Antimalarials and the fight against malaria in Brazil

Malaria, known as the “fevers,” has been treated for over three thousand years in China with extracts of plants of the genus Artemisia (including Artemisia annua, A. opiacea, and A. lancea) from which the active compound is artemisin, a sesquiterpene that is highly effective in the treatment of the disease, especially against young forms of the parasite. South American Indians in the seventeenth century already used an extract of the bark of chinchona tree, commonly named “Jesuits’ powder.” Its active compound was isolated in 1820 and its use spread all over the world being used as a prophylactic drug during the construction of the Madeira–Mamoré railroad in the beginning of the twentieth century. During the 1920s to the 1940s, new antimalarial drugs were synthesized to increase the arsenal against this parasite. However, the parasite has presented systematic resistence to conventional antimalarial drugs, driving researchers to find new strategies to treat the disease. In the present review we discuss how Brazil treats Plasmodium-infected patients

Ignition probability and lean ignition behaviour of a swirled premixed bluff body stabilised annular combustor

Abstract An experimental investigation was performed in a premixed annular combustor equipped with multiple swirl, bluff body burners to assess the ignition probability and to provide insights into the mechanisms of failure and of successful propagation. The experiments are done at conditions that are close to the lean blow-off limit (LBO) and hence the ignition is difficult and close to the limiting condition when ignition is not possible. Two configurations were employed, with 12 and 18 burners, the mixture velocity was varied between 10 and 30 m/s, and the equivalence ratio (ϕ) between 0.58 and 0.68. Ignition was initiated by a sequence of sparks (2 mm gap, 10 sparks of 10 ms each) and “ignition” is defined as successful ignition of the whole annular combustor. The mechanism of success and failure of the ignition process and the flame propagation patterns were investigated via high-speed imaging (10 kHz) of OH* chemiluminescence. The lean ignition limits were evaluated and compared to the lean blow-off limits, finding the 12-burner configuration is more stable than the 18-burner. It was found that failure is linked to the trapping of the initial flame kernel inside the inner recirculation zone (IRZ) of a single burner adjacent to the spark, followed by localised quenching on the bluff body probably due to heat losses. In contrast, for a successful ignition, it was necessary for the flame kernel to propagate to the adjacent burner or for a flame pocket to be convected downstream in the chamber to grow and start propagating upwards. Finally, the ignition probability (Pign) was obtained for different spark locations. It was found that sparking inside the recirculation zone resulted in Pign ∼ 0 for most conditions, while Pign increased moving the spark away from the bluff-body or placing it between two burners and peaked to Pign ∼ 1 when the spark was located downstream in the combustion chamber, where the velocities are lower and the turbulence less intense. The results provide information on the most favourable conditions for achieving ignition in a complex multi-burner geometry and could help the design and optimisation of realistic gas turbine combustors.EU Project ANNULIGHT (765998

Warm season performance of horizontal subsurface flow constructed wetlands vegetated with rice treating water from an urban stream polluted with sewage

The performance of horizontal subsurface flow constructed wetlands vegetated with rice (Oryza sativa L.) was investigated in Campina Grande (7º 13' 11" S; 35º 52' 31" W; 550 m above mean sea level), Paraíba state, northeast Brazil. The pilot-scale system comprised 24 circular tanks (76.80 cm diameter, 54 cm height) batch fed daily with water from a nearby urban stream polluted with sewage. Experimental units were filled with substrate of either sand or gravel and operated under hydraulic retention times of 5 and 10 days. Constructed wetlands demonstrated a very good performance in removing organic matter, fecal indicator microorganisms and nutrients from the influent representing a good alternative for the improvement of water quality of urban and peri-urban water resources. Vegetation was found to be the most important factor affecting their performances being the changes in both substrate and hydraulic retention time investigated herein of minor influence.Keywords: Urban polluted stream, urban polluted water treatment, constructed wetlands, effluent reuse.African Journal of Biotechnology Vol. 12(25), pp. 3992-399

Cranial Masses in Sickle Cell Disease

info:eu-repo/semantics/publishedVersio

Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.

Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer

Brazilian gamma detection device for sentinel lymph node biopsy

OBJECTIVE: To test the effectiveness of an intra-operative gamma detection Brazilian device (IPEN) on sentinel lymph node biopsy (SLNB) procedures. METHODS: Forty melanoma or breast cancer patients with indication for undergoing SLNB were studied. Lymphoscintigraphy was done 2 to 24 hours prior to surgery. Lymphatic mapping with vital dye and gamma detection were performed intraoperatively. For gamma detection Neoprobe ® 1500 was used followed by IPEN (equipment under test) in the first 20 patients and for the remaining half IPEN was used first to verify its ability to locate the sentinel node (SN). Measurements were taken from the radiopharmaceutical product injection site, from SN (in vivo and ex vivo) and from background. It was recorded if the SN was stained or not and if it was found easily by surgeon. RESULTS: There were 33 (82.5%) breast cancer and 7 (17.5%) melanoma patients. Ages varied from 21 to 68 year-old (median age of 46). Sex distribution was 35 (87.5%) women and 5 (12.5%) men. Sentinel node was found in all but one patient. There was no statistical difference between the reasons ex vivo/ background obtained with the measures of both equipments (p=0, 2583-ns). The SN was easily found by the surgeon with both devices. CONCLUSION: The SLNB was successfully performed using either equipment. It was possible to do SLNB with the Brazilian device developed by IPEN without prejudice for the patient.OBJETIVO: Testar a eficácia de equipamento de detecção gama intra-operatória (DGI) desenvolvido pelo IPEN (Brasil), em procedimentos de biópsia de linfonodo sentinela (BLS) no melanoma e no câncer de mama. MÉTODOS: Foram estudados 40 pacientes portadores de melanoma ou câncer de mama com indicação para realização de BLS.Todos pacientes foram submetidos à linfocintilografia e a BLS ocorreu entre 2 a 24 horas após a mesma. Concomitantemente à DGI, realizou-se o mapeamento linfático com corante vital. Foram feitas leituras com o equipamento convencional Neoprobe® 1500 e com o equipamento em teste (IPEN) dos valores de captação do sítio de injeção do radiofármaco, do LS in vivo e ex vivo e da captação de fundo. Foi registrado se o LS estava corado e se o cirurgião teve facilidade para encontrá-lo. Nos primeiros 20 pacientes utilizou-se o equipamento convencional e depois o de teste; nos outros 20, utilizou-se primeiro o equipamento em teste, com objetivo de verificar se o mesmo identificava primariamente o LS. RESULTADOS: Dos quarenta pacientes, 33 eram portadores de tumor de mama e sete de melanoma cutâneo; variação da idade: 21 a 68 anos (mediana= 46 anos); 35 mulheres e 5 homens. Em apenas um paciente o LS não foi encontrado, nem pela DGI nem pelo corante vital. Não houve diferença estatística entre as razões ex vivo/fundo obtidas com os dois equipamentos (p=0, 2583-ns). CONCLUSÃO: É possível realizar o procedimento de BLS com o equipamento brasileiro desenvolvido pelo IPEN, com facilidade e sem prejuízo para o paciente.Hospital Israelita Albert EinsteinIPENUniversidade Federal de São Paulo (UNIFESP)Faculdade de Medicina Anhembi-MorumbiUNIFESPSciEL

Respiratory allergy to Blomia tropicalis: Immune response in four syngeneic mouse strains and assessment of a low allergen-dose, short-term experimental model

<p>Abstract</p> <p>Background</p> <p>The dust mite <it>Blomia tropicalis </it>is an important source of aeroallergens in tropical areas. Although a mouse model for <it>B. tropicalis </it>extract (<it>Bt</it>E)-induced asthma has been described, no study comparing different mouse strains in this asthma model has been reported. The relevance and reproducibility of experimental animal models of allergy depends on the genetic background of the animal, the molecular composition of the allergen and the experimental protocol.</p> <p>Objectives</p> <p>This work had two objectives. The first was to study the anti-<it>B. tropicalis </it>allergic responses in different mouse strains using a short-term model of respiratory allergy to <it>Bt</it>E. This study included the comparison of the allergic responses elicited by <it>Bt</it>E with those elicited by ovalbumin in mice of the strain that responded better to <it>Bt</it>E sensitization. The second objective was to investigate whether the best responder mouse strain could be used in an experimental model of allergy employing relatively low <it>Bt</it>E doses.</p> <p>Methods</p> <p>Groups of mice of four different syngeneic strains were sensitized subcutaneously with 100 μg of <it>Bt</it>E on days 0 and 7 and challenged four times intranasally, at days 8, 10, 12, and 14, with 10 μg of <it>Bt</it>E. A/J mice, that were the best responders to <it>Bt</it>E sensitization, were used to compare the <it>B. tropicalis</it>-specific asthma experimental model with the conventional experimental model of ovalbumin (OVA)-specific asthma. A/J mice were also sensitized with a lower dose of <it>Bt</it>E.</p> <p>Results</p> <p>Mice of all strains had lung inflammatory-cell infiltration and increased levels of anti-<it>Bt</it>E IgE antibodies, but these responses were significantly more intense in A/J mice than in CBA/J, BALB/c or C57BL/6J mice. Immunization of A/J mice with <it>Bt</it>E induced a more intense airway eosinophil influx, higher levels of total IgE, similar airway hyperreactivity to methacholine but less intense mucous production, and lower levels of specific IgE, IgG1 and IgG2 antibodies than sensitization with OVA. Finally, immunization with a relatively low <it>Bt</it>E dose (10 μg per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose <it>Bt</it>E immunization, for the development of allergy-associated immune and lung inflammatory responses.</p> <p>Conclusions</p> <p>The described short-term model of <it>Bt</it>E-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and <it>Bt</it>E induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of <it>Bt</it>E.</p

Effects of combined training performed two or four times per week on 24-h blood pressure, glycosylated hemoglobin and other health-related outcomes in aging individuals with hypertension : rationale and study protocol of a randomized clinical trial

Background: Acute blood pressure lowering after exercise seems to predict the extent of blood pressure reduction after chronic exercise training interventions. Based on that, the same weekly amount of exercise performed more frequently could be more beneficial for controlling blood pressure. Purpose: To compare the effects of a combined training program (resistance plus aerobic exercise) performed four or two times per week on 24-h ambulatory blood pressure and other healthrelated outcomes in middle-aged and older individuals with hypertension. Methods: This study will be a randomized, parallel group, two-arm, superiority trial. Ninety-eight participants aged 50–80 years with a previous physician diagnosis of hypertension will be randomized to perform two or four sessions per week of combined training using the same total weekly overload. Primary outcomes will be 24-h ambulatory blood pressure and glycosylated hemoglobin; secondary outcomes will be endothelial function, physical fitness and quality of life. The outcomes will be assessed at baseline and at the end of 12 weeks period. Results: Our conceptual hypothesis is that a combined exercise program performed four or two times per week with equalized weekly volume/overload will improve all outcomes in comparison to the baseline values, and that reductions in 24-h blood pressure and glycosylated hemoglobin will be more pronounced in the group that trained four times a week than twice. The results of this trial are expected to provide evidences to support that higher weekly frequency of combined training should be emphasized in aging adults with hypertension