Discovery of Benzimidazole Oxazolidinediones as Novel and Selective Nonsteroidal Mineralocorticoid Receptor Antagonists

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The effect of therapy with small doses of mega-3 polyunsaturated fatty acid on renal reserve and metabolic disturbances in patients with primary IGA glomerulopathy

Renal reserve is believed to be diagnostic dynamic method for accessing both early renal failure and renal vascular reactivity. The aim of our study was to follow renal reserve during 12 month therapy with omega-3 polyunsaturated fatty acids. Omega-3 was given orally of a: 540 mg of eicosapentaenic acid and 810 mg of docosaheksenic acid daily. Before and after 12 month of therapy renal reserve (expressed as % change of basal creatinine clearance) was estimated during i.v. dopamine infusion in dose 2 ug/min/b.w. Twelve month therapy was associated with increase of renal reserve (respectively 14.86 +/- 16.35 vs 30.25 +/- 14.27%), HDL cholesterol (respectively 47.55 +/- 11.49 vs 58.05 +/- 7.89 mg/dl) and decrease 24 hrs proteinuria (respectively 3.31 +/- 2.01 vs 1.31 +/- 1.37 g/24 h), total cholesterol TCH (respectively 251.15 +/- 50.91 vs 214.15 +/- 24.09 mg/dl), LDL cholesterol (respectively 170.0 +/- 47.22 vs 124.15 +/- 17.93 mg/dl), serum uric acid (respectively 7.53 +/- 1.01 vs 5.59 +/- 0.88 mg/dl), fasting insulinemia (respectively 11.27 +/- 5.28 vs 9.20 +/- 4.80 U/ml) for p < 0.05. The statistically significant correlation coefficient were found only between following parameters: % renal reserve vs insulin (r = -0.55, p < 0.05), delta 24 h proteinuria vs delta TCH (r = 0.69, p < 0.05), delta 24 h proteinuria vs delta LDL (r = 0.51, p < 0.05). Our study suggest that omega-3 therapy improves renal reserve and its effect is to some extend related to improvement of some metabolic disturbances. Also this therapy ameliorate proteinuria which is linked with lipid lowering effect of omega-3.     

Influence of insertion-deletion polymorphism of the angiotensin converting enzyme gene on left ventricular hypertrophy in patients with aortic stenosis--differences in men and women

The role of different parameters (including genetic factors) on the timing and extend of left ventricle hypertrophy in patients with aortic stenosis is not defined. In our study we analyze the influence of clinical, echocardiographic parameters and I/D polymorphism of the angiotensin converting enzyme gene on the left ventricle hypertrophy (left ventricle mass index) in this group of patients. The study was done with the group of 302 pts with aortic stenosis--120 women and 182 men; mean age 58 +/- 11 yrs. Stepwise (backward) regression was used to assess the influence of the analyzed parameters (age, gender, history of hypertension, EF, MGA, presence of significant coronary artery disease and I/D ACE polymorphism) on the LVH in the all pts and in the women and the men separately. In the whole group the LVMI depends on EF (t = -6.5; p = 0.0001--higher LVMI in lower EF), MGA (t = 3.9; p = 0.0001--higher LVMI in higher MGA) and gender (t = 2.8; p = 0.005--higher LVMI in men). In women LVMI was related with EF (t = -3.6; p = 0.001--higher LVMI in lower EF), age (t = 2.9; p = 0.004--higher LVMI in older pts) and MGA (t = 2.5; p = 0.013--higher LVMI in higher MGA). In men the LVMI depends on EF (t = -4.8; p = 0.0001--higher LVMI in lower EF) and MGA (t = 1.98; p = 0.049--higher LVMI in higher MGA). Significant relationship between LVMI and results of I/D ACE polymorphism was observed both in women and men. I/D polymorphism relationship with LVMI was divergent in these 2 groups--association of higher LVMI with lack of DD type of polymorphism in women and presence of DD polymorphism in men. CONCLUSIONS: 1. Left ventricle hypertrophy in pts aortic stenosis is higher in men than in women. 2. In women left ventricle hypertrophy is related with ejection fraction, maximal aortic gradient, age and I/D ACE polymorphism; in men it is related to EF, MGA and I/D ACE polymorphism. 3. The influence of I/D ACE polymorphism on the left ventricle hypertrophy is divergent in women and men--in women related to the lack of DD polymorphism, in men related to the presence of DD polymorphism.     

Changing associations between progressive cardiovascular autonomic neuropathy and carotid atherosclerosis with increasing duration of type 2 diabetes mellitus

To clarify associations between cardiovascular autonomic neuropathy (CAN) and the progression of carotid artery atherosclerosis in Type 2 diabetic patients, cardiovascular autonomic nerve function was related to carotid artery ultrasound in 61 Type 2 diabetic patients, 5 and 8 years after the diagnosis of diabetes. Between 5 and 8 years after diagnosis, age-adjusted acceleration index (AI) decreased (from -0.306+/-1.034 to -0.702+/-1.072; P=.0139), whereas age-adjusted expiration/inspiration (E/I) ratio was unchanged (-0.583+/-1.038 and -0.828+/-1.028; P=.1164). Intima-media thickness (IMT) increased in both the common carotid artery (CCA; from 0.854+/-0.219 to 0.913+/-0.241 mm; P<.0001) and the carotid bulb (from 1.789+/-0.714 to 2.128+/-0.881 mm; P<.0001), corresponding to a yearly IMT increase of 0.032+/-0.039 mm in the CCA and 0.146+/-0.204 mm in the carotid bulb. This value did not correlate with the AI or E/I ratios. In age-controlled partial correlation in the first examination, AI correlated inversely with mean (r=-.33, P=.018) IMT in the CCA, but not with IMT in the carotid bulb (r=-.14, P=.303). However, in contrast to the first examination, at follow-up, AI correlated inversely with the mean IMT of the carotid bulb (r=-.40, P=.007), lumen diameter of the CCA (r=-.31, P=.034), and plaque score (r=-.29, P=.041), but not with IMT of the CCA (r=-.04, P=.861). There were no correlations between the E/I ratio and carotid variables. In conclusion, CAN was associated with features of carotid atherosclerosis, which, in the carotid bulb, might affect baroreceptor function with the progression of Type 2 diabetes.     

Effects of sinus rhythm restoration in patients with persistent atrial fibrillation: a clinical, echocardiographic and hormonal study

The hemodynamic consequences of atrial fibrillation (AF) may lead to impairment of the left ventricular function and a reduction in exercise capacity. Studies on mechanical and neurohormonal remodelling in patients with AF are becoming increasingly important. The results could possibly enhance treatment strategies of these patients. The aim of this study was to assess changes in exercise capacity, echocardiographic findings and plasma atrial natriuretic peptide (ANP) concentrations in patients with non-rheumatic persistent AF, before and 30 days after successful cardioversion. METHODS: We attempted cardioversion in 42 consecutive patients, aged 58 +/- 8 years, with persistent non-valvular AF of duration 7.1 +/- 7.1 months. They underwent echocardiography examination and submaximal exercise testing 24 h before and 30 days after cardioversion. Exercise capacity was determined during symptom-limited exercise testing, according to a modified Bruce protocol with peak VO2 analysis. Plasma samples of ANP were obtained at rest: before, the day after, and 30 days after cardioversion therapy, and were prepared by refrigerated centrifugation and stored until radioimmunoassay. The control study group, without AF, comprised of 11 subjects. RESULTS: Cardioversion was successful in 35 patients. However, in six of the 35 patients, AF reappeared within 1 month. There were no statistical differences before cardioversion in exercise tolerance and ejection fraction of left ventricle between the group with successful cardioversion and the group with unsuccessful cardioversion or with recurrence of AF. On the 30th day after cardioversion we recorded a significant increase in exercise tolerance: duration of exercise 13.7 +/- 3.2 versus 9.5 +/- 3.4 min, (P < 0.05); peak oxygen consumption 32.2 +/- 3.6 versus 19.85 +/- 3.5 ml/min per kg, (P < 0.05); and ejection fraction of left ventricle 58.6 +/- 9.4 versus 52.7 +/- 10.2% (P < 0.05); in the sinus rhythm group. There was no significant improvement observed in the AF group. The mean baseline ANP level was 58.5 +/- 15.7 pg/ml in the study group and 34.3 +/- 10.2 pg/ml in the control group (P < 0.01). The successful therapy reduced significantly the pretreatment mean plasma ANP concentration from 58.5 +/- 15.7 to 31.4 +/- 15.0 pg/ml, (P < 0.01); the day after cardioversion, in the group of 35 patients. It remained stable for the next 30 days (36.9 +/- 15.2 pg/ml) in the group of 29 patients who remained in sinus rhythm, and increased to 53.4 +/- 16.4 pg/ml in the group of six patients who had recurrence of AF. Plasma ANP did not change in the group of seven patients with unsuccessful cardioversion. CONCLUSIONS: The restoration of sinus rhythm in patients with persistent AF was associated with a significant improvement in cardiac performance and exercise tolerance 1 month after cardioversion. Such improvement was not observed in the group with unsuccessful cardioversion or with AF recurrence. The plasma ANP concentration in patients with AF was significantly reduced after successful cardioversion and remained stable for a period of 30 days.     

Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study

The treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17–60 years), 116 patients were suitable for analysis. MRD level ≥0·1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population ( P  < 0·0001), as well as in the standard risk (SR, P  = 0·0003) and high-risk ( P  = 0·008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0·1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects ( P  = 0·001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.     

Occupational allergic and irritant contact dermatitis in workers exposed to polyurethane foam

Objectives

To evaluate sensitization to chemicals present in work environment after an outbreak of contact dermatitis in workers of vehicle equipment factory, exposed to polyurethane foam, based on 4,4′-diphenylmethane diisocyanate (MDI).

Material and Methods

From among 300 employees, 21 individuals reporting work-related skin and/or respiratory tract symptoms underwent clinical examination, patch testing, skin prick tests, spirometry and MDI sIgE measurement in serum. Patch tests included isocyanates series, selected rubber additives, metals, fragrances, preservatives, and an antiadhesive agent.

Results

Clinical examination revealed current eczema in the area of hands and/or forearms in 10 workers. Positive patch test reactions were found in 10 individuals, the most frequent to diaminodiphenylmethane and 4-phenylenediamine (7 persons). Reactions to an antiadhesive agent were assessed as irritant (5 workers). Except for sensitization to common aeroallergens, no significant abnormalities were found in the remaining tests. Occupational allergic contact dermatitis was diagnosed in 7 workers, irritant contact dermatitis in 10 and coexisiting allergic and irritant contact dermatitis in 3 workers.

Conclusions

In workers manufacturing products from polyurethane foam, attention should be paid to the risk of developing contact dermatitis. Skin problems in our study group were attributable probably to insufficient protection of the skin.     

More than just Alcohol: Marijuana and Illicit Drug Use at Parties Attended by 15–20 Year Olds

Background: Parties are a common setting for marijuana and illicit drug use among adolescents. Objectives: This study examined the context of parties with alcohol, marijuana and illicit drug use attended by adolescents and young adults. Methods: In 2016, an address-based sample of 1,764 15-20-year-olds in 24?U.S. communities participated in an online survey. Parties were categorized as alcohol-only (Alc-only), marijuana?+?alcohol (Mj?+?Alc), and illicit?+?marijuana?+?alcohol (ID?+?Mj?+?Alc) based on survey participants’ observations and self-reported drug use at the last party attended. Multivariable logistic regression was used to identify correlates of substance use at parties. Results: 1,089 participants (61.7%) reported ever attending a party where alcohol was consumed. Of those, 60.1% reported that the last party they attended had Alc-only, 24.9% had Mj?+?Alc, and 10.0% had ID?+?Mj?+?Alc. Older participants were more likely to attend a party with Mj?+?Alc or ID?+?Mj?+?Alc. Participants whose mother had a college degree (compared to less than a college degree) were less likely to attend a party with ID?+?Mj?+?Alc. Parties with Mj?+?Alc and ID?+?Mj?+?Alc were larger and the majority of attendees were under 21. Parties with ID?+?Mj?+?Alc were more likely to be majority female compared to mixed gender. Parties with Mj?+?Alc were more likely to occur at someone else’s home and be in states where medical and recreational marijuana use was legal. Conclusion: One-third of parties attended by 15-20-year-olds had marijuana and/or illicit drug use in addition to alcohol consumption. The identified risk factors of parties with marijuana and illicit drug use can be used to develop targeted prevention strategies.