-
1.
Understanding the Role and Mechanism of Carbonic Anhydrase V in Obesity and its Therapeutic Implications.
Queen, A, Khan, P, Azam, A, Hassan, MI
Current protein & peptide science. 2018;(9):909-923
Abstract
Obesity is a metabolic syndrome leading to several health problems such as hypertension, heart attack, type II diabetes, and even cancer. Carbonic anhydrase VA (CAVA) is a mitochondrial enzyme which is directly associated with the glucose homeostasis and considered as a promising target for obesity and other associated diseases in humans. So far, numerous inhibitors have been designed to inhibit the catalytic activity of CAVA with an assumption for its possible therapeutic uses against type II diabetes and other metabolic diseases. Among these, sulphonamide inhibitors and various non-classical inhibitors are extensively used. The focus of this review is to understand the mechanism and role CAVA in glucose homeostasis to ascertain as a potential drug target of obesity. We have further highlighted different types of inhibitors and their mode of binding and possible consequences with an aim to investigate possible therapeutic used for the treatment of obesity and associated diseases. Along with classical inhibitors, various non-classical inhibitors have proved to be potential inhibitors of CAV which may be employed to combat obesity. Certain phytochemicals are utilized as therapeutic molecules to fight obesity. These phytochemicals have been discussed in detail here.
-
2.
Effect of Tamsulosin in Lower Urinary Tract Symptom Patients With Metabolic Syndrome.
Yoon, H, Yoon, HS, Lee, YS, Cho, ST, Han, DH
Urology. 2016;:135-42
Abstract
OBJECTIVE To investigate the efficacy of tamsulosin, a selective alpha-1 blocker, in lower urinary tract symptoms (LUTS) patients with metabolic syndrome (MS). PATIENTS AND METHODS This prospective, multicenter clinical trial included men and women (20-75 years old) with LUTS, with or without MS. Patients were categorized as MS+ or MS-, respectively, and all of them were administered tamsulosin 0.2 mg per oral once daily for 24 weeks. Patients were assessed based on the International Prostate Symptom Score, King's Health Questionnaire (KHQ), Overactive Bladder Questionnaire, uroflowmetry with postvoid residuals, and MS factors (blood pressure, waist-to-hip ratio, and serum levels of fasting blood glucose, triglyceride, and high-density lipoprotein cholesterol) at baseline and at 4, 12, and 24 weeks of treatment. RESULTS Ninety-two patients were enrolled in this study (53/92 were MS- [57.6%]; 39/92 were MS+ [42.4%]). After 24 weeks of tamsulosin treatment, fasting blood glucose (P = .02) and triglyceride (P < .001) levels of changes were significantly greater in the MS+ group than in the MS- group. Total International Prostate Symptom Score, total Overactive Bladder Questionnaire score, and the scores of each question on the KHQ showed significant improvement after treatment without intergroup differences. In KHQ, although improvements in emotional status, sleep quality, fatigue, and personal distress were greater in the MS+ group (P = .05), the difference between the groups did not reach statistical significance. CONCLUSION Tamsulosin was effective in both LUTS patients with and without MS. Furthermore, tamsulosin had beneficial effects on some of the factors associated with MS.
-
3.
Association of Plasma Ceramides and Sphingomyelin With VLDL apoB-100 Fractional Catabolic Rate Before and After Rosuvastatin Treatment.
Ng, TW, Ooi, EM, Watts, GF, Chan, DC, Meikle, PJ, Barrett, PH
The Journal of clinical endocrinology and metabolism. 2015;(6):2497-501
Abstract
INTRODUCTION The objective of the study was to examine post hoc associations between plasma sphingolipids and lipoprotein kinetics in men with the metabolic syndrome after rosuvastatin treatment. MATERIALS AND METHODS Plasma sphingolipid profiling, determined by tandem mass spectrometry, was performed in a randomized, double-blind, triple-crossover trial (n = 12) of 5-week treatment periods with placebo or rosuvastatin (10 or 40 mg/d) with 2-week washouts between treatments. RESULTS AND DISCUSSION Baseline plasma ceramides were associated with very low-density lipoprotein (VLDL) apolipoprotein (apo)-B-100 concentration (r = 0.58, P < .05) and inversely with VLDL apoB-100 fractional catabolic rate (FCR; r = -0.67, P = .02). Posttreatment changes with rosuvastatin (40 mg/d) in plasma ceramides were inversely associated with VLDL apoB-100 FCR (r = -0.62, P = .03) independent of changes in plasma triglycerides, cholesterol, and low-density lipoprotein-cholesterol. By contrast, baseline and postrosuvastatin treatment plasma sphingomyelin levels were not associated with apoB-100 kinetics. Plasma ceramides and sphingomyelin were not associated with the kinetics or concentrations of high-density lipoprotein apoA-I, and low-density lipoprotein apoB. In the metabolic syndrome, the ability of rosuvastatin to increase VLDL apoB-100 FCR may reflect ceramide-specific mechanistic actions and/or sphingolipid exchange.
-
4.
Inhibiting insulin resistance mechanisms by DTS phytocompound: an experimental study on metabolic syndrome-prone adipocytes.
Catanzaro, R, Lorenzetti, A, Allegri, F, Yadav, H, Solimene, U, Kumaraju, AK, Minelli, E, Tomella, C, Polimeni, A, Marotta, F
Acta bio-medica : Atenei Parmensis. 2012;(2):95-102
Abstract
The present study was designed to determine whether DTS a phytocompound endowed with antioxidant properties, could beneficially modulate nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) in adipocytes. Combined stimulation (CS-treatment) exerted by using 5 microg/ml of LPS together with 100 ng/ml of TNF-alpha significantly enhanced NO production in 3T3-L1 adipocytes. Preincubation of the adipocytes with DTS (10-30 mM) inhibited such phenomenon in a dose-dependent fashion. The production of NO was decreased by 52% at the concentration of 30mM of DTS. The decrease in NO production by DTS was associated also with a decrease in inducible nitric oxide synthase (iNOS) protein and iNOS mRNA expression. Nuclear factor-kappa B (NF-kappaB) was significantly enhanced by CS-treatment, while the pretreatment with 30 mM of DTS prevented the activity by 27%. IL-6 production in 3T3-L1 adipocytes was markedly increased by CS stimulus, and the enhanced secretion of IL-6 was suppressed in a dose-dependent manner by DTS. These results suggest that DTS regulates iNOS expression and NO production in adipocytes through the modulating activation of NF-kappaB and may have a potential clinical application within protocols designed for treating metabolic syndrome. (www.actabiomedica.it).
-
5.
Effect of rosuvastatin monotherapy or in combination with fenofibrate or ω-3 fatty acids on lipoprotein subfraction profile in patients with mixed dyslipidaemia and metabolic syndrome.
Agouridis, AP, Kostapanos, MS, Tsimihodimos, V, Kostara, C, Mikhailidis, DP, Bairaktari, ET, Tselepis, AD, Elisaf, MS
International journal of clinical practice. 2012;(9):843-53
Abstract
BACKGROUND Raised triglycerides (TG), decreased high-density lipoprotein cholesterol (HDL-C) levels and a predominance of small dense low density lipoproteins (sdLDL) are characteristics of the metabolic syndrome (MetS). OBJECTIVE To compare the effect of high-dose rosuvastatin monotherapy with moderate dosing combined with fenofibrate or ω-3 fatty acids on the lipoprotein subfraction profile in patients with mixed dyslipidaemia and MetS. METHODS We previously randomised patients with low-density lipoprotein cholesterol (LDL-C) > 160 and TG > 200 mg/dl to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or ω-3 fatty acids 2 g/day (Rω group, n = 30). In the present study, only patients with MetS were included (24, 23 and 24 in the R, RF and Rω groups respectively). At baseline and after 12 weeks of treatment, the lipoprotein subfraction profile was determined by polyacrylamide 3% gel electrophoresis. RESULTS The mean LDL size was significantly increased in all groups. This change was more prominent with RF than with other treatments in parallel with its greater hypotriglyceridemic capacity (p < 0.05 compared with R and Rω). A decrease in insulin resistance by RF was also noted. Only RF significantly raised HDL-C levels (by 7.7%, p < 0.05) by increasing the cholesterol of small HDL particles. The cholesterol of larger HDL subclasses was significantly increased by R and Rω. CONCLUSIONS All regimens increased mean LDL size; RF was the most effective. A differential effect of treatments was noted on the HDL subfraction profile.
-
6.
The effect of rosuvastatin on incident pneumonia: results from the JUPITER trial.
Novack, V, MacFadyen, J, Malhotra, A, Almog, Y, Glynn, RJ, Ridker, PM
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2012;(7):E367-72
-
-
Free full text
-
Abstract
BACKGROUND Evidence from observational studies have raised the possibility that statin treatment reduces the incidence of certain bacterial infections, particularly pneumonia. We analyzed data from a randomized controlled trial of rosuvastatin to examine this hypothesis. METHODS We analyzed data from the randomized, double-blind, placebo-controlled JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). In this trial, 17,802 healthy participants (men 50 years and older and women 60 and older) with a low-density lipoprotein (LDL) cholesterol level below 130 mg/dL (3.4 mmol/L) and a high-sensitivity C-reactive protein level of 2.0 mg/L or greater were randomly assigned to receive either rosuvastatin or placebo. We evaluated the incidence of pneumonia on an intention-to-treat basis by reviewing reports of adverse events from the study investigators, who were unaware of the treatment assignments. RESULTS Among 17,802 trial participants followed for a median of 1.9 years, incident pneumonia was reported as an adverse event in 214 participants in the rosuvastatin group and 257 in the placebo group (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.69-1.00). In analyses restricted to events occurring before a cardiovascular event, pneumonia occurred in 203 participants given rosuvastatin and 250 given placebo (HR 0.81, 95% CI 0.67-0.97). Inclusion of recurrent pneumonia events did not modify this effect (HR 0.81, 95% CI 0.67-0.98), nor did adjustment for age, sex, smoking, metabolic syndrome, lipid levels and C-reactive protein level. INTERPRETATION Data from this randomized controlled trial support the hypothesis that statin treatment may modestly reduce the incidence of pneumonia. (ClinicalTrials.gov trial register no. NCT0023968.).
-
7.
Comparative study of low doses of rosuvastatin and atorvastatin on lipid and glycemic control in patients with metabolic syndrome and hypercholesterolemia.
Park, JS, Kim, YJ, Choi, JY, Kim, YN, Hong, TJ, Kim, DS, Kim, KY, Jeong, MH, Chae, JK, Oh, SK, et al
The Korean journal of internal medicine. 2010;(1):27-35
Abstract
BACKGROUND/AIMS: This multicenter, open-labeled, randomized trial was performed to compare the effects of rosuvastatin 10 mg and atorvastatin 10 mg on lipid and glycemic control in Korean patients with nondiabetic metabolic syndrome. METHODS In total, 351 patients who met the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) levels > or = 130 mg/dL were randomized to receive either rosuvastatin 10 mg (n = 173) or atorvastatin 10 mg (n = 178) for over 6 weeks. RESULTS After 6 weeks of treatment, greater reductions in total cholesterol (- 35.94 +/- 11.38 vs. - 30.07 +/- 10.46%, p < 0.001), LDL-C (48.04 +/- 14.45 vs. 39.52 +/- 14.42%, p < 0.001), non-high-density lipoprotein cholesterol (- 42.93 +/- 13.15 vs. - 35.52 +/- 11.76%, p < 0.001), and apolipoprotein-B (- 38.7 +/- 18.85 vs. - 32.57 +/- 17.56%, p = 0.002) levels were observed in the rosuvastatin group as compared to the atorvastatin group. Overall, the percentage of patients attaining the NCEP ATP III goal was higher with rosuvastatin as compared to atorvastatin (87.64 vs. 69.88%, p < 0.001). Changes in glucose and insulin levels, and homeostasis model assessment of insulin resistance index were not significantly different between the two groups. The safety and tolerability of the two agents were similar. CONCLUSIONS Rosuvastatin 10 mg was more effective than atorvastatin 10 mg in achieving NCEP ATP III LDL-C goals in patients with nondiabetic metabolic syndrome, especially in those with lower NCEP ATP III target level goals.
-
8.
[JUPITER, what now?].
Perna, GP
Giornale italiano di cardiologia (2006). 2009;(11-12 Suppl 3):33S-38S
Abstract
The JUPITER study was conducted in apparently healthy, non-dyslipidemic subjects, but with high levels of high-sensitivity C-reactive protein (hsCRP), and showed a decrease in LDL cholesterol and hsCRP of 55% and 36%, respectively, with the administration of rosuvastatin at standard doses (20 mg/die), with a significant reduction in the incidence of major cardiovascular events. The event reduction was maximal in patients whose LDL cholesterol and hsCRP levels were lowered to < 70 mg/dl and <2 mg/I, respectively. The publication of the JUPITER data resulted in a wide debate within the international scientific community, particularly related to clinical implications of major findings. The main implications seem to be the confirmation of "the lower is better" philosophy and of the role of hsCRP as a marker to select, among intermediate risk subjects, patients who are actually at higher risk, who need to be treated with highly effective statins with a low side-effect profile, such as rosuvastatin. Patients with the "JUPITER phenotype" (metabolic syndrome + family history of cardiovascular disease) seem to benefit the most from a treatment that includes measurement of hsCRP and rosuvastatin administration.
-
9.
Effects of rosuvastatin and atorvastatin on LDL and HDL particle concentrations in patients with metabolic syndrome: a randomized, double-blind, controlled study.
Rosenson, RS, Otvos, JD, Hsia, J
Diabetes care. 2009;(6):1087-91
-
-
Free full text
-
Abstract
OBJECTIVE The purpose of this study was to examine the effects of statin therapy on lipoprotein particle concentrations in patients with the metabolic syndrome. Changes in lipoprotein particle concentration may predict the risk of coronary heart disease more accurately than lipoprotein cholesterol levels. RESEARCH DESIGN AND METHODS Patients with dyslipidemia and the metabolic syndrome (n = 318) were randomly assigned in a double-blind study comparing 10 mg rosuvastatin (RSV), 10 mg atorvastatin, or placebo daily for 6 weeks. From weeks 6 to 12, patients in the RSV and placebo groups received 20 mg RSV, whereas the ATV group increased their dose to 20 mg daily. Lipoprotein particle concentrations were measured by nuclear magnetic resonance spectroscopy, LDL cholesterol was measured by beta-quantification, and other lipoproteins were measured by standard methods at baseline, 6 weeks, and 12 weeks. Lipoprotein levels were compared by analysis of covariance. RESULTS Statins reduced LDL particle concentration less than LDL cholesterol (-30 to -38 vs. -38 to -51%). Reductions were greater with RSV than with ATV (P < 0.05 for LDL particle concentration and P < 0.001 for LDL cholesterol). Most patients attained LDL cholesterol <2.59 mmol/l (100 mg/dl) at 12 weeks (80% with RSV and 59% with ATV; P = 0.003), but only 27% of patients receiving RSV and 19% receiving ATV attained the goal of LDL particle concentration <1,000 nmol/l (P = 0.07). CONCLUSIONS In patients with the metabolic syndrome, statin-induced changes in LDL cholesterol do not accurately reflect changes in LDL particle concentration. Consequently, despite attainment of LDL cholesterol goals, these patients may retain considerable residual coronary heart disease risk.
-
10.
[The JUPITER study: background and research hypotheses].
Rapezzi, C, Gallo, P
Giornale italiano di cardiologia (2006). 2009;(11-12 Suppl 3):25S-27S
Abstract
Many large-scale studies demonstrated in aggregate that high-sensitivity C-reactive protein (hsCRP) levels are a strong, independent predictor of future vascular events and that hsCRP adds prognostic information on risk at all levels of LDL cholesterol, at all levels of the Framingham risk score, and at all levels of the metabolic syndrome. Moreover, hsCRP predicts risk of recurrent coronary events and has important prognostic value in acute coronary ischemia and after coronary interventions. The JUPITER study was aimed to determine whether long-term treatment with rosuvastatin (20 mg/die) will reduce the rate of major adverse cardiovascular events, defined as the combined endpoint of cardiovascular death, stroke, myocardial infarction, hospitalization for unstable angina, or arterial revascularization among individuals with LDL cholesterol levels < 130 mg/dl (3.36 mmol/I) who are at high risk because of an enhanced inflammatory response as indicated by hsCRP levels > 2 mg/I.