Effect of hepatic vagotomy on plasma insulin levels during fasting in rats

The present investigation was designed to evaluate the effect of a selective hepatic vagotomy (HV) on the insulin response in rats fasted for 24 h when blood glucose levels were or were not maintained by a constant glucose infusion. Rats were divided into three dietary groups: one group of normally fed rats, one group of 24-h fasted rats, and one group of 24-h fasted rats infused with glucose throughout the fasting period. Each of these groups was subdivided into HV and sham-operated (SHM) rats. Fasting without glucose infusion resulted in a significant (p < 0.05) decrease in plasma glucose, liver glycogen, and insulin concentrations and in a significant (p < 0.01) increase in beta-hydroxybutyrate and FFA concentration. Despite the maintenance of plasma glucose concentrations in the glucose-infused groups, the concentrations of liver glycogen and insulin were still decreased (p < 0.01) and the concentrations of beta-hydroxybutyrate were still increased (p<0.05) at the end of the fasting period. However, no significant differences in insulin or in beta-hydroxybutyrate concentration were found between HV and SHM rats. It is concluded that the decline in plasma glucose concentration during fasting does not totally explain the insulinopenic response to fasting, and that the liver, through the mediation of the hepatic vagus nerve, does not seem to contribute to insulinopenia in 24-h fasted rats.     

Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels

The factors responsible for the variability in plasma leptin levels observed among individuals with similar body compositions remain unclear. To examine the impact of dietary variables, we compared the changes in leptin levels induced by fasting and dietary fat restriction with the expected decrease following a significant loss in adipose mass. A 21.4 +/- 3.7% weight loss led to a 76.3 +/- 8.1% decrease in mean plasma leptin level (25.2 +/- 9.3 to 6.1 +/- 3.4 ng/mL, P = 0.0001) in a group of 9 obese males. Despite a weight loss of only 2.6 +/- 0.8%, mean plasma leptin levels fell by 61.9 +/- 25.2% (8.5 +/- 4.5 to 2.4 +/- 0.5 ng/mL, P < 0.01) in 7 nonobese females subjected to 3 days of fasting. Leptin levels in fasted subjects returned to baseline within 12 h of refeeding. Individual high- and low-fat meals given to 19 subjects after an overnight fast had no effect on plasma leptin levels. Reduction in dietary fat content from 37-10% of total calories for 7 weeks was also without effect on plasma leptin levels in these subjects. We conclude that plasma leptin levels primarily reflect total adipose mass, rather than meal consumption or dietary energy source, but that the reduction in leptin levels with ongoing fasting is disproportionate to the reduction in adipose mass. The ability of fasting to deactivate this presumed physiological satiety system may have been advantageous in environments characterized by rapid changes in food availability.     

Elevated plasma endothelin levels in systemic sclerosis

We have developed a technique for off-line analysis of transient otoacoustic emissions. The correlation of two curves was calculated in a moving time-window of 1 ms time sections. By this method it is possible to recognize high-correlation parts, time sections with low correlation, and thus the duration of the emission can be determined. The mean absolute duration of transiently evoked otoacoustic emissions in 36 normal ears was 15.1 +/- 0.69 ms (mean +/- SE). The duration was significantly shorter (9.34 +/- 0.43) in 75 ears with different grades of sensorineural hearing loss. The breakdown of this group into sub-groups according to the width of the high frequency band with elevated threshold showed a correlation between the severity of the hearing loss and the absolute duration.     

The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats

Chronic caloric restriction has been shown to inhibit mammary tumor promotion in the 7,12-dimethyl-benz[a]anthracene (DMBA) rat mammary tumor model. The objectives of this study were to determine (i) the effects of chronic caloric cycling (yo-yo dieting) on mammary tumor promotion by high fat diets and (ii) the effect of three dietary regimens +/- superimposed mammary tumor burden on plasma endothelin-1,2 (ET) levels. Female Sprague-Dawley rats were treated with DMBA (5 mg/rat) and divided into three dietary groups: ad libitum (AL) (containing 15% corn oil); 40% calorie restricted (CR) (containing 20% corn oil so consumption of fat was equivalent between AL and CR); a calorie cycled (CC) group fed alternatively AL and CR diets each 48 h period. After 10 weeks, tumor incidences were: AL, 63%; CR, 27%; CC, 57% (AL versus CR, P < 0.05; CC versus CR, P < 0.05; AL versus CC, NSD). ET levels (pg/ml plasma) were: AL, 16.0 +/- 6.54; CR, 32.31 +/- 0.34; CC, 23.44 +/- 5.04 (AL versus CR, P < 0.01; CC versus CR, P < 0.01; AL versus CC, P < 0.05). Plasma ET levels were independent of tumor incidence and tumor burden, but plasma ET levels were significantly increased in rats with a prior history of calorie restriction. As expected, maintained caloric restriction reduced mammary tumor incidence but intermittent caloric restriction (caloric cycling or yo-yo dieting) was without similar benefit.     

Effects of food restriction on the periodicity of corticosteroids in plasma and on monoamine concentrations in discrete brain nuclei

The concentrations of plasma corticosteroids and of norepinephrine, dopamine and serotonin in microdissected brain regions were measured at 08.00, 12.00 and 20.00 h in male rats fed ad libitum and in rats whose food intake was restricted to 09.30-11.30 h. In ad libitum fed animals, plasma corticosteroids were lowest at 08.00 and highest at 20.00 h. As demonstrated previously, restriction of food availability was associated with appearance of a peak in corticosteroids at 08.00 h. In ad libitum fed animals, serotonin and dopamine concentrations in the median eminence were higher at 20.00 than at 08.00 h. Restriction of food availability significantly decreased the levels of these neurotransmitters at 20.00 h. In the paraventricular nucleus, amygdala, and hippocampus of ad libitum fed animals, serotonin levels were lower at 20.00 than at 08.00 or 12.00 h. In food-shifted animals, this pattern was reversed so that lowest levels of serotonin occured at 08.00 and markedly elevated levels were observed at 12.00 and 20.00 h. No changes were noted in norepinephrine content of the median eminence or paraventricular nucleus of ad libitum fed or food restricted animals. These results indicate that the shift in the periodicity of corticosteroid secretion produced by a restricted feeding regime is accompanied by changes in the periodicity of neurotransmitter concentrations in specific regions of the brain, and that such patterns are dissimilar in different regions.     

Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients. A prospective study

The pharmacokinetics of itraconazole formulated in a hydroxypropyl-beta-cyclodextrin oral solution was determined for two groups of human immunodeficiency virus (HIV)-infected adults with oral candidiasis (group A, 12 patients with CD4+ T-cell count of >200/mm3 and no AIDS, and group B, 11 patients with CD4+ T-cell count of <100/mm3 and AIDS). Patients received 100 mg of itraconazole every 12 h for 14 days. Concentrations of itraconazole and hydroxyitraconazole, the main active metabolite, were measured in plasma and saliva by high-performance liquid chromatography. Pharmacokinetic parameters determined at days 1 and 14 (the area under the concentration-time curve from 0 to 10 h, the maximum concentration of drug in plasma [Cmax], and the time to Cmax) were comparable in both groups. Trough levels in plasma (Cmin) were similar in both groups for the complete duration of the study. An effective concentration of itraconazole in plasma (>250 ng/ml) was reached at day 4. At day 14, Cmin values of itraconazole were 643 +/- 304 and 592 +/- 401 ng/ml for groups A and B, respectively, and Cmin values of hydroxyitraconazole were 1,411 +/- 594 and 1,389 +/- 804 ng/ml for groups A and B, respectively. In saliva, only unchanged itraconazole was detected, and mean concentrations were still high (>250 ng/ml) 4 h after the intake, which may contribute to the fast clinical response. In conclusion, the oral solution of itraconazole generates effective levels in plasma and saliva in HIV-infected patients; its relative bioavailability is not modified by the stage of HIV infection.     

Clinical significance of plasma endothelin levels in patients with biliary atresia

Biliary atresia (BA) is the end-result of a destructive inflammatory process that affects intra- and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tracts with the development of biliary cirrhosis and portal hypertension (PH). Endothelins (ET) are 21-amino-acid peptides of endothelial origin with potent vasoconstrictor activity that bind to various cells of the liver. Nothing is presently known about plasma ET levels in BA. The aim of this study was to determine the clinical significance of plasma ET levels in patients with BA after hepatic portoenterostomy (Kasai's procedure) and to correlate these with liver function tests (LFT) and PH. We measured plasma concentrations of ET in 19 patients with BA (5 boys and 14 girls; mean age 11.6 +/- 5.5 years) after portoenterostomy and 10 age-matched controls. Patients were grouped according to outcome based on LFT: group A consisted of 9 patients with an "unfavorable outcome" and Group B 10 patients with a "favorable outcome". The plasma ET levels were measured using a highly sensitive and specific enzyme immunometeric assay (EIA). No patient had ascites or hepatorenal syndrome. Plasma ET levels were significantly higher in patients with BA than in controls (3.42 +/- 0.42 vs 1.75 +/- 0.39 pg/ml, respectively; P < 0.01) and in patients in group A than in group B. (3.75 +/- 0.25 vs 3.06 +/- 0.23 pg/ml, respectively; P < 0.01). In group A, plasma ET levels were higher in patients with PH (n = 4) than in those without PH (n = 5) (3.99 +/- 0.06 vs 3.64 +/- 0.22 pg/ml, respectively; P < 0.05). We conclude that plasma ET levels are high in patients with BA, especially those with severe biliary cirrhosis, and that ET may partially contribute to development of PH in BA. The results of the present study also suggest that plasma ET concentrations may be a useful marker in the follow-up of patients with BA.     

Brain and plasma levels of cocaine and benzoylecgonine in lead-expose and cadmium-exposed rats following acute or chronic intraperitoneal administration of cocaine

We have cloned a full length cDNA coding for the activin type IIB receptor (GactRIIB) from the goldfish ovary. GactRIIB shares 73 and 70% amino acid identity in the extracellular domain, and 78 and 80% identity in the intracellular domain with the type IIB receptors of the mouse and Xenopus respectively. The intracellular domain of GactRIIB contains two serine kinase consensus sequences, DFKSRN and GTRRYMAPE, in agreement with the reports in other vertebrates that serine/threonine phosphorylation is involved in activin signal transduction. The identity of GactRIIB was confirmed by transient expression in the COS cells followed by activin binding. Iodinated human activin A bound to the GactRIIB-transfected cells and the binding could be completely inhibited by unlabeled activin. Affinity labeling revealed a band of about 85 kDa, which is in agreement with the reported type II receptors in other vertebrates. Together with the fact that activin is expressed in the goldfish ovary, the cloning of activin receptors from the ovary suggests paracrine and autocrine roles for activin in the goldfish ovarian functions.     

Effect of clenbuterol on growth and body composition during food restriction in rats

Clenbuterol was administered as a dietary admixture (4 mg/kg diet) to three groups of male Wistar rats (n = 8) housed individually in metabolism cages and fed for 15 d at 110, 160, and 235% (ad libitum) of estimated requirement for energy maintenance. Untreated groups at each level of energy intake were also included. There was no effect of clenbuterol on food intake in the ad libitum group, but the drug produced significant increases in body weight, feed efficiency, and carcass weight, dressing and protein content at all three levels of energy intake. This effect of clenbuterol was particularly noticeable in the restricted animals. Clenbuterol caused changes in body composition (increased percentage of water and protein, decreased percentage of fat) in the ad libitum rats but had no effect in the restricted groups. The reduction in the growth of the viscera caused by energy restriction was not affected by clenbuterol, apart from in the 110% restricted group, where the gastrointestinal tract was 26% heavier in the clenbuterol-treated rats. The results show that the growth anabolic actions of clenbuterol can be sustained and may be even more marked in rats fed restrictively than in those given ad libitum access to feed.     

Gender-specific changes in thyroid hormone-glucuronidating enzymes in rat liver during short-term fasting and long-term food restriction

Glucuronidation is a major pathway of thyroid hormone metabolism in rats, involving at least three different hepatic UDP-glucuronyltransferases (UGTs): bilirubin UGT, phenol UGT and androsterone UGT. We have studied the effects of short-term (3 days) fasting and long-term (3 weeks) food restriction to one-third of normal intake (FR33) on hepatic UGT activities for thyroxine (T4), triiodothyronine (T3), bilirubin and androsterone in male and female Wistar rats with either a functional (high activity, HA) or a defective (low activity, LA) androsterone UGT gene. Because food deprivation is known to induce centrally mediated hypothyroidism in rats, results were compared with those obtained in methimazole (MMI)-induced hypothyroid rats. Both fasting and FR33 produced largely parallel increases in T4 and bilirubin UGT activities. These effects were greater in males than in females, and were reproduced in MMI-treated rats. In male and female HA rats, fasting induced insignificant increases in T3 UGT activity and had no effect on androsterone UGT activity. In male HA rats, FR33 was associated with an increase in T3 UGT activity, while androsterone UGT activity showed little change. However, in female HA rats both T3 and androsterone UGT activities were markedly decreased by FR33. Triiodothyronine UGT activity in LA rats was strongly decreased compared with HA rats, but was not further decreased by FR33 in female LA rats, supporting the importance of androsterone UGT for T3 glucuronidation. These results demonstrate different sex-dependent effects of food deprivation on hepatic T4 and T3 glucuronidation that are associated with changes in the expression of bilirubin UGT and androsterone UGT, respectively. For the increased T4 and bilirubin UGT activities at least, these effects appear to be mediated by the hypothyroid state of the (semi)starved animals.     

Effects of intermittent food restriction and refeeding on energy efficiency and body fat deposition in sedentary and exercised rats

The effects of body weight cycling on energy metabolism and body fat accumulation were examined in sedentary and exercised rats. Ten rats were sacrificed before the experiment to obtain basal data, and then 90 rats were divided into three groups; control (CN), food restricted (FR) and weight cycling (WC). Food intake in rats of the FR group was restricted constantly to 70% of the intake of the CN group. The rats of WC group were subjected to four bouts of weight cycling consisting of 7-days food restriction followed by 7-days refeeding, but were fed the same total amount of dietary energy as that of the FR group throughout the experimental period. The rats of all groups were meal-fed twice a day. Half of the rats in each group were exercised by running on a treadmill (30 min/day) throughout the experimental period. The body weight, abdominal adipose tissue weight, body fat, body protein and energy restoration for the study in both sedentary and exercised groups were greater in the WC group than in the FR group. The resting metabolic rate of the WC group after four bouts of weight cycling was lower than that of the FR group in the sedentary rats, but this difference was not observed in the exercised rats. Also, the thermic effect of food (TEF) in the sedentary rats for 6 h after a meal was significantly less in the WC group as compared to that of the FR group. However, the TEF for the exercised rats was not different between the two groups. The serum insulin level, activities of lipogenic enzymes and lipoprotein lipase in adipose tissue for the sedentary rats of the WC group were higher than those of the FR group, but did not differ in the exercised rats. These results suggest that weight cycling increases body fat deposition and energy efficiency by decreasing energy expenditure, particularly the TEF, and that exercise training can alleviate the effects of weight cycling on the energy metabolism.     

Effects of food on plasma catecholamine and gastrin levels in patients with duodenal ulcer and normal volunteers

The expression of sugar residues on human epidermal cells was investigated by means of lectin binding, as a way of determining membrane structural changes occurring during the differentiation of the epidermis. Fourteen lectins of different sugar specificity were conjugated with fluorescein isothiocyanate (FITC-lectins) and tested in fluorescence microscopy on frozen sections of normal human epidermis. In parallel, FITC-lectins were tested on psoriatic-involved epidermis to visualize differences in the expression of sugar residues that might occur during abnormal epidermal differentiation. No labelling could be obtained with lectins from Bandeira simplicifolia I, Dolichos biflorus, Limulus poyphemus, Tetragonolobus purpureas, Ulex europeus I, and Triticum vulgaris (group 1 lectins). A "pemphigus-like" intercellular labelling of the whole epidermis, except the stratum corneum, was obtained with lectins from Canavalia ensiformis. Maclura pomifera, Phaseolus vulgaris, and Ricinus communis I (group 2 lectins). A selective intercellular labelling of the stratum spinosum and the stratum granulosum was seen in normal epidermis with lectins from Arachis hypogaea, Glycine max, Helix pomatia, and Sophora japonica (group 3 lectins). In psoriatic epidermis, not only the basal cell layer, but also cells from the adjacent lower stratum spinosum were found to be negative, using FITC-lectins of group 3. These data indicate that the expression of lectin binding sites in normal epidermis differs according to the maturation of the cell from the basal cell to the more mature keratinocyte in the stratum granulosum. They suggest that lectins may be used as markers of epidermal cells in various stages of normal and abnormal differentiation.     

Effects of chronic systemic administration of 5-HT on food intake and body weight in rats

The effects of chronic peripheral administration of 5-HT on food intake and body weight was investigated. In normal male Wistar rats, normal female Wistars, obese Zucker males, ovariectomised Wistar females, or normal Wistar males free fed a cafeteria diet, suppression of the creeping weight gain typical of control animals is observed. In females, this effect is not dependent on the local hormonal environment, because intact and ovariectomised females showed similar responses to treatment. One sex difference is that the weight suppressive effect in males is accompanied by an anorectic effect, whereas this anorectic effect is absent in females. Thus, although reduced food intake may partially explain the suppression of weight gain in males, in females it must be due to other, perhaps metabolic, effects. It is possible that these metabolic effects may also occur in males, suggesting one possible explanation of why the effect was typically larger in males than females.     

Dietary self-selection of golden hamsters in response to acute food deprivation and chronic food restriction.

Adult male golden hamsters were maintained on either Purina Rat Chow (Chow diet) or a self-selection diet consisting of high-protein chow, pure fat, and pure carbohydrate (Choice diet). In Experiment 1, animals were deprived of food for single periods of up to 48 hr. Animals on the Chow diet did not increase intake at any time after deprivation; animals on the Choice diet selectively increased their consumption of fat-derived calories and increased their total caloric intake during the first 6 hr of refeeding, but not thereafter. The nature of the diet did not influence the rate at which animals regained weight following deprivation. In Experiment 2, hamsters were placed on food-restriction schedules (access to food either for 1 hr/day only or on alternate days only) until they lost 20% of starting body weight. Chow-fed animals demonstrated little or no change in food intake either during or after food restriction. Hamsters on the Choice diet consumed more calories and lost weight more slowly than did chow-fed animals during 1-hr/day feeding; intake of fat-derived calories was elevated during restriction. Choice hamsters increased total caloric intake only towards the end of the alternate-days restriction schedule. Choice hamsters were hyperphagic following both types of food-restriction schedules, but no increased preference for fat-derived calories was observed. Factors influencing food consumption of hamsters in response to deprivation and restriction are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Energy balance of rats subjected to continuous and intermittent food restriction

A 64-year-old woman complained of multiple blisters in 1990. She had had a productive cough since 1975. Immunofluorescence study of a specimen obtained from a skin biopsy showed staining in a linear pattern for both IgG and C3 in the epithelial basement membrane zone (BMZ) of the dermal-epidermal junction, and a high titer of anti-BMZ antibody. These findings led to the diagnosis of bullous pemphigoid. Corticosteroid therapy was started, and resulted in some stabilization of the skin lesion. Exertional dyspnea and a productive cough developed gradually, and the patient was referred to our department in 1992. Chest X-ray film and CT findings revealed a diffuse granular shadow and bronchiectatic change, predominantly in the lower lung fields. Laboratory tests showed a high titer of cold hemagglutinin and a high level of serum immunoglobulin A. Pulmonary function tests showed a combined destructive-restrictive defect and hypoxemia (PaO2 = 58.5 Torr). From these findings diffuse panbronchiolitis was diagnosed. A low dose of erythromycin alleviated the patient's pulmonary symptoms and improved the chest radiographic findings.     

Renal and vascular effects of chronic endothelin receptor antagonism in malignant hypertensive rats

The effect of the combined ETA/ETB endothelin receptor antagonist bosentan on blood pressure, vascular hypertrophy, and pathologic renal changes was investigated in a model of malignant hypertension, severe vascular hypertrophy, and enhanced vascular expression of endothelin-1, the deoxycorticosterone acetate (DOCA), and salt-treated spontaneously hypertensive rat (SHR). DOCA-salt treated SHR received 100 mg bosentan per kilogram weight per day mixed with their food. Systolic blood pressure of untreated DOCA-salt SHR rose to 241 +/- 1.5 mm Hg, whereas that of bosentan-treated rats rose to 221 +/- 5.1 mm Hg (P < .01). Cardiac and conduit artery mass were not affected by treatment. Small arteries from the coronary, renal, and mesenteric circulations showed a smaller media width and cross-sectional area of the media in rats treated with bosentan than in untreated rats. The kidneys showed the presence of fibrinoid necrosis in a high percentage of afferent arterioles and glomeruli of untreated DOCA-SHR. Some kidneys of treated rats exhibited less severe vascular hypertrophy and lesser extent of vascular or glomerular fibrinoid necrosis, but the renal injury score of bosentan-treated DOCA-SHR was only at the limit of significance from that of untreated rats (P = .06). These results suggest a role for endothelin-1 in blood pressure elevation and the severe vascular hypertrophy of small arteries of the coronary, renal, and mesenteric vasculature, but not of the heart or larger conduit vessels in the malignant hypertension that SHR develop after treatment with DOCA and salt. Although some bosentan-treated rats showed fewer renal lesions, a significant effect on renal pathology could not be unambiguously demonstrated. Further studies will be necessary to determine whether endothelin antagonists may indeed offer some degree of renal protection and have therapeutic potential in severe or malignant hypertension.