A comparison of the effectiveness, tolerability and safety of high and low carbohydrate diets in women with gestational diabetes

INTRODUCTION: Nutrition therapy is an integral part of the management of gestational diabetes mellitus (GDM). Most women with GDM are treated by nutritional management alone. The goal of our study was to compare low and high carbohydrate diets in their effectiveness, safety and tolerability in women with GDM. MATERIAL AND METHODS: The study group consisted of 30 Caucasian women newly diagnosed with GDM, with a mean age of 28.7 +/- 3.7 years and pregnancy duration of 29.2 +/- 5.4 weeks. The patients were randomised into two groups: those on a low and those on a high carbohydrate diet (45% vs. 65% respectively of energy supply coming from carbohydrates). The presence of urine ketones was controlled every day. After two weeks daily glucose profiles and compliance with the recommended diets were analysed. RESULTS: Glucose concentration before implementation of the diet regimen did not differ between groups. No changes in fasting blood glucose were noticed in the group that had followed a low carbohydrate diet, although a significant decrease in glucose concentration was observed after breakfast (102 +/- 16 vs. 94 +/- 11 mg/dl), lunch (105 +/- 12 vs. 99 +/- 9 mg/dl) and dinner (112 +/- 16 vs. 103 +/- 13 mg/dl) (p < 0.05). In the high carbohydrate diet group fasting and after-breakfast glucose concentration did not change. A significant decrease in glycaemia was noticed after lunch (106 +/- 15 vs. 96 +/- 7 mg/dl) and dinner (107 +/- 12 vs. 97 +/- 7 mg/dl) (p < 0.05). Ketonuria was not observed in either group. Obstetrical outcomes did not differ between groups. CONCLUSIONS: Both high and low carbohydrate diets are effective and safe. A diet with carbohydrate limitation should be recommended to women who experience the highest glycaemia levels after breakfast.     

Goiter and impairment of thyroid function in acromegalic patients: basal evaluation and follow-up.

AIMS: We evaluated morphological, biochemical and cytological thyroid parameters in acromegalic patients, investigated before and after treatment for acromegaly. PATIENTS: 28 acromegalics were investigated before and, in 18 cases, after 2-7 years of therapy. Fourteen patients were from areas of moderate iodine deficiency in Southern Italy. One patient underwent thyroidectomy before entering this study. RESULTS: 19 patients were euthyroid (FT4: 17.7 +/- 0.8 pmol/l and FT3 4.6 +/- 0.2 pmol/l), but TSH was undetectable in 5/19. Among them, TRH-stimulated TSH increase was absent/impaired or exaggerated/delayed in 9 and one cases, respectively. Decreased FT3 and/or FT4 values with low/normal TSH values were detected in 7 cases; TRH-stimulated TSH response was absent/impaired in 2 patients and exaggerated/delayed in another two. Increased free T4 and free T3 concentrations with undetectable TSH levels were found in one. Two euthyroid patients had high TPOAb levels. Goiter was diagnosed in 21 cases and nodules were found in 14/21. 99Tc scintiscan showed "cold" areas in 13/14 cases and a "hot" nodule in the hyperthyroid patient. Acromegalics from iodine deficient areas showed a not significant increase of prevalence of goiter (86 vs. 71 %) and of mean thyroid volume (35 +/- 7 vs. 28 +/- 4 ml, NS), compared to others. Thyroid volume (TV) did not correlate with GH, IGF-1 and TSH levels, the area under the curve of insulin-increase during OGTT, the age of patients or the duration of acromegaly. Fine needle aspiration biopsy (FNAB), performed in 11/14 patients with nodular goiter, showed colloid nodules in 8 cases, hyperplastic nodules in 2 and an adenomatous nodule in one. Neurosurgery, radiotherapy or medical treatment for acromegaly induced a significant decrease of mean GH and IGF-1 levels (21.5 +/- 8.5 vs. 12.9 +/- 9.6 ng/ml, p< 0.005 and 747 +/- 94 vs. 503 +/- 88 ng/ml, p < 0.02, respectively), but both GH and IGF-1 values normalized only in 3 cases. No significant variation of mean TSH levels was found. Although TV normalized in 3 patients, ultrasound evaluation showed a not significant decrease of mean TV and no changes in the diameter and number of nodules. FNAB was unchanged. CONCLUSIONS: Our results suggest that, despite no correlation between serum GH and IGF-1 levels and thyroid volume being found, a decrease in serum GH and IGF-1 levels has favourable effects on thyroid status.     

Relationship of scrotal circumference and testicular volume to age and body weight in the swamp buffalo (Bubalus bubalis)

Scrotal circumference (SC) and testicular volume (TV) were measured in 65 swamp buffalo bulls ranging in age from 7 to 60 months and weighing 130 kg to 560 kg. Ages and body weight (BW) were recorded for each male at the time of measurement to find out if they correlated with SC and TV. SC and TV increased linearly and correlated significantly with age and BW (SC vs age: r = 0.74, p<0.01; SC vs BW: r = 0.88, p<0.01; TV vs BW: r = 0.82, p<0.01). SC measurements ranged from 15.1 +/- 1.1 cm to 24.0 +/- 0.4 cm for ages ranging from 10.0 +/- 0.6 to 48.5 +/- 6.3 months, revealing that testicular size in swamp buffaloes was very much smaller than domestic cattle. The SC norms distributed with age would be useful in the evaluation of swamp buffalo males for breeding soundness.     

Internal carotid flow velocity with exercise before and after acclimatization to 4,300 m.

Cerebral blood flow and O2 delivery during exercise are important for well-being at altitude but have not been studied. We expected flow to increase on arrival at altitude and then to fall as O2 saturation and hemoglobin increased, thereby maintaining cerebral O2 delivery. We used Doppler ultrasound to measure internal carotid artery flow velocity at sea level and on Pikes Peak, CO (4,300 m). In an initial study (1987, n = 7 men) done to determine the effect of brief (5-min) exercises of increasing intensity, we found at sea level that velocity [24.8 +/- 1.4 (SE) cm/s rest] increased by 15 +/- 7, 30 +/- 6, and 22 +/- 8% for cycle exercises at 33, 71, and 96% of maximal O2 uptake, respectively. During acute hypobaric hypoxia in a decompression chamber (inspired PO2 = 83 Torr), velocity (23.2 +/- 1.4 cm/s rest) increased by 33 +/- 6, 20 +/- 5, and 17 +/- 9% for exercises at 45, 72, and 98% of maximal O2 uptake, respectively. After 18 days on Pikes Peak (inspired PO2 = 87 Torr), velocity (26.6 +/- 1.5 cm/s rest) did not increase with exercise. A subsequent study (1988, n = 7 men) of the effect of prolonged exercise (45 min at approximately 100 W) found at sea level that velocity (24.8 +/- 1.7 cm/s rest) increased by 22 +/- 6, 13 +/- 5, 17 +/- 4, and 12 +/- 3% at 5, 15, 30, and 45 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of labour on uterine blood flow in the pregnant ewe.

The effect of labour on cardiac output and uterine blood flow was measured in pregnant ewes at a mean gestation of 124 days using radioactive microspheres labelled with 169Yb and 85Sr. Labour was induced by a continuous infusion of ACTH into the foetal circulation. Cardiac ouput measured before ACTH infusion in seven ewes was 5234 +/- 175-9 ml./min (mean +/- S.E.) and total uterine blood flow was 732 +/- 57-9 ml./min (mean +/- S.E.). Measurements during labour in six ewes showed a significant increase in cardiac output to 6175 +/- 149-6 ml./min (P less than 0-005) but no significant change in uterine blood flow. However, the partition of blood flow was altered; thus myometrial flow increased by 67% from 114 +/- 15-4 ml./min to 190 +/- 13-2 ml./min (P less than 0-005) while placental blood flow decreased, although not significantly, from 618 +/- 55-9 ml./min to 575 +/- 40-7 ml./min. Similar changes were observed in one ewe in spontaneous labour at term and in another ewe receiving an infusion of 4 mg oestradiol 17beta over a 24 hr period. It is concluded that labour is not associated with any major alternation in total uterine blood flow although myometrial blood flow is increased. It is not known whether this is due to the rise in circulating oestrogens which occurs prior to parturition in the ewe, or to other factors such as the work of uterine muscle during labour.     

Influence of high-intensity exercise training and anabolic androgenic steroid treatment on rat tissue glycogen content

To increase tissue glycogen content many athletes use anabolic androgenic steroids (AAS). However, the literature concerning the effects of androgens on glycogen metabolism is conflicting. This study aimed to determine the influence of training and AAS on body weight (bw), triglycerides, glucose, tissue glycogen and transaminases levels. Male Wistar rats, randomized into four groups (sedentary vehicle (SV), sedentary AAS (SA), trained vehicle (TV) and trained AAS (TA)), were treated with nadrolone (5 mg/Kg, 2x/week, i.m.) or vehicle. Trained rats performed jumps into water (4 sets, 10 repetitions, 30 sec rest) carrying a 50-70% body wt-load strapped to the chest (5 days/week,6 weeks). Two days after the last session, the animals were killed (bifatorial ANOVA+Tukey test; P < 0.05). Trained animals presented lower bw (TV:345+/-7 vs. SV:380+/-7 and TA:328+/-4 vs SA:370+/-11 g) and triglycerides levels (TV:77+/-3 vs. SV:98+/-4 and TA:79+/-3 vs. SA:98+/-8 mg/dL) and higher glycogen content in liver (TV:5.3+/-0.2 vs. SV:3.9+/-0.1 and TA:5.3+/-0.3 vs. SA:4.6+/-0,2 mg/100 mg) and in gastrocnemious (TV:0.70+/-0.02 vs. SV:0.49+/-0.01 and TA:0.73+/-0.03 vs. SA:0.57+/-0.02 mg/100 mg) than sedentary ones. In the cardiac muscle, the association between training and AAS increased glycogen content (TA:0.19+/-0.01 > SV:0.13+/-0.01=TV:0.13+/-0.01=SA:0.14+/-0.01 mg/100 mg). In the soleus AAS increased glycogen (SA:0.53+/-0.03 vs. SV:0.43+/-0.01 and TA:0.58+/-0.02 vs. TV:0.48+/-0.01 mg/100 mg). Exercise training and AAS had no effect on blood glucose and transaminases levels. Training and AAS effects on glycogen supercompensation are tissue-dependent and the effects of association between them were only observed in the cardiac muscle. These data emphasize the necessity of more studies to confirm greater effects of AAS than those promoted by physical exercise.     

The use of steroid hormones in superovulation of Nelore donors at different stages of estrous cycle

The objective of the present study was to evaluate the superovulatory response and ova/embryo recovery from Nelore donors following treatment with a controlled internal drug releasing device and estradiol benzoate (CIDR-B program) at different stages of the estrous cycle. The control group (TI; n=40) received a standard superovulation protocol with females of this group being between days 9 and 12 of the estrous cycle (estrus = day 0). The donors that received a CIDR-B program containing 1.9 g progesterone and an intramuscular injection of estradiol benzoate (2 mg) were at day 0 (TII; n=30), between days 2 and 6 (TIII; n=30), days 7 and 12 (TIV; n=30), days 13 and 16 (TV; n=30) and days 17 and 20 (TVI; n=30) of the estrous cycle. Superovulation was induced with 400 IU of p-FSH, divided into eight decreasing doses (80/80; 60/60; 40/40; 20/20) at intervals of 12h. The donors received PGF2alpha (Cloprostenol) 48 h after beginning the treatment and CIDRs were removed 12h later. Artificial inseminations (AI) were performed 12 and 22 h after the initiation of estrus and embryos were collected 7 days after AI. The mean numbers (+/-S.E.M.) of total ova and embryos, viable (transferable) and degenerated embryos were 14.2+/-11.3, 7.4+/-6.9 and 3.2+/-3.5 (TI), 13.3+/-10.4, 7.1+/-6.2 and 3.3+/-4.3 (TII), 13.5+/-7.0, 8.1+/-6.7 and 2.3+/-3.0 (TIII), 17.4+/-9.9, 9.4+/-6.9 and 4.0+/-4.4 (TIV), 16.9+/-8.8, 9.8+/-8.1 and 2.7+/-2.5 (TV) and 13.0+/-7.8, 7.2+/-6.9 and 2.3+/-2.5 (TVI), with no significant differences (P>/=0.05) among groups. Pregnancy rates of 67.1% (TI; n=86/128), 60.8% (TII; n=59/97), 62.5% (TIII; n=73/115), 64.1% (TIV; n=84/131), 72.3% (TV; n=81/112) and 60.6% (TVI; n=63/104) were obtained with embryos transferred from these collections and did not differ significantly (P>/=0.05) among groups. The results of the present study allow us to conclude that a combination of steroid hormones may be used prior to superovulation in Nelore donors, at any stage of the estrous cycle without affecting the efficiency of embryo transfer programs.     

Upper airway muscle responsiveness to rising PCO(2) during NREM sleep.

Although pharyngeal muscles respond robustly to increasing PCO(2) during wakefulness, the effect of hypercapnia on upper airway muscle activation during sleep has not been carefully assessed. This may be important, because it has been hypothesized that CO(2)-driven muscle activation may importantly stabilize the upper airway during stages 3 and 4 sleep. To test this hypothesis, we measured ventilation, airway resistance, genioglossus (GG) and tensor palatini (TP) electromyogram (EMG), plus end-tidal PCO(2) (PET(CO(2))) in 18 subjects during wakefulness, stage 2, and slow-wave sleep (SWS). Responses of ventilation and muscle EMG to administered CO(2) (PET(CO(2)) = 6 Torr above the eupneic level) were also assessed during SWS (n = 9) or stage 2 sleep (n = 7). PET(CO(2)) increased spontaneously by 0.8 +/- 0.1 Torr from stage 2 to SWS (from 43.3 +/- 0.6 to 44.1 +/- 0.5 Torr, P < 0.05), with no significant change in GG or TP EMG. Despite a significant increase in minute ventilation with induced hypercapnia (from 8.3 +/- 0.1 to 11.9 +/- 0.3 l/min in stage 2 and 8.6 +/- 0.4 to 12.7 +/- 0.4 l/min in SWS, P < 0.05 for both), there was no significant change in the GG or TP EMG. These data indicate that supraphysiological levels of PET(CO(2)) (50.4 +/- 1.6 Torr in stage 2, and 50.4 +/- 0.9 Torr in SWS) are not a major independent stimulus to pharyngeal dilator muscle activation during either SWS or stage 2 sleep. Thus hypercapnia-induced pharyngeal dilator muscle activation alone is unlikely to explain the paucity of sleep-disordered breathing events during SWS.     

Plasma glucagon-immunoreactive components in early life in dogs

High plasma concentrations of C-terminal immunoreactive glucagon (IRG) have been found during early life in several mammalian species. We have analyzed the plasma IRG of 12 h to 60 day-old dogs in terms of the 4 peaks (IRG greater than 20,000, IRG9000, IRG3500 and IRG2000) obtained by gel filtration on Bio-Gel P-30. Significant changes with age and in response to administered agents were confined to IRG9000 and IRG3500. IRG9000 was 9-fold higher in 12-36 h old dogs than in adults (108 +/- 24 pg/ml pancreatic glucagon equivalents v. 12 +/- 3 pg/ml, mean +/- SEM) and showed a decline to 2-fold higher (27 +/- 5 pg/ml) at 31-60 days. IRG3500 was higher than in the adult only during the first 36 h of life (36 +/- 5 pg/ml v. 15 +/- 3 pg/ml). Arginine infusion (0.5 g/kg over 15 min) caused an increase in plasma levels of both IRG9000 and IRG3500 in the newborn, whereas in adult dogs only IRG3500 was increased. Insulin injection (0.2 U/kg intravenously) causing a marked hypoglycemia had no significant effect on the plasma level of any IRG component in newborn dogs. Dihydrosomatostatin infusion (10 micrograms/kg bolus +/- 90 micrograms/kg over 30 min) caused a decrease in both IRG9000 and IRG3500. The increased basal level and secretory response to arginine of IRG9000 in newborn dogs may reflect an immaturity of the A cells, whereby more of this component, which may represent a precursor of pancreatic glucagon, is secreted than in the adult. The immature A cells also appear to have an impaired secretory response to hypoglycemia.     

Differences in mechanisms of SR dysfunction in ischemic vs. idiopathic dilated cardiomyopathy

We examined 1) contractile properties and the intracellular Ca(2+) concentration ([Ca(2+)](i)) transient in cardiac myocytes and 2) sarcoplasmic reticulum (SR) Ca(2+) uptake and release function in myocardium from patients with end-stage heart failure caused by ischemic (ICM) vs. idiopathic dilated cardiomyopathy (DCM). The amplitude of cell motion was decreased 43 +/- 6% in ICM and 68 +/- 7% in DCM compared with that in normal organ donors (DN). Time to peak of shortening was increased 43 +/- 15% in DCM, but not in ICM. Prolongation of the relaxation time was more predominant in ICM. In DCM the systolic [Ca(2+)](i) was decreased 27 +/- 9% and diastolic [Ca(2+)](i) was increased 36 +/- 11%. In ICM the diastolic [Ca(2+)](i) was increased 59 +/- 12% but the systolic [Ca(2+)](i) was unchanged. A significant decrease of the ATP-dependent SR Ca(2+) uptake rate associated with the reduction of the SR Ca(2+)-ATPase protein level was found in ICM. In contrast, the significant decrease in SR Ca(2+) release rate was distinct in DCM. The large amount of Ca(2+) retained in the SR associated with a significant decrease in the maximum reaction velocity and increase in the Michaelis-Menten constant in the caffeine concentration-response curve suggests a fundamental abnormality in the SR Ca(2+) release channel gating property in DCM. We conclude that potentially important differences exist in the intracellular Ca(2+) homeostasis and excitation-contraction coupling in ICM vs. DCM. The SR Ca(2+) release dysfunction may play an important pathogenetic role in the abnormal Ca(2+) homeostasis in DCM, and the SR Ca(2+) uptake dysfunction may be responsible for the contractile dysfunction in ICM.     

Soluble LDL-immune complexes in type 2 diabetes and vascular disease.

BACKGROUND AND AIMS: The oxidative modification of LDL has been shown to affect its clearance and to exert cytotoxic and immunogenic effects. The objective of our study was to analyse markers of LDL oxidation-soluble LDL containing immune complexes (LDL-ICs) in type 2 diabetes with micro- and macrovascular disease. PATIENTS AND METHODS: The study included 69 diabetic patients with coronary artery disease (DM + CAD), 78 non-diabetics with CAD, 47 controls, and 27 diabetics with nephropathy and 36 free from complications. OxLDL antibodies and advanced glycated end-products were measured by ELISA, and LDL-IC apo B content after PEG precipitation. RESULTS: Determination of a broad range of oxLDL antibody activity in all study groups showed no significant differences. In contrast, the content of apo B, a component of the antigen moiety of oxLDL-ICs, was higher in CAD and diabetes (+ CAD) than in LDL-ICs isolated from controls (p < 0.001). LDL-ICs did not differ between patients with CAD + DM and CAD patients free from diabetes. LDL-IC levels in diabetic patients with or without microangiopathy were significantly higher than in healthy volunteers (PEG-apo B 0.278 +/- 0.107 vs. 0.165 +/- 105 g/l, p < 0.002; PEG-IgG 151.7 +/- 76 vs. 115.4 +/- 62 g/l, p < 0.05). However, there was no significant difference in the level of circulating LDL-ICs between the subgroup of diabetic patients with nephropathy/retinopathy and patients free of microvascular disease (Ab-oxLDL 27.7 +/- 10.4 vs. 27.1 +/- 9.3 AU, NS; PEG-apo B 0.324 +/- 0.111 vs. 0.287 +/- 0.124 g/l, NS; PEG-IgG 1.68 +/- 0.68 vs. 1.42 +/- 0.80 g/l, NS). There was a statistically significant positive correlation between AGE content and LDL-ICs (r = 0.35, p < 0.009). A significant but inverse correlation was recorded between triglyceride concentration and level of LDL-ICs in DM + CAD (r = - 0.32, p < 0.016) and CAD patients (r = - 0.35, p < 0.002). A highly significant negative correlation between triglycerides and circulating LDL-ICs (r = - 0.54, p < 0.039) was observed in patients with early nephropathy, but not in those with physiological proteinuria. It is known that at a high triglyceride level in type 2 diabetes, the majority of LDL are small and dense, thus being more susceptible to oxidative modification. This could be a possible mechanism explaining why more LDL-ICs, with a level inversely correlating with triglyceride concentration, are generated in diabetes. CONCLUSION: The increased level of circulating LDL-ICs is a risk factor for the general population, including those with diabetes. Our results suggested the contribution of LDL-ICs to the development of atherosclerosis to probably be more significant than the direct contribution of oxLDLAb itself.     

Cyclic GMP and cyclic AMP induced changes in control and hypertrophic cardiac myocyte function interact through cyclic GMP affected cyclic-AMP phosphodiesterases.

We tested the hypothesis that the negative functional effects of cyclic GMP (cGMP) would be greater after increasing cyclic AMP (cAMP), because of the action of cGMP-affected cAMP phosphodiesterases in cardiac myocytes and that this effect would be altered in left ventricular hypertrophy (LVH) produced by aortic valve plication. Myocyte shortening data were collected using a video edge detector, and O2 consumption was measured by O2 electrodes during stimulation (5 ms, 1 Hz, in 2 mM Ca2+) from control (n = 7) and LVH (n = 7) dog ventricular myocytes. cAMP and cGMP were determined by a competitive binding assay. cAMP was increased by forskolin and milrinone (10(-6) M). cGMP was increased with zaprinast and decreased by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxilin-1-one (ODQ) both at 10(-6) and 10(-4) M, with and without forskolin or forskolin + milrinone. Zaprinast significantly decreased percent shortening in control (9 +/- 1 to 7 +/- 1%) and LVH (10 +/- 1 to 7 +/- 1%) myocytes. It increased cGMP in control (36 +/- 5 to 52 +/- 7 fmol/10(5) myocytes) and from the significantly higher baseline value in LVH (71 +/- 12 to 104 +/- 18 fmol/10(5) myocytes). ODQ increased myocyte function and decreased cGMP levels in control and LVH myocytes. Forskolin + milrinone increased cAMP levels in control (6 +/- 1 to 15 +/- 2 pmol/10(5) myocytes) and LVH (8 +/- 1 to 18 +/- 2 pmol/10(5) myocytes) myocytes, as did forskolin alone. They also significantly increased percent shortening. There were significant negative functional effects of zaprinast after forskolin + milrinone in control (15 +/- 2 to 9 +/- 1%), which were greater than zaprinast alone, and LVH (12 +/- 1 to 9 +/- 1%). This was associated with an increase in cGMP and a reduction in the increased cAMP induced by forskolin or milrinone. ODQ did not further increase function after forskolin or milrinone in control myocytes, despite lowering cGMP. However, it prevented the forskolin and milrinone induced increase in cAMP. In hypertrophy, ODQ lowered cGMP and increased function after forskolin. ODQ did not affect cAMP after forskolin and milrinone in LVH. Thus, the level of cGMP was inversely correlated with myocyte function. When cAMP levels were elevated, cGMP was still inversely correlated with myocyte function. This was, in part, related to alterations in cAMP. The interaction between cGMP and cAMP was altered in LVH myocytes.     

Colonic fermentation from lactulose inhibits lipolysis in overweight subjects

One of the strategies to prevent insulin resistance is to reduce circulating free fatty acids (FFA). The aim of this study is to assess the effect of an oral lactulose load on fatty acid metabolism in overweight subjects. Eight overweight subjects received a primed constant intravenous infusion of [1-(13)C]acetate and of [1,1,2,3,3-(2)H(5)]glycerol for 9 h. After 3 h of tracer infusion, patients ingested 30 g lactulose, or saline solution. Arterialized blood samples were collected every 20 min. Basal plasma concentrations of acetate were similar before and between oral treatments as well as glycerol and FFA concentrations. Plasma acetate turnover was 11.4 +/- 2.4 vs. 10.7 +/- 1.4 micromol.kg(-1).min(-1) [not significant (NS)], and plasma glycerol turnover was 3.8 +/- 0.4 vs. 4.8 +/- 1.9 micromol.kg(-1).min(-1) (NS). After lactulose ingestion, acetate concentration increased twofold and then decreased to baseline. Acetate turnover rate increased to 15.5 +/- 2.2 micromol.kg(-1).min(-1) after lactulose treatment, whereas it was unchanged after saline treatment (10.3 +/- 2.2 micromol.kg(-1).min(-1), P < or = 0.0001). In contrast, FFA concentrations decreased significantly after lactulose ingestion and then increased slowly. Glycerol turnover decreased after lactulose ingestion compared with saline, 2.8 +/- 0.4 vs. 3.5 +/- 0.3 micromol.kg(-1).min(-1) (P < or = 0.05). A significant negative correlation was found between glycerol and acetate turnover after lactulose treatments (r = -0.78, P < or = 0.02). These results showed in overweight subjects a short-term decrease in FFA level and glycerol turnover after lactulose ingestion related to a decrease of lipolysis in close relationship with an increase of acetate production.     

Phosphoinositide signalling system in platelets of schizophrenic patients and the effect of neuroleptic therapy.

Alterations in the phosphoinositide signalling system have been proposed as a possible biological marker of schizophrenia. We studied the levels of inositol 1,4,5-trisphosphate (IP3), cytosolic Ca2+ concentrations ([Ca2+]i), and the incorporation of [32P]-orthophosphate into inositol phospholipids and phosphatidic acid (PA) in blood platelets of neuroleptic-treated schizophrenics in comparison with controls. The [Ca2+]i was significantly higher in platelets of one month neuroleptic-treated patients (155+/-5.8 nM) in comparison with controls (95+/-5.4 nM). Neuroleptic therapy decreased the [Ca2+]i, but even after long-term therapy it remained significantly higher (114+/-5.7 nM) than in controls. Differences were also found in the level of IP3 between controls (30+/-4.0 pmol/10(9) platelets), drug-free schizophrenics (52+/-9.0 pmol/10(9) platelets) and treated patients (50+/-6.0 pmol/10(9) platelets). The increased turnover of PA was observed in platelets of neuroleptic-treated schizophrenic patients. The study suggests that the regulation of calcium homeostasis and pathways involved in the phosphoinositide signalling system are altered in the platelets of schizophrenics. Neuroleptic therapy did not remove the observed changes in [Ca2+]i and IP3 levels.     

Effect of glycerol level in Tris-basek extender and equilibration period on quality of frozen goat semen

Twenty ejaculates, 4 from each of 5 native goats, were collected using an artificial vagina, and the effects of glycerol level (4, 6.4 and 9 %) and the equilibration period (1, 3 and 5 h) were studied by split-sample technique. The extender used was Tris egg yolk citric acid fructose glycerol extender. The semen was frozen in 0.5-ml French straws by exposure for 10 min to liquid nitrogen vapor, 5 cm above the liquid nitrogen level. After 14 h of storage in liquid nitrogen, the straws were thawed in water at 37 degrees C for 12 - 15 sec. The percentage of progressively motile sperm (PPM) and the percentage of damaged acrosomes (PDA) were studied after equilibration and after thawing. The mean PPM after thawing was found to be 64.0 +/- 0.90, 66.92 +/- 0.54 and 63.65 +/- 1.07 when semen was frozen with 4, 6.4 and 9 % glycerol and 61.48 +/- 0.81, 65.05 +/- 0.78 and 68.03 +/- 0.87 in 1-, 3- and 5-h equilibrated semen, respectively. The mean PDA after thawing was 7.12 +/- 0.88, 8.23 +/- 0.76 and 10.58 +/- 0.84 when semen was frozen with 4, 6.4 and 9 % glycerol and 7.0 +/- 0.74, 9.0 +/- 0.95 and 9.93 +/- 0.81 in 1-, 3- and 5-h equilibrated semen, respectively. Both PPM and PDA differed significantly (P<0.01) between glycerol levels, between equilibration periods and between stages (after equilibration and after thawing). The PPM also differed significantly due to equilibration period x stage interaction (P<0.01) and glycerol level x stage interaction (P<0.05). The PDA did not differ significantly due to interactions. When the differences between pairs of means were tested by least significant difference, it was found that after equilibration PPM was not significantly affected by either glycerol level or equilibration period, while after thawing, it was significantly higher (P<0.05) for 6.4 % glycerol and 5-h equilibrated semen than for 4 or 9 % glycerol and 1- or 3-h equilibrated semen, respectively. The PDA was lower with 4 % glycerol and 1-h equilibrated semen.     

Measurement of rat plasma adenosine levels during normoxia and hypoxia.

A stop solution containing EDTA, EGTA, dipyridamole, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and d,l-alpha-glycerophosphate has been used to prevent adenosine formation and loss from rat femoral arterial blood samples prepared for measurement of plasma adenosine levels. The femoral arterial plasma adenosine concentration in normoxic rats was 79.2 +/- 12.7 nM. During a 5 min period of hypoxia (8% oxygen) plasma adenosine increased to 190.2 +/- 32.2 nM. A resting plasma adenosine level of circa 80 nM, which is 10X lower than most previous estimates, approximates the threshold levels of adenosine required for arterial dilation.     

Effect of REM sleep on retroglossal cross-sectional area and compliance in normal subjects.

It has been proposed that the upper airway compliance should be highest during rapid eye movement (REM) sleep. Evidence suggests that the increased compliance is secondary to an increased retroglossal compliance. To test this hypothesis, we examined the effect of sleep stage on the relationship of retroglossal cross-sectional area (CSA; visualized with a fiber-optic scope) to pharyngeal pressure measured at the level of the oropharynx during eupneic breathing in subjects without significant sleep-disordered breathing. Breaths during REM sleep were divided into phasic (associated with eye movement, PREM) and tonic (not associated with eye movements, TREM). Retroglossal CSA decreased with non-REM (NREM) sleep and decreased further in PREM [wake 156.8 +/- 48.6 mm(2), NREM 104.6 +/- 65.0 mm(2) (P < 0.05 wake vs. NREM), TREM 83.1 +/- 46.4 mm(2) (P = not significant NREM vs. TREM), PREM 73.9 + 39.2 mm(2) (P < 0.05 TREM vs. PREM)]. Retroglossal compliance, defined as the slope of the regression CSA vs. pharyngeal pressure, was the same between all four conditions (wake -0.7 + 2.1 mm(2)/cmH(2)O, NREM 0.6 +/- 3.0 mm(2)/cmH(2)O, TREM -0.2 +/- 3.3 mm(2)/cmH(2)O, PREM -0.6 +/- 5.1 mm(2)/cmH(2)O, P = not significant). We conclude that the intrinsic properties of the airway wall determine retroglossal compliance independent of changes in the neuromuscular activity associated with changes in sleep state.     

Cyclosporine A dosing-time-dependent effects on plasma creatinine and body weight in male Wistar rats treated for 3 weeks.

Cyclosporine A (CsA) nephrotoxicity was assessed in 120 male Wistar rats (350 +/- 50 g) entrained to a 12-h cycle (light-dark 12:12); plasma creatinine level and body weight were examined in controls and in rats that had been treated daily with oral CsA or vehicle alone (olive oil-ethanol 90:10) for 21 days; daily dosing (40 mg/kg) was at one of six equally spaced given times during the 24-h cycle. The variations observed in both indexes were shown to be circadian dosing stage dependent. Nephrotoxicity was present as early as the third day of treatment with CsA; plasma creatinine level was enhanced by about 50% in rats dosed around the time of the change from darkness to light: at 22 HALO, 146.7 +/- 4.5 mumol/L, against 92.0 +/- 2.8 mumol/L for controls (p less than 0.05); and at 2 HALO, 148.3 +/- 10.0 mumol/L, against 95.0 +/- 4.3 mumol/L for controls (p less than 0.05). Thereafter, a remission episode was observed between days D5-D9. The more drastic effects were seen on days D16 and D21, in animals dosed in the beginning of the dark span (14 HALO): 185 +/- 10 mumol/L for CsA and 98.0 +/- 5.3 mumol/L for controls (p less than 0.01) and, to a lesser extent, in rats treated at the early resting phase (2 HALO): 152.4 +/- 31 mumol/L for CsA and 95.0 +/- 4 mumol/L for controls (p less than 0.05). The normal increase in body weight during the 21-day period (about 14 +/- 8% in controls) was impeded in CsA-administered rats, especially those dosed at the beginning of the activity span (14 HALO) that even suffered weight reduction. Differences in percentages of survivors were noticed, depending on dosing stage. About 40% of the animals in every time CsA-treatment group died, except for those dosed at the end of the resting period (10 HALO), when all animals died. In surviving rats, the cessation of CsA dosing resulted in a reversible effect on the study variables.     

Endothelial function during stimulation of renin-angiotensin system by low-sodium diet in humans

We examined whether physiological stimulation of the endogenous renin-angiotensin system results in impaired endothelium-dependent vasodilatation in forearm resistance vessels of healthy subjects and whether this impairment can be prevented by angiotensin II type 1 receptor blockade. A low-sodium diet was administered to 27 volunteers who were randomized to concomitant treatment with losartan (100 mg once daily) or matched placebo in a double-blind fashion. Forearm blood flow was assessed by venous occlusion plethysmography at baseline and after 5 days. Endothelium-dependent and -independent vasodilation was assessed by intra-arterial infusion of methacholine and verapamil, respectively. The low-sodium diet resulted in significantly decreased urine sodium excretion (placebo: 146 +/- 64 vs. 10 +/- 9 meq/24 h, P < 0.001; losartan: 141 +/- 56 vs. 14 +/- 14 meq/24 h, P < 0.001) and increased plasma renin activity (placebo: 1.0 +/- 0.5 vs. 5.0 +/- 2.5 ng x ml(-1) x h(-1), P < 0.001; losartan: 3.8 +/- 7.2 vs. 19.1 +/- 11.2 ng x ml(-1) x h(-1), P = 0.006) in both the losartan and placebo groups. With the baseline study as the reference, the diet intervention was not associated with any significant change in endothelium-dependent vasodilation to methacholine in either the placebo (P = 0.74) or losartan (P = 0.40) group. We conclude that short-term physiological stimulation of the renin-angiotensin system does not cause clinically significant endothelial dysfunction. Losartan did not influence endothelium-dependent vasodilation in humans with a stimulated renin-angiotensin system.     

Cytokine detection in HIV-1/HHV-8 co-infected subjects

In a previous work we have evaluated some immunologic and haematologic parameters of HIV-1 positive subjects co-infected with HHV-8. A worsening of these values were generally described in these patients as compared with those HIV-1 positive, but negative for HHV-8. Now we have studied the influence of HHV-8 co-infection of HIV-1 positive subjects on the production of some cytokines to make clear the question of its role in the immuno-deregulation of the above-mentioned subjects. In particular we have analysed serum levels of IL-4 and IL-10, Th2 type T cells cytokines, IFN-gamma, an indirect marker of Th1 cells activation and IL-18, a cytokine produced by monocytic-macrophagic cells, which is able to induce IFN-gamma production and Th1 T lymphocytes activation. No significant differences were found as regards the IFN-gamma serum levels (92.1 +/- 24.3 pg ml(-1) in the case of HIV-1 positive/HHV-8 negative subjects and 96.0 +/- 17.4 pg ml(-1) in those HIV-1 positive/HHV-8 positive). In healthy subjects the mean level of this cytokine was 17.6 +/- 5.2 pg ml(-1) (significant difference with both the former values at p < 0.001). Moreover IL-4 and IL-10, which were undetectable in healthy individuals, showed the following values in HIV-1 positive/HHV-8 negative subjects: 31.9 +/- 2.7 pg ml(-1) and 119.8 +/- 85.1 pg ml(-1) respectively and in HIV-1 positive/HHV-8 positive subjects: 30.4 +/- 4.8 pg ml(-1) and 69.4 +/- 65.3 pg ml(-1) (not significant differences). In contrast IL-18 reached a mean level of 1001.2 +/- 360.5 pg ml(-1) in HIV-1 positive/HHV-8 negative subjects, but showed a significant reduction in HIV-1 positive/HHV-8 positive subjects (737.6 +/- 284.3 pg ml(-1) --> p < 0.05) and presented very low levels in healthy individuals (21.3 +/- 30.3 pg ml(-1)). Moreover a significant correlation (-0.984 --> p < 0.001) was noticed between IL-18 reduction in HIV-1 positive subjects co-infected with HHV-8 and the degree of positivity of HHV-8. These data suggest that HHV-8 co-infection has no influence on the switch Th1 --> Th2 in HIV-1 positive subjects, but is able to reduce IL-18 production, useful for Th1 subset restoration.