1. The influence of the antifungal agent clotrimazole on cytosolic glutathione S-transferase activities was studied in male Wistar rats. 2. Animals received clotrimazole by gastric lavage for 3 days (75 mg/kg per day). Hepatic glutathione S-transferase activity was determined with five different substrates: 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), p-nitro-benzyl chloride (PNBC), ethacrynic acid (EA) and trans-4-phenyl-3-buten-2-one (TPBO). 3. The largest increases in glutathione S-transferase activity were found with CDNB, DCNB and PNBC (+61%, +50% and +50%, respectively, when expressed per mg of cytosolic protein). Enzyme activity toward EA was induced to a lower extent (+33%). Changes in the formation of the conjugate of TPBO were relatively small (+22%). 4. These data indicate a differential induction of glutathione S-transferase isoenzymes and suggest that clotrimazole is a phenobarbital-type inducer of enzyme activity.

With regard to existence of high prostacyclin (PGI2) levels during atheromatosis and thrombus formation, resistance of platelets to prostacyclin and its analogues seems to play an important pathophysiologic key role for the clarifying of vasoocclusive phenomena. Platelet resistance to prostacyclin was studied in vitro and ex vivo in 160 atherosclerotic patients (assessed by objective diagnostic criteria) with and without thrombotic complications and in 50 controls. Prostacyclin resistance phenomena were more pronounced and frequent in patients with occlusive complications, the difference from controls being statistically significant. However, there was no significant difference between the controls and the nonthrombotic patient sample. The intraplatelet cAMP levels might be the metabolic basis of the PGI2 resistance phenomenon, because in the patient group, platelet cAMP levels were decreased by 50% after Ca2+ stimulation. Compared to controls beta-thromboglobulin and thromboxane B2 plasma levels were significantly increased (30 +/- 9 to 87 +/- 26 ng/ml and 9 +/- 5 to 54 +/- 21 pg/ml, respectively), confirming the hyperreactivity state of resistant platelets. From the therapeutic point of view, patients with resistant platelets require PGI2 doses that cause, however, increased side effects. We were able to demonstrate in vivo that IV pretreatment with pentoxifylline--a known stimulator of cAMP formation in platelets--followed by a simultaneous and continuous IV infusion of PGI2 + pentoxifylline, permitted us to reduce significantly the mean PGI2 doses needed for triggering an antiplatelet effect, without inducing side effects. In ex vivo studies, PGI2 resistant platelets of atherosclerotic patients pretreated with pentoxifylline showed normalized stimulation response, and platelet cAMP levels increased from 7.8 +/- 2.7 to 15.2 +/- 1.9 pmol/10(8) platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

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La bartonelosis, Verruga Peruana o enfermedad de Carrión, se caracterizan en el estado agudo, por anemia intensa y los síntomas derivados de esta y el estado infeccioso primitivo o secundario que, en ocasiones, es mucho más grave. En el estado crónico la anemia es moderada o ligera y muchas veces pasa desapercibida y aparece brote verrucoso que se repite por ciclos más o menos marcados o por disminución de la resistencia orgánica, y que su aparición se hace con manifestaciones dolorosas.