The cost of genetic diagnosis of suspected hereditary pediatric cataracts with whole-exome sequencing from a middle-income country perspective: a mixed costing analysis.

Up to 25% of pediatric cataract cases are inherited. There is sparse information in the literature regarding the cost of whole-exome sequencing (WES) for suspected hereditary pediatric cataracts. Molecular diagnosis of suspected hereditary pediatric cataracts is important for comprehensive genetic counseling. We performed a partial economic evaluation with a mixed costing analysis, using reimbursement data and microcosting approach with a bottom-up technique to estimate the cost of using WES for genetic diagnosis of suspected hereditary pediatric cataracts from the perspective of the Brazilian governmental health care system. One hundred and ten participants from twenty-nine families in Rio de Janeiro (RJ) were included. Costs of consumables, staff and equipment were calculated. Two scenarios were created: (1) The reference scenario included patients from RJ with suspected hereditary pediatric cataracts plus two family members. (2) The alternative scenario considered other genetic diseases, resulting in 5,280 exams per month. Sensitivity analysis was also performed. In the reference scenario, the total cost per exam was 700.09 United States dollars (USD), and in the alternative scenario, the total cost was 559.23 USD. The cost of WES alone was 527.85 USD in the reference scenario and 386.98 USD in the alternative scenario. Sensitivity analysis revealed that the largest costs were associated with consumables in both scenarios. Economic evaluations can help inform policy decisions, especially in middle-income countries such as Brazil.

A cost-effectiveness analysis of a novel algorithm to sequentially diagnose leprosy based on manufactured tests under the SUS perspective.

Brazil has the second largest number of leprosy cases (a disease with a significant burden) in the world. Despite global and local efforts to eliminate this public health problem, inadequate or late diagnosis contribute to perpetuate its transmission, especially among household contacts. Tests such as the rapid IgM antibody detection (RT) and real-time polymerase chain reaction (RT-PCR) were developed to overcome the challenges of early diagnosis of leprosy. This study aimed to analyze the cost-effectiveness of a new diagnostic algorithm recommended by the Brazilian government to diagnose leprosy in household contacts of confirmed leprosy cases, which includes the RT and RT-PCR tests. A decision tree model was constructed and the perspective of the Brazilian Unified National Health System (SUS) and a 1-year time horizon were adopted. Only direct medical costs related to diagnostic tests were included. Effectiveness was measured as the number of avoided undiagnosed leprosy cases. Different scenarios were analyzed. The sequential use of RT, slit-skin smear (SSS) microscopy, and RT-PCR as recommended by the Brazilian Ministry of Health was compared to a base case (isolated SSS microscopy), yielding an incremental cost-effectiveness ratio of USD 616.46 per avoided undiagnosed leprosy case. Univariate sensitivity analysis showed that the prevalence of leprosy among household contacts was the variable that influenced the model the most. This is the first economic model to analyze a diagnostic algorithm of leprosy. Results may aid managers to define policies and strategies to eradicate leprosy in Brazil.

A cost-effectiveness analysis of a novel algorithm to sequentially diagnose leprosy based on manufactured tests under the SUS perspective / Análise de custo-efetividade de um novo algoritmo para exame sequencial de hanseníase baseado em testes fabricados sob a perspectiva do SUS / Análisis de costo-efectividad de un nuevo algoritmo para el examen secuencial de lepra basado en pruebas fabricadas bajo la perspectiva del SUS

Abstract: Brazil has the second largest number of leprosy cases (a disease with a significant burden) in the world. Despite global and local efforts to eliminate this public health problem, inadequate or late diagnosis contribute to perpetuate its transmission, especially among household contacts. Tests such as the rapid IgM antibody detection (RT) and real-time polymerase chain reaction (RT-PCR) were developed to overcome the challenges of early diagnosis of leprosy. This study aimed to analyze the cost-effectiveness of a new diagnostic algorithm recommended by the Brazilian government to diagnose leprosy in household contacts of confirmed leprosy cases, which includes the RT and RT-PCR tests. A decision tree model was constructed and the perspective of the Brazilian Unified National Health System (SUS) and a 1-year time horizon were adopted. Only direct medical costs related to diagnostic tests were included. Effectiveness was measured as the number of avoided undiagnosed leprosy cases. Different scenarios were analyzed. The sequential use of RT, slit-skin smear (SSS) microscopy, and RT-PCR as recommended by the Brazilian Ministry of Health was compared to a base case (isolated SSS microscopy), yielding an incremental cost-effectiveness ratio of USD 616.46 per avoided undiagnosed leprosy case. Univariate sensitivity analysis showed that the prevalence of leprosy among household contacts was the variable that influenced the model the most. This is the first economic model to analyze a diagnostic algorithm of leprosy. Results may aid managers to define policies and strategies to eradicate leprosy in Brazil.

Resumo: O Brasil tem o segundo maior número de casos de hanseníase (doença com carga significativa) do mundo. Apesar dos esforços globais e locais para eliminar esse problema de saúde pública, o diagnóstico inadequado ou tardio contribui para perpetuar sua transmissão, especialmente entre contatos intradomiciliares. Exames como o teste rápido de anticorpos IgM (RT) e a reação em cadeia da polimerase em tempo real (RT-PCR) foram desenvolvidos para superar as barreiras do diagnóstico precoce da hanseníase. Este estudo teve como objetivo analisar a relação custo-efetividade de um novo algoritmo de diagnóstico recomendado pelo governo brasileiro para diagnosticar a hanseníase em contatos domiciliares de casos confirmados de hanseníase, que inclui os testes RT e RT-PCR. Foi construído um modelo de árvore de decisão e adotada a perspectiva do Sistema Único de Saúde (SUS) considerando o período de um ano. Foram incluídos apenas os custos médicos diretos relacionados aos exames diagnósticos. A efetividade foi medida considerando o número de casos evitados de hanseníase. Diferentes cenários foram analisados. O uso sequencial de RT, baciloscopia e RT-PCR, conforme recomendado pelo Ministério da Saúde, foi comparado a um caso base (baciloscopia isolada), obtendo-se uma razão de custo-efetividade incremental de USD 616,46 por caso evitado de hanseníase. A análise de sensibilidade univariada mostrou que a prevalência de hanseníase entre contatos intradomiciliares foi a variável que mais influenciou o modelo. Este é o primeiro modelo econômico a analisar um algoritmo diagnóstico da hanseníase. Os resultados poderão auxiliar os gestores na definição de políticas e estratégias para a erradicação da hanseníase no Brasil.

Resumen: Brasil tiene el segundo mayor número de casos de lepra (enfermedad con carga significativa) del mundo. A pesar de los esfuerzos globales y locales para eliminar ese problema de salud pública, el diagnóstico inadecuado o tardío contribuye a perpetuar su transmisión, sobre todo entre contactos intradomiciliarios. Los exámenes como la prueba rápida de anticuerpos IgM (RT) y la reacción en cadena de la polimerasa en tiempo real (RT-PCR) se desarrollaron para superar las barreras del diagnóstico precoz de la lepra. El objetivo de este estudio fue analizar la relación de costo-efectividad de un nuevo algoritmo de diagnóstico recomendado por el gobierno brasileño para diagnosticar la lepra en contactos domiciliarios de casos confirmados de lepra, que incluye las pruebas RT y RT-PCR. Se construyó un modelo de árbol de decisión y se adoptó la perspectiva del Sistema Único de Salud (SUS) teniendo en cuenta el periodo de un año. Solo se incluyeron los costos médicos directos relacionados con los exámenes diagnósticos. Se midió la efectividad teniendo en cuenta el número de casos de lepra evitados. Se analizaron distintos escenarios. Se comparó el uso secuencial de RT, baciloscopia y RT-PCR, conforme el Ministerio de Salud recomienda, con un caso base (baciloscopia aislada), y se obtuvo un cociente de costo-efectividad incremental de USD 616,46 por cada caso de lepra evitado. El análisis de sensibilidad univariante mostró que la prevalencia de lepra entre contactos intradomiciliarios fue la variable que más influyó el modelo. Este es el primer modelo económico que analiza un algoritmo diagnóstico de lepra. Los resultados podrán ayudar los gestores a definir políticas y estrategias para erradicar la lepra en Brasil.

Successful treatment of experimental murine vulvovaginal candidiasis with gentian violet.

Aim: This study evaluated the antifungal efficacy of gentian violet (GV) in an experimental vulvovaginal candidiasis (VVC) model. Materials & methods: In vitro susceptibility and cytotoxicity assays were performed to validate the antifungal potential and safety of GV. The antifungal efficacy was then evaluated in vivo through comparative analysis of the fungal burden following treatment with GV or nystatin, as well as assessment of the vaginal tissue by histology and electron microscopy. Results: GV demonstrated a safe antifungal profile against C. albicans, with a significant decrease in fungal burden and an improvement in the inflammatory process evaluated histologically. Conclusion: The results of this study motivate further assessment of GV as a promising alternative for VVC therapy.

Implante transcateter de valva aórtica para o tratamento da estenose aórtica grave: uma revisão sistemática de estudos de avaliação econômica completa / Transcatheter aortic valve implantation for the treatment of severe aortic stenosis: a systematic review of complete economic evaluation studies

Objetivo: Comparar o implante transcateter de valva aórtica (TAVI) ao tratamento conservador em pacientes inoperáveis ou à cirurgia de troca valvar (SAVR) em pacientes com risco cirúrgico alto ou intermediário conforme a Society of Thoracic Surgeons (STS), por meio de uma revisão sistemática de avaliações econômicas completas. Avaliar a variabilidade de modelos econômicos, parâmetros, pressupostos e sua influência nos resultados finais. Métodos: Foi realizada uma busca da literatura nas bases Medline, EMBASE, Cochrane Library, Web of Science, SciELO e International HTA Base e busca manual. Foram incluídas análises econômicas completas baseadas em modelos econômicos publicadas entre 2011 e 2022, em português, inglês e espanhol. A qualidade dos estudos foi avaliada usando o instrumento QHES (Quality of Health Economic Studies). Resultados: Foram incluídos 36 estudos, majoritariamente análises de custo-utilidade (64%), da Europa (41%), utilizando dados de eficácia dos estudos PARTNER. O modelo de Markov (61%) foi predominante. O custo da prótese do TAVI foi um parâmetro de impacto na análise de sensibilidade nos três grupos. Os estudos alcançaram uma boa qualidade no instrumento QHES. Conclusão: O TAVI tendeu a ser custo-efetivo em relação aos comparadores. Os modelos não foram homogêneos nos parâmetros, horizontes temporais e taxa de desconto, podendo impactar a custo-efetividade do TAVI e dificultar a comparação dos resultados entre diferentes países e perspectivas.

ABSTRACT Objective: To compare transcatheter aortic valve implantation (TAVI) to conservative treatment in inoperable patients or to valve replacement surgery (SAVR) in patients at high or intermediate surgical risk according to the Society of Thoracic Surgeons (STS), through a systematic review of comprehensive economic evaluations. Evaluate the variability of economic models, parameters, assumptions and their influence on final results. Methods: A literature search was performed in Medline, EMBASE, Cochrane Library, Web of Science, SciELO and International HTA Base and manual search. Complete economic analyzes based on economic models published between 2011 and 2022 in Portuguese, English and Spanish were included. The quality of the studies was evaluated using the QHES (Quality of Health Economic Studies) instrument. Results: Thirty-six studies were included, mostly cost-utility analyses (64%), from Europe (41%), and using efficacy data from the PARTNER studies. The Markov model (61%) was predominant. The cost of the TAVI prosthesis was the most important parameter in the sensitivity analysis in the three groups. The studies achieved a good quality in QHES instrument. Conclusion: TAVI tended to be cost-effective relative to comparators. The models were not homogeneous in parameters, time horizons and discount rate, which may have an impact on the cost-effectiveness of TAVI, making it difficult to compare the results between different countries and perspectives.

Cost Utility of Vaccination Against COVID-19 in Brazil.

OBJECTIVES: The objective of this study was to evaluate the cost-utility of the Oxford, CoronaVac, and Janssen COVID-19 vaccines from the perspective of the Brazilian public health system. METHODS: A total of 3 microsimulation models were constructed with individual data to evaluate the 3 vaccines. The simulation contains 7 transition states that are related to the natural history of the disease. The model with a daily cycle has a time horizon of 1 year and uses data from 289 days of the pandemic. The analysis was conducted from the perspective of the Brazilian public health system considering direct medical costs. For the model inputs, outpatient and hospital databases were used with information on treated patients stratified by age. Information on mortality was also stratified based on patients' age in the mortality database (SIM). The efficacy of vaccines to reduce the likelihood of patients becoming ill was evaluated independently for each vaccine. Information on the quality of life of patients in outpatient or hospital treatment and the sequelae resulting from the disease were extracted from the literature. The main outcome of the analysis was quality-adjusted life-years (QALYs). RESULTS: The vaccines showed incremental cost-utility ratios ranging from R$-23 161.3/QALY (Oxford) to R$17 757.85/QALY (CoronaVac). The older the population, the lower was the incremental cost-utility ratio. Given a willingness-to-pay threshold of R$17 586/QALY, all the vaccines were considered cost-effective in the probabilistic sensitivity analysis. CONCLUSIONS: The results of the analysis by age group can help in the preparation of a vaccination prioritization plan.

Free interstitial levels of metformin in the liver of healthy and diabetic Wistar rats

Abstract In the present study, free interstitial levels reached by metformin in the liver were investigated in control and diabetic rats by microdialysis. Firstly, a bioanalytical method using an HPLC-UV system to determine the drug concentration in microdialysis samples was validated. The blood glucose levels and biochemical parameters were investigated in control and diabetic animals. Following that, both groups received a dose of 50 mg/kg of metformin iv bolus and the free interstitial levels reached in the liver were assessed by microdialysis. The method was validated according to FDA guidelines being suitable to quantify free concentrations of metformin in the liver of control and diabetics rats. Free exposure to metformin was similar in control and diabetic animals: AUC0-∞ 118.50 ± 40.18 vs 112.93 ± 50.25 µg.h/mL, respectively. The half-life in tissue was similar to that described in the literature for plasma. Hence diabetes induced by streptozotocin after administration of nicotinamide in our study did not damage the renal and hepatic function of the animals. The levels reached in the liver were 1.6 times higher than the free plasma concentrations, demonstrating higher liver penetration of metformin. This is the first investigation in liver interstitial concentration of metformin in control and diabetic rats

Preclinical approaches in vulvovaginal candidiasis treatment with mucoadhesive thermoresponsive systems containing propolis.

Vulvovaginal candidiasis (VVC) is a common vaginitis that affects women, especially in childbearing age, caused by Candida albicans in almost 80% of cases. Considering the limited drug arsenal available and the increasing fungal resistance profile, the search for new therapeutic sources with low toxicity and easy administration should be supported. Propolis has been used as a traditional medicine for multiple diseases, considering its particular composition and pharmaceutical properties that permits its wide applicability; it has also emerged as a potential antifungal agent. Thus, this study performed an in vitro and in vivo investigation into the efficacy of a new mucoadhesive thermoresponsive platform for propolis delivery (MTS-PRPe) in a preclinical murine model of VVC treatment caused by C. albicans. The methodologies involved chemical analysis, an assessment of the rheological and mucoadhesive properties of propolis formulations, in vitro and in vivo antifungal evaluations, histological evaluations and electron microscopy of the vaginal mucosa. The results demonstrated the antifungal activity of propolis extract and MTS-PRP against the standard strain and a fluconazole-resistant clinical isolate of C. albicans, in both in vitro and in vivo assays. These results were similar and even better, depending on the propolis concentration, when compared to nystatin. Thus, the formulation containing propolis exhibited good performance against C. albicans in a vulvovaginal candidiasis experimental model, representing a promising opportunity for the treatment of this infection.

Genetic parameters of girolando crossbred cows in dairy herds in the State of Acre, Brazil / Parâmetros genéticos de vacas mestiças girolando em rebanhos leiteiros no Estado do Acre, Brasil / Parámetros genéticos de vacas cruzadas girolando en ganados lecheros en el Estado de Acre, Brasil

This study aimed at estimating genetic parameters for milk production and conformation characteristics in Girolando crossbred dairy cows reared in the High and Low Acre region using the restricted maximum likelihood methodology, under an animal model. We estimated the variance components and genetic parameters using the REML/BLUP procedure (Restricted Maximum Likelihood Methodology/Best Linear Unbiased Prediction). The estimated average for milk production for 305 days of lactation (P305) was of 1523.25 ± 481.11 kg, with a heritability of 0.38 for this characteristic. The conformation characteristics showed no significant correlation with milk production. The phenotypical correlations between the linear characteristics of type were, in general, positive and moderate. The P305 obtained in this study can be considered low and indicates that there is a possibility of increasing milk production through selection in herds along with the use of tested and proven bulls. The heritability estimate found (0.38) indicates that there is genetic variability for milk production, demonstrating that selection for this characteristic would result in genetic progress.(AU)

Este estudo teve como objetivo estimar parâmetros genéticos para produção de leite e características de conformação em vacas leiteiras mestiças Girolando criadas na região do Alto e Baixo Acre, utilizando a metodologia da máxima verossimilhança restrita, sob modelo animal. As estimativas dos componentes de variância e dos parâmetros genéticos foram realizadas pelo procedimento REML/BLUP (Máxima verossimilhança restrita/Melhor predição linear não viesada). A média estimada para produção de leite aos 305 dias de lactação (P305) foi de 1.523,25 ± 481 kg e a herdabilidade para esta característica foi de 0,38. As características de conformação não apresentaram correlação significativa com a produção de leite. As correlações fenotípicas entre as características lineares de tipo foram em geral positivas e de magnitude moderada. A P305 obtida neste estudo pode ser considerada baixa e indica que existe a possibilidade de aumento da produção de leite através de seleção nos rebanhos, juntamente com a utilização de touros testados e provados. A estimativa de herdabilidade encontrada (0,38) indica que há variabilidade genética para produção de leite, demonstrando que a seleção para esta característica resultaria em progresso genético.(AU)

El objetivo del estudio fue estimar los parámetros genéticos para la producción de leche y las características de conformación en vacas lecheras cruzadas Girolando criadas en la región de Alto y Bajo Acre utilizando el método de máxima verosimilitud restringida, con un modelo animal. Estimamos los componentes de la varianza y los parámetros genéticos mediante el procedimiento REML / BLUP (metodología de máxima verosimilitud restringida / mejor predicción lineal insesgada). El promedio estimado para la producción de leche para los 305 días de lactancia (P305) fue de 1523.25 ± 481.11 kg, con una heredabilidad de 0.38 para esta característica. Las características de conformación no mostraron correlación significativa con la producción de leche. Las correlaciones fenotípicas entre las características lineales de tipo fueron, en general, positivas y moderadas. El P305 obtenido en este estudio puede considerarse bajo y muestra que existe la posibilidad de incrementar la producción de leche a través de la selección en rebaños, junto con el uso de toros probados y comprobados. La estimación de heredabilidad encontrada (0,38) indica que existe variabilidad genética para la producción de leche, lo que demuestra que la selección de esta característica daría lugar a un progreso genético.(AU)

Thrombotic microangiopathy caused by methionine synthase deficiency: diagnosis and treatment pitfalls.

BACKGROUND: Inborn errors of cobalamin (Cbl) metabolism form a large group of rare diseases. One of these, Cbl deficiency type C (CblC), is a well-known cause of thrombotic microangiopathy (TMA), especially in infants. However, there has only been a single published case of TMA associated to Cbl deficiency type G (CblG), also known as methionine synthase deficiency (MSD). CASE DIAGNOSIS/TREATMENT: A 21-month-old boy presented with pallor and oral ulcers during episodes of upper respiratory infection (URI). Further examination revealed signs of TMA, and the patient progressed to acute renal failure (ARF). Renal biopsy showed TMA. Evaluation for infection and autoantibodies were negative. The C3 and C4 complement fractions were normal. Analysis of the bone marrow aspirate suggested megaloblastic anemia and signs of hematopoiesis activation (secondary to peripheral hemolysis). Although the serum vitamin B12 level was normal, the patient was treated with cyanocobalamin, with no improvement. The ARF and hematologic parameters improved with conservative treatment. A severe relapse occurred during the follow-up, with normal ADAMTS13 activity. The presumed diagnosis was atypical hemolytic uremic syndrome, and the patient was started on eculizumab, but his response was poor, even when the dosage was increased. At this point it was also recognized that his developmental speech was delayed. Based on these findings, whole exome sequencing was performed, leading to the detection of two novel deleterious variants in the gene coding for methionine synthase, confirming the diagnosis of MSD. Subsequent treatment consisted of elevating the patient's serum homocysteine level and starting him on hydroxicobalamin, with normalization of all hematologic parameters although the microalbuminuria remained. CONCLUSIONS: Methionine synthase deficiency is very rare and characterized by megaloblastic anemia and neurological symptoms. We report the second case of MSD associated to TMA previously diagnosed as aHUS in which the patient had a poor response to eculizumab.

Uliginosin B, a natural phloroglucinol derivative with antidepressant-like activity, increases Na+,K+-ATPase activity in mice cerebral cortex

ABSTRACT Uliginosin B, a phloroglucinol isolated from Hypericum polyanthemum Klotzsch ex Reichardt, Hypericaceae, has antidepressant-like effect in the forced swimming test in rodents and inhibits monoamines neuronal reuptake without binding to their neuronal carriers. Studies showed the involvement of Na+,K+-ATPase brain activity in depressive disorders, as well as the dependence of neuronal monoamine transport from Na+ gradient generated by Na+,K+-ATPase. This study aimed at evaluating the effect of uliginosin B on Na+,K+-ATPase activity in mice cerebral cortex and hippocampus (1 and 3 h after the last administration) as well as the influence of veratrine, a Na+ channel opener, on the antidepressant-like effect of uliginosin B. Mice were treated (p.o.) with uliginosin B single (10 mg/kg) or repeated doses (10 mg/kg/day, 3 days). Acute administration reduced the immobility in the forced swimming test and tail suspension test and increased Na+,K+-ATPase activity in cerebral cortex 1 h after treating, whereas the repeated treatment induced the antidepressant-like effect and increased the Na+,K+-ATPase activity at both times evaluated. None treatment affected the hippocampus enzyme activity. Veratrine pretreatment prevented uliginosin B antidepressant-like effect in the forced swimming test, suggesting the involvement of Na+ balance regulation on this effect. Altogether, these data indicate that uliginosin B reduces the monoamine uptake by altering Na+ gradient.

Study of antidepressant-like activity of an enriched phloroglucinol fraction obtained from Hypericum caprifoliatum.

CONTEXT: Hypericum caprifoliatum Cham & Schlecht (Guttiferae) extracts have a potential antidepressant-like effect in rodents. However, the molecular mechanisms by which these extracts exert this effect remain unclear. OBJECTIVE: This study evaluated the effect of HC1, a fraction obtained from H. caprifoliatum enriched in phloroglucinol derivatives, on the Na⁺, K⁺ ATPase activity in mouse brain and verified the influence of veratrine on the effect of HC1 in the forced swimming test (FST). MATERIALS AND METHODS: Veratrine (0.06 mg/kg) and HC1 (360 mg/kg) were given alone or combined i.p. 60 and p.o. 30 min, respectively, before FST. The effect of single and repeated administration (once a day for 3 consecutive days) of HC1 (360 mg/kg) on Na⁺, K⁺ ATPase activity was evaluated ex vivo in the cerebral cortex and hippocampus of mice subjected or not to FST. RESULTS: HC1 reduced the immobility time (103.15 ± 18.67 s), when compared to the control group (183.6 ± 9.51 s). This effect was prevented by veratrine (151.75 ± 22.19 s). Mice repeatedly treated with HC1 presented a significant increase in Na⁺, K⁺ ATPase activity, both in cerebral cortex (46 ± 2.41 nmol Pi/min·mg protein) and hippocampus (49.83 ± 2.31 nmol Pi/min·mg protein), in relation to the respective controls (30 ± 2.66 and 29.83 ± 2.31 nmol Pi/min·mg protein respectively). DISCUSSION AND CONCLUSION: The HC1 antidepressant-like effect on FST might be related to its capacity to inhibit Na⁺ influx. HC1 increases hippocampal and cortical Na⁺, K⁺ ATPase activities possibly through long-term regulatory mechanisms.

Repeated administration of an aqueous spray-dried extract of the leaves of Passiflora alata Curtis (Passifloraceae) inhibits body weight gain without altering mice behavior.

ETHNOPHARMACOLOGICAL RELEVANCE: Passiflora alata is a Southern American species that constitutes many traditional remedies as well as phytomedicines used for sedative and anxiolytic purposes in Brazil. However studies on repeated treatment effects are scarce. AIM OF THE STUDY: To evaluate behavioral, physiological and biochemical effects of the repeated treatment with an aqueous spray-dried extract of Passiflora alata leaves containing 2.5% (w/v) of flavonoids (PA) in mice. MATERIAL AND METHODS: Male adult CF1 mice were treated (p.o.) for 14 days with PA (2.5; 25 or 250 mg/kg). The feeding behavior was evaluated at the beginning (1h after the first administration) and at the end of the treatment (15th day). The body weight gain and food consumption were monitored along the days. On day 15 mice were evaluated on plus maze, spontaneous locomotor activity, catalepsy and barbiturate sleeping time tests. Serum glucose, lipids, ALT and AST enzymes were determined. Liver, kidney, perirenal fat, epididymal and peritoneal fat were analyzed. RESULTS: The repeated treatment with the highest dose tested (250 mg/kg) did not alter the mice behavior on open field, elevated plus maze, catalepsy and barbiturate sleeping time tests. Repeated administration of PA 250 decreased mice feeding behavior and weight gain. PA 25 and PA 250 reduced mice relative liver weight and caused mild hepatic hydropic degeneration as well as a decrease in alanine aminotransferase (ALT) serum level. CONCLUSIONS: These results indicate that Passiflora alata does not present central cumulative effects and point to the needs of further studies searching for its hepatotoxicity as well as potential anorexigenic.

Evidence that hyperprolinemia alters glutamatergic homeostasis in rat brain: neuroprotector effect of guanosine.

This study investigated the effects of acute and chronic hyperprolinemia on glutamate uptake, as well as some mechanisms underlying the proline effects on glutamatergic system in rat cerebral cortex. The protective role of guanosine on effects mediated by proline was also evaluated. Results showed that acute and chronic hyperprolinemia reduced glutamate uptake, Na(+), K(+)-ATPase activity, ATP levels and increased lipoperoxidation. GLAST and GLT-1 immunocontent were increased in acute, but not in chronic hyperprolinemic rats. Our data suggest that the effects of proline on glutamate uptake may be mediated by lipid peroxidation and disruption of Na(+), K(+)-ATPase activity, but not by decreasing in glutamate transporters. This probably induces excitotoxicity and subsequent energy deficit. Guanosine was effective to prevent most of the effects promoted by proline, reinforcing its modulator role in counteracting the glutamate toxicity. However, further studies are needed to assess the modulatory effects of guanosine on experimental hyperprolinemia.

[Risk factors related to renal disorders in HIV-1 infected patients]. / Fatores de risco associados a alterações renais em pacientes infectados por HIV-1.

INTRODUCTION: Renal disease has emerged as one of the primary comorbid conditions affecting HIV-infected patients, mainly because antiretroviral therapy has improved survival. This study aimed to detect risk factors possibly associated with altered renal function in HIV-infected patients. METHODS: A cross-sectional study was conducted involving 254 HIV-infected patients attending an outpatient clinic at Santa Casa de Vitoria< They were interviewed and blood samples were collected for CD4 cell counts, HIV-1 viral load, glucose, lipids and creatinine measurements. Urine protein was evaluated in the first voiding urine sample. Glomerular filtration was estimated by simplified modified diet in renal disease (MDRD) and Cockcroft-Gault formulas. RESULTS: One hundred and three (40.6%) patients presented some urinary abnormality, and proteinuria was the most common finding (46; 18.1% patients). Twenty-five (9.8%) patients showed estimated glomerular filtration below 60 ml/min/1.73 m² by MDRD. Multivariate logistic regression showed that low glomerular filtration was positively correlated with black race [OR 9.6 (IC95% 1.28-23.80)], arterial hypertension [OR 3.3 (IC95% 1.28-23.81)], age over fifty-one years-old [OR 3.3 (IC95%1.11-9.90)], proteinuria [OR 5.2 {IC95% 1.67-16.25}]; hematuria [OR 3.2 (1.12-9.29)] and negatively correlated with patients using zidovudine [OR 0.2 (0.04-0.78)]. CONCLUSIONS: Traditional risk factors for renal disease, such as black race, arterial hypertension and advancing age were correlated with low estimated glomerular filtration in the present patient sample.

Fatores de risco associados a alterações renais em pacientes infectados por HIV-1 / Risk factors related to renal disorders in HIV-1 infected patients

INTRODUÇÃO: A doença renal é uma das principais comorbidades envolvendo pacientes infectados com o HIV, em razão da melhora da sobrevida proporcionada pela terapêutica antirretroviral. O objetivo deste estudo foi detectar fatores de risco, possivelmente correlacionados com função renal alterada, em pacientes infectados pelo HIV. MÉTODOS: Estudo transversal foi realizado em 254 pacientes infectados pelo HIV, atendidos em ambulatório na Santa Casa de Vitória. Eles foram entrevistados e submetidos a coletas de amostras de sangue para contagem de células CD4, quantificação de carga viral do HIV-1, dosagens de glicose, lipídeos e creatinina. A proteinúria foi avaliada em amostra de primeira urina da manhã. A filtração glomerular foi estimada com as fórmulas de modified diet in renal disease (MDRD) simplificada e Cockcroft-Gault. RESULTADOS: Cento e três (40,6 por cento) pacientes tinham alguma anormalidade no exame de urina, sendo proteinúria o achado mais comum (46; 18,1 por cento pacientes). Vinte e cinco (9,8 por cento) pacientes tinham filtração glomerular estimada inferior a 60ml/min/1.73m² de acordo com MDRD. A análise de regressão logística multivariada mostrou que baixa filtração glomerular foi positivamente correlacionada com raça negra [OR 9,6 (IC95 por cento 1,28-23,80)], hipertensão arterial sistêmica [OR 3,3 (IC95 por cento 1,28-23,81)], idade acima de 51 anos [OR 3,3 (IC95 por cento1,11-9,90)], proteinúria [OR 5,2 {IC95 por cento 1,67-16,25}]; hematúria [OR 3,2 (1,12-9,29)] e negativamente com pacientes em uso de zidovudina [OR 0,2 (0,04-0,78)]. CONCLUSÕES: Os fatores de risco tradicionais para doença renal como raça negra, hipertensão arterial e idade avançada foram correlacionados com menor filtração glomerular estimada em nossos pacientes.

INTRODUCTION: Renal disease has emerged as one of the primary comorbid conditions affecting HIV-infected patients, mainly because antiretroviral therapy has improved survival. This study aimed to detect risk factors possibly associated with altered renal function in HIV-infected patients. METHODS: A cross-sectional study was conducted involving 254 HIV-infected patients attending an outpatient clinic at Santa Casa de Vitoria< They were interviewed and blood samples were collected for CD4 cell counts, HIV-1 viral load, glucose, lipids and creatinine measurements. Urine protein was evaluated in the first voiding urine sample. Glomerular filtration was estimated by simplified modified diet in renal disease (MDRD) and Cockcroft-Gault formulas. RESULTS: One hundred and three (40.6 percent) patients presented some urinary abnormality, and proteinuria was the most common finding (46; 18.1 percent patients). Twenty-five (9.8 percent) patients showed estimated glomerular filtration below 60ml/min/1.73m² by MDRD. Multivariate logistic regression showed that low glomerular filtration was positively correlated with black race [OR 9.6 (IC95 percent 1.28-23.80)], arterial hypertension [OR 3.3 (IC95 percent 1.28-23.81)], age over fifty-one years-old [OR 3.3 (IC95 percent1.11-9.90)], proteinuria [OR 5.2 {IC95 percent 1.67-16.25}]; hematuria [OR 3.2 (1.12-9.29)] and negatively correlated with patients using zidovudine [OR 0.2 (0.04-0.78)]. CONCLUSIONS: Traditional risk factors for renal disease, such as black race, arterial hypertension and advancing age were correlated with low estimated glomerular filtration in the present patient sample.

Investigação da atividade antihiperglicemiante da farinha da casca de Passiflora edulis Sims, Passifloraceae, em ratos diabéticos induzidos por aloxano / Investigation of antihyperglycemic activity of Passiflora edulis Sims, Passifloraceae, in alloxan-induced diabetic rats

O presente estudo objetivou a modelagem farmacodinâmica da ação antihiperglicemiante da farinha da casca de maracujá (Passiflora edulis Sims, Passifloraceae) em ratos diabéticos induzidos por aloxano. Os animais foram divididos em três grupos (n = 9): grupo diabético tratado com 20 mg/kg, 40 mg/kg ou 160 mg/kg da farinha. As amostras sanguíneas foram coletadas da veia lateral da cauda e a glicemia foi determinada com auxílio de um glucômetro em 0, 1, 2, 4 e 6 h após o tratamento via oral. Observou-se que o efeito antihiperglicemiante da farinha da casca de maracujá foi dependente da dose, obtendo um efeito expressivo observado em quatro horas para todas as doses, sendo mais pronunciado na dose de 160 mg/kg. O efeito, expresso como redução da glicemia basal em relação ao tempo zero, pode ser modelado através de um modelo dose-efeito clássico, o qual permitiu a determinação do efeito máximo (Emax) e da dose necessária para alcançar 50 por cento deste efeito (DE50). Após a modelagem dos dados, obteve-se um valor de Emax = 58,41 por cento e de DE50 = 23,61 mg/kg. Esta abordagem pode permitir a comparação do efeito antihiperglicemiante de Passiflora edulis com outras espécies que apresentem atividade sobre a redução da glicemia, mediada pela presença de fibras solúveis.

This study goals the pharmacodynamic modeling of anti hyperglycemic action of flour of Passion fruit bark (Passiflora edulisSims, Passifloraceae) in alloxan-induced diabetic rats. The animals were divided into three groups (n = 9) that received different doses: 20, 40 or 160 mg/kg of flour. The blood samples were collected from the tail vein and the blood glucose was determined using a glucometer Prestige IQ in 0, 1, 2, 4 and 6 h after the oral treatment. It was observed that the effect of the flour of Passion fruit bark was dose dependent, getting an expressive effect observed in four hours from all doses tested, being more pronounced at the 160 mg/kg dose. This effect was expressed as reduction of basal blood glucose in respect to zero time and can be modeled through a classic dose effect model. It allowed the determination of maximum effect (Emax) and the necessary dose to reach 50 percent of this effect (ED50). After the data modeling, it was gotten a value of Emax = 58,41 percent and ED50 = 23,61 mg/kg. This approach allows the comparison of antyhyperglicemic effect of Passiflora eduliswith other species that present activity lowering the glycemia, through the presence of soluble fibers.