Pharmacokinetics of the anxiolytic beta-carboline derivative abecarnil in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon. Studies on species differences

The pharmacokinetics of abecarnil (isopropyl 6-(benzyloxy)-4-(methoxymethyl)-9H-pyrido [3,4-b] indole-3-carboxylate, ZK 112 119) were studied in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon using 14C-labeled drug and HPLC with fluorescence detection for measurement of unchanged drug. Abecarnil was rapidly and completely absorbed after oral doses of 10 mg/kg. At higher doses, absorption was prolonged and incomplete in the cynomolgus monkey. The bioavailability of abecarnil was 20-30% in all the species investigated. The terminal half-life of the unchanged drug in plasma was relatively similar in all species (0.6-1.7 h). Abecarnil was able to pass the blood-brain barrier achieving concentrations in the brain similar to those in plasma. Tissue distribution of labeled compounds was rapid with highest concentrations in the liver, adrenals, kidneys and pancreas followed by the bone marrow, lungs, heart, fat, spleen, ovaries and thyroid gland. Excretion of radiolabeled compounds proceeded predominantly in the feces of the rat, the rabbit and the cynomolgus monkey.     

Ein Fragebogen zur infertilitätsbedingten Belastung andrologischer Patienten

The infertility distress scale (IBS) has been designed to assess the stress perceived by andrological patients resulting from infertility. This review presents findings from different studies with a total of 769 patients. The scale consists of eight items. The stability of scores is very high even for a mean follow-up of 2 years. The scale correlates highly with an already validated measure of infertility distress. Correlations with measures of depressiveness are in the low to medium range. All in all, the psychometric results indicate that the IBS is a factor-stable, reliable and valid instrument for assessing chronic infertility distress in andrological patients. After the presentation of normative data, the usefulness of the IBS as a screening instrument for identifying highly distressed patients is discussed. Findings supporting the scale's sensitivity to change are also presented. The scale is a useful tool in clinical practice as well as in research.     

Scintigraphic assessment of an ophthalmic gelling vehicle in man and rabbit

Studies of the rate of clearance of a gellan gum formulation (Gelrite) radiolabelled by the inclusion of technetium-99m labelled diethylenetriaminepentaacetic acid were carried out in volunteer subjects and in rabbits. Disposition was followed by gamma scintigraphy and compared with 0.5% w/v hydroxyethylcellulose (HEC) solution and isotonic saline administered to the same subjects. Clearance of all solutions was found to follow bi-exponential kinetics with differences in clearance rates between the two species studied. A significant retention of the gellan gum formulation compared to HEC (p = 0.006) or saline (p = 0.009) was noted in man, but not in the rabbit. In this latter species the HEC showed greater retention compared to Gelrite. The species-specific differences in the precorneal residence of the formulations are attributed to the different physiological responses following instillation of solutions into the eye.     

THE EFFECT OF HYPERTENSIVE EPISODES AND CARDIAC HYPERTROPHY ON THE CANINE CARDIAC BAROREFLEX

1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevation. 2. Five mongrel dogs were exposed to transient blood pressure elevation of between 20 and 30 mmHg, through hindlimb compression using a pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting blood pressure was not altered by the 6 week hindlimb compression intervention. 3. Echocardiographically determined LV mass (mean ± s.e.m.) was 116.0 ± 7.4 g prior to hindlimb compression (baseline) and elevated to 125.4 ± 8.1 g (P= 0.003) after 6 weeks of compression. A reduction in the early (E) to late (A) transmitral diastolic flow ratio (E/A) from 1.80 ± 0.06 at baseline to 1.54 ± 0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance was reduced. 4. The maximum gain of the MAP-HR reflex, studied using the ‘steady-state’ drug technique, when blood pressure was normal, showed a trend for reduction from 3.85 ± 0.43 beats/min per mmHg at baseline to 3.10 ± 0.45 beats/min per mmHg (P= 0.067) after 6 weeks of compression. This gain reduction became significant after β-adrenoceptor blockade with propranolol (3.13 ± 0.55 vs 2.32 ± 0.25 beats/min per mmHg; P= 0.039). Covariant analysis showed a significant inverse correlation between LV mass and maximum gain (r= 0.96; P<0.001) during the 6 week compression period. 5. The MAP-HR reflex changes in this model mimic those present in hypertension and implicate cardiac hypertrophy as one possible mediator.     

Surgery for posterior inguinal wall deficiency in athletes

This study retrospectively evaluated the outcome for patients undergoing herniorraphy for chronic groin pain due to posterior inguinal wall deficiency, and correlated the outcome with preoperative investigation findings. There were 47 patients (with a total of 52 herniorraphies) who were contacted by phone between six and 50 months post surgery. Subjects had a diagnosis of posterior inguinal wall deficiency made on history and clinical examination. Thirty seven patients had an ultrasound scan prior to the surgery (three bilateral) with a total of 40 symptomatic groins scanned. There were 26 abnormal scans (22 posterior inguinal wall deficiency and four hernias) and 14 normal scans. Twenty nine patients had a technetium-99m bone scan with 22 having increased uptake at the symptomatic pubic tubercle, while 13 had increased uptake at other sites in the groin. Seventy seven percent of patients had a full return to sport after surgery and the average time to return to sport was four months. There was no significant difference in outcome between subjects who had an abnormal ultrasound scan on the symptomatic side and those who had a normal scan. There was a significant difference in outcome between patients who had a bone scan with increased uptake at the symptomatic pubic tubercle and those who did not (p < 0.04). Our study supports previous research that good results can be obtained with surgery when posterior inguinal wall deficiency is the sole diagnosis. Ultrasound scan does not appear to aid in predicting surgical outcome, while the role of isotope bone scanning requires further study.     

Risk of acquiring influenza A in a nursing home from a culture-positive roommate.

Influenza A was cultured in 62 double rooms. The roommate was infected in 12 (19.4%). During 3,294 resident-seasons, influenza was cultured in 208 single rooms (6.3%). Those who lived in double rooms with a culture-positive roommate had a 3.07 relative risk (CI95, 1.61-5.78) of acquiring influenza.     

Relief of osteoporotic backache with fluoride, calcium, and calciferol

In a prospective randomized clinical trial comprising 22 postmenopausal women with backache and a halisteretic spine with crush fracture(s), 12 women completed a 12-week therapy with sodium fluoride, calcium and calciferol and 10 with placebo. A statistically significant improvement (p less than 0.05), evaluated by a four-stage scale on pains, infirmity, and consumption of analgesics, was observed in the actively treated patients.