Immunohistochemical localization of DNA adducts in rat liver tissue and phenotypically altered foci during oral administration of 2-acetylaminofluorene

Histological studies using paired immunofluorescence stainingand peroxidase-anti-peroxidase staining were performed on sectionsof rat livers with an antiserum specific for the 2-acetylaminofluorene(AAF)-DNA adduct N-deoxyguanosin-(8-yl)-aminofluorene (dG-8-AF).This is the predominant adduct in rat liver DNA at 5 (80%) and28 (100%) days of AAF feeding. Nuclear staining was observedin livers of male Fischer rats fed 0.02% AAF for these timeperiods, and was not present in livers of animals fed controldiet or detected when specific antiserum, first absorbed withthe immunogen adduct, was utilized. In addition, nuclear stainingwas unchanged after incubation with RNase and abolished afterincubation with DNase. Adducts were not readily detectable whenwhole-liver adduct concentrations were less than an averageof 10⁵ adducts per cell (30–50 fmol/µg DNA). Theoverall pattern of adduct distribution in livers of AAF-fedanimals was distinctly non-uniform. A predominance of nuclearstaining was found in the periportal areas by both immunofluorescenceand immunoperoxidase procedures. In contrast, staining was veryweak in the centrilobular areas. When animals were fed AAF for28 days and control diet subsequently for 7, 14, 21 or 28 days,the overall intensity of the immunohistochemical staining decreasedwith time on control diet. However, the pattern of localizationremained the same as in livers of rats fed AAF for 28 days,with the predominance of adducts being in the periportal areas.In male rats fed 0.02% AAF for 8 weeks, foci positive for -glutamyltranspeptidase(GGT) became apparent, and the nuclei in these areas showedno immunofluorescence, indicating the absence of detectablelevels of the dG-8-AF adduct. Twenty adduct-negative areas inthe median lobes of three rat livers were positive for GGT,which suggests that loss of ability to form adducts in theseregions occurs concomitantly with early phenotypic changes.     

Sexual dysfunction in male and female patients with epilepsy: A study of 86 outpatients

Sexual dysfunction is a well-known complication of chronic somatic illness. Eighty-six consecutive epileptic outpatients, 38 men and 48 women, without accompanying disorders, were studied. The frequency and symptoms of sexual dysfunction were compared with results from previous studies using identical sexological methodology. The previous studies were of diabetic patients and healthy controls. Eight percent of the epileptic men reported a sexual dysfunction compared to 44% of the diabetics and 13% of the controls. Epileptic women, diabetic women, and controls showed no significant differences in sexual dysfunction (29%, 28%, and 25%, respectively). In both sexes, the sexual function measured by frequencies of coitus and masturbation was normal. Most patients had good control of epileptic attacks on a treatment of monotherapy. Hormonal status was generally within normal limits in both men and women; only a few minor differences were found and they showed no correlation with sexual dysfunction. Psychologically and socially the patients did not differ appreciably from normals, and they exhibited a high degree of disease acceptance. This study, using a biopsychosocial approach in understanding sexual dysfunctions, is in contrast with previous, mainly uncontrolled, studies of epileptic patients that reported high frequencies of hyposexuality in males. We conclude that epilepsy does not necessarily increase the risk of sexual dysfunction in male or female.     

Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis

1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract.
2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis.
3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME 30 mg kg⁻¹). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions.
4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.

     

Frequency of Acute Adverse Events to a Non-Ionic Low-Osmolar Contrast Medium: The Effect of Verbal Interview

Abstract: The effect of a standardized verbal interview on the frequency of reported adverse events to an intravenous injection of a non-ionic low-osmolar magnetic resonance (MR) contrast medium was studied during a low noise (low anxiety) magnetic resonance imaging (MRI) examination. During a 26-month period 863 patients had an intravenous bolus (<10 sec.) injection of either 0.1 mmol/kg b.wt. or 0.3 mmol/kg b.wt. gadodiamide, were examined in 0.1 Tesla (T) MRI unit. All patients received written information about the examination, but no specific information about possible adverse events to the contrast medium. During the first 15 months, 479 patients were asked after the examination by the same radiographer the following question "Did you feel anything in relation to or after the contrast medium injection?". If the answer was affirmative, the patient was asked to specify the experience. During the subsequent 11-month period, 384 patients had no interview about whether they felt anything in relation to the contrast medium injection. Only 9 out of 863 patients reported an adverse event and they all belonged to the group, which was interviewed. In 8 cases the adverse events lasted less than 5 min. The ninth patient had an attack of migraine 20 min. after the injection of the contrast medium. In one of the patients, who experiencied nausea, it was necessary to postpone scanning for 2 min. Two of the 9 adverse events were considered to be unrelated to the contrast medium. None of the 121 patients receiving the triple dose reported an adverse event. The frequency of reported adverse events depends on whether this information is obtained by active questioning. All reported adverse events were clinically mild and no dose-response effect was observed.     

Mucoadhesive Polymers in Peroral Peptide Drug Delivery. VI. Carbomer and Chitosan Improve the Intestinal Absorption of the Peptide Drug Buserelin In Vivo

Purpose. To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin. Methods. Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats. Results. All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as -chymotrypsin. Conclusions. The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs.     

The effect of long term and high dose interferon treatment in Chronic hepatitis C

The results of 43 interferon treatments of 35 patients (23 male, 12 female) are reported. The duration of the treatment was 6–18 months, the dose of interferon was 3x3-5 MU weekly. Complete response (HCV RNA became negative) was found in 11, relapse was observed in 3 patients. Partial response (transaminase levels became normal, or less than twice normal value, but patients remained HCV RNA positive) occurred in 23 cases, relapse was obeserved in 16. The therapy had no effect in 9 cases. The higher dose and longer term interferon therapy resulted in a higher rate of response to the treatment and a reduction in the number of relapses. This work was supported by the Hungarian Ministry of Welfare (No. T-10 064/93).