Exposure to paraquat associated with periodontal disease causes motor damage and neurochemical changes in rats.

Exposure to paraquat is possibly involved with the development of several conditions, including neurodegenerative diseases, such as Parkinson's disease (PD). This condition is mainly characterized by the loss of dopaminergic neurons in the nigrostriatal pathway and the development of classical motor symptoms. Etiology includes exposure to environmental factors, such as the paraquat exposure, and inflammatory diseases may exacerbate paraquat neurotoxicity. The aim of the study was to investigate whether the exposure to paraquat associated with the presence of periodontal disease is able to induce motor and biochemical changes in rats similar to that observed in PD. Adult male Wistar rats were sent to ligature. After 48 h, they were sent to daily treatment paraquat (1 mg/kg/day; 2 mL/kg; intragastric) or vehicle for 4 weeks. Twenty-four hours after the last administration, the open field test was performed. The rats were euthanized and the left hemimandibles and striatum were dissected for the analysis of dopaminergic and inflammatory markers. Only the combination of periodontal disease model plus paraquat exposure induced motor impairments. Remarkably, the paraquat exposure increased the ligature-induced alveolar bone loss in hemimandibles. Moreover, only the combination of periodontal disease and paraquat exposure induced the loss of dopaminergic neurons and astrocyte activation in the striatum.

Eco-epidemiological study on sandflies and environmental aspects related to the transmission of leishmaniasis in a municipality of Minas Gerais, Brazil, 2015-2016 / Estudo eco-epidemiológico da fauna flebotomínica e dos aspectos ambientais relacionados à transmissão das leishmanioses em um município de Minas Gerais, Brasil, 2015 - 2016

Diante da escassez de dados sobre a topografia e a sintopia das vísceras abdominopélvicas do tamanduá-bandeira (Myrmecophage tridactyla - Linnaeus, 1758), o presente estudo teve como objetivo elucidar essas características e compará-las com as demais espécies animais, mormente as domésticas. Utilizaram-se três espécimes, dois machos e uma fêmea, provenientes de doação da Polícia Militar Ambiental de Franca ao Laboratório de Anatomia Veterinária da Universidade de Franca, após óbitos por atropelamentos. Os animais foram fixados e mantidos em solução aquosa de formaldeído a 10%, seguidos de dissecação convencional das cavidades abdominopélvicas para posterior inspeção direta e descrição topográfica das vísceras, visando a análises comparativas com outras espécies, cujo posicionamento e cujas particularidades já são bem estabelecidos na literatura. Observou-se que a maioria das vísceras dessas cavidades possuem localização e sintopia similares aos animais domésticos, exceto os rins e os testículos. Diante da metodologia estabelecida e dos resultados obtidos, admite-se que mais espécimes de tamanduás-bandeiras, de ambos os gêneros, devam ser avaliados e registrados cientificamente, visando à confirmação dos dados da atual pesquisa e à preconização anatômica da cavidade abdominopélvica, visto que variações anatômicas individuais são passíveis entre animais da mesma espécie.(AU)

Objetivou-se avaliar a fauna vetorial e os aspectos ambientais e climáticos relacionados à transmissão das leishmanioses. Foi realizado um estudo eco-epidemiológico prospectivo de coleta sistemática de flebotomíneos e inquérito censitário sorológico canino em áreas de um município do Brasil. Para determinar a taxa de prevalência de LVC, foram examinadas amostras de sangue de 1752 cães. Na avaliação entomológica, foram instaladas 24 armadilhas luminosas em 12 residências distribuídas, instaladas no ambiente de peridomicílio e intradomicílio durante 12 meses. Para análise dos aspectos climáticos, utilizou-se a correlação simples de Spearman e para análise espacial foram utilizadas a Lógica Fuzzy e a Função K. A taxa de prevalência em cães foi de 4,1% e 7,1%. No estudo entomológico, foram capturados 431 flebotomíneos. A maior parte (74%) dos espécimes foi capturada no peridomicílio. Em relação à infecção natural, 5,6 % das amostras analisadas por biologia molecular apresentaram positividade à infecção por Leishmania spp.. Em 100% das amostras positivas, encontrou-se infecção por Leishmania infantum. Na análise espacial uma Área apresentou maior concentração de pontos de sobreposição de alta densidade de Lutzomyia longipalpis e cães sororreagentes, indicando maior risco na ocorrência concomitante dos dois eventos. Os resultados mostram que a interface parasito-reservatório-vetor está ativa nas áreas estudadas.(AU)

Recurrent hepatitis C treatment with direct acting antivirals - a real life study at a Brazilian liver transplant center.

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.

Recurrent hepatitis C treatment with direct acting antivirals - a real life study at a Brazilian liver transplant center

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.

Green coffee seed residue: A sustainable source of antioxidant compounds.

Oil extraction from green coffee seeds generates residual mass that is discarded by agribusiness and has not been previously studied. Bioactive secondary metabolites in coffee include antioxidant phenolic compounds, such as chlorogenic acids. Coffee seeds also contain caffeine, a pharmaceutically important methylxanthine. Here, we report the chemical profile, antioxidant activity, and cytotoxicity of hydroethanolic extracts of green Coffea arabica L. seed residue. The extracts of the green seeds and the residue have similar chemical profiles, containing the phenolic compounds chlorogenic acid and caffeine. Five monoacyl and three diacyl esters of trans-cinnamic acids and quinic acid were identified by ultra-performance liquid chromatography/electrospray ionization-quadruple time of flight mass spectrometry. The residue extract showed antioxidant potential in DPPH, ABTS, and pyranine assays and low cytotoxicity. Thus, coffee oil residue has great potential for use as a raw material in dietary supplements, cosmetic and pharmaceutical products, or as a source of bioactive compounds.

The molecular mechanism of Nystatin action is dependent on the membrane biophysical properties and lipid composition.

Nystatin (Nys) is a pore forming broad-spectrum and efficient antifungal drug with significant toxicity in mammalian organisms. In order to develop a non-toxic and more effective Nys formulation, its molecular mechanism of action at the cell membrane needs to be better understood. It is widely accepted that Nys activity and toxicity depend on the presence and type of membrane sterols. Taking advantage of multiple biophysical methodologies, we now show that the formation and stabilization of Nys aqueous pores, which are associated with Nys cytotoxicity, occur in the absence of membrane sterols. Our results suggest that the Nys mechanism of action is driven by the presence of highly ordered membrane domains capable of stabilizing the Nys oligomers. Moreover, Nys pore formation is accompanied by strong Nys-induced membrane reorganization that depends on membrane lipid composition and seems to underlie the Nys cytotoxic effect. Accordingly, in membranes enriched in a gel-phase forming phospholipid, Nys incorporates within the phospholipid-enriched gel domains, where it forms pores able to expand the gel domains. In contrast, in membranes enriched in gel domain forming sphingolipids, Nys-induced pore formation occurs through the destabilization of the gel phase. These results show that the Nys mechanism of action is complex and not only dependent on membrane sterols, and provide further insight into the molecular details governing Nys activity and toxicity.

Rhabdomyolysis as a clinical manifestation of association with ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-α in liver-transplanted patients: a case report and literature review.

BACKGROUND: Rhabdomyolysis is a syndrome characterized by impaired metabolic integrity of myocytes, causing the release of intracellular constituents into the circulation, and can be a serious side effect of drug intake. CASE REPORT: This report describes a unique case of rabdomyolysis secondary in which ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-α in a liver transplant patient was used. A 47-year-old male liver transplant recipient in 2009, who had hepatitis C and incidental hepatocellular carcinoma, underwent immunosuppressive therapy (cyclosporine and sirolimus). The patient is currently in treatment for viral recurrence with pegylated interferon-α and ribavirin; he had a history of hypertriglyceridemia treated with ciprofibrate. He had development of severe and generalized myalgia and fever after the eighth application of pegylated interferon-α and increasing doses of cyclosporine. Laboratorial tests showed acute renal failure and significant increase in creatine kinase. Rhabdomyolysis secondary to interaction of fibrate-cyclosporine-pegylated interferon-α was postulated. CONCLUSIONS: Medical professionals should be aware of possible drug interactions and should monitor patients receiving these drugs.

Liberação de componentes do extrato de Casearia sylvestris Swartz empregando membranas de látex natural como suporte / Analysis of Casearia sylvestris Swartz extract release from natural rubber latex membranes

A membrana de látex natural (NRL - Natural Rubber Latex), manipulada a partir do látex extraído da seringueira Hevea brasiliensis, tem apresentado grande potencial de aplicação no campo da biomedicina e dos biomateriais. Graças a sua biocompatibilidade e baixa taxa de rejeição, ela tem sido utilizada para próteses e enxertos, atuando como estimulante da angiogênese, adesão celular e barreira física a agentes infecciosos. Além dessas aplicações, as membranas são utilizadas como matriz de sistemas de liberação para avaliar o comportamento da liberação de fármacos e extratos de origem vegetal que apresentam propriedades medicinais. O sistema extrato-membrana tem como objeto de estudo uma nova abordagem dessas substâncias no tratamento de feridas visando à cicatrização e regeneração do tecido envolvido. Casearia sylvestris, conhecida popularmente como guaçatonga, pertence à família Salicaceae, conhecida na medicina popular pelos seus efeitos antiulcerogênicos, cicatrizantes, antiofídicos, anti-inflamatórios e antissépticos, propriedades já comprovadas por estudos. Trabalhos recentes demonstraram que a liberação controlada de fármacos e extratos utilizando membranas de látex natural é uma alternativa interessante e promissora para aplicações biomédicas. Assim, o objetivo deste projeto foi estudar a liberação do extrato de Casearia sylvestris incorporado à membrana de látex em soluções com diferentes valores de pH, com o propósito de estudar seu comportamento e sua liberação de forma controlada. A taxa de liberação do extrato do sistema extrato-membrana foi monitorada e analisada utilizando-se o método de espectroscopia ótica (UV). O pH básico age desestabilizando a membrana indicando que o polímero possui a habilidade de proteger o extrato de ser liberado em valores de pH ácidos, direcionando sua aplicação para o sítio de melhor absorção. Além disso, a liberação segue uma função bi-exponencial...

Natural Rubber Latex (NRL) membrane, made from latex extracted from the rubber tree Hevea brasiliensis, has shown great potential for use in the biomedicine and biomaterials area. Thanks to its biocompatibility and low rejection rate, it has been used for implants and grafts, acting as a stimulant of angiogenesis and cell adhesion and as a barrier against infectious agents. Besides these applications, the membranes are used as model release systems, to assess the release behavior of drugs and plant extracts that exhibit medicinal properties. The extract-membrane system represents a new approach to studying these substances, as aids to wound healing and tissue regeneration. Casearia sylvestris, popularly known as guaçatonga, belongs to the family Salicaceae, known in popular medicine for its anti-ulcerogenic, wound healing, anti-ophidian, antiinflammatory and antiseptic properties, all of which are proven by scientific studies. Recent studies have also shown that the controlled release of drugs and extracts from natural latex membranes is an interesting and promising process for biomedical applications. The objective of this project was thus to study the release of Casearia sylvestris extract incorporated into natural rubber membranes. The main concern was to study and optimize the controlled release of the extract at various pHs. The rate of release was monitored and analyzed by the method of optical spectroscopy (UV). Basic pHacts to destabilize the membrane, indicating that the polymer has the ability to protect the extract from being released at acidic pH values. The controlled release follows a bi-exponential function...

Chemopreventive activity of compounds extracted from Casearia sylvestris (Salicaceae) Sw against DNA damage induced by particulate matter emitted by sugarcane burning near Araraquara, Brazil.

Ethanolic extract of Casearia sylvestris is thought to be antimutagenic. In this study, we attempted to determine whether this extract and casearin X (a clerodane diterpene from C. sylvestris) are protective against the harmful effects of airborne pollutants from sugarcane burning. To that end, we used the Tradescantia micronucleus test in meiotic pollen cells of Tradescantia pallida, the micronucleus test in mouse bone marrow cells, and the comet assay in mouse blood cells. The mutagenic compound was total suspended particulate (TSP) from air. For the Tradescantia micronucleus test, T. pallida cuttings were treated with the extract at 0.13, 0.25, or 0.50 mg/ml. Subsequently, TSP was added at 0.3mg/ml, and tetrads from the inflorescences were examined for micronuclei. For the micronucleus test in mouse bone marrow cells and the comet assay in mouse blood cells, Balb/c mice were treated for 15 days with the extract-3.9, 7.5, or 15.0 mg/kg body weight (BW)-or with casearin X-0.3, 0.25, or 1.2 mg/kg BW-after which they received TSP (3.75 mg/kg BW). In T. pallida and mouse bone marrow cells, the extract was antimutagenic at all concentrations tested. In mouse blood cells, the extract was antigenotoxic at all concentrations, whereas casearin X was not antimutagenic but was antigenotoxic at all concentrations. We conclude that C. sylvestris ethanolic extract and casearin X protect DNA from damage induced by airborne pollutants from sugarcane burning.

Pothomorphe umbellata: antifungal activity against strains of Trichophyton rubrum.

Trichophyton rubrum is a dermatophyte, which can cause infections in human skin, hair and nail. Pothomorphe umbellata (L.) Miq. (Piperaceae) is a native Brazilian plant, in which phytochemical studies have demonstrated the presence of steroids, 4-nerolidylcatechol, sesquiterpenes and essential oils. The objective of this study was to analyze the in vitro activity of extracts and fractions of P. umbellata on resistant strains of T. rubrum. The microdilution plate method was utilized to test Tr1, H6 and ΔTruMDR2 strains of T. rubrum; ΔTruMDR2 strain was obtained from H6 by TruMDR2 gene rupture, which is involved in multiple drugs resistance. The highest antifungal activity to all strains was observed for dichloromethane and hexane fractions of the 70% ethanolic extract which showed minimal inhibitory concentration (MIC) and minimal fungicide concentration (MFC) of 78.13 µg/mL. This antifungal activity was also obtained by 70% ethanolic extract, which presented MIC and MFC of 78.13 µg/mL to ΔTruMDR2, whereas the MIC values for Tr1 and H6 were 78.13 and 156.25 µg/mL, respectively. Our results suggest the potential for future development of new antifungal drugs from P. umbellata, especially to strains presenting multiple resistance.