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C Lowy

Publications and source records attributed to C Lowy.

At least 19 recordsLinked to original sources
PubMed2005

Fetal erythrocyte membrane lipids modification: preliminary observation of an early sign of compromised insulin sensitivity in offspring of gestational diabetic women.

AIMS: Intrauterine exposure to diabetes is a significant determinant of the development of obesity and early onset of Type 2 diabetes mellitus in the offspring. Both conditions are characterized by insulin resistance and the latter is associated with reduced membrane arachidonic and docosahexaenoic acids. Hence, we investigated if the membrane arachidonic and docosahexaenoic acids are depressed in the cord blood of babies born to women with gestational diabetes. METHODS: Cord (fetal) and maternal blood were obtained at delivery from control subjects (n = 33) and women with gestational diabetes (n = 40) and analysed for plasma triglycerides and cholinephosphoglycerides, and erythrocyte choline- and ethanolaminephosphoglycerides fatty acids. RESULTS: Babies of gestational diabetic mothers had reduced docosahexaenoic acid in the plasma (5.9 +/- 1.4 vs. 7.1 +/- 2.0, P < 0.01) and erythrocyte (4.0 +/- 2.2 vs. 5.4 +/- 2.9, P < 0.05) cholinephosphoglycerides. Moreover, the total omega-6 and omega-3 fatty acids of the erythrocyte cholinephosphoglycerides were significantly lower (P < 0.05) in these babies. A similar trend was observed in plasma triglycerides and erythrocyte ethanolaminephosphoglycerides. The maternal plasma triglycerides and erythrocyte ethanolaminephosphoglycerides fatty acids profile were not different between the two groups. However, there was a reduction in arachidonic acid and total omega-6 fatty acids in the erythrocyte cholinephosphoglycerides of the gestational diabetic women. CONCLUSION: The altered plasma and erythrocyte fatty acids in the cord blood of babies born to women with gestational diabetes suggests a perturbation in the maternal-fetal nutrient transport and/or fetal lipid metabolism.

Adult↗
PubMed2004

Plasma AA and DHA levels are not compromised in newly diagnosed gestational diabetic women.

OBJECTIVE: The polyunsaturated fatty acids, arachidonic (AA) and docosahexaenoic (DHA), are vital structural and functional components of the neural, vascular and visual systems. There is increased demand for these fatty acids during pregnancy. Diabetes impairs the synthesis of both AA and DHA. We have investigated the possibility that pregnancy-induced diabetes compromises the levels of plasma AA and DHA in newly diagnosed expectant mothers. DESIGN: Cross-sectional study. SETTING: London, UK. SUBJECTS AND METHODS: Venous blood was obtained from 44 women with gestational diabetes mellitus (GDM) and from the same number of nondiabetics, during the third trimester. Fatty acid composition of plasma choline phosphoglycerides (CPG), triglycerides (TG) and cholesterol esters (CE) was analysed. RESULTS: The GDM women had higher levels of AA (20:4n-6; P<0.0001) and AA/linoleic acid ratio (20:4n-6/18:2n-6; P<0.01) in the CPG, and linoleic acid (LA; P<0.0001), total n-6 (P<0.01), DHA (P<0.05) and n-3 metabolites (P<0.05) in TG compared to their nondiabetic counterparts. Similarly, AA (P<0.0001), osbond acid (22:5n-6; P<0.05), total n-6 metabolites (P<0.0001), AA/LA (P<0.0001) and n-6 metabolites/LA (P<0.01) were higher in the CE of the GDM women. There was no difference in the levels of DHA in CPG and CE between the two groups (P>0.05). CONCLUSIONS: The results of this study do not provide evidence that the activity of delta-6 or delta-5 desaturases, which are vital for the synthesis of AA and DHA, is compromised by pregnancy-induced diabetes. However, since the samples were taken at diagnosis, it is conceivable that the duration of the diabetes was too short to have a discernable adverse effect on the levels of AA and DHA in plasma lipids.

Adult↗
PubMed2003

Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes.

AIMS/HYPOTHESIS: Gestational diabetes is a metabolic disorder affecting 2-5% of women and is a predictor of obesity, Type 2 diabetes mellitus and cardiovascular disease. Insulin resistance, a characteristic of gestational diabetes and obesity, is correlated with the fatty acids profile of the red cell and skeletal muscle membranes. We investigated the plasma and red cell fatty acid status of gestational diabetes. The effect of obesity on membrane fatty acids was also examined. METHODS: Fasting blood obtained at diagnosis was analysed for the fatty acids in plasma choline phosphoglycerides and red cell choline and ethanolamine phosphoglycerides. RESULTS: There were reductions in arachidonic acid (controls 10.74+/-2.35 vs gestational diabetes 8.35+/-3.49, p<0.01) and docosahexaenoic acid (controls 6.31+/-2.67 vs gestational diabetes 3.25+/-2.00, p<0.0001) in the red cell choline phosphoglycerides in gestational diabetes. A similar pattern was found in the ethanolamine phosphoglycerides. Moreover, the arachidonic and docosahexaenoic acids depletion in the red cell choline phosphoglycerides was much greater in overweight/obese gestational diabetes (arachidonic acid=7.49+/-3.37, docosahexaenoic acid=2.98+/-2.18, p<0.01) compared with lean gestational diabetes (arachidonic acid=10.03+/-2.74, docosahexaenoic acid=4.18+/-1.42). CONCLUSION/INTERPRETATION: Apparently normal plasma choline phosphoglycerides fatty acids profile in the gestational diabetic women suggested that membrane lipid abnormality is associated specifically with perturbation in the membrane. The fact that the lipid abnormality is more pronounced in the outer leaflet of the membrane where most of receptor binding and enzyme activities take place might provide an explanation for the increased insulin resistance in gestational diabetes and obesity.

Adult↗
PubMed2002

Liver triacylglycerols and free fatty acids in streptozotocin-induced diabetic rats have atypical n-6 and n-3 pattern.

In diabetes there is a decrease in membrane arachidonic (AA) and docosahexaenoic (DHA) acids and a concomitant increase in linoleic (LA) and alpha-linolenic (ALA) acids. This metabolic perturbation is thought to be due to impaired activity of Delta(6)- and Delta(5)-desaturases. Triacylglycerols are the major lipid pool in plasma and liver tissue and have a significant influence on fatty acid composition of membrane and circulating phospholipids. Data on the distribution of n-6 and n-3 polyunsaturated fatty acids of triacylglycerols in diabetes are sparse. We investigated whether streptozotocin-induced diabetes in Sprague-Dawley rats alters fatty acid composition of triacylglycerols and free fatty acids of liver tissue. The animals were fed a breeding diet prior to mating, during pregnancy and lactation. On days 1-2 of pregnancy, diabetes was induced in 10 of the 25 rats. Liver was obtained at post partum day 16 for analysis. Relative levels of LA (P=0.03), dihomo-gamma-linolenic acid (DHGLA) (P=0.02), AA (P=0.049), total n-6 (P=0.02), ALA (P=0.013), eicosapentaenoic acid (EPA) (P=0.004), docosapentaenoic acid (22:5n-3, DPA) (P=0.013), DHA (P=0.033), n-3 metabolites (P=0.015) and total n-3 (P=0.011) were significantly higher in the triacylglycerols of the diabetics compared with the controls. Similarly, liver free fatty acids of the diabetics had higher levels of LA (P=0.0001), DHGLA (P=0.001), AA (P=0.001), n-6 metabolites (P=0.002), total n-6 (P=0.0001), ALA (P=0.003), EPA (P=0.015), docosapentaenoic (22:5n-3, P=0.003), DHA (P=0.002), n-3 metabolites (P=0.005) and total n-3 (P=0.001). We conclude that impaired activity of desaturases and/or long chain acyl-CoA synthetase could not explain the higher levels of AA, DHA and n-6 and n-3 metabolites in the diabetics. This seems to be consistent with an alteration in the regulatory mechanism, which directs incorporation of polyunsaturated fatty acids either into triacylglycerols or phospholipids.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2001

Placental transfer of lactate, glucose and 2-deoxyglucose in control and diabetic Wistar rats.

Placental transfer of lactate, glucose and 2-deoxyglucose was examined employing the in situ perfused placenta. Control and streptozotocin induced diabetic Wistar rats were infused with [U-14C]-glucose and [3H]-2-deoxyglucose (2DG). The fetal side of the placenta was perfused with a cell free medium and glucose uptake was calculated in the adjacent fetuses. Despite the 5-fold higher maternal plasma glucose concentration in the diabetic dams the calculated fetal glucose metabolic index was not significantly different between the 2 groups. Placental blood flow was reduced in the diabetic animals compared with controls but reduction of transfer of [U-14C]-glucose and [3H]-2-deoxyglucose and endogenously derived [14C]-Lactate to the fetal compartment, could not be accounted for by reduced placental blood flow alone. There was no significant net production or uptake of lactate into the perfusion medium that had perfused the fetal side of the placenta in either group. The plasma lactate levels in the fetuses adjacent to the perfused placenta were found to be higher than in the maternal plasma and significantly higher in the fetuses of the diabetic group compared with control group. In this model the in-situ perfused placenta does not secrete significant quantities of lactate into the fetal compartment in either the control or diabetic group.

Animals↗
PubMed2001

Maternal diabetes and its cell membrane abnormalities as they affect the foetus: implications for the mother and birth defects.

My brief is to discuss maternal diabetes and its implications for birth defects. The perinatal mortality in Britain has fallen in the last 70 years from 60 per 1000 live births to less than 10. For the baby of the diabetic mother there has been a more dramatic decrease from 249 per thousand live births reported by Peel and Oakley in 1949 to approximately 30 in the Swedish cohort in 1993. However even in countries such as Sweden with one of the lowest figures there is still a three fold higher perinatal mortality for the baby of the diabetic mother compared with the background population. There has been a much less dramatic decrease in the incidence of congenital malformations. Peel and Oakley reported an incidence of 6.9% in 1949, and Hanson from Sweden in 1993 reported only a marginally lower incidence of 6.1%. Recent observations indicate that gestational diabetes (GDM) may be associated with increased incidence of fetal malformation and perinatal mortality. The most frequent and significant morbidity is fetal macrosomia, which in turn is associated with increased risk of birth injuries and asphyxia, (Persson and Hanson. 1998). Detection and definition of congenital malformation vary but in spite of this and the much better maternal diabetic control, congenital malformation today forms a major cause of the perinatal morbidity and mortality.

Adult↗
PubMed2000

Arachidonic and docosahexaenoic acids are strongly associated in maternal and neonatal blood.

BACKGROUND: The red cell membrane fatty acid composition has frequently been used as an index of essential fatty acid (EFA) nutrition. After birth there is a decline in plasma arachidonic acid (AA) and docosahexaenoic (DHA) acids in babies fed on conventional formula which contains only the parent linoleic and alpha-linolenic acids. In human studies, the red cell phosphoglyceride composition appears to be more constant than that of plasma. In infants fed fish oil without AA, the AA proportions fall in the plasma but much less so in the red cells. This result might be considered to mean that there is no need for preformed AA. On the other hand, in a study where the levels of AA fell there was reduction of infant growth. Indeed, where cell membrane composition does change there is often an associated alteration in physiological functions of membranes. We therefore felt it worth investigating the balance between AA and DHA in a physiological situation where plasma levels are known to change, namely in pregnancy. PURPOSE: The aim of the study was to investigate a relationship between blood phosphoglyceride AA and DHA in pregnant women and neonates. SUBJECTS: Health pregnant women from London, England (n=193) and their term babies (n=45); healthy pregnant women from Seoul, South Korea (n=40) and their term babies (n=40); and preterm neonates (n=72) from London. METHOD: Blood samples were taken from British and Korean pregnant women during the third trimester, and from term and preterm babies at birth. These samples were taken for routine monitoring purposes in Korea and were a part of a study on pregnancy outcome for which ethical permission was granted from the East London and The City Health Authority and Lambeth, Southwark and Lewisham Health Authority. Approval was also obtained from the Ethical Committee of the Asan Medical Centre, Seoul, South Korea. RESULTS: AA and DHA correlated in plasma choline phosphoglycerides (CPG) of the British mothers (r=0.52 P<0.0001). The correlation coefficients and significance were much stronger in the red cell CPG and even more so in the term and preterm infant red cell CPGs ( r=0.75, 0.80 and 0.88, respectively). Similarly, AA and DHA correlated in red cell CPGs of the Korean women and their term babies. There was also a significant relationship between the two fatty acids in red cell ethanolamine phosphoglycerides in the mothers and their babies. Both linoleic (LA) and alpha-linolenic acids (ALA) were inversely associated with AA and DHA in some of the phosphoglyceride fractions of the mothers and babies. CONCLUSIONS: Although AA and DHA have different primary dietary origins, there were significant relationships between AA and DHA in the phosphoglycerides of the red cell membrane. This finding seems surprising if the red cell composition is determined by diet. These results suggest a physiological mechanism which attempts to maintain an appropriate balance between AA and DHA. It is plausible that there is an optimum balance between AA and DHA for membrane stability, deformability, enzyme and receptor function. SPONSORSHIP: The British Diabetic Association, March of Dimes Birth Defects Foundation and The Christopher H.R. Reeves Charitable Trust. European Journal of Clinical Nutrition (2000) 54, 50-56

Adult↗
PubMed1999

Eating in labour. A randomised controlled trial assessing the risks and benefits.

The aim of this study was to determine whether permitting women in labour to eat a light diet would: (i) alter their metabolic profile, (ii) influence the outcome of labour, and (iii) increase residual gastric volume and consequent risk of pulmonary aspiration. Women were randomised to receive either a light diet (eating group, n = 48) or water only (starved group, n = 46) during labour. The light diet prevented the rise in plasma beta-hydroxybutyrate (p = 2.3 x 10(-5)) and nonesterified fatty acids (p = 9.3 x 10(-7)) seen in the starved group. Plasma glucose (p = 0.003) and insulin (p = 0.017) rose in the eating group but there was no difference in plasma lactate (p = 0.167) between the groups. There were no differences between the groups with respect to duration of first or second stage of labour, oxytocin requirements, mode of delivery, Apgar scores or umbilical artery and venous blood samples. Relative gastric volumes estimated by ultrasound measurement of gastric antral cross-sectional area were larger (p = 0.001) in the eating group. This was supported by the observation that those from this group who vomited, vomited significantly larger volumes than those in the starved group (p = 0.001). We conclude that eating in labour prevents the development of ketosis but significantly increases residual gastric volume.

3-Hydroxybutyric Acid↗
PubMed1999

The pituitary-adrenal axis in idiopathic retinal vasculitis.

AIMS: To determine whether patients with idiopathic retinal vasculitis have altered production of cortisol and dehydroepiandrosterone sulphate (DHEA-S), and whether differences in these variables occur between those who are sensitive (SS) and resistant (SR) to steroids. METHODS: 20 patients with retinal vasculitis (off treatment) and 10 control subjects were prospectively recruited. Morning cortisol and DHEA-S levels were measured, and cortisol secretion rates and short synacthen tests (SST) carried out in patients before treatment, when on prednisolone 20 mg/day, and in controls. RESULTS: There were no differences in any variables between patients and controls. For retinal vasculitis patients pretreatment, the SST was lower in SR patients (p=0.02). More of the SR patients had ischaemic retinal vasculitis ( p<0.001). CONCLUSIONS: Cortisol and DHEA-S are not involved in the pathogenesis of retinal vasculitis. SR in retinal vasculitis may be associated with a defective hypothalamic-pituitary-adrenal axis.

Adult↗
PubMed1999

Post-natal modulation of heart and liver phosphoglyceride fatty acids in pups.

BACKGROUND: Maternal dietary fats alter tissue fatty acids of the fetus and suckling pups. However, the possible change in tissue composition in response to the high oxygen tension extrauterine milieu independent of diet is not well understood. METHODS: We have compared the fatty acids of heart and liver choline (CPG) and ethanolamine (EPG) phosphoglycerides of rat offspring at birth and post-natal day 15. Sprague-Dawley rats were fed a breeding diet prior to mating, pregnancy and lactation. A proportion of each litter was sacrificed and the liver and heart were obtained for analysis. Changes in fatty acid composition specific to tissue (heart and liver) and phosphoglyceride (CPG and EPG) occurred post-natally. RESULTS: Relative levels of palmitate and oleate decreased and those of stearate increased in both the heart and liver phosphoglycerides of the suckling pups. There was a reduction in arachidonate/linoleate ratio primarily due to the increase in linoleic acid. With the exception in the heart EPG, the levels of arachidonic acid did not decrease concomitantly. Although the fatty acid composition of the diet did not change between pregnancy and lactation, docosahexaenoic and total n-3 increased in heart CPG and EPG and liver CPG of the suckling pups. Evidently, membrane fatty acid modulation, independent of maternal dietary fat, occurs in the extrauterine environment. It seems to favour the accretion of linoleic, arachidonic, docosahexaenoic and total n-3 fatty acids. CONCLUSION: Since there appears to be some parallel between the very preterm human neonate and rat pups with regard to nutrient store at birth and the neonatal developmental time window, our results may have relevance for the understanding of fatty acid metabolism and turnover in the human neonate.

Animal Feed↗
PubMed1999

Maternal diet high in fat reduces docosahexaenoic acid in liver lipids of newborn and sucking rat pups.

The effect of a maternal diet high in fat, similar to Western foods, and of diabetes on liver essential fatty acid composition of the mother and the newborn and sucking pups was investigated. Female Sprague-Dawley rats were fed on either a low-fat (42 g/kg) or a high-fat (329 g/kg) diet for 10 d before mating, throughout pregnancy and post-partum. On the first day of pregnancy, diabetes was induced by intravenous administration of streptozotocin in half the animals from the two diet groups. Half the pups were killed at birth, and the remaining pups and mothers at days 15 and 16 respectively. At birth, there was a significant reduction in the proportions of docosahexaenoic acid (DHA) in the liver phosphoglycerols and neutral lipids of the pups of both high-fat control and diabetic mothers compared with those of low-fat control and diabetic mothers. Diabetes decreased arachidonic (AA) and linoleic acid values in both the low- and high-fat groups at birth. The sucking pups of both the high-fat control and diabetic mothers exhibited a significant reduction in DHA and a concomitant compensatory increase in AA and a lowering in DHA-AA balance. In the mothers, the high-fat diet significantly increased the proportions of DHA in ethanolamine phosphoglycerols but had no observable effect in choline phosphoglycerols and neutral lipids. In the fetus the DHA level (g/100 g total fatty acids) was disproportionately reduced by the maternal high-fat diet. The adverse effect of the high-fat diet on the level of DHA (g/100 g total fatty acids) was greater in the neonate (and by implication the fetus) than in the sucking pups or mothers. It is concluded that a distortion of the biochemistry is induced in the offspring through a maternal high-fat diet, without genetic predisposition.

Animals↗
PubMed1998

Cognitive effects of pituitary tumours and their treatments: two case studies and an investigation of 90 patients.

OBJECTIVES: Two case studies are reported of patients with pituitary adenomas who had been treated with trans-sphenoidal surgery, one with and one without adjunctive radiotherapy, in whom memory impairment was found. Further to this, neuropsychological investigations of 90 patients were carried out (1) to establish the prevalence of such deficits, and (2) to try to determine their cause. METHODS: Two case studies are described. For the expanded study, patients were recruited from the data base of the endocrinology department of St Thomas's Hospital, London, if they had previously been treated for a pituitary adenoma in the past 30 years. Ninety patients were contacted and assessed with a wide range of neuropsychological tests. They were divided into five treatment groups: those who had received transfrontal surgery with radiotherapy, trans-sphenoidal surgery with or without radiotherapy, radiotherapy only, and a bromocriptine therapy group, as well as a group of 19 healthy control subjects matched for age and sex. RESULTS: In the two patients presented, both showed severe memory impairments compared with their intact intellectual ability. The more severely affected patient had received adjunctive radiotherapy, and superimposition of the 90% isodose fields on a postoperative MRI examination suggested involvement of the diencephalic structures. In the group study, significant deficits in anterograde memory were also obtained on two measures (WMS-R, RMT) for all patient groups when compared with the healthy controls, although these impairments varied in degree and were less in the bromocriptine group. However, the individual surgical and radiotherapy treatment groups did not differ significantly from one another. By contrast, general intellectual function (IQ) remained intact for all groups, as did performance on supplementary cognitive tests, including measures of frontal lobe or "executive" function, language comprehension, and speed of mental processing. Psychiatric morbidity and tumour aetiology did not seem to relate to the presence of memory deficits. CONCLUSIONS: Anterograde memory deficits were seen in the two case studies and in all our treatment groups when compared with the healthy controls, and these occurred in the context of preserved intellectual function. The present findings suggest that these memory deficits result from treatment rather than from the underlying tumour, but there was no difference between the effects of surgery and radiotherapy. It is suggested that they result from damage to diencephalic structures implicated in memory.

Adenoma↗
PubMed1997

The effect of maternal glycemic control on fetal growth in diabetic pregnancies.

In this prospective study, we examined the effect of maternal glycemic control on fetal growth in pregnancies complicated by pregestational diabetes. One hundred and sixty-five pregestational diabetic pregnancies were studied with serial ultrasound scans and fetal growth was examined as a function of maternal glycemic control. There was a significant, although small, reduction in fetal biparietal diameter growth rate in the presence of poor maternal glycemic control during the first half of the pregnancy. In the second half of pregnancy, maternal hyperglycemia contributed to fetal macrosomia. We conclude that in pregnancies with pregestational diabetes, maternal hyperglycemia affects fetal growth in a biphasic manner. As a result of that, although babies born to diabetic mothers appear of relatively overall normal size and weight, they may have smaller heads than their potential and more fat.

Adult↗
PubMed1997

Association of gestational diabetes with abnormal maternal vascular endothelial function.

OBJECTIVE: To evaluate vascular endothelial function in isolated small arteries from women with gestational diabetes. METHODS: Small subcutaneous arteries (mean luminal diameter approximately 250 microns) were dissected from biopsies obtained at caesarean section in 14 normotensive women with gestational diabetes and in 18 normotensive nondiabetic pregnant women. Vascular function was determined after mounting the arteries on a small vessel myograph. RESULTS: Pre-constricted arteries from gestational diabetic pregnant women demonstrated poor relaxation to acetylcholine, an endothelium-dependent vasodilator (pEC50, mean [SE], 6.98 [0.10] vs normal pregnant, 7.28 [0.08], P < 0.03; % maximum relaxation, median [range], 88.2 [42.4-99.4] vs normal pregnant 94.2 [71.8-100.0], P < 0.01). In the presence of indomethacin relaxation to acetylcholine was similar in both groups suggesting a deficiency in dilator prostaglandin synthesis in the arteries from the diabetic women. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine further reduced sensitivity of arteries to acetylcholine but to a similar degree in both normal pregnant and gestational diabetic women. Relaxation to sodium nitroprusside, an indicator of sensitivity of the vascular smooth muscle to nitric oxide, was similar in both groups. CONCLUSIONS: Maternal vascular endothelial dysfunction may contribute to the increased incidence of cardiovascular disorders in women with gestational diabetes.

Acetylcholine↗