Modulatory activity of antioxidants against the toxicity of Rifampicin in vivo

The World Health Organization (WHO) has shown concern about the burden of tuberculosis in the developing countries. Even though rifampicin is an effective drug in the management of tuberculosis, it has been documented to have some toxic effects in humans. Therefore, this study intends to investigate the modulatory effect of vitamins C and E on the hepatotoxicity, sperm quality and brain toxicity of Rifampicin. Forty Wistar albino rats were used, 10 animals per group. Group 1 animals received 0.3 mL of distilled water, the Group 2 animals received the therapeutic dose of rifampicin, Group 3 animals received therapeutic doses of rifampicin plus vitamin E, while Group 4 received therapeutic doses of rifampicin and vitamin C. The administration was performed orally during three months; the animals were sacrificed by cervical dislocation at the end of that period. Blood samples were collected and liver function and lipid profile was analyzed using fully automated clinical chemistry device. The liver, brain and reproductive organs underwent histopathological examination. Sperm samples were collected from the epididymis to achieve count and motility and morphological analysis. Results showed rifampicin alone to raise (p < 0.05) liver function enzymes (Aspartate amino transferase [AST], Serum alanine amino transferase [ALT] and Total Bilirubin) when compared with controls. While the vitamin E treated group showed remarkable protection, the vitamin C treated group showed questionable protection against the rifampicin induced liver damage. Sperm count results showed an important (p < 0.05) increase in the sperm quality in vitamin E and C treated groups. However, the vitamin E plus Rifampicin treated group showed increased lipid peroxidation. The histopathological findings revealed structural damages by rifampicin in liver, brain and epididymis while some remarkable architectural integrity was observed in the antioxidant-treated groups. It can be concluded that vitamin E or C improved sperm quality and protected against the brain damage caused by rifampicin. Moreover, vitamin E demonstrated remarkable hepatoprotection against rifampicin induced damage while vitamin C shows a questionable hepatoprotection.

Monitoring the treatment of sepsis with vancomycin in term newborn infants

A prospective study was conducted to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 term newborn infants with sepsis. Purpose: The therapeutic response of neonatal sepsis by Staphylococcus sp. treated with vancomycin was evaluated through serum concentrations of vancomycin, serum bactericidal titers (SBT), and minimum inhibitory concentration (MIC). METHOD: Vancomycin serum concentrations were determined by the fluorescence polarization immunoassay technique , SBT by the macro-broth dilution method, and MIC by diffusion test in agar . RESULTS: Thirteen newborn infants (59.1%) had adequate peak vancomycin serum concentrations (20--40 mg/mL) and one had peak concentration with potential ototoxicity risk (>40 µg/mL). Only 48% had adequate trough concentrations (5--10 mg/mL), and seven (28%) had a potential nephrotoxicity risk (>10 µg/mL). There was no significant agreement regarding normality for peak and trough vancomycin method (McNemar test : p = 0.7905). Peak serum vancomycin concentrations were compared with the clinical evaluation (good or bad clinical evolution) of the infants, with no significant difference found (U=51.5; p=0.1947). There was also no significant difference between the patients' trough concentrations and good or bad clinical evolution (U = 77.0; p=0.1710). All Staphylococcus isolates were sensitive to vancomycin according to the MIC. Half of the patients with adequate trough SBT (1/8), also had adequate trough vancomycin concentrations and satisfactory clinical evolution. CONCLUSIONS: Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. SBT interpretation should be made in conjunction with the patient's clinical presentation and vancomycin serum concentrations. Those laboratory and clinical data favor elucidation of the probable cause of patient's bad evolution, which would facilitate drug adjustment and reduce the risk of toxicity or failing to achieve therapeutic doses.

131I-induced changes in rat thyroid gland function

Therapeutic doses of 131I administered to thyrotoxic patients may cause thyroid failure. The present study used a rat model to determine thyroid function after the administration of different doses of 131I (64-277 µCi). Thirty male Fisher rats in the experimental group and 30 in the control group (untreated) were followed for 6 months. The animals were 4 months old at the beginning of the experiment and were sacrificed at an age of 9 months. Hormone concentration was determined before 131I administration (4-month-old animals) and three times following 131I administration, when the animals were 7, 8, and 9 months old. The thyroid glands were removed and weighed, their volume was determined and histopathological examination was performed at the end of the experiment. Significant differences in serum triiodothyronine and thyroid-stimulating hormone concentration, measured at the age of 7, 8, and 9 months, were found in the experimental group. During aging of the animals, the concentration of thyroxin fell from 64.8 ± 8.16 to 55.0 ± 6.1 nM in the control group and from 69.4 ± 6.9 to 25.4 ± 3.2 nM in the experimental group. Thyroid gland volume and weight were significantly lower in the experimental than in the control group. Thyroid glands from the experimental group showed hyaline thickness of the blood vessel wall, necrotic follicles, a strong inflammatory reaction, and peeling of necrotic cells in the follicles. In conclusion, significant differences in hormone levels and histopathological findings indicated prolonged hypothyroidism after 131I administration to rats, which was not 131I dose dependent.

ASSESSMENT OF IVERMECTIN THERAPEUTIC EFFICACY ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN MICE EXPERIMENTALLY INFECTED

In this study we evaluated the potential action of ivermectin on third-stage larvae, both at migratory and encysted phases, in mouse tissues after experimental infection with Lagochilascaris minor. Study groups I and II consisted of 120 mice that were orally administered 1,000 parasite eggs. In order to assess ivermectin action upon migratory larvae, group I (60 mice) was equally split in three subgroups, namely I-A, I-B, and I-C. On the 7th day after inoculation (DAI), each animal from the subgroup I-A was treated with 200 µg/Kg ivermectin while subgroup I-B was given 1,000 µg/Kg, both groups received a single subcutaneous dose. To assess the drug action on encysted larvae, group II was equally split in three subgroups, namely II-A, II-B, II-C. On the 45th DAI each animal was treated with ivermectin at 200 µg/Kg (subgroup II-A) and 1,000 µg/Kg (group II-B) with a single subcutaneous dose. Untreated animals of subgroups I-C and II-C were used as controls. On the 60th DAI all animals were submitted to larva search. At a dose of 1,000 µg/Kg the drug had 99.5% effectiveness on third-stage migratory larvae (subgroup I-B). Ivermectin efficacy was lower than 5% on third-stage encysted larvae for both doses as well as for migratory larvae treated with 200µg/Kg.

High and low doses of antimony (Sb v) in American cutaneous leishmaniasis: a five years follow-up study of 15 patients

Seventeen patients proceeding from the municipality of Rio de Janeiro, Brazil presenting with the cutaneous ulcerative form of American leishmaniasis were treated with one ampoule of pentavalent antimony daily for 30 days. With this regimen the individuals doses varies greatly: from 3.8 mg/kg of body weight to 22.3 mg/kg. After five years, patients receiving either a smaller dose or a bigger one, showed the same therapeutic result: cutaneous scars and no mucosal lesions.

Assessment of Therapeutic Response of Plasmodium vivax and Plasmodium falciparum to Chloroquine in a Malaria Transmission Free Area in Colombia

In order to determine the frequency of therapeutic failures to chloroquine (CQ) in patients with malaria due to either Plasmodium falciparum or P. vivax, and to explore the usefulness of a malaria-free city as a sentinel site to monitor the emergence of drug resistance, 53 patients (44 infected with P. vivax and 9 with P. falciparum) were evaluated at the Laboratory of Parasitology, Universidad del Valle in Cali, Colombia. Patients received 25 mg/kg of CQ divided in three doses over 48 h; they were followed during 28 days according to WHO/PAHO protocols. While therapeutic failures to CQ in the P. vivax group were not detected, the proportion of therapeutic failures in the P. falciparum group was high (78%) and consistent with the reports from endemic areas in Colombia. The diverse origin of cases presenting therapeutic failure confirmed that P. falciparum resistant to CQ is widespread in Colombia, and further supports the change in the national antimalarial drug scheme. Monitoring of drug resistance in malaria free areas would be useful to identify sites requiring efficacy evaluation, and in some situations could be the most appropriate alternative to collect information from endemic areas where therapeutic efficacy studies are not feasible.

Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni

The efficacy of oral praziquantel in the treatment of schistosomiasis has been considered low by most public health institutions. In this paper, we compared the efficacy of two dosages of praziquantel (80 mg/kg vs. 50 mg/kg) in patients with chronic schistosomiasis mansoni. Two hundred eighty-eight patients with schistosomiasis from a community in Brazil were randomly divided into two groups: 145 patients (Group 1) received 80 mg/kg body weight of oral praziquantel divided in two equal doses with 1 h interval and 143 patients (Group 2) received 50 mg/kg body weight of oral praziquantel. To keep the study masked, patients in Group 2 received placebo 1 h after the first dose. All patients were subjected to clinical and ultrasonographic examination. Cure assessment was performed by repeating two stool examinations, by a quantitative method, at 30, 90 and 180 days after treatment. The morbidity of schistosomiasis was low, with a few cases of light periportal thickening and 16 cases of mild splenomegaly. The cure rates were 89.7% for Group 1 and 83.9% for Group 2. There was no difference in the efficacy of both therapeutic dosages of praziquantel assayed. The adverse reactions were more frequent with higher dosage.

Therapeutic concentration of morphine reduces oxidative stress in glioma cell line

Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.

Produção da bananeira 'Prata anã'(AAB) em função de diferentes doses e fontes de potássio

Dentre os nutrientes exigidos pela bananeira, o K é o que mais influencia na produção desta cultura. Este trabalho teve por objetivos comparar os efeitos de duas fontes de K (cloreto de potássio e sulfato de potássio) sobre a produção, bem como estimar as doses de K para obter a máxima eficiência física (MEF) e econômica (MEE) e determinar o nível crítico de K na folha da bananeira 'Prata anã' (AAB) irrigada, cultivada na região semiárida do norte de Minas Gerais, Brasil. O experimento foi realizado em Latossolo Vermelho-Amarelo (LVA), textura média. Os tratamentos foram originados do fatorial (4 x 2), sendo quatro doses de K (0, 400, 800 e 1200 kg /ha ano de K2O) e duas fontes de K (KCl e K2SO4), gerando oito tratamentos, que foram distribuídos em blocos ao acaso, com quatro repetições. Não houve diferenças entre os efeitos do KCl e K2SO4 sobre a produção da bananeira. A análise econômica demonstrou que o KCl apresentou maior viabilidade para ser utilizado como fonte de K. As doses estimadas para a MEF nos 2º e 3º ciclos de produção, utilizando-se o KCl, foram de 827 e 835 kg ha-1 ano-1 de K2O, respectivamente. Já para a MEE, as doses foram de 157 e 670 kg/ha ano de K2O, respectivamente. Os níveis críticos foliares de K, obtidos nos 2º e 3º ciclos de produção, foram de 2,85 dag kg-1 para a MEF e, para a MEE, de 2,41 e 2,80 dag kg-1, respectivamente.

Lucratividade do milho em razão das fontes, doses e épocas de aplicação de nitrogênio

O nitrogênio é o nutriente aplicado em maior quantidade na cultura do milho, o mais limitante para o crescimento e desenvolvimento da planta e o que mais onera o custo de produção. Este trabalho teve como objetivo avaliar o efeito das fontes, doses e épocas de aplicação de nitrogênio nos custos de produção e na lucratividade da cultura do milho irrigado cultivado em plantio direto no município de Selvíria (MS), nas safras 2007/2008 e 2008/2009. O experimento foi desenvolvido na área experimental pertencente à Faculdade de Engenharia - UNESP, em um Latossolo Vermelho distrófico. Os tratamentos foram constituídos de três fontes de N (entec®, sulfato de amônio e ureia) e cinco doses (0, 50, 100, 150 e 200 kg ha-1), aplicadas em duas épocas (semeadura ou cobertura). Foram estimados o custo operacional total (COT), a receita bruta (RB), o lucro operacional (LO), índice de lucratividade (IL), a produtividade de equilíbrio e o preço de equilíbrio. Concluiu-se que o sulfato de amônio e a ureia foram as fontes de N que possibilitaram resultados econômicos mais satisfatórios. As doses de 50 kg ha-1 de N como sulfato de amônio ou ureia foram os tratamentos que proporcionaram os maiores índices de lucratividade, os quais foram obtidos quando a adubação nitrogenada foi realizada na época de cobertura.

Fontes, doses e formas de aplicação de fósforo para o algodoeiro no Cerrado da Bahia

Ainda são insuficientes, nas condições do Cerrado baiano, as informações sobre fontes, doses e formas de aplicação de P para o algodoeiro, importantes para o aumento da produtividade e qualidade da fibra. Em vista disso, o objetivo deste trabalho foi definir fontes, doses e formas de aplicação de P para a cultura do algodoeiro em solo de textura média do Cerrado da Bahia. Para tanto, foi conduzido um experimento, em plantio convencional, utilizando-se o fatorial 2 x 4 x 2 + 7 (fontes P x doses x formas de aplicação + sete tratamentos adicionais (combinações de proporções das fontes e mais o tratamento controle (sem P)), com quatro repetições. As fontes avaliadas foram superfosfato triplo (ST), fosfato de Arad (FA) nas doses de 60, 120, 180 e 240 kg ha-1 de P2O5 aplicadas a lanço ou no sulco de semeadura. Os tratamentos adicionais foram constituídos de proporções de ST e FA para a dose de 100 kg ha-1 de P2O5. Foram avaliadas características de produção (altura de plantas, estande, produtividade, percentagem de fibra, peso médio do capulho), teor de P foliar e P disponível no solo e características de qualidade da fibra. Não houve efeito significativo de fontes, doses e formas de aplicação sobre a produtividade do algodão em caroço. Quanto s características de qualidade da fibra, o uso de fosfato de Arad melhorou a percentagem de fibra e o micronaire, enquanto o superfosfato triplo aumentou o comprimento da fibra. A combinação das duas fontes resultou em maior peso médio do capulho para as proporções 25+75 e 75+25 (ST+FA) em relação 50+50 (ST+FA).

Effect of N and K doses in nutritive solution on growth, production and coffee bean size

An adequate supply of nutrients is essential for obtaining high yields of coffee. The objective of this study was to evaluate the effect of N, K and the N:K ratio on vegetative and reproductive growth of coffee. For this purpose, coffee plants were grown in nutrient solution containing K in the concentrations of 1.08; 2.15; 3.23 and 5.38 mmol L-1 combined with a dose of 6 mmol L-1 N, resulting in the N:K ratios (w/w): 1:0.5; 1:1; 1:1.5 and 1:2.5. The control treatment consisted of the doses 3 and 1.61 mmol L-1 of N and K respectively, resulting in the N:K ratio (w/w) 1.0:1.5. The following variables were evaluated: height, stem diameter, number of nodes of the eighth plagiotrofic branch (index branch), pairs of plagiotrofic branches and number of nodes in the orthotropic branch every three weeks from the beginning of the experiment. Additionally, it was evaluated the chemical composition of processed beans and leaves between the flowering and the rapid expansion stage of the cherry beans, production of cherry beans per plant and classification of beans according to the size. N influenced mainly the characteristics of vegetative growth and K influenced mainly the reproductive growth evaluated by the production. The lowest production resulted in the highest percentages of beans retained on sieves with holes larger than 16/64", while the highest production promoted an increase in the percentage of beans retained on sieves with holes smaller than 16/64".

Análise de crescimento e produtividade do pak choi cultivado sob diferentes doses de nitrogênio

O objetivo deste trabalho foi avaliar a influência de diferentes doses de nitrogênio no crescimento e produtividade do pak choi. O experimento foi conduzido, em cultivo protegido, de outubro a novembro de 2007, em Marechal Cândido Rondon, PR. O delineamento experimental foi de blocos casualizados, com cinco tratamentos (0, 60, 105, 150 e 195 kg ha-1 de N) e quatro repetições. O nitrogênio foi aplicado em três diferentes épocas (transplantio, 7 e 14 dias após o transplantio). Foram realizadas cinco coletas das plantas, semanalmente, avaliando-se a produção de massa da matéria seca e área foliar, para obtenção das taxas de crescimento absoluto e relativo, taxa assimilatória líquida, razão de área foliar e área foliar específica. Na colheita, foram avaliados altura da planta, diâmetro e matéria fresca da parte aérea e produtividade. Incrementos na adubação nitrogenada até a dose de 195 kg ha-1 proporcionam incrementos no crescimento e produtividade do pak choi.

Crescimento de girassol como flor em vaso em função de doses de paclobutrazol

O girassol (Helianthus annuus L.), que é comumente cultivado para produção de sementes e óleo, também apresenta potencial de uso como planta ornamental. Entretanto, seu porte elevado dificulta essa utilização, principalmente como flor em vaso. Objetivou-se neste experimento avaliar os efeitos do regulador de crescimento paclobutrazol sobre o crescimento de plantas de girassol em vaso, cultivadas em sistema hidropônico, dentro de estufa, em vasos preenchidos com sílica moída. Os dois genótipos de girassol utilizados foram BRS Oásis, com capítulo marrom e altura média de 1,85 m, e Helio 358, com capítulo amarelo e altura média de 1,45 m. As doses de paclobutrazol avaliadas foram 0; 0,5; 1; 2; 4; e 6 mg L-1 , aplicadas diretamente no substrato de sílica moída. A solução nutritiva utilizada foi a de Hoagland, e as plantas foram mantidas sob aeração constante. O delineamento experimental foi o de blocos casualizados, em esquema fatorial com cinco repetições, totalizando 60 parcelas. Avaliaram-se a altura das plantas e a massa de matéria seca de raiz, caule, folhas e de capítulos. Houve efeito do paclobutrazol sobre o crescimento das plantas. O uso do paclobutrazol na dose de 2mgL-1 reduz a altura do girassol, porém não afeta a qualidade da inflorescência, o que pode viabilizar o seu uso na produção de flores de girassol como ornamentais. A sensibilidade ao paclobutrazol é maior para o genótipo Helio 358 em relação ao genótipo BRS Oásis.

Efeito de doses de boro no crescimento vegetativo de girassol em diferentes classes de solos

A baixa disponibilidade de boro (B) no solo é um dos fatores que mais limita a produção do girassol, planta oleaginosa caracterizada por ampla adaptabilidade climática. O objetivo desta pesquisa foi avaliar a influência de doses de boro, aplicadas em distintas classes de solos, no desenvolvimento do girassol cultivar Hélio 863. As amostras foram coletadas na camada de 0-20 cm dos solos: Argissolo Acinzentado (PAC); Argissolo Vermelho-Amarelo (PVA); Neossolo Litólico (RL); Argissolo Vermelho eutrófico (PVe); Neossolo Flúvico (RY) e Vertissolo Háplico (VX). O delineamento experimental foi em blocos casualizados, em esquema fatorial 6 x 4 (solos x doses), com quatro repetições. A unidade experimental foi representada por uma planta por vaso. Os solos apresentaram efeito significativo (p < 0,01) sobre todos os parâmetros de crescimento estudados. As plantas de girassol cultivadas nos solos RY, VX, PAC e RL apresentaram a maior área foliar, os maiores capítulos, o maior teor de boro foliar e maior número de folhas e altura de plantas, respectivamente. A adubação com boro não influenciou a produção de fitomassa seca do girassol cv. Hélio 863.