BACKGROUND Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs. OBJECTIVES We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis. METHODS Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays. FINDINGS Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism. MAIN CONCLUSIONS γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment. Leishmaniasis efficacy context A serum (Leishmania amazonensis cycle assays macrophages G G2M GM G2 M tested Moreover PLA pretreated. pretreated pre treated. pre-treated Also parasitism

ABSTRACT Acute wound dressings can be based on PVA hydrogels, which present many characteristics of an ideal dressing, e.g., fluid uptake, a moisturized environment, etc. The lack of antimicrobial properties leads to the addition of natural active agents. The present work aims to manufacture and compare PVA gels loaded with Barbatimão bark extract, Leucaena bark extract, Aloe vera, and Lavender essential oil. They were characterized by FTIR, swelling tests, SEM, actives release. There were interactions between PVA and the active agents. The addition of Leucaena and Barbatimão increased the PVA ability to swell, but the opposite was found for Aloe vera and Lavender essential oil. PVA-Lavender essential oil samples presented interconnected pores, while samples with essential oil or extracts presented high crystallinity. Lavender essential oil and Aloe vera presented the highest release. The Barbatimão and Leucaena samples’ release may be related to the samples’ swelling, but the initial release of Aloe vera and Lavender samples was diffusion controlled by swelling. Their long-term release was dose-dependent for Aloe vera, while it was a non-Fickian diffusion for Lavender essential oil related to the hydrogel’s relaxation step. There is a synergistic effect when Aloe vera and Lavender essential oil are loaded in PVA hydrogels. hydrogels dressing eg e g e.g. uptake environment etc agents extract FTIR tests SEM swell PVALavender pores crystallinity longterm long term dosedependent dose dependent nonFickian non Fickian hydrogel s step e.g

RESUMO Objetivo: Avaliar e comparar a eficácia clinica do uso intra-articular do ácido épsilon aminocaproico (AEAC) versus o ácido tranexâmico (ATX) na prótese total do joelho. Métodos: Estudo clínico prospectivo, centro-único, duplo-cego e randomizado. Sessenta pacientes com osteoartrose de joelho foram incluídos. Os participantes foram divididos em dois grupos de 30 pacientes. No grupo ATX, foi aplicado 1 g de ATX (0.05 g/ml) intra-articular e, no grupo AEAC, foram aplicados 4 g de AEAC (0.2 g/ml) intra-articular. Valores séricos da hemoglobina (Hb) e hemtatócrito (Ht) foram dosados no pré-operatório e com 24 e 48 horas após a cirurgia. A amplitude de movimento e a dor também foram avaliadas no exame clínico. O índice WOMAC foi utilizado para avaliar a função do joelho antes e após dois meses da cirurgia. Resultados: Foram avaliados 56 (93.3%) pacientes até o segundo mês pós-operatório. Depois da cirurgia, não houve diferenças entre os grupos (p > 0.05) na queda do valor de Hb e Ht com 24 ou 48 horas. Com relação à avaliação da dor, WOMAC e ganho de flexão do joelho, não houve vantagem significativa para nenhum dos grupos até os 60 dias depois da cirurgia(p > 0.05). Conclusão: A queda do valor da Hb e do Ht durante as primeiras 48 horas pós-operatórias e o risco de transfusão foram similares com o uso intra-articular de 1 g de ATX e 4 g de AEAC na artroplastia total do joelho. Os possíveis benefícios com relação ao controle da dor, ganho de flexão e função foram similares entre as duas drogas. Nível de Evidência II, Ensaio-Clínico Prospectivo, Randomizado, Duplo Cego, Centro-Único.

ABSTRACT Objective: To examine and compare the clinical efficacy of intraarticular epsilon aminocaproic acid (EACA) and tranexamic acid (TXA) in total knee arthroplasty (TKA). Methods: This study was a prospective, single-center, double-blinded randomized controlled trial, including sixty patients with osteoarthritis of the knee divided into two groups of 30 patients. In the TXA group, 1 g of TXA (0.05 g/ml) was applied intraarticularly, and in the EACA group, 4 g of EACA (0.2 g/ml) was applied intraarticularly. Serum hemoglobin (Hgb) and hematocrit (Htb) were measured during the preoperatively and 24 and 48 hours postoperatively. The range of motion and pain were evaluated by clinical examination. To evaluate knee function before and 2 months after surgery, the Western Ontario and McMaster Universities Index (WOMAC) questionnaire was used. Results: In total, 56 (93.3%) patients were evaluated up to the second postoperative month. No significant difference between the groups (p > 0.05) was found in the decrease in Hgb or Htb at 24 or 48 hours. Regarding assessment of the pain, WOMAC score and gain in knee flexion, no significant advantages up to 60 days after surgery (p > 0.05) were found. Conclusions: The decrease in Hgb and Htb during the first 48 hours postoperatively and the risk of transfusion were similar with the intraarticular use of 1 g of TXA and 4 g of EACA in TKA. The possible benefits regarding knee pain, gain in flexion and function were also similar for the two drugs. Level of Evidence II, Randomized, Double-Blinded, Single-Centre, Prospective Clinical Trial.

BACKGROUND: The RHD gene is highly polymorphic, which results in a large number of RhD variant phenotypes. Discrepancies in RhD typing are still a problem in blood banks and increase the risk of alloimmunization. In this study, the RhD typing strategy at a blood bank in Brazil was evaluated.METHODS: One-hundred and fifty-two samples typed as RhD negative and C or E positive by routine tests (automated system and indirect antiglobulin test using the tube technique) were reevaluated for RhD status by three methods. The method with the best performance was implemented and evaluated for a period of one year (n = 4897 samples). Samples that were D positive exclusively in the confirmatory test were submitted to molecular analysis.RESULTS: The gel test for indirect antiglobulin testing with anti-D immunoglobulin G (clone ESD1) presented the best results. Seventy samples (1.43%) previously typed as RhD negative showed reactivity in the gel test for indirect antiglobulin testing and were reclassified as D positive. D variants that may cause alloimmunization, such as weak D type 2 and partial DVI, were detected.CONCLUSION: The confirmatory RhD test using the gel test for indirect antiglobulin testing represents a breakthrough in transfusion safety in this blood center. Our results emphasize the importance of assessing the blood group typing strategy in blood banks.

OBJETIVO: verificar a viabilidade do transplante autógeno de testículos na parede abdominal e omento, em ratos, sem anastomose vascular, analisando a estrutura histológica das células testiculares após o implante. MÉTODOS: foram utilizados 60 ratos Wistar, machos, de 10-12 semanas de idade, distribuídos em três grupos: grupo controle: 20 ratos sem orquiectomia, com operação simulada; grupo 2: 20 ratos com orquiectomia bilateral sendo um testículo implantado no omento maior; grupo 3: 20 ratos com orquiectomia bilateral, sendo um testículo implantado na parede abdominal. Após dois meses eles foram mortos e os testículos avaliados pelo exame anatomopatológico. RESULTADO: o peso dos implantes teve perda de 0,62g no grupo 2, de 0,73g no grupo 3 e no grupo controle houve aumento de 0,1g. Ao estudo anatomopatológico, no grupo controle a estrutura testicular foi preservada; no grupo 2 encontrou-se 80% de inflamação e necrose, não foram visualizadas células de Sertoli ou de Leydig, em dois animais encontraram-se túbulos seminíferos; no grupo 3 encontrou-se 75% de inflamação e 60% de necrose, somente em um conseguiu-se visualizar células de Sertoli e em três células de Leydig. CONCLUSÃO: não é viável o transplante autógeno de testículo sem anastomose vascular em ratos no omento maior e na parede abdominal.

OBJECTIVE: To verify the feasibility of autologous transplantation of testes to the abdominal wall and omentum of rats without vascular anastomosis, analyzing the histological structure of the testicular cells after implantation. METHODS: We used 60 male Wistar rats, 10-12 weeks of age, which were divided into three groups: control group: 20 rats without orchiectomy with sham operation; group 2: 20 rats undergoing bilateral orchiectomy, with one of the testicles being implanted into the greater omentum; and group 3: 20 rats submitted to bilateral orchiectomy, with one testicle implanted in the abdominal wall. After two months they were euthanized and the testes evaluated by histopathology. RESULTS: the weight of the implants had a loss of 0.62 g in group 2, 0.73 g in group 3, whilst in the control group testes increased by 0.1 g. In pathological studies, the testicular structure was preserved in the control group; in group 2 there was 80% of inflammation and necrosis, Sertoli and Leydig cells were not visualized, and seminiferous tubules were found in two animals; in group 3 we found 75% of inflammation and a 60% necrosis, Sertoli cells could be visualized in only one specimen, while Leydig cells were seen in three. CONCLUSION: autologous transplantation of testis to the greater omentum and abdominal wall without vascular anastomosis is not viable in rats.

OBJETIVO: Descrever os resultados maternos e perinatais utilizando 12,5 µg de misoprostol sublingual para indução do parto em gestantes com feto vivo a termo. MÉTODOS: Realizou-se um estudo multicêntrico, tipo ensaio clínico, aberto e não randomizado, no período de julho a dezembro de 2009. Foram incluídas 30 gestantes com indicação de indução do parto, a termo, feto vivo, escore de Bishop menor ou igual a seis, apresentação cefálica, peso fetal estimado menor que 4.000 g e índice de líquido amniótico maior que cinco. Foram excluídas mulheres com cicatriz uterina, alteração da vitalidade fetal, anomalias congênitas, gestação múltipla, restrição de crescimento intrauterino, hemorragia genital e contraindicações ao parto vaginal. O comprimido de misoprostol sublingual 12,5 µg foi administrado a cada seis horas, até o início do trabalho de parto, máximo de oito doses. RESULTADOS: O trabalho de parto foi induzido satisfatoriamente em 90% das gestantes. As médias dos intervalos entre a primeira dose e o início das contrações uterinas e o parto foram de 14,3±11,7 horas e 25,4±13 horas, respectivamente. A frequência de parto vaginal foi de 60%. A taquissistolia ocorreu em duas gestantes, sendo revertida em ambos os casos sem necessitar de cesariana. A eliminação de mecônio foi observada em quatro pacientes e o escore de Apgar foi menor que sete no quinto minuto em um recém-nascido. CONCLUSÃO: Os desfechos maternos e perinatais foram favoráveis depois da indução do parto com misoprostol sublingual na dose de 12,5 µg a cada seis horas. No entanto, são necessários ensaios clínicos controlados comparando esse esquema posológico com outras doses e vias de administração

PURPOSE: To describe the maternal and perinatal outcomes after the use of 12.5 µg of sublingual misoprostol for labor induction in women with term pregnancy and a live fetus. METHODS: We conducted a multicenter, open and non-randomized clinical trial during the period from July to December 2009. We included 30 pregnant women with an indication for labor induction at term, carrying a live fetus, with a Bishop score of six or less, cephalic presentation, estimated fetal weight of less than 4,000 g and an amniotic fluid index greater than five. We excluded women with a previous uterine scar, non-reassuring fetal status, congenital anomalies, multiple pregnancy, intrauterine growth restriction, genital bleeding, and contraindications of vaginal delivery. A tablet of 12.5 µg sublingual misoprostol was administered every six hours, until the beginning of labor, with the maximum of eight doses. RESULTS: Labor was successfully induced in 90% of pregnant women. The mean interval between the first dose and the onset of uterine contractions and delivery was 14.3±11.7 hours and 25.4±13 hours, respectively. The frequency of vaginal delivery was 60%. Uterine tachysystole occurred in two pregnant women, being reversed in both cases without the need for cesarean section. Meconium-stained amniotic fluid was observed in four patients, and an Apgar score of less than 7 at five minutes in only one newborn. CONCLUSION: Maternal and perinatal outcomes were favorable after induction of labor with sublingual misoprostol at a dose of 12.5 µg every six hours. However, controlled trials are needed to compare this regimen with other doses and routes of administration.

Fatores estruturais que modulam a atividade das porfirinas englobam os ligantes equatoriais, o metal central e o número e estrutura dos seus ligantes axiais. A esses fatores se associam o microambiente fornecido por apoproteínas, solventes e membranas. Porfirinas são bastante utilizadas para a construção de estruturas supramoleculares com diferentes aplicações. A modulação da atividade das porfirinas tem sido freqüentemente obtida pela imitação da natureza, ou seja, fornecimento de diferentes microambientes. A associação das porfirinas a nanoestruturas lipídicas pode mudar a atividade destes compostos de tal forma a mimetizar diferentes enzimas como a SOD, citocromo P450, peroxidases e outros. As formas reativas das porfirinas são estados de alta valência: metal-oxo-πcátion e metal-oxo produzidos pela reação com peróxidos e perácidos. A modulação da atividade de porfirinas por nanoestruturas lipídicas também tem sido obtida para hemeproteínas uma vez que nanoestruturas lipídicas afetam a conformação das proteínas.

The structural factors modulating porphyrin activity encompass pyrrole and equatorial ligands, as well as the central metal and the number and structure of their axial ligands. Of equal importance is the microenvironment provided by apoproteins, solvents and membranes. Porphyrins are often used to construct supramolecular structures with different applications. The modulation of activity of the porphyrins has been frequently achieved by mimicking nature, i.e., by the provision of different microenvironments for these molecules. The association of porphyrins to surfactant- and lipid-containing nanostructures has changed the activity of these compounds to mimic different enzymes such as SOD, cytochrome P450, peroxidases and others. In determined conditions, the reactive forms of the porphyrins are high-valence states of oxo-metal-πcations and oxo-metal produced by the reaction with peroxides and peracids. The modulation of porphyrin activity by surfactant- and lipid-containing nanostructures has also been achieved for hemeproteins, as the lipid nanostructures affect the conformation of proteins.