Biomedical subjects

A Sirek

Publications and source records attributed to A Sirek.

At least 37 records · Page 2Linked to original sources

PubMed1977

The effect of sex hormones on glycosaminoglycan content of canine aorta and coronary arteries.

Hyaluronate (HA), heparan sulfate (HS), dermatan sulfate (DS) and isomeric chondroitin sulfates (CS) were measured in vascular walls of 9-10 months old normal and hypophysectomized female beagles treated with sex hormones. Following hypophysectomy the animals were maintained for 8 weeks without any hormonal replacement therapy and then they were exposed for 3 weeks to parenteral treatment with sex hormones. One group received twice weekly 25 mg testosterone, another group was given the same amount of progesterone, and a third group received on day 1 and day 14, estrogens in 2 injections, consisting of a mixture of 10 mg short-acting estradiol-17-phenylpropionate and 2.5 mg long-acting estradiol benzoate. After 11 weeks all animals were sacrificed, coronary arteries and aortas were immediately removed and the latter were divided into three segments: arch, thoracic and abdominal. Removal of the pituitary led to a reduction of the HA content in the aortic arch and thoracic segment, but coronary arteries and abdominal aorta were not affected. The main consequence of hypophysectomy both in the entire aorta and in coronary arteries was a sharp reduction of the sulfated glycosaminoglycan (GAG) content. All three hormones produced a modest rise in the HS content of coronary arteries. A more definite response was seen in the thoracic aorta where each of the three hormones raised the low DS content to normal levels. Concerning the effect of sex hromones on aortic GAG other than DS, TESTOSTERONE RAISED THE CS content towards normal in thoracic and abdominal segments, while estrogen by doubling the normal HA concentration was particularly potent in the abdominal aorta. It is conceivable that the different sensitivity of various segments of aorta and coronary arteries to sex (and other) hormones in terms of regulating GAG metabolism may prove to be of relevance to the uneven distribution of lesions in degenerative vascular disease.

Animals↗

PubMed1977

Effect of ergot alkaloids on sulfonylurea-stimulated insulin secretion in dogs.

The insulinogenic response to a standard i.v. dose of a sulfonylurea can be markedly augmented in normal, conscious dogs if they are given 30 min earlier a single i.v. dose of dihydroergotamine (DHE). Since the parent substance ergotamine posssed no such amplifying properties, further experiments were conducted to clarify the essential structural requirements that have to be fulfilled for an ergot alkaloid to act as an amplifier of sulfonylurea-stimulated insulin secretion. Amine alkaloids ergonovine, dihydroergonovone and dihydromethylergonovine had no amplifying potency, but the hydrogenated amino acid alkaloids dihydroergocornine, dihydroergocristine and dihydroergokryptine (Hydergine) were almost as potent amplifiers as was DHE. The data indicate that (a) DHE, Hydergine and by inference all hydrogenated amino acid alkaloids are potent amplifiers of sulfonylurea-stimulated insulin secretion; (b) saturation of the double bond at C9 and C10 of the lysergic acid moiety and the pressence of an amino acid side chain are essential structual requirements for an ergot alkaloid to function as an amplifier of the action of sulfonylureas; and (c) it appears that these compounds are acting chiefly by mechanisms other than alpha-adrenergic and serotonergic receptor blockade, perhaps as regulatory molecules inducing positive cooperative changes in integral proteins of the plasma membrane of beta cells.

Animals↗

PubMed1977

Failure of ergotamine to alter the lipolytic effect of somatotropin in dogs.

Hypophysectomized dogs were injected intravenously with bovine somatotropin (GH), and plasma free fatty acid (FFA) concentrations were measured over a period of 2 h. The response consisted of an initial reduction in the concentration of plasma FFA followed by a rebound and a delayed rise above baseline values. When the animals were given a single intravenous injection of ergotamine tartrate 30 min prior to the administration of GH, the biphasic pattern with the sluggish rise in plasma FFA was retained. This finding is contrary to the results of identical experiments conducted by us with dihydroergotamine, which proved to be a potent amplifier of the lipolytic effect of GH. Since the only difference between these two compounds is the presence or absence of the double bond at C9 and C10 of the lysergic acid moiety, it appears that unless this bond is saturated the alkaloid is not capable of functioning as a biological amplifier.

Animals↗

PubMed1976

Lack of somatotropin effect on glycosaminoglycan content of canine coronary arteries.

Eight beagles, 10 months of age, were surgically hypophysectomized and subsequently maintained without hormonal replacement therapy for 8 weeks. Four of the animals then received daily injections of bovine somatotropin (0.2 mg/kg subcutaneously for 3 weeks), while the remaining 4 were treated with saline. Six age-matched intact beagles served as normal controls. Following sacrifice, the aorta and both coronary arteries were dissected from each dog and analyzed for glycosaminoglycans (GAG, mucopolysaccharides). Four fractions were determined : hyaluronic acid (HA), heparan sulfate (HS), dermatan sulfate (DS), and the isomeric chondroitin sulfates (CS). In coronary arteries hypophysectomy had no effect on HA, but caused a significant reduction of HS, DS, and CS concentrations resulting in a marked lowering of the total GAG content. Treatment with somatotropin (GH) had no appreciable effect on any one of the four GAG constituents. The lack of sensitivity of coronary arteries to GH is contrary to the effectiveness of the hormone in raising sulfated GAG in aortas, which was previously demonstrated by us in hypophysectomized dogs and now confirmed again in the present series of experiments. The data support our hypothesis that there is a differential sensitivity to GH in the various parts of the vascular system.

Animals↗

PubMed1976

Lipolysis as a function of cell numbers and fat content: comparison between isolated rat and dog adipocytes.

The lipolytic responses to dihydroergotamine (5 mug/mi) of isolated rat adipocytes andto epinephrine (50 ng/m1 and 1 mug/m1) of both rat and dog adipocytes were measured over a period of two hours. Glycerol release was calculated as a function of either glycerol ester content or of cell number per incubation vial. The conventional calculation based on glyceride content gave the following results: a) epididymal fat cells from rats weighing less than 160 gm were more sensitive to dihydroergotamine and epinephrine than were fat cells from heavier animals weighing close to 200 gm; b) dog adipocytes from abdominal subcutaneous tissue were less sensitive to eipnephrine than were rat adipocytes. No such differences were noted when the same data were calculated on the basis of cell numbers per incubation vial: the lipolytic response was uniform with rat adipocytes obtained either from the lighter or the heavier weight groups, and so was the response of dog and rat cells. These results indicate that in the type of studies where receptor-dependent hormone and drug effects are measured, the number of cells per incubation vial is an important parameter to be considered in evaluating a lipolytic response.

Abdominal Muscles↗

PubMed1974