PubMed Health⌕ Search

Biomedical subjects

B Bonet

Publications and source records attributed to B Bonet.

31 records · Page 2Linked to original sources
PubMed1994

Effects of estrogens on lipoprotein metabolism and cardiovascular disease in women.

Estrogen use is associated with protection from cardiovascular disease in postmenopausal women. This benefit appears to be magnified among women with pre-existing heart disease. The possible bias of intrinsically better health in women using estrogen has not been ruled out in observational studies. Therefore, two double-blind randomized clinical trials are underway in postmenopausal women. One in women with coronary disease is known as HERS (Heart Estrogen-progestin Replacement Study) and another in predominantly healthy women is the WHI (Women's Health Initiative). Several mechanisms of estrogen mediated protection from cardiovascular disease have been identified including increased HDL, lower LDL, lower VLDL-cholesterol/triglyceride ratio, increased clearance of intermediate density lipoprotein (IDL) and LDL via an upregulated LDL receptor, diminished penetration and degradation of LDL in the arterial wall, an inhibition of LDL oxidation by various estrogens and a reversal of inappropriate acetylcholine (EDRF)-mediated vasoconstriction in arteriosclerotic vessels. The predominating mechanism is not known, but estrogen replacement therapy is both likely to be beneficial to female health, pending randomized trials, as well as a tool to understand mechanisms of prevention of coronary artery disease.

Adolescent↗
PubMed1992

Metabolism of very-low-density lipoprotein triglyceride by human placental cells: the role of lipoprotein lipase.

Several studies have shown lipoprotein lipase (LPL) activity in human placenta, but the quantitative significance and cellular specificity of LPL in this organ are unknown. The objective of this report is to investigate the metabolism of very-low-density lipoprotein triglycerides (VLDL-TG) by the placenta, the role of LPL in this process, and the types of cells involved. Placental cells were obtained by enzymatic digestion (collagenase, hyaluronidase, and DNA-ase) and separated on a 40% Percoll gradient. The trophoblasts were the predominant cell type (80% to 85% pure) isolated at d = 1.033 to 1.048 and macrophages were predominant at d = 1.077 to 1.100 (greater than 95% pure), as characterized by eight immunocytochemical assays using cell protein-specific monoclonal antibodies. Macrophages represented 50% to 60% of cells isolated, and trophoblasts, 40% to 50%. LPL activity was assessed by VLDL-TG hydrolysis in primary 3- to 4-day tissue culture. In a representative experiment, LPL activity (nmol fatty acids (FA)/mg protein/24 h) was 101.3 +/- 5.3 in macrophages and 29.9 +/- 6.5 in the predominant trophoblast cell types, with approximately 20% of these amounts incorporated and reesterified. VLDL-TG hydrolysis and cell lipid uptake in both placental cell types was essentially abolished by a monoclonal anti-LPL antibody. When compared with a model of hepatocytes (Hep G2 cells), the hydrolysis of VLDL-TG was almost undetectable in these cells. In contrast, free fatty acids (FFA) uptake by Hep G2 cells was fourfold to sixfold greater than that by macrophages and trophoblasts, respectively. In conclusion, macrophages and trophoblasts are the two predominant placental cells isolated by enzymatic digestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1992

Prediction of infant birth weight by GDM screening tests. Importance of plasma triglyceride.

OBJECTIVE: We measured plasma glucose, GHb, GPro, IRI and TG at 24-28-wk gestation to determine the extent of elevations in GDM and relationships to glucose intolerance and infant macrosomia. RESEARCH DESIGN AND METHODS: Plasma samples were obtained 1 h after ingestion of 50 g glucose after an overnight fast in 521 randomly selected negative screenees, 264 positive screenees with GTT-, and 96 positive screenees with GTT+ (GDM). RESULTS: Screening test values in GDM subjects exceeded the GTT- group, whose values exceeded those of negative screenees: glucose, 9.6*, 8.7*, 6.3 mM; GHb, 5.2*, 4.9*, 4.7%; GPro, 3.1*, 3.0*, 2.8%; IRI, 791*, 662*, 410 pM; and TG, 2.3*, 1.9, 1.9 mM, (*P < 0.005 vs. negative screenees). TG was the only test elevated in the GDM but not in the GTT- groups. Screening test values correlated with GTT values in the following order (strongest to weakest): glucose* > TG* > GHb* > IRI > GPro (*statistical significance). Plasma TG was the only screening test significantly associated with birth weight corrected for gestational age (birth-weight ratio) (r = 0.09-0.16) (P < 0.05 to < 0.01) and was of the same order as 1- and 2-h GTT associations with birth weight (r = 0.13 and 0.14, respectively) (P < 0.05 to < 0.01). Plots of TG/birth-weight ratio increased linearly to the 80-90th TG percentile in negative screenees and GTT- subjects. GDM subjects followed this trend but with more variation. Above the 90th percentile for TGs, birth-weight ratio trended lower, significantly so when the groups were combined (P < 0.05). In multivariate analysis, TG was associated with birth-weight ratio even when maternal prepregnancy weight and pregnancy weight gain associations with TG and birth-weight ratio were controlled (P < 0.019). CONCLUSIONS: Of the five screening tests evaluated, all were elevated in GDM, but TG is the best discriminator of GDM from the GTT- group, and it is the only test significantly related to birth-weight ratio--and to glucose intolerance besides glucose itself. The TG association with birth weight is not explained fully by maternal weight. The results suggest that plasma TG may be a physiological contributor to infant birth weight. Further evaluation of plasma TG in GDM screening is justified, but GHb, GPro, and IRI appear to hold less promise.

Analysis of Variance↗
PubMed1991

Hypocaloric diets and ketogenesis in the management of obese gestational diabetic women.

The extent to which given levels of caloric restriction will improve glycemic status but increase plasma ketone bodies in gestational diabetic women has received little attention. After reviewing the underlying physiology, we present data on two feeding studies investigating the question. In the first, a weight-maintaining approximately 2400-kcal/day diet was fed on a metabolic ward to 12 gestational diabetic women for 1 week. In the second week, subjects were randomized to a continuation of the 2400-kcal/day diet or to a 1200-kcal/day diet. Twenty-four-hour mean glucose levels remained unchanged in the control group but declined in the calorie-restricted group (6.7 mM or 121 mg/dl in week 1 vs 5.4 mM or 97.3 mg/dl in week 2) (p less than 0.01). Nine-hour overnight fasting plasma insulin also declined but oral glucose tolerance did not improve with caloric restriction. Fasting plasma beta-hydroxybutyrate rose in the calorie-restricted group, along with an increase in ketonuria, but not in the control group. A second study compared the impact of a 33% calorie-restricted diet or insulin to a full-calorie diet in a similar 2-week experimental design and measured hepatic glucose output and insulin sensitivity with dideuterated glucose before and during an insulin clamp. Diet in three subjects improved fasting and 24-hr mean glucose by 22 and 10%, respectively, whereas prophylactic insulin in three subjects produced 0 and 4% reductions, respectively. On average, ketonuria after a 9-hr fast declined to an equivalent degree with both treatments. Hepatic glucose output and insulin sensitivity were not statistically significantly altered by gestational diabetes or the therapeutic interventions compared to nondiabetic normal weight or obese pregnant controls. In conclusion, 50% caloric restriction improves glycemic status in obese women with gestational diabetes but is associated with an increase in ketonuria, which is of uncertain significance. An intermediate 33% level of caloric restriction (to 1600-1800 kcal daily) may be more appropriate in dietary management of obese woman with gestational diabetes mellitus and more effective than prophylactic insulin. Further studies are required to confirm these findings.

Animals↗
PubMed1991

Maternal hypothyroidism during the first half of gestation compromises normal catabolic adaptations of late gestation in the rat.

Female rats were mated and thyroidectomized on the same day. Some animals were kept without treatment and killed on day 12 or 21 of gestation (T). Others were subsequently treated daily with 1.8 micrograms L-T4/100 g BW for either the first 12 days and then not treated from that time until day 21 [T+T4(I+0)] or else not treated for the first 12 days and then treated from days 12-21 [T+T4(0+II)]. A final group received treatment during the entire 21-day study [T+T4(I+II)] and was used as the control. The net maternal body weight increased until day 12 of gestation in T+T4(I+II) rats, but not in T animals. On day 21 net maternal body weight was significantly lower in T and T+T4(0+II) than in T+T4(I+II) rats. Lipoprotein lipase activity in the lumbar fat pads increased from days 0 to 12 of gestation and decreased on day 21, whereas in the heart the change was in the opposite direction, and these changes were greater in T+T4(I+II) rats than in T rats. Incorporation of [U-14C]glucose administered in vivo into liver [14C]fatty acids or [14C]glycogen was significantly lower in T rats than in T+T4(I+II) on either the 12th or 21st day of gestation. The response of plasma triglyceride, glycerol, or beta-hydroxybutyrate levels to 24 h of starvation was similar in 12-day pregnant rats regardless of whether they were treated with T4, whereas on day 21 the change was greater in T+T4(I+II) or T+T4(I+0) animals than in T or T+T4(0+II) animals. Results show that maternal hypothyroidism during the first half of gestation impaired the anabolic events occurring during this phase and compromised the normal catabolic response during late gestation even when T4 treatment was restored. However, once maternal metabolic stores were built up normally during the first half of gestation, maternal hypothyroidism during late gestation did not affect the mother's normal metabolic adaptation, including the accelerated response to starvation.

Adipose Tissue↗
PubMed1991

Intermediary metabolism in pregnancy. First theme of the Freinkel era.

During the first half of gestation in the rat, maternal net body weight increases rapidly, whereas in the second half of gestation, the mass of maternal structures declines, coincident with the rate of maternal fat accumulation. Enhanced maternal food intake, extrahepatic tissue lipoprotein lipase (LPL) activity, and adipose tissue lipogenesis are responsible for the progressive accumulation of maternal fat. However, during late gestation, decreased fat synthesis in maternal adipose tissue, enhanced lipolytic activity, and decreased LPL activity deplete maternal fat depots. These changes, plus enhanced endogenous production of triglyceride-rich lipoproteins, are also responsible for maternal hypertriglyceridemia. This condition benefits the offspring in two ways: 1) enhanced LPL activity in maternal liver when fasting increases triglyceride consumption for ketone body synthesis, giving the basis for accelerated starvation; and 2) induction of LPL activity in the mammary gland before parturition diverts maternal circulating triglycerides to milk synthesis in preparation for lactation. The magnitude of the maternal-fetal glucose transfer was higher than that of any of the other substrates studied, including alanine, and despite actions to spare glucose, this transfer causes maternal hypoglycemia, which is especially intense in the fasting condition. This increases sympathoadrenal activity in the mother, which may contribute to her active gluconeogenesis. Glycerol was a more efficient glucose precursor than alanine and pyruvate, and whereas glycerol placental transfer is very small, it is proposed that the fetus benefits from this product of adipose tissue lipolysis when it is previously converted into glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1991

Mechanism of the HDL2 stimulation of progesterone secretion in cultured placental trophoblast.

Lipoprotein cholesterol (C) supports the high rate of progesterone production by the human placenta as endogenous cholesterol synthesis is low. To study underlying mechanisms whereby lipoproteins, including high density lipoprotein-2 (HDL2), stimulate progesterone secretion, trophoblast cells were isolated from human term placentas and maintained in primary tissue culture. Lipoproteins were added at several concentrations and medium progesterone secretion was determined. HDL2 (d 1.063-1.125 g/ml) as well as low density lipoproteins (LDL) (d 1.019-1.063 g/ml) but not HDL3 (d 1.125-1.21 g/ml) stimulated progesterone secretion in a dose-dependent manner, with HDL2 cholesterol entering the cell and serving as substrate for progesterone synthesis. Conversely, LDL and HDL2 produced a significant decrease in [2-14C]acetate incorporation into cell cholesterol. Cholesterol-depleted lipoproteins did not stimulate progesterone secretion. The stimulating effect of LDL was abolished by apolipoprotein modification by cyclohexanedione or reductive methylation and by the addition of anti-LDL receptor antibody or 10 microM chloroquine to the medium. [14C]acetate conversion into cholesterol was accelerated by these procedures. However, HDL2 stimulation of progesterone secretion and reduction of [14C]acetate incorporation into cholesterol was not blocked by chemical modification of apolipoproteins, anti-LDL receptor antibody, or chloroquine. Treatment of HDL2 with tetranitromethane or dimethylsuberimidate also did not block the stimulation of progesterone. To determine whether the capacity of HDL2 to deliver cholesterol to the trophoblast cells was restricted to subfractions differing in apoE content, HDL2 was chromatographed on heparin-Sepharose and three fractions (A, B, and C) were obtained. Fraction A was poorest in apoE and free cholesterol, fraction B contained the majority of cholesterol, and fraction C was the richest in apoE and free cholesterol. When added to trophoblast cells, fraction A stimulated little progesterone secretion, fraction B stimulated moderately, and fraction C did so greatly. Modification of these subfractions with cyclohexanedione or reductive methylation did not inhibit these effects. In conclusion, HDL2 stimulated progesterone secretion in human trophoblast cell culture. Contrary to LDL, the HDL effect was not mediated by apolipoproteins or the LDL receptor pathway. The ability of HDL2 to stimulate progesterone secretion is consistent with the passive transfer of free cholesterol to the cell membrane from a physicochemically specific subfraction of HDL. This mechanism may be an auxiliary source of cholesterol for human steroidogenic cells.

Antibodies, Monoclonal↗
PubMed1988

Different response to maternal hypothyroidism during the first and second half of gestation in the rat.

Female rats were mated and thyroidectomized (T) on the same day and divided into four groups. Three groups were subsequently treated daily with 1.8 micrograms L-T4/100 g body wt: 1) for the first 12 days [T + T4 (I)]; 2) from the 12th day until death [T + T4 (II)]; or 3) for the entire 21-day study [T + T4 (I + II)]. The other T animals were maintained without treatment. (T), and another group of mated rats were sham operated (C). Maternal body weight increase during gestation did not differ between T + T4 (I + II) and C dams, whereas it was smaller in T dams from the 7th gestational day onward. Neither interruption of T4 treatment in the T + T4 (I) rats after the 12th day nor treatment initiated at that time in the T + T4 (II) group modified their body weights. At day 21, the weights of the maternal conceptus-free body and liver, the placenta, and the fetuses were lower in the T and T + T4 (II) animals than in either the C and the T + T4 (I + II) animals. Maternal plasma T4 and pituitary GH content were reduced, and plasma TSH was enhanced in both T and T + T4 (I) dams. In fetuses, plasma TSH concentration was augmented in T and T + T4 (I) rats and unchanged in T + T4 (II) animals when compared with those of T + T4 (I + II). Pituitary GH content was reduced in T and T + T4 (II) fetuses and unchanged in the T + T4 (I) group. We propose that maternal thyroidectomy greatly decreases the thyroid hormone levels in embryonic structures during the first half of gestation and inhibits normal maternal metabolic changes during this period. In addition to interfering with normal fetal development, these effects reduce the quantity of maternal substrates available to fetuses during the last phase of gestation. In contrast, when maternal hypothyroidism occurs during the second half of gestation, the effects are not as detrimental because fetal thyroid gland activity is adequate, and maternal catabolic adaptations are not impaired.

Adaptation, Physiological↗
PubMed1986

Postnatal development of brain TRH, serum TSH and thyroid hormones in the male and female rat.

The postnatal development of immunoreactive TRH in the central nervous system (CNS), serum TSH and thyroid hormones was studied in both male and female normal rats. While in most structures of the CNS, TRH increased until day 20-30, serum TSH values peaked at day 15 as did T4. Significant differences were also obtained between both sexes in these parameters. These data further support the fact that pituitary-thyroid axis maturation is independent of brain TRH.

Age Factors↗
PubMedDate not supplied

Effect of acipimox on plasma lipids and glucose/insulin in pregnant rats.

To determine how a reduction in maternal hypertriglyceridemia during late pregnancy may affect glucose/insulin relationships, pregnant and virgin rats were orally treated with acipimox, a potent antilipolytic agent. In 20-day pregnant rats receiving 80 mg of acipimox, plasma triglycerides (TG), free fatty acids (FFA), and glycerol decreased more than in virgin rats shortly after the drug (up to 7 hours), when compared with animals treated with distilled water, whereas plasma glucose level was unaffected by the treatment in either group of rats. When acipimox was given every 12 hours from day 17 to day 20 of pregnancy, plasma TG, FFA, and glycerol levels progressively increased, whereas they either decreased or did not change in virgin rats receiving the same treatment, with no effect in plasma glucose levels in either group. Fetal body weight was lower than in controls in 20-day pregnant rats that received acipimox for 3 days. On day 20 of pregnancy, 3 hours after receiving acipimox or distilled water, rats received a 2 g glucose/kg oral load and it was found that the change in plasma glucose was similar in both groups, whereas the increase in plasma insulin was greater in pregnant rats treated with acipimox. However, no difference was found in either variable after the oral glucose load in virgin rats receiving acipimox or distilled water. No differences in plasma glucose levels were found after intravenous (i.v.) administration of insulin in pregnant rats treated or not treated with acipimox. In conclusion, present results show that administration of acipimox during the last days of gestation inhibited lipolysis and decreased fetal weight. Over a short period of time, in pregnant rats, reductions of plasma FFA and TG after acipimox treatment improved the glucose-induced insulin release, but did not seem to have any effect in peripheral insulin resistance.

Animals↗
PubMedDate not supplied

[Pseudotumor cerebri associated with maxillary sinusitis: clinico-pathological study].

INTRODUCTION: The pseudotumor cerebri is characterized by increased intracranial pressure in the absence of a space occupying lesions or obstruction to the circulation of cerebrospinal fluid (CSF). Increased pressure but normal composition of the CSF is the diagnostic criterion. Ear infections and other infections such as sinusitis have been cited as possible, but rare, causes. CLINICAL CASE: A 12 year old girl presented with diplopia 10 days after starting treatment for sinusitis. On examination there was paresia of the VI cranial nerve to the left eye and marked bilateral papilledema. She had normal visual acuity with visual field measurements showing increased blind spot field in both eyes. Resonance studies only showed maxillary sinusitis. CSF pressure was 35 cm H2O, with 40 lymphomonocytes and normal biochemical findings. After 15 cm of CSF had been removed treatment was started with acetazolamide, dexamethasone and cefotaxime. A week later the diplopia had disappeared and the CSF pressure was 25, with no cells present. Two months later the visual fields and fundus oculi were normal. After follow-up for one year there was no recurrence. CONCLUSIONS: We describe a case of pseudotumor cerebri associated with maxillary sinusitis. We do not know whether this is a chance association or whether there was a pathophysiological basis. The possibility should be considered so as to treat the cause or predisposing factor. The initial CSF pleocytosis would support the possibility of a relationship of the pseudotumor with an infectious condition (meningeal irritation or para-infectious pleocytosis meningeal irritation or para-infections pleocytosis in the context of an ENT infection), which might have precipitated the problem by interfering with the reabsorption of CSF.

Acetazolamide↗