Marte Lorenzana-Jiménez

Effect of the menstrual cycle in ethanol pharmacokinetics

Differences in ethanol pharmacokinetics within the menstrual cycle have previously been reported and attributed to variations in body composition, hormonal influences and gastric emptying. To establish the role of the menstrual cycle in ethanol pharmacokinetics associated with changes in body composition, ethanol blood concentrations were measured in nine healthy women during the midfollicular (P1, days 8–10) and midluteal (P2, days 22–24) phases of the menstrual cycle after a postprandial oral ethanol dose (0.3 g kg−1). Total body water was assessed by dual‐energy x‐ray densitometry (DEXA) on both occasions. Median total body water did not vary during either phase of the menstrual cycle (P1 = 54.54%, P2 = 54.66%; P = 0.9296). Median area under the ethanol concentration–time curve (AUC) was lower during P1 (215.33 mg.h dl−1) than during P2 (231.33 mg.h dl−1)(P = 0.8253). No significant differences were found on ethanol pharmacokinetics in either phase of the menstrual cycle.

Vasoconstrictor effect of Cissus sicyoides on guinea-pig aortic rings

1. The effect of the aqueous extract of Cissus sicyoides (CS) on isolated guinea pig aortic rings was studied. CS contracts the smooth muscle of the aorta in a dose-response relation. 2. The extract of CS increases the norepinephrine contraction in normal calcium and in solutions without calcium. 3. Lanthanum inhibits the contraction induced by CS. 4. The vasoconstrictor effect of CS was increased in solutions without calcium or with low calcium, which is an inverse calcium-dependent contraction. 5. Prolonged exposure to calcium-free solution did not abolish CS contraction. These contractions can be elicited repeatedly even after 6 hr of continuous exposure to calcium-free solutions. 6. Caffeine reduces contractile response induced by CS in normal calcium, as well as in solutions without calcium. 7. Our results support the idea that the aqueous extract of CS acts at the membrane level, increasing the calcium entry through the membrane as well as acting on the internal calcium deposits, possibly on the sarcoplasmic reticulum.

Enhancement of hydralazine hypotension by low doses of isoniazid. possible role of semicarbazide-sensitive amine oxidase inhibition

The influence of pretreatment with 1 through 300 mg/kg ip of isoniazid (ISO) on blood pressure and heart rate responses to 0.1 mg/kg iv of hydralazine (HYD) was assessed in rats anesthetized with chloralose--urethane. HYD hypotension was significantly enhanced by ISO at doses between 3 and 300 mg/kg ip. Heart rate was not influenced by HYD in control or pretreated animals. Depressor responses to 0.2 mg/kg iv of pinacidil (PIN) were also potentiated by ISO at 100 and 300, but not at 30 mg/kg. Similarly, ISO decreased cerebral gamma-aminobutyric acid (GABA) at the two highest doses; 30 mg/kg was without effect. Pretreatment of rats with ISO at 1 through 300 mg/kg failed to influence HYD-induced relaxation of aortic rings. These results were interpreted as indicating that potentiation of HYD hypotension by high doses of ISO is not specific for that vasodilator and is related to decreased cerebral GABA, as postulated previously. Lower doses could specifically potentiate the HYD-induced hypotensive effect by inhibition of semicarbazide-sensitive amine oxidase (SSAO), since both ISO and HYD are potent inhibitors of this enzyme. In support of this hypothesis, the SSAO inhibitors, benserazide (100 mg/kg ip) and mexiletine (50 mg/kg ip), were also found to enhance HYD hypotension.

Lack of pathogenicity and toxicity of the mycoinsecticide Metarhizium anisopliae var. acridum following acute gastric exposure in mice.

Metarhizium anisopliae var. acridum, monospore culture EH-502/8 (CNRCB MaPL40), isolated in Mexico from Schistocerca piceifrons ssp. piceifrons (Orthoptera: Acrididae) was tested for acute oral intragastric pathogenicity and toxicity in CD-1 mice. Animals were inoculated with one dose (10(8) conidia/animal) of viable (72 mice), non-viable (24 mice) conidia and compared to 18 control mice. Clinical observations were done daily; mycological and histological tests were performed during necropsies after the inoculation. No mice showed clinical symptoms of illness or died during the study. The fungus was able to persist in some organs until day 3, but did not cause any damage to the host. The gross pathology observed was splenomegaly in mice inoculated with viable and non-viable conidia. Non-germinated conidia, observed in several organs, suggest hematogenous spread, but without any histopathological tissue reaction. Results support the non-pathogenic and non-toxic status of this fungal strain when administered in a single intragastric dose to mice.

Behavioral effects of chronic toluene exposure in the developing rat

The effects of acute and chronic toluene exposure on the hypnotic effect, the righting reflex latencies and the blood and tissue toluene contents were studied in rats during development. The data showed a progressive significant prolongation of the hypnotic effect latencies until the third and fourth postnatal weeks, followed by a significant continuous declining trend until the eighth week postpartum. The measure of the righting reflex latencies followed an opposite temporal course compared to that of hypnotic effect measurements. The acute and chronic toluene exposure did not reveal significant differences in toluene concentrations of blood, brain and liver tissues. The data suggest that chronic toluene treatment may probably be inducing behavioral manifestations of a tolerance phenomenon combined with maturational influences in the developing rat.

Toluene and benzene inhalation influences on ventricular arrhythmias in the rat.

We have previously found that toluene did not share the capacity of benzene for increasing the arrhythmogenic action of epinephrine in the rat, but appeared to elicit the opposite effect. The present experiments were carried out to verify this observation in rats subjected to more severe ventricular arrhythmias. In animals previously inhaling either air, toluene or benzene and anesthetized with pentobarbital, arrhythmias were produced by coronary ligation or aconitine. In both models, toluene decreased and benzene increased the number of ectopic ventricular beats in the 30 min following induction of arrhythmia. Gas chromatographic measurement of toluene levels in the heart during and after inhalation revealed essentially constant concentrations at the time of arrhythmia evaluation, equivalent to approximately one-third the peak levels observed at the end of inhalation. Although the mechanism of the effect of toluene on arrhythmia could not be ascertained, nonspecific membrane stabilization or central serotonergic stimulation were considered as possible explanations. Since both mechanisms could be operant also in the case of benzene, the opposite effects of the solvents on arrhythmia could not be readily accounted for.