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Biomedical subjects

C Lim

Publications and source records attributed to C Lim.

13 recordsLinked to original sources

Effect of ethanol on prostaglandin E2 receptor in rat submandibular salivary glands.

The dose-dependent effects of acute ethanol treatment on the prostaglandin E2 (PGE2) receptor in submandibular salivary glands was investigated. Rat submandibular-gland segments were preincubated with Dulbecco's modified Eagle's medium in the absence and the presence of various concentrations of ethanol (0.1-5%). After incubation, membranes were prepared and assayed for PGE2 receptor binding using [3H]-PGE2. Ethanol had no effect on receptor binding at concentrations below 1%, but binding was stimulated by higher concentrations. A 30% increase in binding occurred with 2.5% ethanol and 50% with 5% ethanol. This increase was due to an alteration of the binding characteristics. Scatchard analysis of the data from the control and 5% ethanol groups revealed that the ethanol-induced increase in PGE2 receptor binding was mainly due to a 26 and 58% decrease in the dissociation constant (Kd) for the high- and low-affinity binding sites, respectively. A 31% decrease of binding capacity (Bmax) was also observed in the low-affinity binding sites. The results demonstrate that PGE2 receptor binding in submandibular glands is not altered by acute treatment with ethanol at physiological doses. The receptor binding is also relatively stable on pretreatment with 1% ethanol. It is suggested that the increase of receptor binding induced by high concentrations of ethanol may be a spontaneous response to the decrease of PGE2 synthesis in the tissues.

Animals

Visual field differences for clockwise and counterclockwise mental rotation.

Geometric line drawings were presented to normal subjects in the left visual field (LVF) or right visual field (RVF) at various degrees of rotation from a centrally presented vertical standard. The task of the subject was to indicate with a reaction time (RT) response whether the laterally presented stimulus could be rotated into the vertical standard or if it was a rotated mirror image of the standard. In Study 1, an overall right hemisphere superiority was found for RT and accuracy on match trials. Most interestingly, interactions between Visual Field and Rotation Angle for the match accuracy data and between Visual Field and Direction of Rotation (clockwise or counterclockwise) for the match RT slopes were found. These interactions suggested that clockwise rotations were more readily performed in the LVF and counterclockwise rotations in the RVF, consistent with other literature for mental rotation. The purpose of Study 2 was to replicate this finding of visual field differences for rotation direction using a design in which direction and degree of rotation were varied orthogonally. No main effect of Visual Field was found. However, significant interactions between Visual Field and Rotation Angle were found for both RT and accuracy, confirming the presence of visual field differences for rotation direction in a new sample of subjects. These differences were discussed in terms of the possibly greater relevance of medially directed stimuli and a possible hemispheric bias for rotation direction, and in terms of interhemispheric transmission factors.

Adolescent

Cigarette smoking reduces human salivary eicosanoids.

The effect of cigarette smoking on salivary eicosanoid levels was investigated in 10 smoker and 10 non-smoker volunteers. The smokers consumed an average of 20 cigarettes/day for the past 5 years or longer. The smoking status was validated by salivary cotinine level. Eicosanoids were extracted from saliva with ethanol, and the radioimmunoassay was performed to determine the concentrations of four major eicosanoids, i.e. prostaglandin E2 (PGE2), PGF2 alpha, 6-sulphidopeptide-containing leukotrienes (LTs) and 12-hydroxyeicosatetraenoic acid (12-HETE). The levels of PGE2, PGF2 alpha, and LTs were significantly lower in the saliva of smokers as compared to that of the non-smokers (1.74 +/- 0.32 vs 2.41 +/- 0.64, p = 0.006; 0.36 +/- 0.12 vs 0.54 +/- 0.18, p = 0.04; 2.24 +/- 0.96 vs 4.92 +/- 1.29, p = 0.006; mean +/- SD, ng/ml saliva). No significant differences were found in the levels of 12-HETE between the two groups. The results suggest that cigarette smoking reduces the concentrations of both the cyclooxygenase and 5-lipoxygenase products in saliva.

Cotinine

Hemodynamic effects of carvedilol after acute oral administration in hypertensive and normal subjects.

Forearm hemodynamics using pulsed Doppler flowmetry were studied in nine healthy volunteers and 12 patients with mild-to-moderate hypertension before and after acute oral administration of the beta-blocking and vasodilating agent carvedilol. Both the 25- and the 50-mg dose produced a significant blood pressure reduction by comparison with placebo in normotensive and hypertensive subjects. Only the 50-mg dose caused a decrease in forearm vascular resistance in hypertensive subjects. The decrease disappeared after wrist occlusion. Although brachial artery diameter did not change, a significant decrease in tangential tension was observed. This study provides evidence that carvedilol produced arteriolar dilation within the forearm of hypertensive subjects in association with a decrease in brachial artery tangential tension.

Administration, Oral

Effect of electroconvulsive therapy on serum concentration of alpha-1-acid glycoprotein.

Recent studies have shown significant alterations in serum alpha-1-acid glycoprotein (AGP) concentration in epileptic patients, the major protein to which basic drugs bind in serum. To date, there have been no reports in the literature investigating the effects of generalized seizures as a result of repeatedly administered electroconvulsive therapy (ECT) on this serum protein. As the cyclic antidepressants are basic drugs that bind avidly to AGP, an alteration of AGP concentration by ECT could represent a mechanism of interaction between two somatic treatments for depression. We therefore determined the serial AGP concentrations of 10 patients undergoing repeated ECT. AGP concentrations were determined by radial immunodiffusion on serum samples obtained at each treatment session (course of treatment ranged from 4 to 12 sessions over 8 to 32 days). The mean (SD) AGP concentrations prior to and at the end of ECT were 88.7 (18.3) mg/dl and 97.8 (24.8) mg/dl, respectively. Variability in AGP concentration was observed over the course of treatments with no consistent trend (intrapatient coefficients of variation averaged 11.5%). These data suggest that serial ECT does not produce consistent, significant changes in serum AGP concentrations and should have limited effects on altering the serum protein binding and, therefore, pharmacological effects of concurrently administered cyclic antidepressants.

Adolescent

Hippocampus and the blood supply to TE: parahippocampal pial section impairs visual discrimination learning in monkeys.

In the base of each temporal lobe in 4 monkeys (Macaca fascicularis) we sectioned the pia mater in an antero-posterior line along the most medial part of the inferior temporal visual association cortex (area TE), lateral to the parahippocampal cortex. This pial section interrupts the blood flow in branches of the posterior cerebral artery which cross the parahippocampal gyrus en route to area TE. Histologically, the brains of 2 of these animals did not show any abnormalities in cresyl violet stained material, apart from the small cortical damage along the line of the pial section itself. Of the remaining two animals, one had a small unilateral infarct in TE and one had bilateral infarcts in TE. All of these animals were impaired in visual discrimination learning, and the severity of impairment was correlated only imperfectly with the severity of infarction. These results show that pial section along the medial boundary of area TE can affect visual discrimination learning without producing large infarcts. Further, since aspiration lesions of the hippocampal formation require the pia mater to be sectioned in a similar way to that reported here, the effects of such aspiration lesions on visual learning and memory may be mediated in part by effects on TE.

Animals

Impairment by ethanol of prostaglandin production in rat salivary glands.

Sublingual salivary acini and submandibular tissue were incubated in DMEM medium in the presence of various concentrations (0-5%) of ethanol and the content of the three major prostaglandins, PGE2, PGF2 alpha and 6-keto-PGF1 alpha, were determined by radioimmunoassay. In In the sublingual gland, ethanol caused a decrease in PGE2 and PGF2 alpha levels, but had no effect on 6-keto-PGF1 alpha, while all three prostaglandins were affected in the submandibular gland. At 2.5% ethanol, the production of PGF2 alpha and PGE2 in sublingual gland decreased by 10% and reached maximum inhibition at 5% ethanol, at which concentration there was a 20 and 30% decrease in their levels. In submandibular gland, 2.5% ethanol caused a 20% decrease in PGE2, 30% in PGF2 alpha and 50% in 6-keto-PGF1 alpha; 40% inhibition in PGE2, 57% in 6-keto-PGF1 alpha and 65% in PGF2 alpha occurred in the presence of 5% ethanol. These findings suggest that alcohol impairs the function of salivary glands by inhibiting prostaglandin production.

6-Ketoprostaglandin F1 alpha

Stereoselective protection of exogenous and endogenous atrial natriuretic factor by enkephalinase inhibitors in mice and humans.

We compared the relative potencies of sinorphan and retorphan, the S- and R-enantiomers of acetorphan a potent inhibitor of enkephalinase (EC 3.4.34.11), to inhibit membrane metalloendopeptidase in vivo and to protect exogenous and endogenous ANF after oral administration. In mice, sinorphan was 2-3 fold as potent as retorphan in inhibiting the specific in vivo binding of [3H]acetorphan to kidney enkephalinase. The same potency ratio was found for the enhancement of trichloroacetic acid-precipitated radioactivity in kidneys of mice that had received 125I-ANF, which is used as a test for the protection of the hormone against inactivation in vivo. In nine healthy human volunteers who had received a low oral dosage of sinorphan or retorphan in a double-blind, placebo-controlled, randomized trial, sinorphan was also 2-3 fold more potent than retorphan in inhibiting plasma enkephalinase activity. These effects were accompanied by a related rise in plasma ANF immunoreactivity, which also reflected the difference in the effectiveness of the two compounds. Sinorphan was also more potent than retorphan in enhancing urinary cyclic GMP excretion and sodium excretion in five of these subjects. These data indicate that, in humans as in rodents, enkephalinase plays a crucial role in the inactivation of ANF, its partial inhibition in vivo being accompanied by a significant protection of the exogenous or endogenous hormone as well as by typical ANF-like responses. Thus orally administered sinorphan appears to be a promising compound for therapeutic use in cardiovascular and renal diseases in which ANF has been postulated to exert beneficial effects.

Administration, Oral

Pathology of the vitamin C deficiency syndrome in channel catfish (Ictalurus punctatus).

Channel catfish fingerlings fed purified diets devoid of vitamin C showed reduced growth rate, deformed spinal columns, external and internal hemorrhages, erosion of fins, dark skin color and reduced bone collagen content after 8 to 12 weeks, whereas fish fed a diet containing 30 mg/kg of vitamin C had none of these anomalies after 22 weeks. A dietary level of 30 mg of vitamin C per kg was insufficient to prevent distortion of gill filament cartilage, although 60 mg of vitamin C per kg was sufficient. Vertebral collagen percentages of 25 or below and liver ascorbic acid levels of 30 microgram/g or below appeared to be indicative of vitamin C deficiency in channel catfish fingerlings. Epidermis and dermis were almost completely healed and extensive collagen fiber formation had commenced in the somatic muscle, in experimentally inflicted wounds after 10 days in fish fed the vitamin C-free diet. Skin and muscle at the wound site were almost regenerated to normal after 10 days in fish fed 60 mg of vitamin C per kg of diet.

Animals