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Biomedical subjects

S C Cunnane

Publications and source records attributed to S C Cunnane.

At least 145 records · Page 8Linked to original sources
PubMed1980

Interactions between zinc, essential fatty acids and prostaglandins: relevance to acrodermatitis enteropathica, total parenteral nutrition, the glucagonoma syndrome, diabetes, anorexia nervosa and sickle cell anaemia.

Many of the features of zinc deficiency and of essential fatty acid (EFA) deficiency are similar in both animals and humans. The two agents interact in various ways. EFAs are important in zinc absorption, probably after conversion to prostaglandins (PGs). Zinc seems necessary for at least two stages in EFA metabolism, the conversion of linoleic acid to gamma-linolenic acid, and the mobilisation of dihomogammalinolenic acid (DGLA) for the synthesis of 1 series PGs. Zinc may also be important in the conversion of DGLA to arachidonic acid and in arachidonic acid mobilisation for 2 series PG formation. These interactions shed considerable light on a number of clinical syndromes, including acrodermatitis enteropathica, total parenteral nutrition, diabetes mellitus, the glucagonoma syndrome and sickle cell anaemia. There is substantial evidence to suggest that anorexia nervosa is due to a combined deficiency of zinc and EFAs. Understanding of the roles of zinc and EFAs in these various clinical situations is likely to lead to improved therapy.

Acrodermatitis↗
PubMed1980

Enhanced vascular reactivity to various vasoconstrictor agents following pinealectomy in the rat: role of melatonin.

The mesenteric vascular bed preparation of control and pinealectomized (PX) male Wistar rats was used to examine vascular reactivity to two concentrations each of norepinephrine, serotonin, angiotensin, and potassium. Vasoconstrictor responses to 50- and 100-ng injections of norepinephrine and 0.5- and 1.0-microgram injections of serotonin were 30-40% higher in preparations from PX rats. Reponses to 100 ng but not to 50 ng of angiotensin were also significantly higher in preparations from PX rats. Responses to 1.5- and to 3.0-mg injections of potassium did not differ significantly in either case. In vivo injection of 20 microgram of melatonin 3 h prior to dissection of the preparation, or in vivo perfusion of 20 ng melatonin per millilitre of buffer completely reversed the increased vascular response to all vasoconstrictor agents tested in the PX preparations, but had little effect in control preparations. Also observed in PX rats was a significant increase in blood pressure, serum sodium, and increased body and heart weight. Arterial wall sodium was also elevated in PX rats. These changes may be relevant to the increased vascular reactivity of PX rats. The increased vascular responsiveness of PX rats may be specific for agents that stimulate calcium release from intracellular stores (norepinephrine, angiotensin) rather than those that stimulate calcium influx from extracellular fluid (potassium). Melatonin lack may be the cause of the vascular changes in the PX rats as both in vivo and in vitro it lowered the vasoconstrictor effects of the agents tested, but only in PX rats; it had no significant effect in the control rats.

Angiotensin II↗
PubMed1979

The nutritional regulation of T lymphocyte function.

Prostaglandin (PG) E1 plays a major role in the regulation of thymus development and T lymphocyte function and the evidence for this is reviewed. The production of PGE1 is dependent on nutritional factors with linoleic acid, gamma-linolenic acid, pyridoxine, zinc and vitamin C playing key roles. Inadequate intake of any one of these will lead to inadequate PGE1 formation and defective T lymphocyte function. Megadoses of any one are likely to be only minimally effective in the absence of adequate intakes of the others. By careful attention to diet it should be possible to activate T lymphocyte function in the large number of diseases including rheumatoid arthritis, various auto-immune diseases, multiple sclerosis, and cancer in which such function is defective. It is possible that T lymphocytes may require both endogenous and exogenous PGE1 in order to function adequately. It is therefore of particular interest that many cancer cells and virally infected cells are unable to make PGE1 because they cannot convert linoleic acid to gamma-linolenic acid. The direct provision of gamma-linolenic or dihomo-gammalinolenic acids in these situations is worthy of full investigation.

Animals↗
PubMed1979

The pineal and regulation of fibrosis: pinealectomy as a model of primary biliary cirrhosis: roles of melatonin and prostaglandins in fibrosis and regulation of T lymphocytes.

Pinealectomy leads to increased formation of fibrous tissue in the abdominal cavity, increased skin pigmentation and elevated cholesterol and alkaline phosphatase levels. It also leads to reduced formation and/or action of prostaglandin (PG) E1 and thromboxane (TX) A2. PGE1 plays an important role in enhancing function of T suppressor lymphocytes which control overactive antibody-producing B lymphocytes. In primary biliary cirrhosis there are increased skin pigmentation, hepatic fibrosis, elevated cholesterol and alkaline phosphatase levels, defective T lymphocytes and hyperactive B lymphocytes. Primary biliary cirrhosis may be a pineal deficiency disease. Serotonin is important in the pineal and the serotonin antagonist methysergide may cause retroperitoneal fibrosis by interfering with pineal function. There is a good deal of other evidence which suggests that melatonin PGE1 and TXA2 are important in the regulation of fibrosis in other situations such as "collagen" diseases, lithium-induced fibrosis and cardiomyopathies. This suggests that enhancement of formation of PGE1 and TXA2 may be of value in diseases associated with excess fibrosis and defective T suppressor cell function. PGE1 levels may be raised by zinc, penicillin, penicillamine and essential fatty acids. TXA2 levels may be raised by low dose colchicine. These new approaches to treatment may prove safer and more effective than existing ones. They may be of value in disorders such as cardiomyopathy, Hodgkin's disease and other lymphomas, multiple sclerosis, Crohn's disease, atopy and other diseases in which defective T cell function is suspected.

Animals↗
PubMed1979

Alteration of tissue zinc distribution and biochemical analysis of serum following pinealectomy in the rat.

Eight weeks following pinealectomy in adult male Wistar rats, zinc levels of various tissues were found to be significantly altered: zinc in thoracic aorta was significantly increased, and in serum, pituitary, adrenal, heart, lung, and body hair, it was decreased. Serum biochemical analysis indicated that there was a significant elevation of cholesterol, alkaline phosphatase, sodium, urea, and creatinine in serum from pinealectomised rats. Liver, spleen, and thymus weights were lower following pinealectomy, although hearts were increased. The effects of pinealectomy on zinc levels in serum and tissues and on serum cholesterol and alkaline phosphatase may be related to its effects on vascular reactivity and liver fibrosis.

Adrenal Glands↗
PubMed1979

Thymic changes in muscular dystrophy and evidence for an abnormality related to prostaglandin synthesis or action.

In Bar Harbor 129 dystrophic mice, thymic development is abnormal. Before weaning, the thymus is slightly smaller than in phenotypically normal littermates; after weaning, however, the lymphoid elements undergo rapid atrophy. The epithelial elements, in contrast, display hyperlasia. Thymectomy has no influence on the course of the disease, and it is possible that the thymic changes are a reflection of a fundamental metabolic abnormality. Thymic lymphoid tissue development seems to require normal levels of PGE1. Levels that are either too high or too low both result in abnormalities. We have investigated the effects of PGE1 in smooth muscle and have demonstrated that while some PGE1 is required for both calcium release and calcium removal, high levels of PGE1 block both processes. We propose that the muscular dystrophies are related to defects in PG synthesis and action. Myotonic dystrophy may be due to PGE11 excess, whereas Duchenne dystrophy may in part be due to PGE1 deficiency.

Aging↗
PubMed1979

Copper inhibits pressor responses to noradrenaline but not potassium. Interactions with prostaglandins E1, E2, and I2 and penicillamine.

Low concentrations of copper inhibited responses to norepinephrine and angiotensin (IC50 3 X 10(-6) M) but not to potassium in rat mesenteric vascular preparations perfused either with buffer or indomethacin and prostaglandin (PGE2). The dose-response curve was not shifted by indomethacin, imidazole, or PGE2 but was moved to the right by 2.8 X 10(-11) M PGE1 and to the left by 2.8 X 10(-7) M PGE1. These effects of copper are similar to the effects of PGI2 in the preparation. Copper moved the PGI2 dose-response curve against noradrenaline in parallel to the left, suggesting that the two were interacting at some point. Penicillamine, which may stimulate PGE1 synthesis, had PGE1-like interactions with the copper effect, suggesting that its value in Wilson's disease may be partly due to antagonism of the biological action of copper as well as to its copper-chelating properties.

Animals↗
PubMed1979

Prolactin and zinc effects on rat vascular reactivity: possible relationship to dihomo-gamma-linolenic acid and to prostaglandin synthesis.

Ovine PRL at low concentrations potentiated pressor responses to norepinephrine and angiotensin in an isolated perfused rat mesenteric vascular preparation. Higher concentrations inhibited these pressor responses. Pressor responses to potassium which depend on extracellular calcium entry into the muscle were unaffected by PRL at any concentration. Either cortisol or lithium could completely block the PRL effect. Dihomo-gamma-linolenic acid (DHGL) and prostaglandin E1 had effects similar to those of PRL in that they potentiated norepinephrine responses at low concentrations, inhibited at high ones, and had no effect on potassium responses. Arachidonic acid and prostaglandin E2 potentiated both norepinephrine and potassium responses and had no inhibitory effects at high concentrations. Neither lithium nor cortisol blocked the effects of DHGL or arachidonic acid. Zinc had actions similar to those of PRL and DHGL, but which could be blocked only by lithium and not by cortisol. These results are consistent with the concept that PRL increases synthesis of the 1 series of prostaglandins by mobilizing DHGL. They provide further evidence that zinc may play a role in some actions of PRL.

8,11,14-Eicosatrienoic Acid↗
PubMed1978

A defect in thromboxane A2 synthesis may be a factor predisposing to cancer.

A failure of thromboxane (TX) A2 synthesis may be a factor in cancer. Such a loss could explain the susceptibility to mutation, the excess prostaglandin production, the glycolytic mode of metabolism and the deranged calcium pumping characteristic of cancers. Ionising radiation and phorbols both have actions similar to inhibitors of TXA2 synthesis whereas colchicine and oxygen have actions consistent with stimulation of TXA2 synthesis. The concept accounts logically for hitherto unexplained features of cancer and suggests new strategies for the prevention and treatment of cancer.

Animals↗