Hormonal and gestational parameters in female rats submitted to the pilocarpine model of epilepsy

Endocrine and reproductive alterations are frequently reported to occur in women with temporal lobe epilepsy as well as in female rats in different experimental models of limbic seizures. As previously reported, women with epilepsy have lower fertility rates than women without epilepsy (Tanganelli, P., Regesta, G., 1992. Neurology (suppl.) 42 (5), 89-93; Cummings, L.N., Guidice, L., Morrel, M.J., 1995. Epilepsia 36, 355-359). In order to investigate the possible substrate of endocrine alterations in epilepsy, hormonal and gestational parameters were studied in female rats submitted to the pilocarpine model of epilepsy. The results demonstrated that the oestrus cycle is altered following pilocarpine-induced status epilepticus and such alteration lasted for several weeks. Progesterone, LH and FSH levels decreased and estradiol levels increased significantly during the period of spontaneous and recurrent seizures. The frequency of seizures during pregnancy and lactation decreased. These results document that significant changes in gonadal, hypophyseal and hypothalamic hormones, as well as in sexual behaviour, occur following status epilepticus induced by pilocarpine administration.     

Inactivation of aconitase and oxoglutarate dehydrogenase in skeletal muscle in vitro by superoxide anions and/or nitric oxide

Strips of rat soleus muscle were incubated in media containing a superoxide generating system and/or the nitric oxide donor sodium nitroprusside (SNP) before the maximal catalytic activities of aconitase, citrate synthase, and oxoglutarate dehydrogenase were measured. The maximal activities of aconitase and oxoglutarate dehydrogenase were both decreased by 25-30% by superoxide anions; however, only the maximal activity of aconitase was decreased, by approximately 50%, by incubation of muscles with SNP. Furthermore, when both superoxide and NO were present in the medium, aconitase activity was decreased by 70%. The maximal activity of citrate synthase was not affected by any of the treatments. This is the first time that superoxide anions or NO has been shown to inactivate aconitase and oxoglutarate dehydrogenase in skeletal muscle. It is suggested that these effects may be responsible for some alterations in skeletal muscle metabolism, and these possibilities are discussed.     

The behavioral development of rats with prenatal hypoinsulinemia

Influence of the prenatal hypoinsulinaemia (streptozocin diabetes) on the behaviour of the offsprings of Wistar rats was studied from 1 to 20 postnatal days. In experimental pups there were slower weight increment, later eye opening, later development of elementary behavioural acts (grooming elements, rearing, sniffing), and later formation of complex behavioural patterns (investigation of an environment) than in the control offsprings of healthy females.     

Contrast media-induced ventricular fibrillation: an experimental study of the effects of dimeric contrast media during wedged catheter injection in dogs

Expression/induction of the 72 and 60 kDa heat shock proteins (HSPS 72 and 60) in cultured human keratinocytes by high calcium was studied with immunofluorescent staining and the flow cytometric method. Normal human keratinocytes cultured in serum free, low calcium medium (Ca2+, 0.1 mM) at 3-passage weakly expressed HSP 60, but not HSP 72, as fine granules in the cytoplasm. HSP 72 was induced in the perinuclear cytosomal area and then in the nucleus after transferring the cells in high calcium medium (Ca2+, 1.8 mM). Whereas the nuclear accumulation began to decrease 24 h after the treatment, the perinuclear cytosomal staining continued. High calcium also augmented the expression of HSP 60 as coarse granules in the cytoplasm. Flow cytometric analyses quantitatively revealed the induction of HSP 72 and the upregulation of HSP 60 by high calcium treatment. Our results clearly demonstrated that extracellular calcium concentration modifies the level of expression of HSP 72 and 60 in normal human keratinocytes, indicating the importance of the careful attention to medium condition in evaluating the expression of HSPS 72 and 60 in cultured keratinocytes.     

Effect of ifosfamide treatment on glutathione and glutathione conjugation activity in patients with advanced cancers

Several studies have suggested that the glutathione/glutathione S-transferase (GSH/GST) system is involved in resistance of tumors toward ifosfamide and other cytostatic agents. Besides, ifosfamide metabolites (in vitro) as well as ifosfamide treatment (in vivo) have been shown to decrease cellular GSH availability. In the present study, the in vivo effects of three different ifosfamide treatment schedules on the GSH/GST system were studied in patients with advanced cancers (n = 24): continuous i.v. infusions of 1300 mg/m2 daily for 10 days and 5000 mg/m2/day for 24 h, as well as a 4-h infusion of 3000 mg/m2 daily for 3 days. The GSH/GST system was characterized by administering bromisoval, a probe drug to assess GSH conjugation activity in vivo, as well as by daily monitoring of GSH concentrations in blood cells and plasma. Bromisoval pharmacokinetics was assessed before and at the end of the ifosfamide treatment. Blood cell GSH levels decreased significantly (P < 0.05) during the 3- and 10-day ifosfamide treatment schedules; the 24-h treatment had no effect. The ifosfamide treatment schedules had only minimal effects on bromisoval pharmacokinetics. Assuming that the kinetics of the probe drug provide an accurate reflection of enzyme activity, this suggests that GST activity remains unchanged. Because GSH conjugation of bromisoval enantiomers requires both GST activity and GSH availability, these results also indicate that, despite the 35% decrease in GSH in blood cells of two patient groups, the GSH availability of the cancer patients was not rate-limiting for GSH conjugation of bromisoval enantiomers. If GSH levels in blood cells reflect those in tumors/other tissues, the present results indicate that ifosfamide may be used clinically to decrease GSH levels. However, whether a 35% decrease is sufficient to increase tumor sensitivity toward (other) cytostatics remains uncertain.     

Computerized medication instruction for psychiatric inpatients admitted for acute care

We studied the efficacy and feasibility of using computer-based instruction to provide medication information to hospitalized patients with acute psychotic conditions. Patients were randomly assigned to receive computer-based (n = 21) or personal instruction (n = 21); for the final analyses the computer group was expanded to include 13 patients from a pilot study. Outcome measures were knowledge retention (indicated by changes in test scores) and compliance with medication regimens after discharge (indicated by telephone follow-up at one week, one month, and three months). The subjects reacted positively to the computer program. Knowledge retention and compliance were similar in the computer and control groups. We conclude that psychiatric inpatients admitted for acute care can participate in, and learn from, computerized medication instruction.