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Effect of nebivolol on cardiovascular changes associated with a rat model of insulin-resistance.

Nebivolol is a vasodilator that combines beta-adrenergic blocking activity with a relaxant effect on vascular smooth muscle cells (VSMC) mediated by the endothelial nitric oxide (NO) pathway. FFR provide a model of dietary-induced insulin-resistance syndrome, which has been used to study the pathophysiological mechanisms associated with this syndrome. Our main objective was to examine the effect of long-term administration of nebivolol on metabolic and cardiovascular variables in fructose-fed rats (FFR), a model in which an altered bioavailability of NO has been already described. Male Wistar rats were randomly assigned to 4 groups (n = 8 each): I. Control (C); II. Control + nebivolol (C+N): 1 mg/kg(-1) x day(-1) in drinking water during the last 4 weeks. III. FFR: rats receiving fructose in drinking water as a 10% (w/v) solution during 8 weeks, and IV. FFR+N: idem II plus III. During the 8 weeks experimental period, variations in systolic blood pressure (SBP), glucose tolerance test (GTT) and plasma thiobarbituric acid-reactive substances (TBARS) were assessed. At the end of this experimental period, rats were killed and heart and kidneys were excised for calculation of relative heart weight (RHW) and histological evaluation of lumen to media ratio (L/M) in renal arteries. Rats from FFR group increased their SBP and RHW, showed glucose intolerance and an increment in lipid peroxidation. Moreover, FFR showed vascular remodeling in renal arteries evidenced by changes in L/M. Although the metabolic changes were not reverted by the administration of nebivolol, this drug successfully decreased SBP, TBARS levels and reverted structural changes such as cardiac hypertrophy and renal arterial remodeling. Data demonstrate that nebivolol administration could participate in the reversion of cardiovascular structural changes associated with the insulin-resistance syndrome.

Adrenergic beta-Antagonists↗

Malabsorption of carbohydrates and depression in children and adolescents.

BACKGROUND: Previous studies have shown an association between sugar malabsorption and depressive symptoms in adult women. Incompletely absorbed sugars may form nonabsorbable complexes with tryptophan, an amino acid precursor of serotonin, decreasing its availability. As serotonin is the most important neurotransmitter involved in depressive disorders, its depletion could lead to the onset of depression. METHODS: The authors' aim was to study the possible association between malabsorption of sugars (lactose and fructose) and depressive symptoms in adolescent patients of Spanish origin. The authors studied two groups of patients. Group G included 14 patients previously diagnosed with sugar intolerance. In these, the authors assessed depressive symptoms. Group P consisted of seven patients suffering from major depression. In these, the authors performed functional sugar absorption tests. The authors studied the metabolic pathway of tryptophan in both groups. RESULTS: In the group with sugar malabsorption, there was a 28.5% prevalence of depressive symptoms that was higher than expected in our population. In the group with depression, the authors found a higher than expected prevalence of sugar intolerance (71.42% versus 15% in controls). CONCLUSIONS: The unexpected prevalences obtained for the groups studied suggest that there may be an association between sugar intolerance and depressive symptoms during adolescence.

Adolescent↗

Galactose consumption induces conditioned flavor avoidance in rats.

Recent findings revealed that intragastric infusions of galactose conditioned a flavor avoidance in adult rats. To determine whether the galactose-conditioned avoidance was due to the infusion procedure, we investigated the flavor conditioning effect of orally consumed galactose. Food-restricted rats drank a flavored galactose solution, a flavored fructose solution and a flavored saccharin solution in separate one-bottle training sessions; grape, cherry and orange flavors were used. Because fructose is sweeter than galactose, saccharin was added to the galactose solution to increase its palatability. Pre- and posttraining preferences for the galactose and fructose solutions were evaluated in two-bottle choice tests. Also, preferences for the sugar-paired flavors were evaluated in two-bottle tests with the flavors presented in saccharin. In Experiment 1, rats were trained with flavored 80 g/L fructose, 80 g/L galactose + 2 g/L saccharin, and 2 g/L saccharin solutions (20 mL/d). Their preference for the flavored galactose solution changed (P < 0.01) from 76% (pretraining) to 19% (posttraining). The rats also avoided (P < 0.05) the flavor paired with the galactose solution in choice tests with the fructose-paired flavor and the saccharin-paired flavor. Similar pre- to posttraining preference reversals were obtained in Experiments 2 and 3, which used 20 g/L galactose and fructose solutions, and 20 g/L galactose and fructose solutions mixed with 20 g/L glucose, respectively. These findings, together with the intragastric infusion data, demonstrate that galactose has aversive postingestive consequences in adult rats even at low concentrations (20 g/L). Unlike lactose intolerance, which is due to intestinal malabsorption, this galactose-induced flavor avoidance is presumably due to the slow and incomplete postabsorptive metabolism of galactose.

Animals↗

[Comparative studies during postoperative infusion of glucose or a combination of glucose, fructose and xylitol over five days (author's transl)].

Two groups of 12 cholecystectomized or vagotomized patients were given central venous infusions of either a combination of glucose, fructose and xylitol at the ratio of 1:2:1 or of glucose alone for 5 days. The dose was increased stepwise from 1.43 g/kg/h on operation day up to 7.14 g/kg/24 h on the fourth day after surgery, which equals 100-500 g/24 h for the average 70 kg patient. On both infusion regimens mean blood glucose values ranged from 98-124 mg/100 ml. Urinary losses of infused substrates amounted to 0.2-0.8 g/24 during glucose infusion and to 2.22-13.4 g/24 h during infusions of the carbohydrate combination. Regarding mean blood or serum values of lactate, pyruvate, uric acid, sodium, potassium, phosphorus, insulin and free fatty acids, no significant differences were found between the two types of carbohydrate infusion. Side effects were not observed. The results obtained allow conclusion that in clinical situations with moderate stress, such as the selective operations mentioned above, the combination of glucose, fructose and xylitol studied offers no advantage over glucose alone. However, in severely ill patients presenting with more pronounced glucose intolerance, further studies with sugar substitutes are warranted.

Cholecystectomy↗

Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome 9q22.3 and evaluation in non-insulin-dependent diabetes mellitus.

PCR primers specific to the human liver fructose-1,6-bisphosphatase (FBP) gene were designed and used to isolate a cosmid clone. Physical mapping of the FBP cosmid by FISH, and genetic mapping of an associated GA repeat polymorphism (PIC = 0.35), located the liver FBP gene to chromosome 9q22.3 with no recombination between FBP and the index markers D9S196 (Zmax = 13.2), D9S280 (Zmax = 11.7), D9S287 (Zmax = 15.6), and D9S176 (Zmax = 14.4). Amplification using FBP exon-specific primers with a YAC contig from this region of chromosome 9 further refined the placement of FBP genomic sequences to an approximately 1.7-cM region flanked by D9S280 and D9S287, near the gene for Fanconi anemia group C. Precise localization of the FBP gene enabled evaluation of FBP as a candidate gene for maturity-onset diabetes of the young (MODY) and non-insulin-dependent diabetes (NIDDM) in both Caucasian and African-American families, using the highly informative markers D9S287 and D9S176. Although FBP is a rate-limiting enzyme in gluconeogenesis, using both parametric and nonparametric analysis there was no evidence for linkage of FBP to diabetes in these families.

Animals↗

Fructose and sorbitol malabsorption in ambulatory patients with functional dyspepsia: comparison with lactose maldigestion/malabsorption.

The aim of this study was to study sugar maldigestion/malabsorption in patients with functional dyspepsia using H2 breath testing. End-expiratory breath H2 after separate challenges with lactose (25 g), fructose (25 g), and sorbitol (5 g) were used to determine malabsorption, as well as small bowel transit time (SBTT). Five hundred twenty patients with functional dyspepsia received all three challenges. Smaller groups were also tested after lactulose (10 g, N = 36) and glucose (50 g, N = 90) challenges. Fructose and sorbitol were closely linked with respect to absorption and malabsorption status. Only in the case of lactose maldigestion/malabsorption was there a greater than random prevalence of malabsorption (P < 0.001) for fructose and sorbitol. In contrast to lactose, ethnic origin did not influence fructose or sorbitol malabsorption, and females predominated among fructose and sorbitol malabsorbers. In Jews, the prevalence of lactose maldigestion/malabsorption decreased in the age group of 25-55 and subsequently rose after 55, while fructose and sorbitol malabsorption decreased progressively with advancing age. With respect to small bowel transit time (SBTT), in the case of sorbitol and lactulose, it was significantly greater (P < 0.05) than those for fructose and lactose. Multiple sugar malabsorptions are common when lactose maldigestion/malabsorption is present.

Breath Tests↗

[Carbohydrates--no glucose--in parenteral nutrition. A fading concept?].

An update is made on the binominal use/benefit of non-glucose carbohydrates (polyalcohols or polyols) in parenteral nutrition. The most recently published results, despite the controversy from different areas, have motivated the updating of the criteria metabolic aspects, indications and contraindications of the different carbohydrates alternatives of glucose (xylitol, sorbitol, glycerol, fructose), in the parenteral nutrition of patients with different degrees of aggression and situations of glucose intolerance or insulin resistance. It is known that, due to causes which are not entirely understood, non-glucose carbohydrates have not yet been considered as effective energy sources alternative to glucose in clinical situations described as unfavorable for their use. However, we may consider that in view of our own experience and that of previous publications, these carbohydrates have not only not decreased their use expectancy but, on the contrary, have increased as their advantages were clinically confirmed, without the appearance of major complications in this therapeutic modality. For this reason we consider that the understanding of the characteristics and the different metabolic aspects (pharmacological dose) of the polyols must make us review their clinical use, both alone as in different combinations.

Fructose↗

Effect of skim milk and dahi (yogurt) on blood glucose, insulin, and lipid profile in rats fed with high fructose diet.

In the present study, the effect of skim milk and the fermented milk product named dahi (yogurt) on plasma glucose, insulin, and lipid levels as well as on liver glycogen and lipid contents in rats fed with high fructose diet has been investigated. Rats were fed with high fructose diet (21%) supplemented with skim milk, dahi (10 g/day each), or no milk product (control group) for 6 weeks. After 6 weeks of high fructose diet administration, the plasma glucose became significantly higher in control animals (246 mg/dL), whereas it was lower in skim milk (178 mg/dL)- and dahi (143 mg/dL)-fed rats. The glucose tolerance became impaired at the third week of feeding of high fructose diet in control animals, whereas in skim milk- and dahi-fed animals achievement of glucose intolerance was delayed until the fourth and fifth week, respectively. Blood glycosylated hemoglobin and plasma insulin were significantly lower in skim milk (10% and 34%, respectively)- and dahi (17%, and 48%, respectively)-fed animals than those of the control group. Plasma total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and very-low-density lipoprotein-cholesterol and blood free fatty acids were significantly lower in skim milk (13%, 14%, 14%, 19%, and 14%, respectively)- and dahi (22%, 33%, 30%, 33%, and 29%, respectively)-fed animals as compared with control animals. Moreover, the total cholesterol, triglyceride, and glycogen contents in liver tissues were also lower in skim milk (55%, 50%, and 36%, respectively)- and dahi (64%, 27%, and 4%, respectively)-fed animals as compared with control animals. In contrast, high-density lipoprotein-cholesterol in plasma was higher in skim milk (14%)- and dahi (29%)-fed animals as compared with control animals. These results indicate that skim milk and its fermented milk product, dahi, delay the progression of fructose-induced diabetes and dyslipidemia in rats and that these may be useful as antidiabetic food supplements that can be included in daily meals of the diabetic as well as normal population.

Animals↗

Oxalate-induced encephalitis after infusions of sugar surrogates.

The case of a 55-year-old female with oxalate-induced lethal encephalitis following infusions of sugar surrogates is reported. Renal failure and subsequent central coma developed following the use of xylitol, fructose and sorbitol above the recommended dosages. The patient died due to raised intracranial pressure. Cerebral damage was caused by encephalitis due to calcium oxalate crystals. Oxalosis induced by sugar surrogates may be explained either by dose-dependent toxic effects or genetically fixed intolerance.

Biopsy↗

Conditioned flavor avoidance, preference, and indifference produced by intragastric infusions of galactose, glucose, and fructose in rats.

The postingestive reinforcing and satiating effects of intragastric (i.g.) infusions of 16% galactose, glucose, and fructose were compared in adult female rats. In Experiment 1, food-restricted rats were trained to drink (30 min/day) flavored solutions (the CS+Gal and CS+Glu) paired with intragastric (i.g.) infusions of galactose and glucose; other flavors (the CS-) were paired with IG water infusions. In subsequent choice tests, the rats strongly preferred (91%) the CS+Glu to the CS-, but avoided the CS+Gal (21%) in favor of the CS-. In Experiment 2, the rats were trained with a CS+Fru paired with i.g. fructose infusions and a CS- paired with i.g. water. In the choice test they consumed similar amounts of CS+Fru and CS- (CS+Fru preference = 51%). In other choice tests they preferred the CS+Glu (>80%) to CS+Fru and CS+Gal, and the CS+Fru (81%) to CS+Gal. Satiation tests were performed in Experiment 3 by adapting the rats to drink a 3% sugar + 0.2% saccharin solution paired with i.g. water infusions (30 min/day). On different test days 16% sugar instead of water was infused. IG galactose, glucose, and fructose produced comparable reductions in sugar+saccharin intake in the first test session. These findings demonstrate that, while the three sugars had similar satiating effects, they differed substantially in their postingestive flavor conditioning effects. The glucose and fructose results confirm prior data indicating that only glucose generates potent postingestive reinforcing stimuli. The galactose-induced flavor avoidance indicates that this sugar has a negative postingestive consequence. This may be due to the slow and incomplete hepatic metabolism of this sugar in adult rats. Conceivably, galactose intolerance may contribute to the lactose avoidance in adult animals.

Analysis of Variance↗

Oxalate-induced encephalitic reactions to polyol-containing infusions during intensive care.

Fifteen of 5800 neuropathologically examined brains showed oxalosis with an intense inflammatory reaction comparable to ethylene glycol intoxication. All patients had received intensive care therapy with infusions of high amounts of xylitol, sorbitol, mannitol, or fructose, mostly together with glucose. The encephalitic reaction induced by calcium oxalate crystals was manifested by clinical symptoms of cerebral damage. A genetically fixed polyol intolerance is hypothesized to explain polyol-induced oxaloses in brain, kidney, and partly also in myocardium.

Adolescent↗