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Biomedical subjects

N Moore

Publications and source records attributed to N Moore.

At least 91 records · Page 5Linked to original sources

Influence of rifampin on the pharmacokinetics of pefloxacin.

Pefloxacin and rifampin are frequently associated in the antibiotic therapy of deep-seated, and especially bone-located, infections. The influence of rifampin, a potent drug metabolism enzyme inducer, on the pharmacokinetics of pefloxacin was studied in a randomized crossover trial involving eight young healthy male volunteers. Every volunteer received either pefloxacin alone (period A) or pefloxacin after a 10-day induction by rifampin (period B) given as a 900 mg daily oral dose, and both periods were separated by a 3-week washout period. During both periods, pefloxacin was given during 3 days as a 400 mg b.i.d. oral dose (six doses) followed by a 400 mg intravenous dose on the fourth day. The kinetics of pefloxacin are significantly influenced by rifampin: The minimum (12-hour) plasma concentration, area under the concentration-time curve, and elimination half-life decreased respectively from 4.26 +/- 1.57 to 2.70 +/- 1.00 mg/L, 78.91 +/- 22.82 to 57.81 +/- 16.69 mg.hr/L, 14.46 +/- 3.46 to 10.08 +/- 2.44 hours (p less than 0.05). The renal clearance of pefloxacin was unchanged, but the plasma clearance increased from 94.04 +/- 39.04 to 126.82 +/- 47.36 ml/min (p less than 0.05). The plasma clearance of N-demethyl and N-oxide metabolites were similar for both periods, but the cumulative renal excretion (0 to 96 hours) decreased significantly (p less than 0.01) for period B versus period A. This definite but moderate inductive effect of rifampin on the pharmacokinetics of pefloxacin does not suggest a dose modification of pefloxacin in therapeutic association with rifampin, but pefloxacin assay in plasma seems to be advisable.

Adult↗

Liver glutathione and cytochrome P450 activity in experimental infection: study of the relative effects of infectious stress and malnutrition.

OBJECTIVE: To study the effects of infection and malnutrition on liver glutathione and cytochrome P450 (P450) in rats. DESIGN: Controlled experimental groups (12 groups). ANIMALS: Adult male Sprague-Dawley rats. INTERVENTIONS: Experimental endocarditis, pyelonephritis, or peritonitis were caused. Controls included free-fed rats and sham-operated rats, pair-fed to infected animals. Infection was verified by tissue culture. Rats were killed 3 days (acute infection) or 10 days (chronic infection, except endocarditis) after the induction of infection. RESULTS: Sham rats had lower liver weights, liver/body weight, and liver glutathione values than controls. Infected rats had larger liver weights and liver/body weight ratios and liver glutathione content than shams, and larger liver/body weight ratios than controls (acute infection). Infected rats had lower P450 values than both shams and controls. CONCLUSION: The malnutrition associated with infection caused decreased liver weight and glutathione content. Infection increased the liver weight, and liver glutathione content, but caused severe reduction in liver P450. If the same finding is true in infected patients, it could have consequences for the management of such patients.

Animals↗

Evolution of atenolol kinetics when hypothyroidism is corrected.

A single oral dose of atenolol 100 mg was given to 7 hypothyroid patients (4 F, 3 M), before and after correction of hypothyroidism, mean delay 3.5 months (2 to 6.5 months). There was no change in the elimination parameters of atenolol, but the maximal plasma atenolol concentration was increased (1.66 to 7.37 mg.l-1) as was the AUC (14.9 to 52.1 mg.l-1.h) when the hypothyroidism had been treated. Only one patient differed: he had had a supra-selective vagotomy, and had similar curves before and after treatment of the hypothyroidism, both being similar to the plasma concentration curves found in the other patients after correction of the hypothyroidism. The results suggest an increase in the bioavailability of atenolol when hypothyroidism is corrected. The findings in the patient with vagotomy suggest that the decreased bioavailability during hypothyroidism might be related to changes in intestinal pH. Further studies are needed of the impact of hypothyroidism on gastric and pancreatic or biliary function and its consequences for drug absorption, and drug pharmacokinetics.

Adult↗

Acamprosate appears to decrease alcohol intake in weaned alcoholics.

Five hundred and sixty-nine alcoholics were included in a double-blind placebo-controlled randomized multicenter study of the effects of Acamprosate (calcium acetylhomotaurinate (CA), 1.3 g/day) on indicators of alcoholic relapse after withdrawal. One hundred and eighty-one patients in the CA group versus 175 in the placebo group completed the three-month study. The major efficacy criterion was plasma gamma-glutamyl transpeptidase (GGT), as an indicator of recent alcohol ingestion. This analysis was completed by criteria concordance analysis on a number of indicators of alcohol intake. Patients in both groups were similar initially. After 3 months of treatment, the patients in the CA group had significantly lower GGT (1.4 +/- 1.56 versus 2.0 +/- 3.19 times normal, P = 0.016). All significant differences (P less than 0.05) or trends (0.10 greater than P greater than 0.05) were in favor of a superior effect of CA over placebo. The major side-effect of CA was diarrhea (present in 13% of CA patients versus 7% of placebo, P = 0.04). CA proved superior to placebo on the evolution of markers of alcohol ingestion at three months, in this large-scale multicenter study. It could be a new modality in the drug therapy of alcoholism, not involving an antabuse effect, an antidepressant action, or conditioning.

Acamprosate↗

Alcohol and GABA: ethanol intake modifies hippocampal nipecotic acid binding in ethanol-preferring and non-preferring rats.

3H-nipecotic acid (3H-NIP) binding to GABA uptake recognition sites was studied in the hippocampus of 3 groups of male, Long Evans rats: Group 1: ethanol-naive rats (ENR); Group II: ethanol-preferring rats (DR) and non-preferring rats (NDR), which had consumed about 5 g.kg-1.d-1 and 1 g-1.d-1 of alcohol respectively in the form of a 12% ethanol solution prior to 3H-NIP binding analysis; Group III: DR and NDR who had had no access to ethanol for 21 d after the initial exposure of ethanol solution (28 d). Binding studies showed that ethanol drunk by both DR and NDR in Group II decreased 3H-NIP binding (Bmax decreased) with an enhancement of affinity (KD decreased). In rats subjected to withdrawal of ethanol (Group III), affinity of 3H-NIP for GABA uptake sites was higher than in controls (Group I), but lower than in Group II, Bmax in this group being higher than in the 2 other groups. In Group III, KD was higher in DR than in NDR. These results showed that ethanol intake, in a free-choice paradigm, altered 3H-NIP binding, and that differences in ethanol intake between DR and NDR were associated with differences in sensitivity of hippocampal GABA uptake sites. These differences in 3H-NIP binding could either precede ethanol intake, or be a direct result from it. The results, together with data from other laboratories suggest that: 1), 3H-NIP binding sites are involved in the regulation of ethanol intake; 2), 1 factor responsible for individual differences in ethanol response is reflected by the GABA uptake system.

Animals↗

Challenges for continuing education of public health nurses in Florida.

Perceived continuing education needs among public health nurses at the staff and supervisory levels were investigated. A questionnaire was adapted for each and administered at participating county public health units. Results indicated a high level of agreement between staff nurses and supervisors. Further analysis of the data suggested a relationship between the nurses' perception of continuing education needs and the realities of their nursing practice. Public health nurses, educators, and administrators face the challenge of refocusing continuing education needs and activities on the broad scope of this area of specialty.

Adult↗

[Vasoactive factors of endothelial origin].

The discovery of powerful vasoactive compounds synthetized by the vascular endothelium has led to the elaboration of new physiopathological concepts. We review the present state of knowledge about the role, potential therapeutic virtues, and physiopathological consequences of the three major endothelial vasoactive factors: 1. Prostacyclin (PG12), a powerful vasodilator, and the most potent known inhibitor of platelet aggregation, derived from arachidonic acid metabolism: 2: Endothelium-derived relaxing factor (EDRF) a powerful vasodilator thought to be a short-acting nitroxide; 3: Endothelin, a 21 amino-acid peptide with potent vasoconstricting properties.

Arteriosclerosis↗

Formation of nuclear anomalies in rat intestine by benzidine and its biliary metabolites.

Administration of benzidine (BZ) by intraperitoneal injection (i.p.) to rats (0-100 mg/kg) produced, after 24 h, a dose-dependent formation of nuclear anomalies (micronuclei, pyknotic and karyorrhectic nuclei) in intestinal epithelial cells analysed both in isolated cell suspensions and in the intestinal crypts in tissue sections. When bile collected (0-4 h) from rats treated with BZ (150 mg/kg, i.p.) was infused into the duodenum of recipient rats, nuclear anomalies were observed in mucosal epithelial cells, after 24 h, with a similar distribution to that in rats given BZ by i.p. injection. The formation of nuclear anomalies in the intestine is in accord with the intestinal carcinogenic effect of BZ and is, at least partially, dependent on exposure of epithelial cells to biliary metabolites of BZ.

Animals↗