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Biomedical subjects

M S Manku

Publications and source records attributed to M S Manku.

At least 19 recordsLinked to original sources
PubMed1991

Fatty acid levels in the brains of schizophrenics and normal controls.

Essential fatty acids are important constituents of the brain. There is evidence that levels in blood of certain essential fatty acids and their eicosanoid derivatives may be abnormal. We now report that in the frontal cortex of schizophrenic patients there are significant differences from normal in the fatty acid composition of phosphatidylethanolamine. These differences from normal were not found in the cerebellar cortex.

Aged↗
PubMed1991

Essential and other fatty acids in plasma in schizophrenics and normal individuals from Japan.

Plasma phospholipid and cholesterol ester fatty acid levels were measured in samples from normal individuals, schizophrenics, and patients with affective and paranoid disorders in Japan. The schizophrenics were divided into groups with normal and reduced platelet sensitivity to the aggregation-inhibiting effects of prostaglandin (PG) E1. As in samples from schizophrenics in several other countries, linoleic acid levels were significantly below normal, as was the ratio of linoleic acid to its metabolites. Phospholipid fatty acid levels were normal in patients with paranoid or affective disorders. When the schizophrenics were divided into those with and without an abnormal response to PGE1, oleic acid was higher and eicosapentaenoic acid lower in those patients with an abnormal response. This study lends further support to the idea that schizophrenics may differ from controls in their essential fatty acid and eicosanoid metabolism.

Adult↗
PubMed1991

The effects of evening primrose oil, safflower oil and paraffin on plasma fatty acid levels in humans: choice of an appropriate placebo for clinical studies on primrose oil.

In a number of diseases, plasma levels of linoleic acid are normal or elevated while those of gamma-linolenic acid (18:3n-6, GLA) and further metabolites are below normal. Evening primrose oil (EPO), similar to safflower oil (SFO) except that it contains 8-9% of 18:3n-6, has been proposed as a therapeutic agent in these diseases, such as atopic eczema. There is argument as to whether an appropriate placebo for clinical studies on EPO should be an inert material such as paraffin, or a linoleic acid--containing oil such as SFO. We have therefore compared in normal humans the effects on plasma fatty acids of administering EPO, SFO and paraffin for 10 days. Paraffin had no effect on any fatty acid in any fraction. EPO raised the level of 20:3n-6 (dihomo-gamma-linolenic acid, DGLA) the immediate metabolite of GLA but had no significant effect on arachidonic acid. In surprising contrast, SFO raised the levels of linoleic and of arachidonic acids, without raising those of DGLA. This suggests that linoleic acid may be rapidly converted to arachidonic acid by a tightly linked enzyme sequence: GLA, in contrast, may be rapidly converted to DGLA but then only slowly on to arachidonic acid. These results are consistent with recent in vitro observations by others on rat hepatocytes and human fibroblasts.

Adult↗
PubMed1991

Abnormalities of essential fatty acid distribution in the plasma phospholipids of patients with bladder cancer.

We have examined the composition of the essential fatty acids in the plasma phospholipid fractions of 98 patients with histologically proven bladder cancer. These patients were attending hospital for regular follow-up by check cystoscopy. Patients were divided into two groups, depending on the cystoscopic findings, of either active (tumour recurrence seen) or inactive (no evidence of tumour recurrence) disease. Compared with a normal population, the plasma levels of most of the fatty acids, including arachidonic acid, were significantly lower in the 98 cancer patients (P less than 0.001, t-test). We were unable, however, to demonstrate any significant differences (Mann-Whitney U-test) between the active and inactive disease groups. Plasma levels of the essential fatty acids are abnormal in patients with bladder cancer; they do not help, however, to distinguish those patients with active disease from those with inactive disease. This may arise because the deficit in essential fatty acids we have demonstrated is a predisposing factor for the development of bladder cancer rather than a metabolic consequence of the tumour. Further studies are needed to establish the possible clinical role of measurement of essential fatty acids in patients with bladder carcinoma.

Aged↗
PubMed1991

Essential fatty acids in plasma of patients with leprosy.

We have investigated the fatty-acid composition of plasma phospholipids in 61 patients with leprosy of various clinical types with either a short or long duration of treatment. All patients had significantly decreased levels of linoleic acid and alpha-linoleic acid, the parent fatty acids of the n-6 and n-3 families, respectively. Patients with a treatment duration of more than 6 months had significantly low levels of arachidonic acid and eicosapentaenoic acid compared to controls or to patients with a treatment duration of less than 6 months. There were no differences in the fatty-acid composition between multibacillary patients and paucibacillary patients. We conclude that dietary supplementation with essential fatty acids may be indicated in patients with leprosy, particularly in those with a long treatment duration.

Arachidonic Acid↗
PubMed1990

Age-associated reduction of prostacyclin and thromboxane synthesis is inversely related to plasma cholesterol levels: modulation by dietary cholesterol supplementation.

Abnormalities of vasoactive eicosanoid synthesis with age are reported. We observed an age-associated reduction of vascular prostacyclin production and thrombin-stimulated thromboxane A2 production in blood. Amounts of production of these eicosanoids were inversely related to plasma cholesterol levels. However, there were no such relationships in rats supplemented with cholesterol. Dietary cholesterol supplementation induced a reduction of thromboxane A2/prostacyclin ratio regardless of age. These results suggest that age-associated changes of blood cholesterol levels are closely linked with vasoactive eicosanoid synthesis and that excessive consumption of cholesterol may induce a compensatory reaction by reducing the thromboxane A2/prostacyclin ratio.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

The effects of low, medium and high dose aspirin on intimal proliferation in autologous vein grafts used for arterial reconstruction.

Bilateral femoral vein grafts were implanted in 47 adult mongrel dogs to determine the effects of aspirin on intimal hyperplasia. The animals were fed a commercially-prepared 2% cholesterol diet before and for 6 weeks following operation. Twelve animals served as the controls while the remaining animals were divided into three groups receiving low, medium, and high dose aspirin. Eleven animals received 75 mg of aspirin daily, 11 animals were fed 225 mg of aspirin daily and the remaining 13 animals received 650 mg of aspirin daily. A coagulation profile was carried out before operation and at 2, 4 and 6 weeks following operation. The grafts were harvested at 6 weeks and intimal thickness was measured with a Zeiss computerized interactive image-analyzing system. The prothrombin time, partial thromboplastin time, and platelet count were unchanged in all animals. The bleeding time was prolonged in animals receiving aspirin (P less than 0.02). Intimal thickness measured 4 +/- 0.2 microns before implantation and increased at 6 weeks to 39 +/- 5 microns in the control group. Aspirin failed to reduce intimal hyperplasia. Intimal thickness measured 37 +/- 2 microns in those animals receiving 75 mg of aspirin daily, 35 +/- 3 microns after a daily dose of 225 mg of aspirin and 51 +/- 4 microns in the high dose group receiving 650 mg of aspirin daily. Our data indicates that aspirin fails to reduce intimal proliferation in canine vein grafts which suggests that alternative or combined drug therapy may be necessary to reduce the incidence of late graft failure.

Animals↗
PubMed1979

Progesterone interferes with the actions of prostaglandin (PG) E1 but not those of PGE2 or PGF2 alpha in a rat vascular preparation.

In the mammary gland some actions of prolactin seem mediated by PGs. Progesterone blocks several of the mammary effects of prolactin. We therefore investigated the effects of 100 ng/ml progesterone (within the normal human plasma concentration in pregnancy) on the vascular effects of PGE2, PGEF2 alpha and PGE1. Progesterone had no effects on the responses to PGE2 and PGF2 alpha but significantly (p less than 0.01) attenuated the actions of low concentrations of PGE1. It may have enhanced the actions of high PGE1 concentrations. Progesterone appears able to block some effects of PGE1 and to imitate others.

Animals↗
PubMed1979

Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. I. Effects of ethanol.

Ethanol, over the concentration range 33 to 300 mg/100 ml (7.2-65.2 x 10-3 M) caused a dose dependent and highly significant enhancement of conversion of 14C-dihomogammalinolenic acid (DGLA) to prostaglandin (PG) El and to thromboxane (Tx) B1 by human platelets. Ethanol had no significant effect on conversion of 14C-arachidonic acid to PGE2 and TxB2. This concentration range is the one involved in human alcoholic intoxication. The effect could be related to enhanced transport of DGLA to the active site of the cyclo-oxygenase enzyme complex, to a modification of the enzyme complex which changes the way it metabolizes DGLA but not arachidonic acid or to two different enzymes. Whatever the mechanism it seems that it is possible to regulate selectively the formation of 1 and 2 series PGs probably at the cyclo-oxygenase level. The physiological and clinical implications of this are discussed.

8,11,14-Eicosatrienoic Acid↗
PubMed1979

Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. II. Effects of vitamin C.

Vitamin C over the concentration range 10 to 100 microgram/ml (5.7-57 x 10-5 M) caused a dose dependent and highly significant enhancement of conversion of 14C-dihomogammalinolenic acid (DGLA) to prostaglandin (PG) E1 and to thromboxane (Tx) B1 by human platelets. Vitamin C had no effect on conversion of 14C-arachidonic acid to PGE2 and TxB2. The concentration range is relevant to physiology: in some cells which concentrate the vitamin, such as polymorphonbuclear leucocytes and the adrenal cortex, vitamin C concentrations may be substantially higher than 100 microgram/ml. Vitamin C can therefore selectively enhance the formation of cyclo-oxygenase generated products from DGLA without changing formation of those from AA. This effect can account for a number of the known actions of vitamin C including its effect on the immune system. The implications of this finding are discussed.

8,11,14-Eicosatrienoic Acid↗
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 regulation of prostaglandin E1 formation: a candidate for one of the fundamental mechanisms involved in the actions of vitamin C.

Vitamin C stimulates the formation of PGE1 in human platelets. The effect occurs over the physiologically relevant range of concentrations. PGE1 is required for T lymphocyte function and plays a major part in the regulation of immune responses. PGE1 is also important in the regulation of collagen and ground substance metabolism, in cholesterol metabolism and in regulation of responsiveness to insulin. It is proposed that defective formation of PGE1 could account for many of the features of scurvy and for many of the reported therapeutic effects of vitamin C. If correct, vitamin C will be of value only in conjunction with an adequate supply of dihomogammalinolenic acid, the precursor of PGE1. Essential fatty acids, pyridoxine and zinc are all required to achieve this.

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

The mechanism of coronary artery spasm: roles of oxygen, prostaglandins, sex hormones and smoking.

A reduced oxygen supply to the heart causes coronary vasodilatation in the first instance. But if the hypoxia is severe or prolonged, the dilatation passes off and coronary vasospasm develops leading to a vicious circle with a further reduction of myocardial oxygenation. The spasm is associated with increased outflow of prostaglandin (PG)-like material and can be prevented or reversed by inhibitors of PG synthesis such as indomethacin or antagonists of PG action such as chloroquine. The spasm does not appear to be caused by thromboxane (TX) A2 since selective inhibitors of TXA2 synthesis enhance the hypoxic spasm and by themselves can cause spasm even in oxygenated hearts. The mechanism may be related to loss of negative feedback control of the PG pathway by TXA2. Oxygen may enhance TXA2 production and reduce formation of vasoconstrictor PGs, while smoking, because of the formation of carboxyhaemoglobin, may have the opposite effect. Oestradiol and testosterone do not influence the hypoxic spasm but progesterone at physiological concentrations blocks it completely. Progesterone may be the protective female hormone and the increased susceptibility to myocardial infarction in women on oral contraceptives may be related to reduced formation of endogenous progesterone.

Coronary Circulation↗