Evaluation of kidney and liver subacute toxicity induced by Bezalip-Pravastatin-Lopid antihyperlipidaemic compounds in rats.

Renal and hepatic subacute toxicity induced by the antihyperlipidaemic drugs: Bezalip-Pravastatin and Lopid was investigated in rats using serum biochemical parameters. Toxicological evaluation was performed in serum samples following the administration of the therapeutic dose regimens of the compounds that were previously shown to be effective in inhibition of 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase, the enzyme controlling the rate-limiting step in the synthesis of cholesterol, and acyl-CoA cholesterol acyl transferase (ACAT) which converts intracellular free cholesterol to cholesterol ester. Renal and hepatic subacute toxicity was evaluated by measuring enzyme activity or concentrations of: alanine aminotransferace, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyltransferase, glucose, potassium, sodium, blood urea nitrogen, uric acid and creatinine. The use of the above serum biochemical parameters indicated that the overall toxicity impact of antihyperlipidaemic drugs was Bezalip = Pravastatin < Lopid. We have found that the Pravastatin--in contrast to the above antihyperlipidaemic drugs--only transiently affects the biochemical parameters associated with toxicity, but, it affects some of the biochemical parameters associated with hepatic and renal toxicity, up to a significantly lower extent than the antihyperlipidaemic drugs.

Value of routine diagnostic criteria of bullous pemphigoid.

BACKGROUND AND DESIGN: The clinical, histologic, and direct (DIF) and indirect (IIF) immunofluorescence findings are used in a critical, although arbitrary, manner in the routine diagnostic process of bullous pemphigoid (BP). Our purpose was to estimate their relative value. In the present retrospective study, a follow-up of at least 18 months was used as a prerequisite for the final diagnosis of BP (63 patients) and controls (n=159). RESULTS: The clinical, histologic, DIF, and IIF diagnostic criteria of BP were found to vary independently of each other. Positive DIF was the most sensitive (90.5%) typical for BP histology and positive IIF were the most specific (99%). Immunopathologic tests were the most valuable, especially in the atypical varieties of BP. Nearly 25% of patients in this group would have been misdiagnosed if IF tests had not been performed. Atypical cases (40%) seemed to represent a clinical continuum over the whole spectrum of the disease. Patients with exclusively immunoglobulin G (IgG) and C3 basal membrane zone (BMZ) deposits were significantly more often seropositive than the rest of the DIF-positive cases; however, the class of BMZ immunoreactants varied according to the site of biopsy. C3 was almost invariably deposited at the BMZ of DIF-positive patients. When Igs were also present, they were only exceptionally (5% of cases) of greater fluorescence intensity than C3. CONCLUSIONS: The combination of clinical data plus one positive immunopathologic test provide the best combination of sensitivity and specificity (98%), and seem to be most appropriate in defining patient populations for study purposes. The relationship between the classes of immunoreactants should be better evaluated with reference to the site of skin biopsy. It may be suggested, however, that the likelihood of BP existence is very low when in vivo C3 is absent or of lower intensity of fluorescence than the concomitant Ig(s).