Snake Venom Peptides and Low Mass Proteins: Molecular Tools and Therapeutic Agents.

Snake venoms are natural sources of biologically active molecules that are able to act selectively and specifically on different cellular targets, modulating physiological functions. Thus, these mixtures, composed mainly of proteins and peptides, provide ample and challenging opportunities and a diversified molecular architecture to design and develop tools and agents of scientific and therapeutic interest. Among these components, peptides and small proteins play diverse roles in numerous physiological processes, exerting a wide range of pharmacological activities, such as antimicrobial, antihypertensive, analgesic, antitumor, analgesic, among others. The pharmaceutical and cosmetic industries have recognized the huge potential of these privileged frameworks and believe them to be a promising alternative to contemporary drugs. A number of natural or synthetic peptides from snake venoms have already found preclinical or clinical applications for the treatment of pain, hypertension, cardiovascular diseases and aging skin. A well-known example is captopril, whose natural peptide precursor was isolated from Bothrops jararaca snake venom, which is a peptide-based drug that inhibits the angiotensin-converting enzyme, producing an anti-hypertensive effect. The present review looks at the main peptides (natriuretic peptides, bradykinin-potentiating peptides and sarafotoxins) and low mass proteins (crotamine, disintegrins and three-Finger toxins) from snake venoms, as well as synthetic peptides inspired by them, describing their biochemical, structural and physiological features, as well as their applications as research tools and therapeutic agents.

Diallel analysis to choose parents for black bean (Phaseolus vulgaris L.) breeding.

In this study, conducted in two different seasons, we aimed to choose parents to obtain promising segregating populations for the extraction of black bean (Phaseolus vulgaris L.) lines that are superior in terms of disease resistance, plant architecture, and grain yield. Twelve parents were arranged in two groups to compose a partial diallel in a 5 x 7 scheme. Group 1 was composed of parents with black grains and erect plant architecture, while group 2 was composed of parents that had carioca grains and were resistant to the main fungal diseases that occur in the common bean. The following traits were evaluated: severity of angular leaf spot (ALS), plant architecture (PAG), and grain yield (YIELD). The data were analyzed according to a partial diallel model using parents and F1 hybrids. In the genetic control of ALS and PAG, additive effects were predominant, while for YIELD, additive effects were predominant in one season and dominance effects were in another season, because it is a more complex trait than ALS and PAG. For YIELD, we observed an interaction between general combining ability and specific combining ability between seasons. The genes that control ALS, PAG, and YIELD were in eight of the 12 parents evaluated in the diallel. The cultivar 'BRS Estilo' is suitable to use as a parent in common bean breeding in terms of ALS, PAG and YIELD. Recurrent selection is the most recommended option for simultaneously breeding for PAG, YIELD, and resistance to angular leaf spot in bean culture.

Genetic progress resulting from forty-three years of breeding of the carioca common bean in Brazil.

We aimed to evaluate 40 common bean cultivars recommended by various Brazilian research institutions between 1970 and 2013 and estimate the genetic progress obtained for grain yield and other agronomic traits. Additionally, we proposed a bi-segmented nonlinear regression model to infer the year in which breeding began to show significant gains in Brazil. The experiment was carried out in Viçosa/MG and Coimbra/MG, in the dry and winter seasons of 2013. For this, a randomized complete block design with three replications was employed. The following traits were evaluated: number of pods per plant (NPP); number of seeds per pod (NSP); 1000-seed weight (W1000); grain yield (Yield); plant architecture (Arch); and grain aspect (GA). Genotypic means were estimated over years using linear mixed models, and genetic gains were estimated using bi-segmented nonlinear regression models. In summary, the methodology proposed in the present study indicated that bean breeding programs in Brazil began to influence Yield beginning in 1990, resulting in a gain of 6.74% per year (68.15 kg/ha per year). The years from which estimated genetic progress for NPP (5.62% per year), NSP (4.59% per year), W1000 (2.08% per year), and GA (1.36% per year) began to increase were 1994, 1990, 1989, and 1986, respectively.

Effect of generations and environments in the analysis of a partial diallel to improve bean earliness.

The objective of this study was to select genitors based on F1 and F2 generations, evaluated in different environments, to obtain segregating populations for the identification of strains showing improved earliness, yield, and carioca-type grains. Nine bean strains were crossed in a partial diallel scheme (4 x 5), in which group 1 included 4 strains with early cycles and group 2 included 5 elite strains. The F1 and F2 generations and the genitors were assessed in Coimbra and Viçosa in randomized blocks with 3 replications. The following characteristics were evaluated: days between sowing and emergence, and grain yield. We observed an interaction between the effects of general combining ability and specific combining ability with the environments (crop, location, and generation) for both grain earliness and yield. Genetic analysis of earliness revealed a predominance of additive effects and grain yield dominance effects. The strain Goiano Precoce may be used as a genitor in breeding programs to improve earliness, while strains RP1 and VC33 can be used to increase grain yield. We observed genetic complementation between strains Goiano Precoce and RP1, BRSMG Madrepérola and BRS Estilo for earliness and between RP1 and Rosinha Precoce for grain yield.

Comparison of findings using ultrasonography and cystoscopy in urogenital schistosomiasis in a public health centre in rural Angola.

BACKGROUND: Schistosomiasis is a chronic disease caused by infection with parasitic worms of the genus Schistosoma. In sub-Saharan Africa, infections with S. haematobium are most common. Cystoscopic examination (CE) has been accepted as the goldstandard test for detecting the late manifestations of schistosomiasis, including urothelial cancer of the bladder. However, this procedure is invasive and 10-40% of tumours may remain undetected. A non-invasive examination and a new generation of biomarkers are needed for better monitoring of the disease. OBJECTIVE: To assess the usefulness of ultrasound (US) scans for monitoring of structural urinary tract disease by local public health services in areas of Angola in which urogenital schistosomiasis is endemic. METHODS: A cohort of 80 S. haematobium-infected patients was selected in order to compare changes in the bladder wall detected by US with those observed on CE. RESULTS: There was a notable correlation between the findings observed on CE and US. Patients with lesions of the bladder mucosa such as neoplasms, ulcers or granulomas detected by CE also had changes in bladder wall thickness on US. The results support increased use of portable US machines for non-invasive examination of the bladder by local general practitioners. CONCLUSION: US examination should be an integral part of the investigation of haematuria and used in all S. haematobium control programmes. General practitioners may find it useful for more accurate diagnosis of haematuria and to identify bladder wall alterations in both adults and children in schistosomiasis-endemic regions.

Decreased susceptibility to local anesthetics-induced convulsions after paradoxical sleep deprivation.

The effect of 50% convulsant (CD50) and 50% lethal (LD50) doses of lidocaine, bupivacaine and pentylenetetrazol were determined in mice stressed by paradoxical sleep deprivation (PSD). The results showed a reduced mortality after high doses of local anesthetics and decreased seizure susceptibility induced by bupivacaine after 48 h and 72 h of PSD. On the other hand this stressful manipulation increased the susceptibility to pentylenetetrazol-induced convulsions. These data may suggest a different mechanism of action for these drugs. Possible alterations in drug metabolism or on aminergic transmission after PSD may be involved in the protection to the toxic effect of the local anesthetics.

Effect of captopril on bradykinin inactivation by human foetal placental circulation.

The inactivation of bradykinin on passage across the human foetal placental circulation was investigated in six full-term human placentas. The placentas were perfused with a modified Krebs-Henseleit solution and placenta perfusion pressure was recorded. Samples collected at the arterial inflow and at the venous effluent were assayed on the isolated guinea-pig ileum as an estimation of bradykinin activity. Bradykinin (100 ng ml-1) was infused through the foetal placental vessels before and during captopril 4 X 10(-7) M. Bradykinin produced a transient increase in placental vascular resistance that was not potentiated by captopril. Bradykinin activity was completely abolished after passage through the foetal placental circulation, and the inactivation was blocked by captopril. These data suggest that angiotensin I converting enzyme (kininase II) might occur in the foetal placental vessels.