aug-MIA-QSAR modeling of antimicrobial activities and design of multi-target anilide derivatives

The antibacterial activity against Bacillus subtilis, Staphylococcus aureus and Escherichia coli, as well as the antifungal activity against Aspergillus niger of a series of anilide derivatives have been modeled using augmented multivariate image analysis applied to quantitative structure–activity relationship (aug-MIA-QSAR). This QSAR approach is based on 2D molecular shape, as well as atomic sizes and colors to encode chemical, physical and biological properties. Predictive models with r² from 0.65 to 0.83 were used to estimate the antimicrobial activities of novel anilide analogs, which were built from the combination of substructures of the most active antimicrobial compounds along the series. Given the synergistic effect of different substituents to provide new molecules, promising compounds were proposed, highlighting a considerable multi-antimicrobial activity.     

Short-term in vivo inhibition of nitric oxide synthase with L-NAME influences the contractile function of single left ventricular myocytes in rats

The main purpose of this study was to investigate the effects of short-term L-NAME treatment on the contractile function of left ventricle (LV) myocytes and the expression of proteins related to Ca(2+) homeostasis. Data from Wistar rats treated with L-NAME (L group, n = 20; 0.7?g/L in drinking water; 7?days) were compared with results from untreated controls (C group, n = 20). Cardiomyocytes from the L group showed increased (p?< 0.05) fractional shortening (23%) and maximum rate of shortening (20%) compared with the C group. LV from the L group also showed increased (p?< 0.05) expression of the ryanodine receptor 2 and Na(+)/Ca(2+) exchanger proteins (76% and 83%, respectively; p?< 0.05). However, the L and C groups showed similar in vivo hemodynamic parameters of cardiac function. In conclusion, short-term NOS inhibition determines an increased expression of Ca(2+) regulatory proteins, which contributes to improving cardiomyocyte contractile function, preserving left ventricular function.     

Triploidization in the streaked prochilod Prochilodus lineatus inferred by flow cytometry,blood smears and karyological approaches

The streaked prochilod Prochilodus lineatus is an important fish species from the Neotropical region. In this study, a protocol of triploidization was established by temperature shock. Fertilized eggs were shocked at 2 min post-fertilization at 0, 38, 40 and 42°C. At 0°C, the embryos were maintained for 30 min, while the rest for 2 min. Heat shocked embryos and control (during all experiment) were incubated at 27°C. The ploidy status was confirmed by flow cytometry, erythrocyte diameter, conventional cytogenetics (Giemsa staining), chromosome banding and fluorescence in situ hybridization using 5S and 18S rDNA probes. Heat-shock at 40°C produced 96.7% of triploids and such a procedure did not reduce the fertilization, hatching rate and the percentage of normal embryos. The use of chromosome banding and FISH gave rise to effective procedure to identify triploids. The data obtained here is innovative for the species and bring new information for basic and applied studies.     

Genetic diversity and structure of landrace accessions,elite lineages and cultivars of common bean estimated with SSR and SNP markers

Molecular Biology Reports - Common bean (Phaseolus vulgaris L.) is an important source of proteins, fibers and minerals for humans, being grown mainly in developing countries and representing a...     

Jaburetox,a urease-derived peptide: Effects on enzymatic pathways of the cockroach Nauphoeta cinerea

Jaburetox is a recombinant peptide derived from one of the Canavalia ensiformis urease isoforms. This peptide induces several toxic effects on insects of different orders, including interference on muscle contractility in cockroaches, modulation of UDP-N-acetylglucosamine pyrophosphorylase (UAP) and nitric oxide synthase (NOS) activities in the central nervous system of triatomines, as well as activation of the immune system in Rhodnius prolixus. When injected, the peptide is lethal for R. prolixus and Triatoma infestans. Here, we evaluated Jaburetox toxicity to Nauphoeta cinerea cockroaches, exploring the effects on the central nervous system through the activities of UAP, NOS, acid phosphatases (ACP), and acetylcholinesterase (AChE). The results indicated that N. cinerea is not susceptible to the lethal effect of the peptide. Moreover, both in vivo and in vitro treatments with Jaburetox inhibited NOS activity, without modifying the protein levels. No alterations on ACP activity were observed. In addition, the enzyme activity of UAP only had its activity affected at 18 hr after injection. The peptide increased the AChE activity, suggesting a mechanism involved in overcoming the toxic effects. In conclusion, our findings indicate that Jaburetox affects the nitrinergic signaling as well as the AChE and UAP activities and establishes N. cinerea as a Jaburetox-resistant model for future comparative studies.     

Effect of a denture cleanser on the concentration of volatile sulphur compounds and denture biofilm in institutionalised elderly

doi:10.1111/j.1741‐2358.2009.00341.x
Effect of a denture cleanser on the concentration of volatile sulphur compounds and denture biofilm in institutionalised elderly Objective: To determine the effectiveness of a denture cleanser in reducing the concentration of volatile sulphur compounds (VSC) and its antimicrobial action. Background: Micro‐organisms from the denture biofilm can cause local and systemic disease and halitosis. Denture cleansers are important adjuncts in oral care, but there is limited investigation on their effect in malodour compounds. Material and methods: Nineteen institutionalised elderly who wore at least an upper denture were selected; their VSC concentrations were measured and the denture biofilm was collected. In phase 1, the subjects wore their old denture and data were collected before (B₀) and after 7(A₁), 14(A₂), 28(A₃) days of continuous daily use of the denture cleanser. In phase 2, new dentures were inserted and measurements were made at 30(A_1.1), 60(A_2.2), 90(A_3.3) days of treatment. Results: The VSC concentration increased from B₀ to A₁ (p < 0.05)_, but no differences were found for the others intervals of times. Total micro‐organism data did not show a statistical difference between times in Phase I, but in Phase II, there was a statistical difference (p < 0.05) and a progressive re‐colonisation was observed. Conclusion: Within the limits of this study, it was concluded that the denture cleanser had no antimicrobial effect and VSC levels were not reduced.     

Delta-aminolevulinate dehydratase activity in red blood cells of rats infected with Trypanosoma evansi

The aim of this study was to evaluate the activity of delta-aminolevulinate dehydratase (δ-ALA-D) in red blood cells of rats infected with Trypanosoma evansi and establish its association with haematocrit, serum levels of iron and zinc and lipid peroxidation. Thirty-six male rats (Wistar) were divided into 2 groups with 18 animals each. Group A was non-infected while Group B was intraperitoneally infected, receiving 7·5×106 trypomastigotes per animal. Each group was divided into 3 subgroups of 6 rats and blood was collected during different periods post-infection (p.i.) as follows: day 5 (A1 and B1), day 15 (A2 and B2) and day 30 PI (A3 and B3). Blood samples were collected by cardiac puncture to estimate red blood cell parameters (RBC), δ-ALA-D activity and serum levels of iron, zinc and thiobarbituric acid reactive substances (TBARS). Rats in group B showed a significant (P<0·05) reduction of RBC count, haemoglobin concentration and haematocrit at days 5 and 15 p.i. The activity of δ-ALA-D in blood was significantly (P<0·001) increased at days 15 and 30 p.i. δ-ALA-D activity in blood had a significant (P<0·05) negative correlation with haematocrit (r=-0·61) and haemoglobin (r=-0·70) at day 15 p.i. There was a significant (P<0·05) decrease in serum iron and zinc levels and an increase in TBARS levels (P<0·05) during infection. The δ-ALA-D activity in blood was negatively correlated with the levels of iron (r=-0·68) and zinc (r=-0·57) on day 30 p.i. It was concluded that the increased activity of δ-ALA-D in blood might have occurred in response to the anaemia in remission as heme synthesis was enhanced.     

Importance of the sarcoplasmic reticulum and adrenergic stimulation on the cardiac contractility of the neotropical teleost <Emphasis Type="Italic">Synbranchus marmoratus</Emphasis> under different thermal conditions

Experiments were carried out to investigate the heart rate of Synbranchus marmoratus after changing the temperature of the water contained in the experimental chamber of the acclimated fish (from 25 to 35°C and from 25 to 15°C). Then, an isometric cardiac muscle preparation was used to test the relative importance of Ca²⁺ released from the sarcoplasmic reticulum and Ca²⁺ influx across the sarcolemma for the cardiac performance under different thermal conditions: 25°C (acclimation temperature), 15 and 35°C. Adrenaline and ryanodine were used to modulate the Ca²⁺ flux through the sarcolemma and the sarcoplasmic reticulum, respectively. Ryanodine reduced the peak tension by approximately 47% at 25°C, and by 53% at 35°C; however, it had no effect at 15°C. A high adrenaline concentration was able to ameliorate the negative effects of ryanodine. Despite increasing the peak tension, adrenaline increased the times necessary for contraction and relaxation. We conclude that the sarcoplasmic reticulum is active in contributing Ca²⁺ to the development of tension at physiological contraction frequencies. The adrenaline-stimulated Ca²⁺ influx is able to increase the peak tension, even after addition of ryanodine, at physiologically relevant temperatures and pacing frequencies.     

Can electrons travel through actin microfilaments and generate oxidative stress in retinol treated Sertoli cell?

In early reports our research group has demonstrated that 7 μM retinol (vitamin A) treatment leads to many changes in Sertoli cell metabolism, such as up-regulation of antioxidant enzyme activities, increase in damage to biomolecules, abnormal cellular division, pre-neoplasic transformation, and cytoskeleton conformational changes. These effects were observed to be dependent on the production of reactive oxygen species (ROS), suggesting extra-nuclear (non-genomic) effects of retinol metabolism. Besides 7 μM retinol treatment causing oxidative stress, we have demonstrated that changes observed in cytoskeleton of Sertoli cells under these conditions were protective, and seem to be an adaptive phenomenon against a pro-oxidant environment resulting from retinol treatment. We have hypothesized that the cytoskeleton can conduct electrons through actin microfilaments, which would be a natural process necessary for cell homeostasis. In the present study we demonstrate results correlating retinol metabolism, actin architecture, mitochondria physiology and ROS, in order to demonstrate that the electron conduction through actin microfilaments might explain our results. We believe that electrons produced by retinol metabolism are dislocated through actin microfilaments to mitochondria, and are transferred to electron transport chain to produce water. When mitochondria capacity to receive electrons is overloaded, superoxide radical production is increased and the oxidative stress process starts. Our results suggested that actin cytoskeleton is essential to oxidative stress production induced by retinol treatment, and electrons conduction through actin microfilaments can be the key of this correlation.