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Biomedical subjects

R A Hall

Publications and source records attributed to R A Hall.

At least 127 records · Page 7Linked to original sources

High density lipoprotein cholesterol and apolipoprotein a-1 concentrations in non-insulin dependent diabetics treated by diet and chlorpropamide.

Fasting serum concentrations of high density lipoprotein cholesterol (HDLC) and apolipoprotein A-I (apo A-I) were determined in non-insulin dependent diabetes at diagnosis, diabetics treated by diet alone, diabetics treated by diet plus chlorpropamide, and normal controls matched for sex, age and body weight. Serum concentrations of HDLC and apo A-I were decreased in all groups of diabetics. There were no significant differences in HDLC and apo A-I concentrations between the diabetics at diagnosis and those treated by diet alone or diet plus chlorpropamide. Neither HDLC nor apo A-I concentrations were correlated with glucose concentrations. The results indicate that serum concentrations of HDLC and apo A-I are reduced in non-insulin dependent diabetics at diagnosis, and are not significantly affected by chronic diet and chlorpropamide therapy.

Apolipoprotein A-I↗

Plasma high density lipoprotein cholesterol in streptozotocin diabetic and non-diabetic mice after prolonged administration of glibenclamide, chlorpropamide and metformin.

A possible influence of oral hypoglycaemic drugs on plasma high density lipoprotein cholesterol (HDL-C) concentrations was examined in streptozotocin diabetic and non-diabetic mice. Treatment of streptozotocin diabetic mice with glibenclamide (0.4 mg/kg/day), chlorpropamide (10 mg/kg/day) or metformin (60 mg/kg/day) for 28 weeks did not significantly alter plasma total cholesterol (TC) or HDL-C in streptozotocin diabetic mice. Plasma TC and HDL-C were not related to the prevailing plasma glucose concentration. Non-diabetic mice treated with glibenclamide or metformin for 46 weeks showed no changes in TC or HDL-C. However, chlorpropamide increased TC and HDL-C, and lowered the TC : HDL-C molar ration after 46 weeks in non-diabetic mice. The effect of chlorpropamide was associated with an excessive gain in weight.

Animals↗

Urinary metabolites of timolol from humans and laboratory animals. Syntheses and beta-adrenergic blocking activities.

Syntheses are reported for three metabolites (2-4) of timolol (1) formed by oxidative metabolism of the morpholine ring. GLC-MS comparisons are presented which establish that the two metabolites whose structures were previously in question are identical with their synthetic counterparts 2 and 3. In 2, metabolic oxidation of the 4-morpholinyl group of 1 had occurred at the carbon next to oxygen to give the 2-hydroxy-4-morpholinyl moiety, whereas in 3, the morpholine of 1 has been oxidized one step further and then ring opened to produce the N-(2-hydroxyethyl)glycine substituent. Biological testing of synthetic samples of the three major metabolites from human urine (3, 4, and 6) indicated that only 4, in which the morpholine moiety has been degraded to a 2-hydroxyethylamino group, had significant beta-adrenergic blocking activity (one-seventh that of timolol in anesthetized dogs).

Adrenergic beta-Antagonists↗

Several standard elective operations for duodenal ulcer: ten to 16 year clinical results.

A survey was undertaken of 558 men with duodenal ulcer who had been treated ten to 16 years previously by truncal vagotomy and drainage, truncal vagotomy and antrectomy and subtotal gastrectomy. Of the 558, 65 had died and 111, presumed living, could not be traced, leaving 382 available for assessment. Between 75 and 85% of the traced patients were considered to have an excellent or very good result, which is a slight improvement on the previously published results in this same group of patients at five to eight years follow-up. Some of the side effects of operation had diminished slightly in frequency and there had been no significant increase in the incidence of recurrent ulceration since the previous survey. Anemia was an uncommon finding. As between the various forms of operation, truncal vagotomy and antrectomy and subtotal gastrectomy demonstrated significantly better protection against proven recurrent ulcer than did truncal vagotomy and pyloroplasty (p less than 0.05). Compared with truncal vagotomy and gastroenterostomy, however, the results of both resection operations, though better, did not achieve statistical significance at p - 0.5 level (p less than 0.1). In regard to Visick gradings the resection procedures had better scores, but the differences were not significant at the p - 0.05 level, except for vagotomy and antractomy as compared with vagotomy and pyloroplasty. But it is stressed that in formulating a policy of surgical therapy for duodenal ulcer the greater inherent immediate risks of resection operations need to be borne in mind.

Drainage↗

Response of the organs of rabbits to feeding during the first days after birth.

An experiment described previously showed a large increase in weight and protein of the intestinal mucosa of suckling piglets during the first 24 h after birth. This did not take place in piglets that were starved. The results might have been partly due to the inclusion of protein molecules in the mucosa in process of absorption. Rabbits do not absorb large quantities of protein after birth, and the experiment has now been repeated on them. The gastrointestinal tract of suckled rabbits also grew rapidly in the first 24 h, but again not in those that were given only water, which is in line with the suggestion that colostrum contains a factor which stimulates the growth of the gastrointestinal tract. The brain gained weight in the suckled animals, due to incorporation of lipid and protein. It gained weight too in the starving rabbits, demonstrating its high priority for nutrients at a time when its growth velocity is at its peak.

Adipose Tissue↗

Beta adrenoceptor blocking properties of MK-761.

MK-761 is a new class of compound which has beta adrenoceptor antagonist and vasodilating properties in a single molecule. The compound has in vitro beta adrenoceptor blocking activity in the isolated cat heart papillary muscle and isolated rat atria. Unlike propranolol, it did not depress contactile force. Intrinsic sympathomimetic activity was not observed in vitro, (isolated cat papillary muscle, isolated atria) but the compound has some intrinsic sympathomimetric activity because it slightly increased heart rate in reserpinized rats. MK-761 was found to be approximately as potent as timolol and pindolol in blocking cardiac and vascular beta adrenergic receptors in anesthetized dogs. The drug was not, however, cardioselective. Oral beta adrenoceptor blocking activity was observed in rats at doses similar to those which decreased blood pressure.

Adrenergic beta-Agonists↗

The relationship between stimulation-induced potassium release and amylase secretion in the mouse parotid.

1. The output of amylase from superfused mouse parotid segments in response to stimulation with acetylcholine (ACh), phenylephrine and isoprenaline during exposure to solutions with varying potassium concentrations was monitored by an on line automated fluorometric method. 2. During stimulation with ACh or phenylephrine a 10-fold increase in superfusion fluid potassium concentration caused an immediate very marked reduction in amylase output which was fully reversible. A 10-fold reduction in potassium concentration resulted in a prominent rise in amylase output. During stimulation with isoprenaline there was no effect on the amylase output of varying the extracellular potassium concentration. Acetylcholine and phenylephrine caused potassium release from the mouse parotid whereas isoprenaline had no such effect. 3. It appears that under conditions where stimulation-induced potassium release is enhanced there is also an enhanced amylase secretion and vice cersa. There may therefore be a link between passive potassium transport and amylase secretion.

Acetylcholine↗

Thyroid dysfunction in female psychiatric patients.

Biochemical screening for thyroid dysfunction in 98 unselected female psychiatric admissions led to the diagnosis of hypothyroidism in three cases which would otherwise have passed unrecognized. It is suggested that female psychiatric patients over the age of 40 should routinely be screened for thyroid disorder.

Adult↗

Timolol maleate, a new beta-adrenergic receptor blocking agent.

Some pharmacodynamic properties of an oxypropanolamine substituted novel heterocyclic compound are described. Initial studies involve comparison of the racemic mixture, dl-timolol maleate, with the beta-adrenergic receptor blocking agent propranolol in the rat, dog and cat. dl-Timolol maleate is shown to be a potent inhibitor of cardiovascular beta-adrenergic receptors activated by isoproterenol or adrenergic nerve stimulation. Blockade of alpha-adrenergic receptors is not observed even after extremely high doses. The compound is approximately 3 times more potent than propranolol in suppressing isoproterenol-induced cardioacceleration by the i.v. route of administration. dl-Timolol maleate is also extremely well absorbed when given orally, being then about 10 times more active than propranolol. Unlike propranolol, neither dl-timolol maleate nor its optical isomers possess demonstrable local anesthetic activity. Similar to propranolol and other beta-adrenergic receptor blocking agents, activity of the compound resides predominantly in the l-isomer (timolol maleate.

Adrenergic beta-Antagonists↗