Evaluation of inhibitory effect of diphenhydramine on benzodiazepine dependence in rats

Effect of diphenhydramine was investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg, daily x days). The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock aggression (FSA) and audiogenic seizures. Diphenhydramine was administered orally in the dose schedules of once daily (10, 20 and 40 mg/kg) and twice daily (5, 10 and 20 mg/kg) in separate groups during the withdrawal period. The withdrawal signs observed in control group (without diphenhydramine) were hyperkinesia, hyperthermia, hyperaggression and audiogenic seizures. Hyperkinesia and hyperthermia were blocked in all the groups of diphenhydramine-treated rats. FSA was inhibited only by diphenhydramine (10 and 20 mg/kg) given twice daily. Audiogenic seizures were completely blocked by once daily (20 and 40 mg/kg) as well as twice daily (20 mg/kg) doses of diphenhydramine. It may be concluded that diphenhydramine exerts a protective effects on benzodiazepine withdrawal syndrome.     

University Students'' Knowledge and Awareness of HPV

BACKGROUND: The purpose of this study was to evaluate the knowledge, attitudes, and behaviors of university students regarding the human papillomavirus (HPV). METHODS: A random sample of 500 university students was mailed a self-administered questionnaire that elicited their knowledge and awareness about HPV and compared their knowledge and attitudes with those of other sexually transmitted diseases (STDs). Among the 480 deliverable addresses, 289 students responded (response rate 60%). RESULTS: Only 37% of respondents had ever heard of HPV, and the median score on a 13-item knowledge scale was only 3. Of seven STDs assessed, respondents indicated they knew the least about HPV and perceived that this STD has received the least educational effort. In multivariate analyses, predictors of lower knowledge and awareness about HPV were male gender and sexual behavior (having multiple partners, not using condoms). CONCLUSIONS: Despite the high prevalence of HPV among young adults, most students knew very little about this infection. Implementing HPV educational programs and measuring their effectiveness should be a priority.     

Synthesis and antimicrobial activity of Schiff and Mannich bases of isatin and its derivatives with pyrimidine.

Isatin and its derivatives have been reacted with 4-(4'-chlorophenyl)-6-(4"-methyl phenyl)-2-aminopyrimidine to form Schiff bases and the N-Mannich bases of these compounds were synthesized by reacting them with formaldehyde and several secondary amines. Investigation of antimicrobial activity of the compounds was made by the agar dilution method against 28 pathogenic bacteria, eight pathogenic fungi and anti-HIV activity against replication of HIV-1 (III B) in MT-4 cells. The compounds are significantly active against bacteria and fungi.     

Comparison of qualitative and quantitative in vitro ginsenoside production in callus cultures of three Panax species

The qualitative and quantitative difference in the various ginsenoside constituents of the crude butanol-soluble saponin fractions of callus cultures of two Indian species of Panax namely P. sikkimensis and P. pseudoginseng have been compared with that of P. quinquefolium (American ginseng). The 45-50 days old calli of the two Indian species, though found to accumulate crude ginsenoside at levels (0.9% and 1.1%, respectively) comparable to that in P. quinquefolium (1.2%), P. pseudoginseng callus showed high productivity of ginsenosides Rf (40.57%) and Ro (19.60%). P. quinquefolium calli on the other hand accumulated more of Rb and Rg group of ginsenosides but while the former appeared to be a Rg (2) accumulator the callus of the later was rich in the Rg (1) fraction.     

Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers

Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence. Received: 9 February 1998/Final version: 8 May 1998     

Buprenorphine pharmacokinetics: relative bioavailability of sublingual tablet and liquid formulations.

Buprenorphine is an effective new treatment for opiate dependence. This study compared the bioavailability of buprenorphine from a tablet to that from a reference solution. Six men experienced with, but not dependent on, opiates (DSM-III-R) were each administered 7.7 mg of buprenorphine in liquid form and 8 mg in tablet form 1 week apart in a balanced crossover design. Plasma levels were measured by electron capture capillary gas chromatography (GC), and concentration-time curves were constructed. Pharmacokinetic data were analyzed by analysis of variance. The bioavailability from the tablet was approximately 50% that from the liquid and was not affected by saliva pH. Lower bioavailability from the tablet may be due to slow dissolution.     

A comparison of esmolol and labetalol for the treatment of perioperative hypertension in geriatric ambulatory surgical patients

This is an open randomized study comparing the efficacy and safety of i.v. esmolol and labetalol in the treatment of perioperative hypertension in ambulatory surgery. Twenty-two elderly patients undergoing cataract surgery under local anaesthesia were studied. The main inclusion criteria were development of systolic blood pressure greater than 200 mmHg or diastolic greater than 100 mmHg. Esmolol was given as a bolus 500 micrograms.kg-1 i.v. followed by a maintenance infusion (150-300 micrograms.kg-1.min-1). Labetalol was given as a bolus of 5 mg i.v. followed by 5 mg increments as needed up to a maximum of 1 mg.kg-1. Esmolol and labetalol both produced reductions in systolic and diastolic blood pressure (P less than 0.05) within ten minutes of administration which lasted for at least two hours. Reduction of blood pressure by esmolol was accompanied by a decrease in HR (P less than 0.05). Two patients developed extreme bradycardia (HR less than 50 beats.min-1) and esmolol had to be discontinued. Labetalol, in contrast, induced only a moderate decrease in HR. None of the patients treated with labetalol experienced any prolonged side effects such as orthostatic hypotension. In conclusion, esmolol may produce considerable bradycardia in elderly patients when hypertension is not accompanied by tachycardia. Labetalol was easier to administer in the ambulatory setting and one-tenth the cost of esmolol.     

Evaluation of oxygen saturation monitoring by pulse oximetry in neonates in the delivery system

The pulse oximeter was evaluated for use in neonates in the delivery room. One hundred neonates, delivered vaginally or by Caesarean section with general or epidural anaesthesia, were studied. After delivery, pulse oximetry probes were placed simultaneously on the ulnar side of the right hand and on the right Achilles tendon to determine whether there was a difference in arterial oxygenation (SpO2). Measurements of SpO2 were taken at 1, 5, 10 min, and 24 hr after delivery. At one and five minutes, SpO2 recorded from the right hand was higher than that recorded from the lower extremities (71.9% +/- 6.5% vs 63.4% +/- 4.3% and 83.3% +/- 4.2% vs 76% +/- 4.1%, mean +/- SD, respectively). At ten minutes these differences diminished, and had almost completely disappeared after 24 hr. These results can be explained by the presence of R-L shunting at the ductus arteriosus level, producing reduced SaO2 in the lower extremities. Oxygen saturation did not differ between neonates delivered vaginally or by Caesarean section, regardless of the presence or type of anaesthesia. We concluded that neonates remain relatively desaturated in the immediate postpartum period and that the SpO2 obtained from the right hand is a better index of neonatal oxygenation than that obtained from the heel.     

Evidence for central histaminergic mechanism in foot shock aggression

The role of central histaminergic system in foot shock induced aggression was studied in mice. Histamine administered by intracerebral (IC) injection (25–200 g) produced a significant increase in fighting episodes in a dose dependent manner. It was observed that mepyramine (H₁ blocker) given intraperitoneally (IP) significantly increased and metiamide (H₂ blocker) given IC decreased significantly the fighting response. To determine the nature of receptors involved in histamine induced facilitation of aggressive behaviour, histamine was administered IC in mice pretreated with mepyramine or metiamide. Mepyramine pretreatment further increased the facilitatory effect of histamine while metiamide blocked the enhancement of aggressiveness by histamine. Combined pretreatment with metiamide and mepyramine decreased significantly the fighting counts which remained unaffected after histamine. Haloperidol did not block the enhancement of aggression by histamine or mepyramine. However, atropine pretreatment partially inhibited the histamine induced increase in the fighting counts. Results of pretreatment with metiamide and atropine were similar to those obtained with pretreatment of metiamide and mepyramine. Metiamide alone or in combination with atropine failed to affect the facilitatory effect of amphetamine on the foot-shockaggression. It is concluded that central histamine H₂ receptors have a facilitatory role and H₁ receptors an inhibitory role on aggressive behaviour in mice induced by foot-shock. Since histamine per se had a facilitatory effect on foot-shock induced aggression, the central H₂ receptors seem to dominate over the H₁ receptors.