Hepatic photosensitization in buffaloes intoxicated by Brachiaria decumbens in Minas Gerais state, Brazil.

The aim of this paper is to report the study of hepatogenous photosensitization in buffaloes during two outbreaks provoked by ingestion of Brachiaria decumbens in Minas Gerais state, Brazil. Ten young buffaloes in outbreak 1 and seven buffaloes in outbreak 2 were intoxicated by B. decumbens. Nine clinically healthy buffaloes raised under the same conditions as the sick animals served as the control group. All animals were subjected to clinical examination, and serum was collected to measure gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), direct bilirubin (DB), indirect bilirubin (IB) and total bilirubin (TB) as indicators of liver function and urea and creatinine as indicators of renal function. Histopathology of liver fragments from five different animals was carried out. During the outbreaks and every two months for one year, samples of grass from paddocks where the animals got sick were collected for quantitative evaluation of the saponin protodioscin, combined with observations of pasture characteristics and daily rainfall. Clinical signs included apathy, weight loss, restlessness, scar retraction of the ears and intense itching at the skin lesions, mainly on the rump, the tail head, neck and hindlimbs, similar to the signs observed in other ruminants. Only the GGT enzyme presented significantly different (P < 0.01) serum levels between intoxicated animals (n = 17) and healthy animals (n = 9), indicating liver damage in buffaloes bred in B. decumbens pastures. Microscopy of the liver showed foamy macrophages and lesions of liver disease associated with the presence of crystals in the bile ducts, which have also been found in sheep and cattle poisoned by grasses of the genus Brachiaria. During the outbreaks, protodioscin levels were higher than 3%, and shortly after, these levels were reduced to less than 0.80%, suggesting a hepatic injury etiology. The outbreaks took place at the beginning of the rainy season, and there was a positive correlation between saponin and the amount of rainfall, as well as between saponin and the amount of green leaves in the pasture. These findings indicate that the grass was more toxic in this period. This is the first report of photosensitization by B. decumbens in buffalo.

Cyclosporine bioequivalence study: quantification using fluorescence polarization immunoassay (FPIA) and radioimmunoassay (RIA).

OBJECTIVE: The aim of study was to compare the bioavailability of 2 cyclosporine capsule formulations (100 mg; Sigmasporin Microoral from Novaquímica Divisão Nature's Plus Farmacêutica Ltd., Brazil, as test formulation and Sandimmune Neoral from Novartis Biociências S.A., Brazil, as reference formulation) in 24 healthy male volunteers. METHODS: The study was open, randomized, with a 2-period crossover, a 1-week washout interval between doses. Blood samples were obtained over a 12-hour interval after each oral administration of cyclosporine (2 capsules of 100 mg of each formulation). Cyclosporine blood concentrations were quantified using a fluorescence polarization immunoassay (FPIA) method provided by Abbott Axsym System and Cyclo-Trac SP. Whole-blood radioimmuoassay (RIA) kit was provided by DiaSorin. These assays provided concentration-time curves for cyclosporine in blood concentration from which the following pharmacokinetic parameters were obtained: AUC(last), AUC(inf), Cmax. RESULTS: Geometric mean and 90% confidence intervals (CI) of Microoral/Neoral as percent ratios were 94.5% (90.8-98.4%) for AUC(last), 93.8% (89.7-98.1%) for AUC(inf), and 98.1% (94.5-101.8%) for Cmax when cyclosporine was determined using FPIA and 96.1% (91.9 to 100.6%) for AUC(last), 95.2% (90.2-100.5%) for AUC(inf), and 99.4% (96.4-102.4%) for Cmax using RIA. CONCLUSION: Since the 90% CI for Cmax, AUC(last) and AUC(inf) ratio were within the 80-125% interval proposed by US-FDA, it is concluded that Sigmasporin Microoral 100 mg capsule formulation is bioequivalent to Sandimmune Neoral 100 mg capsule formulation with regard to both rate and the extent of absorption.

Terbinafine quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry: application to a bioequivalence study.

A method based on liquid chromatography with positive ion electrospray ionization and tandem mass spectrometry is described for the determination of terbinafine in human plasma using naftifine as internal standard. The method has a chromatographic run time of 5 minutes and was linear in the range 1.0 to 2000 ng/mL. The limit of quantification was 1.0 ng/mL; the intraday precision was 3.6%, 3.8%, 3.5%, and 4.1%; and the intraday accuracy was -2.7%, 7.7%, 4.8%, and -2.7% for 5.0, 80.0, 250.0, and 1500.0 ng/mL, respectively. The interday precision was 4.9%, 1.7%, 2.4%, and 4.6% and the interday accuracy was 0.3%, 5.8%, 6.5%, and -1.4% for the same concentrations. This method was used in a bioequivalence study of two tablet formulations of terbinafine. Twenty-four healthy volunteers (both sexes) received a single oral dose of terbinafine (250 mg) in an open, randomized, two-period crossover study. The 90% CI of geometric mean ratios between Terbinafina (Medley S/A Indústria Farmacêutica, Campinas, Brazil) and Lamisil (Novartis Biociências S/A, São Paulo, Brazil) were 90.5% to 110.0% for C max, 92.2% to 108.1% for AUC last, and 91.3% to 107.5% for AUC 0-inf. Because the 90% CI for the above-mentioned parameters were included in the 80% to 125% interval proposed by the US FDA, the two formulations were considered bioequivalent in terms of rate and extent of absorption.

Placental and fetal candidiasis. Presentation of a case of an abortus.

The authors present a case of intrauterine fetal infection by candida, in an abortion of four months, associated with an I.U.D. In the placenta and adnexa we observed an acute inflammation consisting of extraplacental membranitis, omphalitis, chorio-amnionitis and choriovasculitis with a marked villitis and intervillitis. In the fetus, involvement of the skin, lungs and pharynx was observed. This case represents, probably the 15th reported instance of congenital fetal candidiasis, and the first case of a candida hematogenic placental infection acquired from the fetal blood. The fetus undoubtedly acquired its infection by an ascending route, through the contamined amniotic fluid.