Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase

Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47^phox subunits, elevated level of p47^phox phosphorylation, and enlarged phospho‐p47^phox and p67^phox content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho‐p47^phox and p67^phox. Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.     

First report of a naturally patent infection with Dirofilaria immitis in an otter (Lutra lutra)

Parasitology Research - Dirofilaria immitis causes a severe and life-threatening cardio-pulmonary disease in Europe, Asia, Africa, and the Americas; also, zoonotic infections have been reported....     

Reliability and Validity of Assessing User Satisfaction With Web-Based Health Interventions

BackgroundThe perspective of users should be taken into account in the evaluation of Web-based health interventions. Assessing the users’ satisfaction with the intervention they receive could enhance the evidence for the intervention effects. Thus, there is a need for valid and reliable measures to assess satisfaction with Web-based health interventions.ObjectiveThe objective of this study was to analyze the reliability, factorial structure, and construct validity of the Client Satisfaction Questionnaire adapted to Internet-based interventions (CSQ-I).MethodsThe psychometric quality of the CSQ-I was analyzed in user samples from 2 separate randomized controlled trials evaluating Web-based health interventions, one from a depression prevention intervention (sample 1, N=174) and the other from a stress management intervention (sample 2, N=111). At first, the underlying measurement model of the CSQ-I was analyzed to determine the internal consistency. The factorial structure of the scale and the measurement invariance across groups were tested by multigroup confirmatory factor analyses. Additionally, the construct validity of the scale was examined by comparing satisfaction scores with the primary clinical outcome.ResultsMultigroup confirmatory analyses on the scale yielded a one-factorial structure with a good fit (root-mean-square error of approximation =.09, comparative fit index =.96, standardized root-mean-square residual =.05) that showed partial strong invariance across the 2 samples. The scale showed very good reliability, indicated by McDonald omegas of .95 in sample 1 and .93 in sample 2. Significant correlations with change in depressive symptoms (r=−.35, P<.001) and perceived stress (r=−.48, P<.001) demonstrated the construct validity of the scale.ConclusionsThe proven internal consistency, factorial structure, and construct validity of the CSQ-I indicate a good overall psychometric quality of the measure to assess the user’s general satisfaction with Web-based interventions for depression and stress management. Multigroup analyses indicate its robustness across different samples. Thus, the CSQ-I seems to be a suitable measure to consider the user’s perspective in the overall evaluation of Web-based health interventions.     

Pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients after the first intravenous administration of 400 mg

PurposeTo investigate the pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients after the first intravenous administration of 400 mg.Material/methods.Plasma concentrations were measured in 20 critically ill patients (mean [SD]; age, 55.5 [16.5] years; weight, 80.3 [16.9] kg; and creatinine clearance, 110.0 [71.5] mL/min). Four blood samples were drawn at the following time points 0, 0.5, 6, 8 hours after infusion. Ciprofloxacin concentrations were determined by high-performance liquid chromatography. Results. In the cases where ciprofloxacin was applied in targeted antibiotic therapy the minimum inhibitory concentrations (MIC) were ≤0.5 mg/l. The maximum and minimum plasma concentrations of ciprofloxacin were 1.74 (0.58-7.90) and 0.45 (0.16-2.96) mg/l, respectively. The main pharmacokinetic parameters for ciprofloxacin in the analyzed patients were as follows: k_el, 0.21 h^?1; t_1/2kel, 3.37 h; AUC_0-inf, 10.10 mg×h/l; AUMC_0-last, 15.36 mg×h²/l; MRT, 1.71 h; V_d, 214.8 l; Cl, 39.70 l/h. Considering the maximum value of MIC (0.5 mg/l) only 30% and 25% of analyzed patients had desired values of the PK/PD indexes AUIC>125 and C_max /MIC>10, respectively.Conclusions.The target plasma concentrations after the first dose of ciprofloxacin were reached only in a few critically ill patients. Considerable inter-subject variability for PK/PD parameters in ICU patients requires systematic monitoring.     

Comparative study of ecophysiological and biochemical variation between the Baltic and North Sea populations of the invasive soft shell clam Mya arenaria (L. 1758)

Seasonal variations of environmental factors, such as temperature and salinity, require metabolic acclimatization in sedentary benthic fauna distributed over a wide geographical range. The soft-shell clam Mya arenaria inhabits the coastal waters of the North Atlantic including North America and Europe. In Europe, M. arenaria populations are distributed from Iceland to the Mediterranean Sea, including the North Sea, the Baltic Sea and the Black Sea. Seasonal changes in physiological parameters (gonad index, condition index, biochemical composition and respiration rate) of M. arenaria from the Baltic Sea (the Gulf of Gdańsk, Poland), and the North Sea (Versee Meer, the Netherlands) were studied. The sex ratio of both populations did not differ from 1:1 and the seasonal gonad index was higher in the Baltic population. The average condition index changed seasonally at both studied sites, and was also higher in the Baltic population (except the autumn) compared to the North Sea. In both studied populations, the content of proteins, lipids and carbohydrates in the soft tissue followed the seasonal variations, and it was higher in the Baltic population. The respiration rate was lower in the Baltic population, and seasonal changes in the respiration rate seem to be correlated with changes in the water temperature. Based on the results obtained in the present study, we suggest that Mya arenaria is characterized by a large phenotypic plasticity and differences in the observed physiological traits are due to acclimatization to ambient environmental conditions.     

Histochemical Studies on Activity and Distribution of Acid Phosphatase,Non-specific Esterase,and E 600-resistant Esterase in Jejunal Mucosa During Acute Radiation Disease

Summary

Histochemical studies on activity and localization of some enzymes (acid phosphatase, non-specific esterase, E 600-resistant esterase) in the jejunal mucosa of guinea-pigs have been performed at certain stages of radiation disease induced by x-rays.

Results obtained revealed a positive correlation between acid-phosphatase activity and advances of disease. The activity increase of this enzyme in the mucosal cells signifies intensifying catabolic processes. After irradiation, changes of thiolacetic esterase activity were observed which seem to be related to the stages of radiation and which may implicate fatty-acid metabolism. Reaction to E 600-resistant esterases increased linearly to time after irradiation, indicating catabolic activation in the intestinal mucosa.     

Cyclin-dependent kinase 4/6 inhibitors in hormone receptor-positive early breast cancer: preliminary results and ongoing studies

The cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitors (CDK4/6i) induce cell cycle arrest in the G1 phase what eventually can prevent the proliferation of cancer cells. The CDK4/6i have changed the landscape of treatment options for ER-positive, HER2-negative metastatic breast cancer. Currently, palbociclib, ribociclib, and abemaciclib are approved by the US Food and Drug Administration in this setting. This success encouraged the researchers to examine CDK4/6i activity in (neo)adjuvant setting. In this review, clinical data to date and ongoing clinical trials with palbociclib, ribociclib, and abemaciclib in the early breast cancer are discussed. A literature search of these topics was carried out using PubMed and data reported at international oncology meetings and clinicaltrials.gov were included. Currently, we have the early promising data from Phase II clinical trials of CDK4/6i efficacy in the neoadjuvant setting in women with HR-positive breast cancer. Moreover, there are numerous studies that are in progress today in (neo)adjuvant setting.