Bactericidal and neurotoxic activities of two myotoxic phospholipases A2 from Bothrops neuwiedi pauloensis snake venom.

Two basic myotoxic PLA(2)s, namely BnpTX-I and II, were isolated from Bothrops neuwiedi pauloensis snake venom through three chromatographic steps: ion-exchange chromatography on CM-Sepharose, gel filtration on Sephadex G-50 and reverse phase HPLC on a C18 column. Both PLA(2)s showed a M(r) around 14,000 for the monomer and 28,000 for the dimer (as estimated by SDS-PAGE), pI approximately 7.8 and approximately 121 amino acid residues cross-linked by seven disulfide bonds. The N-terminal sequences revealed significant homology with Asp49 basic myotoxic PLA(2)s from other snake venoms. The catalytic and anticoagulant activities of BnpTX-I were higher than those of BnpTX-II. Both were able to induce cytotoxicity in vitro, as well as, myotoxicity, edema and lethality in mice. BnpTX-I also induced neurotoxic effect on mouse neuromuscular preparations and bactericidal activity on Eschericia coli and Staphylococcus aureus. After chemical modification of BnpTX-I with BPB or incubation with EDTA or Mn(2+) ions, the catalytic activity was completely abolished, while the toxic and pharmacological activities were partially reduced. Interaction with heparin inhibited the cytotoxic and bactericidal effects. Anti-BthTX-I, anti-BthTX-II and anti-115-129-C terminal antibodies strongly recognize both BnpTX-I and II. It is shown that the neurotoxic effect induced by B. neuwiedi pauloensis venom is due to the presence of myotoxic PLA(2)s. The data also corroborate the hypothesis of a partial dissociation between toxic and enzymatic domains. In addition, BnpTX-I displays a heparin binding C-terminal region, which is probably responsible for the cytotoxic and bactericidal effects.     

Impact of atomic layer deposited TiO2 on the photocatalytic efficiency of TiO2/w-VA-CNT nanocomposite materials

Titanium oxide (TiO₂) has been widely investigated as a photocatalytic material, and the fact that its performance depends on its crystalline structure motivates further research on the relationship between preparation methods and material properties. In this work, TiO₂ thin films were grown on non-functionalized wave-like patterned vertically aligned carbon nanotubes (w-VA-CNTs) via the atomic layer deposition (ALD) technique. Grazing incidence X-ray diffraction (GIXRD) analysis revealed that the structure of the TiO₂/VA-CNT nanocomposites varied from amorphous to a crystalline phase with increasing deposition temperature, suggesting a “critical deposition temperature” for the anatase crystalline phase formation. On the other hand, scanning transmission electron microscopy (STEM) studies revealed that the non-functionalized carbon nanotubes were conformally and homogeneously coated with TiO₂, forming a nanocomposite while preserving the morphology of the nanotubes. X-ray photoelectron spectroscopy (XPS) provided information about the surface chemistry and stoichiometry of TiO₂. The photodegradation experiments under ultraviolet (UV) light on a model pollutant (Rhodamine B, RhB) revealed that the nanocomposite comprised of anatase crystalline TiO₂ grown at 200 °C (11.2 nm thickness) presented the highest degradation efficiency viz 55% with an illumination time of 240 min. Furthermore, its recyclability was also demonstrated for multiple cycles, showing good recovery and potential for practical applications.

Amorphous or anatase crystalline TiO₂/VA-CNT nanocomposites were grown controlling the synthesis temperature. Photocatalytic degradation of RhB of 55% was achieved after 240 min. The immobilized material remains active after 4 cycles of use.     

Comparison of cardiac function in male and female diabetic rats

To examine the influence of sex differences in the STZ model of diabetes, we studied left ventricular function in hearts from 6 week old male and female rats. Significantly lower values for +dP/dt occurred in male diabetic rats compared with their own controls or female diabetics at most left atrial filling pressures. Decreases in this value for female diabetic rats compared to their own controls occurred only at high left atrial pressures. It appears that diabetes mellitus produces greater myocardial dysfunction in male diabetic rats.     

Association of Pre-S/S and Polymerase Mutations with Acute and Chronic Hepatitis B Virus Infections in Patients from Rio de Janeiro,Brazil

Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy.     

Opioid-based micro and nanoparticulate formulations: alternative approach on pain management

Context Opioids have been used as the reference treatment on chronic pain. However, they are related to serious adverse effects which affect the patient compliance to treatment, as well as, his quality of life. Particulate formulations have been investigated as an alternative to improve opioid efficacy and safety. Objective Summarise the available studies concerning micro and nanoencapsulated opioid formulations discussing their biopharmaceutical characteristics, such as composition, size, in vitro release, pharmacokinetic and antinociceptive profile. Methods Papers available in 1995–2015 at Medline, Science Direct and Web of Science databases were collected and assessed. Searches were performed using varied combinations of the keywords of this work. Results Opioid-loaded particles showed prolonged drug release with maintenance of serum therapeutic concentrations and extended analgesia when compared with the free drugs. The side effects incidences were reduced or maintained the same. Conclusion Particulate formulations can significantly increase both potency and safety profiles of opioids.     

Sex-Dependent Effects of the Intake of NOVA Classified Ultra-Processed Foods on Syndrome Metabolic Components in Brazilian Adults

Longitudinal studies evaluating the relationship between UPF consumption and the incidence of Metabolic Syndrome (MetS) and its components are still scarce. This study aimed to evaluate the effect of UPF consumption on the incidence of MetS and its components in adults. A prospective study was conducted with 896 participants from the 1978/79 Ribeirão Preto cohort, São Paulo, Brazil. UPF consumption was evaluated in %kcal and %g at ages 23–25 years. Incidence of MetS and its components were estimated at ages 37–39 years, according to the Joint Interim Statement criteria. Poisson regression was used to assess associations, and interactions with sex were investigated. UPF consumption had no association with MetS (%kcal Adjusted PR: 1.00; 95% CI: 0.99–1.01; %g Adjusted PR: 1.00; 95% CI: 0.99–1.01). However, women with higher UPF consumption, in %kcal and %g, had a higher risk of abdominal obesity (%kcal: p = 0.030; %g: p = 0.003); and women with higher UPF consumption, in %g, had a higher risk of low HDL-cholesterol (p = 0.041). For the other components of MetS, no significant associations were observed in either sex. These findings suggest evidence of no association between UPF consumption and MetS; however, consumption of UPF was associated with increased WC and low HDL-c, but only in women.     

Anterior clear spaces in keratoconus

Anterior clear spaces were observed prospectively at slit-lamp examination in 26 of 69 consecutive eyes (38%) with keratoconus. Two corneal buttons with this finding were examined by light and electron microscopy and revealed breaks in Bowman's layer. Anterior clear spaces should be considered in the spectrum of clinical findings in keratoconus.     

Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)

Background  

Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy (CT), its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients.