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J Verhaeghe

Publications and source records attributed to J Verhaeghe.

At least 37 records · Page 2Linked to original sources

Maternal semistarvation and streptozotocin-diabetes in rats have different effects on the in vivo glucose uptake by peripheral tissues in their female adult offspring.

Previous work in humans and rats has revealed a link between perinatal growth retardation and glucose intolerance in adulthood. Both maternal semistarvation and severe diabetes are accompanied by perinatal growth retardation in rats. In this study, we compared the effect of these conditions on tissue glucose uptake in their female offspring. Glucose uptake was measured as glucose metabolic index (GMI), using 2-deoxy-[1-3H]-glucose, in the postabsorptive state and during euglycemic hyperinsulinemia. The GMI was measured in insulin-sensitive tissues (5 skeletal muscles, diaphragm and white adipose tissue) and in two noninsulin-sensitive tissues (duodenum and brain) of adult offspring of normal dams, dams rendered diabetic with streptozotocin on d 11 of pregnancy, and dams fed half normal rations from d 11 of pregnancy. Whole-body insulin resistance, measured by decreased glucose infusion rate during hyperinsulinemia, was milder in offspring of semistarved rats (O-SR) than in offspring of diabetic rats (O-DR). The basal GMI did not differ among the three groups in any tissue except tibialis anterior; during hyperinsulinemia, GMI was significantly greater in the insulin-sensitive tissues of all three groups. GMI of skeletal muscles and adipose tissue during hyperinsulinemia did not differ between control rats and O-SR; in contrast, the GMI was 25-50% lower in skeletal muscles of O-DR during hyperinsulinemia than in those of control rats or O-SR. Thus, maternal semistarvation and diabetes have dissimilar effects on peripheral insulin sensitivity of the adult female offspring. Because both conditions are associated with perinatal growth retardation and fetal hypoinsulinemia, other mechanisms must be identified to explain impaired glucose uptake by skeletal muscles in the offspring of diabetic rats.

Adipose Tissue↗

Intrauterine tracheal obstruction, a new treatment for congenital diaphragmatic hernia, decreases amniotic fluid sodium and chloride concentrations in the fetal lamb.

OBJECTIVE: To evaluate the effect of fetal tracheal occlusion on sodium and chloride concentrations in amniotic and tracheal fluid. SUMMARY BACKGROUND DATA: Intrauterine tracheal occlusion has been proposed to reverse pulmonary hypoplasia, an important prognostic factor in congenital diaphragmatic hernia. In early human trials, technical failure of the obstructive device has been reported. METHODS: Eight fetal lambs (gestational age = 95 days) were subjected to fetal tracheoscopy, and amniotic and tracheal fluid samples were taken. In multiple pregnancies (n = 6), amniotic fluid was also sampled from the contralateral amniotic sac and used as a control. Subsequently, endotracheal obstruction, using a detachable balloon, was performed. After 14 days, all fetuses were delivered, and sodium and chloride concentrations in amniotic and tracheal fluid were measured again. Statistical analysis was done using a two-tailed Student's t test, paired or unpaired as appropriate. RESULTS: In controls, between 95 and 109 days gestational age, no significant changes occurred in sodium or chloride concentrations in amniotic or tracheal fluid. After 2 weeks of tracheal obstruction, however, chloride and sodium concentrations in amniotic fluid decreased (chloride = 76.7 mEq/L vs. 107.6 mEq/L, p = 0.0003; sodium = 109.6 mEq/L vs. 125.9 +/- 5.2 mEq/L, p = 0.019). A concomitant increase in chloride and sodium concentration was observed in tracheal fluid (chloride = 145.4 mEq/L vs. 130.0 mEq/L, p = 0.047; sodium = 153.1 mEq/L vs. 142.9 mEq/L, p = 0.051). When comparing groups at 109 days, chloride and sodium concentrations in amniotic fluid were markedly lower in the treated group versus controls (p = 0.0004 and p = 0.05 for chloride and sodium, respectively). CONCLUSION: Complete tracheal occlusion in ovine fetuses results in a significant decrease of amniotic fluid sodium and chloride concentrations.

Amniotic Fluid↗

Effects of recombinant human growth hormone and insulin-like growth factor-I, with or without 17 beta-estradiol, on bone and mineral homeostasis of aged ovariectomized rats.

This study aimed to evaluate whether recombinant human growth hormone (rhGH) or insulin-like growth factor-I (rhIGF-I) can reverse or prevent further bone loss in aged osteopenic ovariectomized (OVX) rats and to compare their effects with those of 17 beta-estradiol (E2). Twelve-month-old rats were OVX, remained untreated for 8 weeks, and subsequently received daily subcutaneous (SC) injections of rhGH (75 micrograms/day), rhIGF-I (250 micrograms/day), E2 (1.5 micrograms/day), and their respective combinations during 8 weeks, and were then compared with sham-operated, pretreatment OVX, and saline-treated OVX rats. A single sc injection of rhGH resulted in peak hGH concentrations after 90 minutes, with a half-life of 124 minutes; the highest plasma IGF-I concentrations were reached 45 minutes after rhIGF-I injection (+57% vs. baseline) with a gradual decline thereafter. Measurements included: biochemical parameters of bone remodeling (plasma osteocalcin and urinary pyridinolines); histomorphometry of proximal tibial metaphysis; DXA of femur; biomechanical analysis of femur and fifth lumbar vertebra (L5); plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and calbindin-D9K in duodenal mucosa. Whereas all E2-treated OVX rats had much suppressed bone remodeling, rhGH or rhIGF-I had no effect on any biochemical or histomorphometrical parameter of remodeling. The bone mineral density (BMD) at the distal femoral metaphysis as well as parameters of strength at L5 were maintained at pretreatment values in OVX rats treated with E2, GH, or IGF-I, but not in saline-treated OVX rats; their effects were not additive, however. Trabecular bone volume in the tibial metaphysis was also higher in rats treated with these agents than in saline-treated rats, but this was more apparent at the primary than at the secondary spongiosa, suggesting that their mechanism of action is on primary spongiosa formation or breakdown. E2 alone was ineffective to augment the BMD at the femoral diaphysis; however, the diaphyseal BMD was 12-14% higher (p < 0.01) after 8 weeks of GH treatment than in pretreatment or saline-treated OVX rats and sham-operated rats, while IGF-I was less effective than GH, GH or IGF-I treatment had no effect on plasma 1,25(OH)2D3 or duodenal calbindin-D9K concentrations, but the combination of GH or IGF-I with E2 potentiated the effect of E2 to stimulate calbindin-D9K concentrations and urinary calcium excretion, indicating "hyperabsorption hypercalciuria." In conclusion, the administration of rhGH and rhIGF-I, like that of E2, into aged OVX rats prevents further loss of bone mass and strength at sites containing trabecular bone. In addition, rhGH increases cortical bone mass above pretreatment values.

Absorptiometry, Photon↗

Combined surgery and brachytherapy in the treatment of some cancers of the bladder (partial cystectomy and interstitial iridium-192).

Eighty-five bladder cancers were treated at the Urology Clinic of Nancy and the Centre Alexis Vautrin from 1975 to 1992 with short course preoperative radiation therapy (3 x 3.5 Gy), conservative surgery and brachytherapy by iridium-192. The tumours were classified according to the 1979 UICC pTNM classification. There were 27 pT1, 31 pT2 and 22 pT3, two pT4 and three pTx. The pT1-pT2 cases received only one brachytherapy (50 Gy at least) after the short course preoperative irradiation. The pT3 cases received only 30 Gy of brachytherapy and an external irradiation boost (generally 40 Gy to the node areas and 30 Gy to the tumour, but the dose varied during the time course). Surgery was often preceded by an endoscopic resection consisting of a tumoral resection or a partial cystectomy according to the localisation. The plastic vector tubes were put into place at the time of partial cystectomy. Until 1983 the radioactive wires were loaded into the vector tubes on the day following surgery, thereafter it was done one week later. The 85 patients were classified into two groups: 63 patients who were untreated previously and 22 patients who had received one or more endoscopic resections for recurrences. The median follow-up was 84 months. The local controls at 5 years were 78% in the first group versus 56% in the second group (p = 0.005) with an overall survival of 73 and 65%, respectively. The local control did not vary according to the differentiation (grade 1/2 vs. grade 3). The local control for pT1, pT2, pT3 was 85, 64 and 70% with a specific survival of 85, 76 and 72%, and an overall survival of 78, 66 and 66%. Among early complications, delay in healing of the bladder wall with subsequent vesico-cutaneous fistula depends mainly on the loading time of radioactive wires after surgery and is rare if the loading is delayed by one week. The late complications depend mostly on dosimetric factors. We found 24 grade 1, three grade 2, four grade 3 and one grade 4. The following factors are significant: the surface treated (> 14 cm2), a distance between the sources of more than 2 cm and, especially, activity of the wires of more than 2 mCi/cm (this factor was found in the five complications of grade 3 and 4), the other factors were not significant in univariate analyses.

Brachytherapy↗

C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in cord serum of twins: genetic versus environmental regulation.

OBJECTIVE: Our purpose was to examine the regulation of fetal serum concentrations of insulin (C-peptide), insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1, which are growth-regulating factors in the fetus, in monozygotic and dizygotic twin pairs. STUDY DESIGN: Cord serum samples were collected from 110 twin pairs and compared with 178 nonsibling singleton pairs with the same gestational age. Five twin pairs were excluded from the statistical analyses because of severe intrauterine growth restriction and placental abnormalities in one. Zygosity was assigned by histologic examination of the placenta and by a questionnaire sent to the mother when the twins were > or = 6 months old. Analyses included the calculation of correlation coefficients, between-pair variation, and univariate genetic analysis. RESULTS: Cord serum C-peptide concentrations were highly correlated in monozygotic (r = 0.94) and dizygotic twins (r = 0.79) but not in singleton pairs (r = -0.05); the between-pair variation was also smaller in twins than in singletons. Genetic analysis demonstrated a large contribution of the common environment to the variance in C-peptide concentrations (80%) and a smaller genetic contribution (12%). Insulin-like growth factor-I concentrations were better correlated in monozygotic (r = 0.82) than in dizygotic twins (r = 0.42), with a smaller between-pair variation in the former group (22% +/- 4% vs 51% +/- 5%). Univariate genetic analysis indicated that insulin-like growth factor-I levels were regulated predominantly by genetic mechanisms (93% in boys and 77% in girls). The regulation of insulin-like growth factor-II was more complex, with a gender-specific genetic contribution (50% for both sexes combined, 63% for girls but only 5% for boys). Insulin-like growth factor binding protein-1 was regulated by genetic mechanisms (41%) and the common environment (32%) but also by the specific or unique environment of each fetus (27%). In all five twins with intrauterine growth restriction of one member insulin-like growth factor binding protein-1 concentrations were markedly higher in the growth-restricted fetus. CONCLUSIONS: Insulin secretion in twin fetuses is determined primarily by their common, probably maternal, environment, whereas insulin-like growth factor-I production is predominantly genetically regulated. Insulin-like growth factor-II and insulin-like growth factor binding protein-1 are regulated by both genetic and environmental factors. Of these growth-regulating factors, insulin-like growth factor binding protein-1 appears to be the best marker of intrauterine growth restriction in the individual case.

C-Peptide↗

Umbilical cord osteocalcin in normal pregnancies and pregnancies complicated by fetal growth retardation or diabetes mellitus.

A homologous radioimmunoassay for human osteocalcin was used to measure cord serum osteocalcin concentrations in normal pregnancies and in pregnancies complicated by intrauterine growth retardation (IUGR) and diabetes. The mean osteocalcin concentrations in term newborns (100-110 micrograms/l) were comparable with levels that we previously measured in pubertal children. There was a small increase in mean osteocalcin concentrations during the third trimester of fetal life, with the maximum at 35 weeks; between weeks 36 and 41, the osteocalcin levels dropped by 13%. Osteocalcin was 20% lower in IUGR neonates than in age- or weight-matched newborns. The newborns of diabetic mothers had markedly lower osteocalcin concentrations than the weight-matched neonates, and 16 of the 19 samples were more than 1 SD below the mean of the gestational-age osteocalcin regression curve. Cord serum osteocalcin appears to be a useful parameter in studying normal and abnormal fetal mineralization.

Female↗

Effects of IGF-I, alone and in combination with 17 beta-oestradiol, on bone remodelling parameters in ovariectomised rats.

We studied the effects of recombinant human IGF-I (250 micrograms/day) and/or 17 beta-oestradiol (E2; 5 or 50 micrograms/kg/day), s.c., for 28 days, on plasma IGF-I and 1,25-(OH)2 vitamin D3 concentrations and on biochemical indices of bone remodelling (plasma osteocalcin, urinary pyridinolines) in 3 month-old rats that had been ovariectomised (OVX) 6 weeks before. Ten weeks after ovariectomy, plasma 1,25-(OH)2D3 was increased, but IGF-I and bone remodelling indices were within the normal range. RhIGF-I administration to OVX rats increased both IGF-I and 1,25-(OH)2D3 concentrations, as well as plasma osteocalcin and urinary pyridinoline excretion. By contrast, E2 decreased plasma IGF-I and 1,25-(OH)2D3 and the markers of bone remodelling. The combination of rhIGF-I and E2 resulted in intermediate effects. Multiple regression analysis showed that IGF-I correlated with plasma osteocalcin, and also with the urinary excretion of pyridinolines. The data shows that rhIGF-I stimulates bone remodelling in growing OVX rats, and that circulating IGF-I is a determinant of bone remodelling in vivo.

Amino Acids↗

Efficacy and safety of rilmenidine in elderly patients--comparison with hydrochlorothiazide. The Belgian Multicentre Study Group.

The aim of this trial was to study the treatment of hypertension in the elderly, comparing a new oxazoline antihypertensive agent, rilmenidine, with the diuretic hydrochlorothiazide (HCZ). After 2 weeks on placebo, 88 elderly patients (mean age 75 years; 65 women), corresponding to strict inclusion criteria, were randomized to 8 weeks double-blind monotherapy with rilmenidine 1-2 mg/day (n = 46) or HCZ 25-50 mg/day (n = 42), with administration of potassium supplements as required. Particular emphasis was placed on the evaluation of safety: blood screens were repeated after 2, 4, and 8 weeks of treatment and symptoms were systematically evaluated every 2 weeks. The rilmenidine and HCZ groups were comparable at randomization, with baseline supine systolic/diastolic blood pressures of 167/101 mm Hg and 172/101 mm Hg, respectively. Both drugs induced a significant decrease in blood pressure: at 8 weeks, supine blood pressure had decreased to 154/89 mm Hg and to 155/87 mm Hg in the rilmenidine and HCZ groups, respectively (difference not significant between groups). Changes in heart rate did not differ significantly between groups (-3 bpm at 8 weeks). Drug-related symptoms were rare and the incidence was similar in both groups. Weight decreased significantly in the HCZ group by 1 kg (p < 0.001) and did not change in the rilmenidine group. After 8 weeks of monotherapy, expected variations in serum biochemistry were detected in the HCZ group, resulting in a significant difference in comparison with the rilmenidine group: serum potassium and chloride decreased significantly and uric acid levels increased significantly in the HCZ group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats.

Spontaneously diabetic BB rats were sham operated (SO) or ovariectomized (OVX) within days after onset and studied after 4, 8, and 12 weeks. Analyses included histomorphometry of proximal tibial metaphyses, biochemical analyses of humeri, DXA analyses, and biomechanical testing of femora. In SO diabetic rats, no osteoblasts, osteoid tissue, or osteoclasts were present on the trabecular bone surface, but trabecular bone volume (TBV) remained normal compared with control BB rats. The concentration of IGF-I per dry weight of humerus was decreased after 12 weeks of diabetes, whereas the concentrations of calcium and osteocalcin did not change. DXA analysis showed normal bone mineral density (BMD) at both diaphyseal and metaphyseal femoral areas. On biomechanical testing, angular deformation, energy absorption, and torsional strength of the femora were decreased after 8-12 weeks of diabetes, but stiffness was normal. Ovariectomy in diabetic rats caused a decrease in femoral BMD especially at the metaphysis, and there was a trend toward decreased TBV in the tibial metaphysis; TBV loss was less marked than in control OVX rats, however. The increase in BMD at the femoral diaphysis, measured after 12 weeks of OVX in control rats, was absent in diabetic rats. Multiple-regression analysis indicated that the presence of diabetes but not ovariectomy, weight, and mineral content correlated with decreased energy absorption, angular deformation, and strength of the femora. The data infer that the (near) absence of unmineralized bone matrix in severely diabetic rats alters bone microarchitecture and ultimately results in brittle bones, which is not predicted by BMC or BMD measurements.

Absorptiometry, Photon↗

Time-related increase of biochemical markers of bone turnover in androgen-deficient male rats.

Bone loss during androgen deficiency has been associated with accelerated bone turnover and imbalance between bone formation and resorption but the relative increase of both phenomena is not well described. Serum osteocalcin as marker of bone formation and urinary excretion of pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone resorption were measured in both orchidectomized (ORCH, n = 8) and sham-operated (SHAM, n = 8) aged (12-month-old) male rats from 2 days before until 66 days after surgery. PYD and DPD were significantly higher in the ORCH group compared to the SHAM group starting from 21 days after surgery until the end of the experiment. Serum osteocalcin was only significantly increased in the ORCH group at 30 and 40 days. The maximal increase of serum osteocalcin was also smaller than the increase in PYD and DPD (30% versus 74% and 112%, respectively). The two markers of bone resorption were correlated with osteocalcin (r = 0.63 for PYD and r = 0.71 for DPD). Based on these results, we conclude that (1) bone resorption, as measured by PYD and DPD, increased during androgen deficiency; (2) moreover, the increase of bone resorption, as measured by DPD and PYD, was followed by a more moderate increase in bone formation as measured by serum osteocalcin, supporting the hypothesis that androgen deficiency causes accelerated bone turnover and imbalance between bone resorption and bone formation.

Amino Acids↗

1,25-Dihydroxyvitamin D3 and osteocalcin in maternal and fetal guinea pigs.

Maternal and fetal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and osteocalcin were measured in guinea pigs, to examine their potential use as animal models for fetal bone development and calcium homeostasis. Measurements were performed on days 42, 57 and 63 of gestation. Maternal serum total 1,25(OH)2D3 concentrations were increased only at the end of gestation (day 63). However, because the vitamin D binding protein (DBP) and albumin levels were decreased by 35-50% from day 42 onwards, the unbound 1,25(OH)2D3, calculated as the 1,25(OH)2D3/DBP molar ratio, was increased before day 63. Osteocalcin concentrations during gestation were 50-54% of levels found in nongravid animals. Fetal serum total 1,25(OH)2D3 concentrations were 20% of those in maternal guinea pigs. Since DBP levels were only 9-15% of maternal levels, the unbound 1,25(OH)2D3 was consistently higher in fetuses, from day 42 onwards. There was a rise in total and unbound 1,25(OH)2D3 between days 57 and 63 of fetal life. Osteocalcin concentrations were higher in fetal than in adult guinea pigs, and reached peak values on day 57 (1023 micrograms/l, i.e. 4.2 times higher than in adult female guinea pigs). Fetuses of guinea pigs that had received a restricted food supply for 14 days (days 49-63) had normal 1,25(OH)2D3 concentrations, but decreased osteocalcin concentrations compared with normal fetuses. The data obtained in fetal guinea pigs are comparable with those found in human fetuses, and suggest that the guinea pig may be a suitable model for studies on fetal bone and mineral development.

Animals↗

C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in umbilical cord serum: correlations with birth weight.

OBJECTIVE: Our purpose was to determine the correlation between birth weight and hormones or growth factors believed to be involved in fetal growth: insulin, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1. STUDY DESIGN: Five hundred thirty-eight cord serum samples were analyzed for insulin-like growth factor-I, insulin-like growth factor-II, C-peptide, and insulin-like growth factor binding protein-1 by immunoassay. Samples included all gestational ages in the third trimester and a large range of birth weights. RESULTS: Cord serum insulin-like growth factor-I concentrations increased until 39 weeks (+84% from 28 to 29 weeks), followed by a 21% decline at 41 weeks. Insulin-like growth factor-I levels were decreased by 40% in small-for-gestational-age (< 10th percentile) newborns and were increased by 28% in large-for-gestational-age (> 90th percentile) newborns in the absence of diabetes. Insulin-like growth factor-I levels were best correlated with birth weight (R = 0.48, p < 0.001). Cord serum insulin-like growth factor-II concentrations were sixfold to tenfold higher than those of insulin-like growth factor-I and were 8% to 10% (p < 0.001) higher in large-for-gestational-age than in average-weight and small-for-gestational-age newborns. Cord serum C-peptide concentrations were 28% and 34% higher in large-for-gestational-age than in average-for-gestational-age and small-for-gestational-age newborns, respectively. Insulin-like growth factor binding protein-1 levels were increased in preterm average-for-gestational-age and in term small-for-gestational-age newborns compared with term average-for-gestational-age newborns and showed a negative correlation with birth weight (R = -0.43, n = 131, p < 0.001). Insulin-like growth factor binding protein-1 was not correlated with C-peptide concentrations. CONCLUSIONS: Insulin-like growth factors I and II and insulin are all related to fetal growth and weight gain, and insulin-like growth factor-I correlates best with birth weight. Insulin is mainly related to fetal overgrowth (macrosomia). Insulin-like growth factor binding protein-1 may be a growth inhibitor in the fetus.

Adult↗

Increased clearance of 1,25(OH)2D3 and tissue-specific responsiveness to 1,25(OH)2D3 in diabetic rats.

The kinetics of 1,25-dihydroxyvitamin D3 [1,25(OH)2-D3] and the in vivo response to 1,25(OH)2D3 (7.5, 15, and 30 ng/100 g body wt), infused or injected subcutaneously for 12-14 days, were studied in male spontaneously diabetic and control BB rats. In control rats, increasing doses of 1,25(OH)2D3 produced parallel increases in plasma 1,25(OH)2D3 and calcium, urinary calcium, duodenal CaBP9K, and renal CaBP28K. 1,25-(OH)2D3 at 30 ng/100 g markedly raised plasma osteocalcin and osteoblast/osteoid surfaces in the tibial metaphysis, but inhibited bone mineralization rate. In diabetic rats, plasma 1,25-(OH)2D3 concentrations were decreased, and the rise of plasma 1,25(OH)2D3 during 1,25(OH)2D3 infusion was blunted, but the free 1,25(OH)2D3 index remained normal or above normal. Diabetic rats had an increased metabolic clearance rate of 1,25-(OH)2D3 (0.38 +/- 0.015 vs. 0.24 +/- 0.007 ml.min-1.kg-1), with no further increase in 1,25(OH)2D3-infused diabetic rats; their relative production rate of 1,25(OH)2D3 was unchanged. The responses of plasma and urinary calcium, duodenal CaBP9K, and renal CaBP28K to infused 1,25(OH)2D3 were normal, as was duodenal calcium absorption in 1,25(OH)2D3-injected diabetic rats. However, the virtual absence of osteoblasts/osteoid in trabecular bone was unaltered in diabetic rats infused with 30 ng/100 g 1,25(OH)2D3, with only minimal increase of their low plasma osteocalcin levels. 1,25(OH)2D3 treatment therefore cannot be expected to reverse diabetic osteopenia.

Animals↗

In vivo glucose utilization by individual tissues in virgin and pregnant offspring of severely diabetic rats.

Adult offspring of diabetic rats or SDF rats are characterized by insulin resistance in the liver and extrahepatic tissues; this insulin resistance does not worsen during pregnancy. In this study, we determined the glucose metabolic index in tissues of anesthetized virgin and pregnant control and SDF rats in basal conditions and during a euglycemic hyperinsulinemic clamp. Tissues comprised insulin-sensitive tissues (five skeletal muscles, diaphragm, and periovarian white adipose tissue) and control tissues (duodenum and cerebrum). In addition, this study measured the GMI of placenta and fetuses. In basal conditions, SDF rats showed a slight decrease (9-29%) in the GMI of skeletal muscles compared with control rats; it was not altered by pregnancy in any of the tissues. During physiological hyperinsulinemia, virgin SDF rats exhibited a 25-70% decrease in the GMI of skeletal muscles compared with control rats; this decrease was not observed in diaphragm, or in adipose tissue in which the GMI was found to be increased. During pregnancy, SDF rats did not show an additional drop in the GMI of skeletal muscles, whereas the GMI of both skeletal muscles and adipose tissue was clearly diminished (25-60%) in control rats. The GMI of skeletal muscles was therefore comparable in pregnant control rats and SDF rats. The placental, but not fetal, GMI was increased by 24% during hyperinsulinemia in control rats; the placental and fetal GMIs, in basal and hyperinsulinemic conditions, were similar in control rats and SDF rats. In conclusion, skeletal muscles, but not white adipose tissue, are involved in the peripheral insulin resistance of the SDF rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Functional dyspepsia versus other functional gastrointestinal disorders: a practical approach in Belgian general practices.

This paper identifies the symptom profile associated with the four main diagnoses of functional digestive disorders (dyspepsia, gastro-oesophageal reflux disease (GORD), gastritis, and constipation) made by general practitioners in Belgium. Results are also presented from a multicentre study in which the effects of cisapride, administered as an oral tablet or suspension, were evaluated in patients with these functional digestive disorders. Analysis of symptom patterns revealed that early satiety and postprandial abdominal bloating were the most prominent symptoms, followed by eructation (belching), heartburn, regurgitation, postprandial epigastric burning or discomfort, and nausea. These symptoms occurred in all diagnostic groups. However, different symptom patterns were associated with each of the disorders; for example, heartburn and regurgitation were the core symptoms in patients diagnosed as having GORD, early satiety and abdominal bloating were characteristic of patients diagnosed with dyspepsia, and fasting or postprandial pain were characteristic of patients given the diagnosis of gastritis. Therefore, it appears that these diagnoses used by general practitioners in Belgium closely correspond to reflux-like, dysmotility-like and ulcer-like dyspepsia, as defined by an international working party. Cisapride improved the core symptoms in about 80% of patients with GORD or dyspepsia, relieved all epigastric symptoms in about 80% of patients with gastritis, and significantly decreased the use of laxatives and increased stool frequency in constipated patients. Cisapride was well tolerated and thus appears to be a useful option in the treatment of functional digestive disorders in a general practice setting.

Adult↗

Calciotropic hormones during reproduction.

This review summarizes the reported effects of the menstrual cycle, pregnancy and lactation on serum concentration of the calciotropic hormones PTH and 1,25(OH)2D. A midcycle rise in PTH and 1,25(OH)2D has been observed, but in the majority of studies there was no change in PTH and 1,25(OH)2D concentrations throughout the menstrual cycle. Both total and free 1,25(OH)2D levels are increased during pregnancy. The renal 1,25(OH)2D production is stimulated, and there is some evidence of 1,25(OH)2D production by decidua/placenta and fetal kidney in vitro; the decidual/placental production should not be overestimated in vivo. The increased renal 1 alpha-hydroxylase activity is possibly mediated by estrogens and PTH, although the effect of pregnancy on PTH remains uncertain. Increased serum 1,25(OH)2D concentrations probably result in a rise of intestinal calcium absorption during pregnancy. There is a postdelivery drop in PTH and 1,25(OH)2D levels, but they are increased when lactation is prolonged, or in mothers nursing twins. The l alpha-hydroxylase activity during lactation may be stimulated by PTH, but also by prolactin.

Animals↗

The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats.

Spontaneously diabetic BB rats have a markedly depressed longitudinal bone growth and bone formation/turnover. In this study, male diabetic BB rats were infused intraperitoneally or subcutaneously for 2 weeks with hormones that are believed to stimulate skeletal growth and/or trabecular bone formation: insulin (3 or 4 U/day), human GH (hGH; 400 mU/day), recombinant human insulin-like growth factor-I (rhIGF-I; 300 or 600 micrograms/day) and testosterone (80 micrograms/100 g body weight per day). Saline-treated diabetic BB rats had decreased plasma concentrations of IGF-I and osteocalcin (OC) (OC, 3.7 +/- 0.3 vs 13.1 +/- 0.8 (S.E.M.) nmol/l in controls); bone histomorphometry showed decreased epiphyseal width, osteoblast surface (0.04 +/- 0.04 vs 1.5 +/- 0.3%) and osteoid surface, and mineral apposition rate (MAR) (1.8 +/- 0.5 vs 7.9 +/- 0.6 microns/day). Testosterone and hGH infusions had no effect on weight loss or on decreased skeletal growth and bone formation of diabetic rats, nor did they increase plasma IGF-I concentrations. Insulin infusions into diabetic rats resulted in hyperinsulinaemia and accelerated weight gain. The epiphyseal width, osteoblast/osteoid surfaces and OC levels of insulin-treated rats were normalized or stimulated well above control values (osteoblast surface, 4.3 +/- 0.8%; plasma OC, 16.1 +/- 1.4 nmol/l); the MAR (4.0 +/- 0.9 microns/day) was only partly corrected after the 2-week infusion. Infusions of rhIGF-I into diabetic rats doubled but did not restore plasma IGF-I levels to normal; weight gain, however, was similar to that in control rats. IGF-I treatment had no effect on epiphyseal width, osteoblast/osteoid surfaces and OC concentrations, but improved the decreased MAR (4.6 +/- 1.2 microns/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗