Effects of isometric exercise on blood cell adrenoceptors in essential hypertension

The effect of handgrip (HG) isometric exercise on plasma catecholamines, alpha 2-adrenoceptors on platelets and beta 2-adrenoceptors on lymphocytes was studied in normotensive subjects (NT) and essential hypertensive subjects (HT). Whereas systolic blood pressure (SBP) increases were similar in NT and HT subjects, diastolic blood pressure (DBP) and heart rate (HR) increased more in the former group. Baseline values and changes in plasma epinephrine (E) and norepinephrine (NE) did not differ between both groups. No differences were apparent in alpha 2-adrenoceptor density and affinity between NT and HT subjects before or after the test. HG isometric exercise induced a similar increase in beta 2-adrenoceptors on lymphocytes of 22 +/- 7 and 13 +/- 5% in NT and HT subjects, respectively. Affinity to the beta 2-adrenoceptors under baseline conditions was somewhat lower in HT (8.1 +/- 0.4 pM) than in NT subjects (6.5 +/- 0.5 pM), and this difference persisted during the test. Our results indicate that there are no differences in alpha 2- and beta 2-adrenoceptor densities either at baseline conditions or after HG isometric exercise between NT and HT subjects. Small differences noted in affinity to the beta 2-adrenoceptors require further investigation.     

A 90-Day Inhalation Toxicity Study with Benomyl in Rats

A 90-Day Inhalation Toxiaty Study with Benomyl in Rats. WARHEIT,D. B., KELLY, D. P., CARAKOSTAS, M. C., AND SINGER, A. W. (1989).Fundam Appl Toxicol./ 12, 333-345. Benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate,CAS Registry No. 17804-35-2] is a fungicide and the possibilityfor inhalation exposure exists for field workers. To assessthe toxicity of benomyl, groups of 20 male and 20 female CDrats were exposed nose-only 6 hr a day, 5 days a week, to concentrationsof 0, 10, 50 or 200 mg/m³ of a benomyl atmosphere. At the midpoint(approximately 45 days on test) and at the end of the exposureperiod, blood and urine samples for clinical evaluation werecollected from 10 rats/group/sex, and these animals were sacrificedfor pathological examination. Similar evaluations were performadon all remaining rats at the end of the 90-day test period.After approximately 45 days on test, compoundrelated degenerationof the olfactory epithelium was observed in all males and in8 of 10 female rats exposed to 200 mg/m³ benomyl. Two male ratsexposed to 50 mg/m³ had similar, although less severe, areasof olfactory epithelial degeneration. After approximately 90days of exposure, the remaining 10 rats/group/sex were sacrificedand examined. Of these rats, all of the males and females exposedto 200 mg/m³ had olfactory degeneration, along with 3 malesexposed to 50 mg/m³ of benomyl. No other observed lesions wereinterpreted to have been caused by the benomyl exposure. Inaddition, male rats exposed to 200 mg/m³ benomyl had depressedmean body weights compared to controls and this finding correlatedwith a reduction in food consumption. Based on pathologicalobservations, 10 mg/m³ represents the no-observable-effect level(NOEL) for the male rats, and 50 mg/m³ is the NOEL for the femalerats.     

Outflow of aqueous humor following cyclodialysis or ciliochoroidal detachment in rabbit

Cyclodialysis and ciliochoroidal detachment were performed in three eyes of three rabbits and in three eyes of another three rabbits, respectively. After aspiration of the aqueous humor, 0.1 ml of 10% sodium fluorescein was injected intracamerally, and the eyeball was enucleated between 30 minutes and one hour after injection and prepared for fluorescence microscopy. Sodium fluorescein concentrations in the supraciliary space were much greater in the group with cyclodialysis or ciliochoroidal detachment than in the normal control group. These results suggest that (1) in the eye with cyclodialysis, the aqueous humor may freely gain access to the supraciliary space through the cleft between the anterior chamber and the supraciliary space and then be removed rapidly and (2) in the eye with ciliochoroidal detachment, the aqueous humor may pass through the uveoscleral outflow pathway.     

Hypothermia protects brain function in acute carbon monoxide poisoning

The role of body temperature in the morbidity and mortality resulting from acute severe carbon monoxide (CO) poisoning (2400 ppm CO, 90 min) was investigated using an unanesthetized animal model. Modified Levine prepared female rats (left common carotid artery and jugular cannulated) displayed a lower rate of recovery period (4 hr) re-warming, and an increased mortality rate and behaviorally-assessed neurologic index (NI) compared to normal rats. This indicated their greater susceptibility to CO hypoxia, although the degree of CO-induced hypothermia was the same in both groups. The whole-body cooling of Levine rats to a similar extent prior to CO exposure increased somewhat the post-CO re-warming rate, and marginally decreased NI and mortality during CO exposure (in-CO). In contrast, maintenance of constant body temperature by external heating during CO exposure resulted in a negative post-CO re-warming rate and sharply increased NI and in-CO mortality. Normal euthermic rats were much less severely affected by CO. The results suggest that hypothermia, whether CO-induced or produced by prior cooling, provides measurable protection of brain function during acute severe CO poisoning, and that maintenance of body temperature increases in-CO mortality and interferes with ability to thermoregulate and increases NI in survivors.     

Enantiomeric interaction of flurbiprofen in the rat

Flurbiprofen [FL, (+/-)-2-(2-fluoro-4-biphenylyl)propionic acid] is a 2-arylpropionic acid nonsteroidal anti-inflammatory drug which is commercially available as a racemate. The anti-inflammatory activity of FL, however, appears to be mainly due to the S enantiomer. Recently, it has been postulated that, in both humans and rats, the two enantiomers of FL may interact when racemic doses are given. This study examines the above postulate in the rat by administration of single iv doses of racemic FL (10 mg/kg), and R- and S-FL (5 mg/kg of each). Plasma concentrations (0-12 h) of the enantiomers were measured using a stereospecific HPLC assay. A significant interaction was noticed between the enantiomers: mean AUC +/- SD of R-FL was reduced from 115.3 +/- 21.3 to 49.0 +/- 10.4 mg/L.h as a result of S-FL coadministration. A trend towards reduced S-FL plasma concentration was also evident when the enantiomer was given as the racemate [mean AUC +/- SD; 176.8 +/- 37.7 racemate versus 241.4 +/- 86.2 mg/L.h alone]. The reduction in S-FL, however, was not significant due perhaps to the observed interanimal variation. While the enantiomeric interaction caused a significant enlargement of the volume of distribution of R-FL, it failed to alter the terminal half-life of the enantiomer. It is suggested that the interaction is a result of displacement from plasma protein binding sites of one enantiomer by the other.