Renal and antibacterial effects induced by myotoxin I and II isolated from Bothrops jararacussu venom.

Bothrops jararacussu myotoxin I (BthTx-I; Lys 49) and II (BthTX-II; Asp 49) were purified by ion-exchange chromatography and reverse phase HPLC. In this work we used the isolated perfused rat kidney method to evaluate the renal effects of B. jararacussu myotoxins I (Lys49 PLA2) and II (Asp49 PLA2) and their possible blockage by indomethacin. BthTX-I (5 microg/ml) and BthTX-II (5 microg/ml) increased perfusion pressure (PP; ct120=110.28+/-3.70 mmHg; BthTX I=171.28+/-6.30*mmHg; BthTX II=175.50+/-7.20*mmHg), renal vascular resistance (RVR; ct120=5.49+/-0.54 mmHg/ml.g(-1)min(-1); BthTX I=8.62+/-0.37*mmHg/ml g(-1)min(-1); BthTX II=8.9+/-0.36*mmHg/ml g(-1)min(-1)), urinary flow (UF; ct(120)=0.14+/-0.01ml g(-1)min(-1); BthTX I=0.32+/-0.05*ml g(-1)min(-1); BthTX II=0.37+/-0.01*ml g(-1)min(-1)) and glomerular filtration rate (GFR; ct120=0.72+/-0.10 ml g(-1)min(-1); BthTX I=0.85+/-0.13*ml g(-1)min(-1); BthTX II=1.22+/-0.28*ml g(-1)min(-1)). In contrast decreased the percent of sodium tubular transport (%TNa(+); ct(120)=79,76+/-0.56; BthTX I=62.23+/-4.12*; BthTX II=70.96+/-2.93*) and percent of potassium tubular transport (%TK(+);ct120=66.80+/-3.69; BthTX I=55.76+/-5.57*; BthTX II=50.86+/-6.16*). Indomethacin antagonized the vascular, glomerular and tubular effects promoted by BthTX I and it's partially blocked the effects of BthTX II. In this work also evaluated the antibacterial effects of BthTx-I and BthTx-II against Xanthomonas axonopodis. pv. passiflorae (Gram-negative bacteria) and we observed that both PLA2 showed antibacterial activity. Also we observed that proteins Also we observed that proteins chemically modified with 4-bromophenacyl bromide (rho-BPB) decrease significantly the antibacterial effect of both PLA2. In conclusion, BthTx I and BthTX II caused renal alteration and presented activity antimicrobial. The indomethacin was able to antagonize totally the renal effects induced by BthTx I and partially the effects promoted by BthTx II, suggesting involvement of inflammatory mediators in the renal effects caused by myotoxins. In the other hand, other effects could be independently of the enzymatic activity of the BthTX II and the C-terminal domain could be involved in both effects promoted for PLA2.     

Hérida Regina Nunes SALGADO,et al:Microbiological assay for the determination of azithromycin in ophthalmic solutionsMicrobiological assay for the determination of azithromycin in ophthalmic solutions

IntroductionAzithromyciniscommercializedbypharmaciesinBrazilinophthalmicsolutionform. Despitetheproveneffectivenessandsafetyinitstreatment, thisdrug,untilthen, doesnotpossessamethodologyofstandar dizedanalysisforophthalmicsolutionsinofficialcom pendiumsan…     

Patterns and determinants of psychoactive drug use in Lisbon University students – a population-based study

OBJECTIVE: To study the patterns and determinants of psychoactive drug use by Lisbon University students. MATERIALS AND METHODS: A cross-sectional survey was conducted, from January to April 2000, in a probabilistic sample of 1,147 students. Information about use of psychoactive drugs and co-variates was collected by a questionnaire administered by trained interviewers. Psychoactive drugs were considered to be all medicines classified in group N (nervous system) of the ATC system except the anesthetics (subgroup N01) and the analgesics (subgroup N02). RESULTS: 91 students (7.9%) had taken psychoactive drugs during the fortnight before the interview, 39 of whom (42.8%) mentioned continuous use. The prevalence of use was significantly higher in females (9.6%), older than 25 years (13.1%), married (16%), who considered themselves to have a weak health status (21.7%), as under intense stress (15.5%). After adjustment by multivariate analysis the variables sex, self-evaluation of health status and daily stress retained a higher significant association with psychoactive drug use. A total of 132 drugs were reported as being used in that period. Tranquilizers (ATC = N05B or N05C) were used by 82 students (7.2%), while 22 (1.9%) consumed psychoactive stimulants (N06B) and 19 (1.7%) antidepressants (N06A). In all of these therapeutical subgroups, females had higher consumption prevalence than males, but the difference was statistically significant only for tranquilizers (P < 0.001). Anxiety, depression and insomnia were the most frequently stated health problems. More than 90% of drug consumers considered they had a compliant attitude and about 60% considered themselves well-informed about adverse effects of the drug used. The reported prevalence of self-medication for psychoactive drugs used was 12.8%. CONCLUSIONS: The prevalence of psychoactive drug use among students of Lisbon University was higher than expected, considering age group and the usual health status of this population. The administration of a questionnaire was a very useful tool to characterise the pattern of use and the consumer's knowledge about the drugs consumed.     

Antiangiogenesis beyond VEGF inhibition: A journey from antiangiogenic single-target to broad-spectrum agents

Although the inhibition of angiogenesis is an established modality of cancer treatment, concerns regarding toxicity and drug resistance still constitute barriers to be overcome. For almost a decade since the approval of bevacizumab in 2004, the efforts on antiangiogenic therapeutics have been mainly focused in inhibiting the VEGF pathway. The ongoing understanding of the complexity of the angiogenic process has broadened the spotlight to include concurrent and downstream players to the list of targeted inhibitors. In this review, we summarize the currently existing and the promising antiangiogenic treatments, envisioning an apparent evolutionary trend towards the development of angiogenesis inhibitors of three modalities: single-target, multi-target, and broad-spectrum agents. The clinical efficacy and some structural aspects of monoclonal antibodies, small molecules, endogenous and synthetic angiogenesis inhibitors and their molecular targets are discussed, and the targeting of endothelial cells with the use of cytotoxic drugs in a metronomic schedule is appraised. The reader is invited to revisit current expectations about antiangiogenic therapy in an attempt to set consistent clinical endpoints from which patients could gain real and lasting clinical benefits.     

Effect of Pro-Ecological Cooling and Lubrication Methods on the Sharpening Process of Planar Blades Used in Food Processing

This work presents the results of an experimental study of the sharpening of planar technical blades used in the fish processing industry. Sharpening was carried out in the grinding process using several environmentally friendly methods of cooling and lubricating the machining zone (MQL method, CAG nozzle, hybrid method that is a combination of MQL and CAG methods, as well as WET flooding method as reference). The purpose of the research was to determine the possibility of reducing the negative environmental impact of the sharpening process of technical blades by minimizing the expenditure of coolant. The application of the MQL method and the hybrid MQL + CAG method provided a very good realization of the lubricating function so that the share of friction of dulled cutting vertices against the workpiece surface is reduced, which manifests itself in the reduction of the grinding force and the correlated grinding power. In the case of grinding under cooled compressed air delivery conditions, the average cutting force was as much as 91.6% higher (F = 22.63 N) compared to the result obtained for the most favorable flooding method, demonstrating the insufficient quality of the blade shaped under such conditions. A comprehensive comparison of test results on grinding power gain, cutting force and surface texture suggests that the most favorable sharpening results were obtained using the environmentally friendly MQL method of cooling and lubricating the grinding zone.     

Effect of the Granularity of Cubic Boron Nitride Vitrified Grinding Wheels on the Planar Technical Blades Sharpening Process

The most widely used method for shaping technical blades is grinding with abrasive tools made of cubic boron nitride (cBN) grains and vitrified bond. The goal of this work was to determine the effect of grinding wheel grain size (cBN grain number according to FEPA standards: B126, B181 and B251), kinematics (grinding with the circumference, face and conical surface of the wheel) and feed rate (v_f = 100; 150; 200 mm/min) on the effects of the grinding process evaluated by the cutting force of the blade after machining F, blade surface texture parameters (Sa, St, Smvr, Str, Sdq, Sdr and Sbi) as well as blade surface morphology. An analysis of output quantities showed that grinding wheels made of B181 cBN grains are most favorable for shaping planar technical blades of X39Cr13 steel in the grinding process.     

Adhesive Bioinspired Coating for Enhancing Glass-Ceramics Scaffolds Bioactivity

Bioceramic scaffolds, composed of a biphasic composite containing bioactive glass and hydroxyapatite, were prepared in this work to overcome the intrinsic limits of the two components taken separately (in particular, their specific reactivities and dissolution rates, which should be tunable as a function of the given clinical requirements). To mimic the biological environment and tune the different stages of cellular response, a coating with gelatin and chondroitin sulphate via Layer-by-Layer (LbL) assembly was presented and discussed. The resulting functionalized scaffolds were affected by the coating in terms of microstructure and porosity. In addition, the LbL coating significantly enhanced the seeded cell behaviour, with high adhesion, proliferation and osteogenic activity, as revealed by the alkaline phosphatase activity and overexpression of osteopontin and osteocalcin.     

Evaluation of the Hepatocellular Carcinoma Predictive Scores PAGE-B and mPAGE-B among Brazilian Patients with Chronic Hepatitis B Virus Infection

Hepatitis B virus (HBV) is intrinsically oncogenic and related to hepatocellular carcinoma (HCC). Predictive scores of HCC have been developed but have been poorly studied in admixed populations. Therefore, we aimed to evaluate the performance of PAGE-B and mPAGE-B scores for HCC prediction in HBV Brazilian patients and factors related to HCC occurrence. This is a retrospective study that evaluated patients followed at a tertiary university center. A total of 224 patients were included, with a median follow-up period of 9 years. The mean age at HBV diagnosis was 38.71 ± 14.19 years, predominantly males (66.1%). The cumulative incidence of HCC at 3, 5, and 7 years was 0.993%, 2.70%, and 5.25%, respectively, being related in the univariate logistic regression analysis to male sex (p = 0.0461), older age (p = 0.0001), cirrhosis at HBV diagnosis (p < 0.0001), and higher values of PAGE-B and mPAGE-B scores (p = 0.0002 and p < 0.0001, respectively). Older age, male sex, and cirrhosis at HBV diagnosis were independently associated with HCC occurrence. The AUROCs of PAGE-B and mPAGE-B were 0.7906 and 0.7904, respectively, with no differences between them (p = 0.9767). In conclusion, both PAGE-B and mPAGE-B showed a correct prediction of HCC above 70% in this cohort.