5% cases and 42.4% controls were males (p=0.0003), 38.8% and 30.0% were obese (p=0.0001). MS was significantly associated with VTE (OR 1.97, 1.57–2.47), and the association linearly increased with the number of MS features (p for trend <0.001). At multivariate analysis, MS but not obesity remained associated with VTE (OR 1.92, 1.50–2.46 and 1.14, 0.88–1.47, respectively). All individual features of MS, but HDL cholesterol, were independently associated with VTE. Conclusions: The results of this meta-analysis confirm the association between MS and VTE and suggest that MS (and visceral obesity defined by increased waist circumference) could be a more important predictor of VTE than obesity defined by BMI. Disclosures: No relevant conflicts of interest to declare.

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