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Biomedical subjects

C Lowy

Publications and source records attributed to C Lowy.

At least 73 records · Page 4Linked to original sources

Contribution of circulating maternal lipids to fetal tissues in the guinea pig.

Using a constant infusion of [1-14C] palmitic acid into 7 late pregnant guinea-pigs the contribution of circulating maternal lipid to the fetuses was assessed. Within the mother plasma radioactivity was found mainly in free fatty acid with only a small amount circulating as triacylglycerol. In contrast in the fetal plasma [14C] was distributed as one-quarter free fatty acid and three-quarters triacylglycerol, with total [14C] levels being four-fold higher than in the maternal plasma after 160 min of infusion. [14C] Triacylglycerol was found in the fetal liver within 10 min of commencing infusion and levels rose to 12 times the levels of [14C] triacylglycerol in the fetal plasma (per/g or ml) by 100-160 min. [14C] Distribution into the lipid moieties of fetal tissues was found to change with time. By 100-160 min the distribution was: liver, triacylglycerol 83%, phospholipid 7%, free fatty acid 4%; fat, triacylglycerol 80%; heart, triacylglycerol 38%, phospholipid 33%, free fatty acid 9%; kidney, triacylglycerol 15%, phospholipid 58%, free fatty acid 10%; muscle, triacylglycerol 70%, phospholipid 10%, free fatty acid 10%; lung, phospholipid 75%; brain, phospholipid 80%. It was concluded that free fatty acid transferred from the mother contributes substantially to fetal lipids in late gestation in this species.

Animals↗

Hypogonadotrophic hypogonadism resistant to hCG and responsive to LHRH: report of a case.

The treatment of hypogonadotrophic hypogonadism with gonadotrophin releasing hormone (LHRH) has proved difficult in the past because of a progressive decline in the pituitary gonadotrophin response. These early studies generally used large relatively infrequent doses of natural LHRH (Davies et al., 1977) or analogues with a prolonged action (Smith et al., 1979). Recently, several reports have indicated that the lack of gonadotrophin response to LHRH can be overcome by frequent administration of low doses of natural LHRH in a pulsatile fashion (Belchetz et al., 1978; Crowley et al., 1980; Jacobson et al., 1979; Schoemaker et al., 1981; Valk et al., 1980). However, it is not known whether those patients with hypogonadotrophic hypogonadism who fail to respond to human chorionic gonadotrophin (hCG) (Bardin et al., 1969) are capable of responding to LHRH. In this case report of a patient with hypogonadotrophic hypogonadism who was resistant to prolonged hCG therapy, normal pituitary gonadotrophin and testosterone responses were obtained following pulsatile LHRH administration. The sperm count rose to 11 X 10(6)/ml. His wife became pregnant and was delivered of a normal healthy female infant after an uneventful pregnancy.

Adult↗

Conversion of thyroxine to 3,3',5'-triiodothyronine in the guinea pig placenta: in vivo studies.

Studies of placental inner-ring deiodination of T4 were carried out in pregnant guinea pigs, by in situ placental perfusion. When [131I]T4 and [125I]rT3 were administered to the mother, the ratio of fetal side to maternal side [131I]rT3 was more than 10 times greater than the corresponding ratio for [125I]rT3. When radiolabeled T4 was supplied to the fetal side of the placenta in perfusion fluid, and the perfusate recycled through the placental circuit, there was a progressive increase in labeled rT3 concentration in the perfusate. These results indicate that the guinea pig placenta actively deiodinates both maternal and fetal T4 in the inner ring in vivo. We found evidence of very little outer ring deiodination of either T4 or rT3. The quantitative contribution of placental deiodination of maternal T4 to circulating rT3 in the fetus appears to be small; however, placental deiodination of fetal T4 (about 0.5 nmol/kg fetal BW X day) could contribute significantly to fetal rT3 levels. Our observations are consistent with the hypothesis that placental inner-ring deiodination of T4 plays a part in the regulation of fetal iodothyronine metabolism.

Animals↗

Placental transfer of free fatty acids: factors affecting transfer across the guinea-pig placenta.

Using an in situ perfusion of the fetal side of the guinea-pig placenta the quantitative effects of changes in the perfusate flow rate and albumin concentration, and of changes in the transplacental free fatty acid (FFA) concentration gradient on FFA transfer across the placenta were investigated. Unidirectional transfer from mother to perfusate was assessed by the transfer of [14C]palmitic acid given as a constant infusion to the mother. The results of bidirectional FFA flux were assessed by measuring total unlabelled FFA accumulated by the perfusate during a single passage through the placenta. In 4 animals a factorial experiment was performed using perfusate in which the albumin concentration was changed from 1 to 3g/dl, whilst the flow was maintained at either 1 or 3 ml/min. A change from 1 to 3g/dl albumin averaged over both flow rates caused a significant increase in labelled palmitate, and unlabelled net FFA transfer, both for each ml of perfusuate (P less than 0.05, P less than 0.001) and for each minute of perfusion (P less than 0.005, P less than 0.001, respectively). A change from 1 to 3 ml/min flow rate averaged over both albumin concentrations caused a significant (P less than 0.001) decrease in labelled palmitate but no change in unlabelled FFA transfer per ml, but caused significant increases in labelled and unlabelled (P less than 0.05, P less than 0.001) FFA transfer per minute. From the results of these experiments and 32 more non-factorial experiments it was found that, whilst maternal and perfusate FFA concentrations were in the normal range, maternal plasma FFA levels significantly correlated (P less than 0.01) with net FFA transfer to the perfusate. When maternal plasma FFA levels became elevated then this relationship broke down. Inflowing perfusate FFA levels significantly (P less than 0.001) negatively correlated with net transfer, which changed direction and resulted in FFA transfer from perfusate to maternal blood when inflowing perfusate levels exceeded 1.7 microM/ml. It was concluded that the increases reported in fetal plasma albumin and flow rate as gestation advances enable the fetus to obtain increasing amounts of circulating maternal lipid. If this lipid is not extracted by the fetus then the reduction in the transplacental gradient will reduce net fat transfer to the fetus.

Animals↗

Insulin secretory response to oral glucose load, diabetic microangiopathy and diabetic control: a study in non-insulin dependent diabetics.

To study the importance of the residual insulin secretion for the degree of diabetic control and for the development of microangiopathy 55 patients with non-insulin-dependent diabetes mellitus (NIDDM) were studied. A 1 hr oral glucose tolerance test was performed at diagnosis and 5-10 yr later. At diagnosis all patients were free of microangiopathy, at reassessment 24 patients had evidence of microangiopathy, i.e. retinopathy, neuropathy or nephropathy, alone or in combination. The glucose induced increments of insulin levels (delta IRI) at reassessment correlated inversely with the degree of diabetic control, measured by Haemoglobin A1 (r = -0.466, p less than 0.01), and with the mean fasting blood glucose throughout the follow up period (r = -0.491, p less than 0.01). delta IRI at diagnosis was similar in patients with and without microangiopathy, and at reassessment, although lower in the microangiopathy group (11.2 +/- 2.1 vs. 16.4 +/- 2.1 microunits/ml, p less than 0.1). The difference between the 2 groups did not reach statistical significance. When patients were separated into those treated with diet alone and those treated with oral antidiabetic agents, delta IRI at reassessment was significantly lower in patients on oral agents (10.5 +/- 1.9 vs. 17.2 +/- 2.2 microunits ml, p less than 0.01), but the prevalence of microangiopathy was not different between 2 groups (37% and 52%, respectively). These findings show that in patients with NIDDM the residual beta cell function is important for the degree of diabetic control, but a direct relationship between the degree of insulin deficiency and the presence of diabetic microangiopathy is not established.

Administration, Oral↗

The clearance and placental transfer of free fatty acids and triglycerides in the pregnant guinea-pig.

Bolus injections of [14C]palmitic acid and endogenously prepared very low density lipoprotein (VLDL) were given to 12 guinea-pigs in late gestation in whom the fetal side of the placenta was perfused in situ. Disappearance of [14C] palmitate in the mother was rapid, with a half life of 2.4 min. The [14C] palmitic acid which crossed the placenta into the perfusate disappeared in parallel with the maternal label but with a delay time of 1.6 min. Following injection of [14C] labelled very low density lipoprotein maternal plasma [14C] triglyceride declined rapidly (half life of 0.7 to 9.8 min) and gave rise to [14C] free fatty acids in the plasma. These fatty acids disappeared at a slower rate (half life of 13.5 min) than found following [14C]palmitate bolus. No [14C] triglyceride appeared to cross the placenta, but triglyceride derived free fatty acids did with a delay time of 9.4 min. In experiments performed after 55 days gestation quantities of [14C] free fatty acids were higher in the perfusate than in maternal plasma implying hydrolysis of triglyceride within the placenta. It is concluded that maternal triglyceride may make a considerable contribution to fetal lipids which increases with gestational age.

Animals↗

Development of diabetic microangiopathy and diabetic control. A study in non-insulin-dependent diabetics.

The relationship between the development of microangiopathy and the degree of diabetic control was investigated in 61 noninsulin-dependent diabetics after 5-10 years of known duration of diabetes. The degree of diabetic control was assessed by fasting blood glucose (FBG) at the last assessment, haemoglobin A1 (HbA1) and by the mean of all the fasting blood glucose values throughout the follow up (MWFBG). The 29 patients who developed microangiopathy had higher FBG at last assessment (10.1 +/- 0.6 vs 8.2 +/- 0.5 mmol/l, p less than 0.02), HbA1 (13.4 +/- 0.8 vs 11.0 +/- 0.6%, p less than 0.02) and MWFBG (8.0 +/- 0.4 vs 7.5 +/- 0.4 mmol/l, p less than 0.05) than those without microangiopathy. The FBG values at each year of the follow-up were higher in the microangiopathy group. HbA1 determined in 1979 correlated with the mean FBG values of each one of the years 1975-1978 (r = 0.575, r = 0.646, r = 0.657, r = 0.631, p less than 0.001, respectively). These data support the hypothesis that in noninsulin-dependent diabetics the development of microangiopathy is related to the degree of diabetic control.

Blood Glucose↗

Home monitoring of blood-glucose. Method for improving diabetic control.

64 diabetic patients measured their own blood-glucose concentration with "Dextrostix' (Ames) and an 'Eyetone' (Ames) meter. The records made at home by 53 of these patients have shown that this led to a significant improvement in blood-glucose control. A majority (64%) were able to maintain "good" control (80% of blood-glucose recordings equal to or less than 10 mmol/l for periods as long as 478 days). This hitherto unobtainable degree of control of blood-glucose was achieved mostly with conventional insulin regimens of twice-daily 'Actrapid' (Novo Laboratories Ltd.) and 'Leo-Retard' (Leo Laboratories Ltd.). Adjustments of insulin dosage and type were found to be much easier and more predictable than with urine-glucose analysis. No significant complications were encountered. Hypoglycaemic episodes were less frequent. 70% of patients preferred blood-tests to urine tests and 92% would like to buy their own meter "if the price was right." The results suggest that self-monitoring of blood-glucose by diabetics makes possible, for the first time, the achievement of near normoglycaemia. This may reduce the incidence of long-term diabetic complications.

Adolescent↗

The effects of energy and carbohydrate restriction in patients with chronic diabetes mellitus.

Thirty-five freshly presenting, diabetic patients received 5 hour, 100 g oral glucose tolerance tests when first seen and after a period of carbohydrate and energy restriction. After treatment, the significant improvement in glucose tolerance was accompanied by increased insulin secretion and lower concentrations of blood ketone bodies, lactate, glycerol, FFA, triglycerides, cholesterol and pre-beta lipoprotein. There were no significant changes in serum growth hormone or blood pyruvate concentrations. Improvement in glucose tolerance was greater in patients who were obese (greater than 115% of desirable body weight for height) on presentation and was related to the improvement in insulin secretion and the diminished lipolysis. An hypothesis to explain the changes in insulin secretion is prosposed. Eleven out of the 35 patients showed sufficient improvement in glucose tolerance to require no treatment other than diet.

Adolescent↗