Assessment of a synthetic steroid and flutamide on dopamine, GSH and H2O2 levels in rat brain in presence of fructose.

UNLABELLED: Flutamide is a drug used in the treatment of androgen-dependent disorders. However, this treatment is usually accompanied by some adverse side effects. The aim of this work was to analyse the effect of flutamide and to compare this effect with that of a synthetic steroid - 3ß-propionyloxy-5-androsten-17-one (PPA) - on levels of dopamine and some oxidative stress markers. For this, thirty-six male young Wistar rats (65g) were recruited and divided into 6 groups. The groups were then treated as follows: Group 1 (control), dimethyl sulfoxide (DMSO); group 2, flutamide (4 mg/kg); group 3, PPA; group 4, DMSO + fructose; group 5, flutamide + fructose; and group 6, PPA + fructose. The treatments were administered intraperitoneally at a daily dose of 4 mg/kg for 10 days. In the last day of treatment, blood samples were obtained and used to assess the levels of glucose and cholesterol. The animals were then sacrificed and their prostate gland and brains were obtained for measurement of 5α-reductase, glutathione (GSH), calcium, H2O2, and dopamine in cortex, hemispheres, and medulla/oblongata, using previously validated methods. RESULTS: Dopamine levels decreased while GSH increased significantly in cortex and hemispheres of animals that received PPA plus fructose. Also in the same group, GSH decreased in cerebellum/medulla oblongata when compared with control group. Peroxidation decreased significantly in all tissues of the groups, while ATPase activity witnessed a significant decrease in cortex and an increase in hemispheres of animal groups treated with flutamide and PPA both in combination with fructose. CONCLUSION: The steroid, 3ß-propionyloxy-5-androsten-17-one, may in part act as a neuroprotector mediated by the increase of GSH and decrease of H2O2. Besides, imbalance in steroid homeostasis may alter the metabolism of dopamine.

D-psicose increases energy expenditure and decreases body fat accumulation in rats fed a high-sucrose diet.

We investigated the anti-obesity effects of D-psicose by increasing energy expenditure in rats pair-fed the high-sucrose diet (HSD). Wistar rats were divided into two dietary groups: HSD containing 5% cellulose (C) and 5% d-psicose (P). The C dietary group was further subdivided into two groups: rats fed the C diet ad libitum (C-AD) and pair-fed the C diet along with those in the P group (C-PF). Resting energy expenditure during darkness and lipoprotein lipase activity in the soleus muscle were significantly higher in the P group than in the C-PF group. Serum levels of glucose, leptin and adiponectin; glucose-6-phosphate dehydrogenase activities in the liver and perirenal adipose tissue; and body fat accumulation were all significantly lower in the P group than in the C-PF group. The anti-obesity effects of D-psicose could be induced not only by suppressing lipogenic enzyme activity but also by increasing EE in rats.

Assessment of gustatory responses to different sugars in harnessed and free-moving bumblebee workers (Bombus terrestris).

For bumblebee colony survival, sugar responses are crucial as nectar is the main carbohydrate source and flower choice is likely determined by sugar composition. This study used a bioassay both with harnessed and with free-moving workers of the bumblebee Bombus terrestris to study the gustatory response to the 3 major plant sugars by both groups. In harnessed workers of B. terrestris, a concentration of 5.5% of fructose and glucose was required to induce the proboscis extension reflex in 50% of the workers, whereas for sucrose, a much higher concentration of 40% was needed. In contrast, free-moving workers given a choice between 30% glucose, 30% sucrose, 30% fructose, and water showed a strong preference for sucrose (66% of individuals) compared with 18% for glucose and 16% for fructose; water was never chosen. Familiarization with 30% fructose provoked a significant increase in preference toward fructose, indicating plasticity. In addition, by amputation of the tarsi, it was found that tarsi plays a role in the sugar response with especially the foreleg tarsi being involved in the response to fructose. Our results demonstrated that sugar response is different in free-moving versus harnessed bumblebee workers and that tarsi plays a role in sugar perception.

Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women.

BACKGROUND/OBJECTIVES: The results of short-term studies in humans suggest that, compared with glucose, acute consumption of fructose leads to increased postprandial energy expenditure and carbohydrate oxidation and decreased postprandial fat oxidation. The objective of this study was to determine the potential effects of increased fructose consumption compared with isocaloric glucose consumption on substrate utilization and energy expenditure following sustained consumption and under energy-balanced conditions. SUBJECTS/METHODS: As part of a parallel arm study, overweight/obese male and female subjects, 40-72 years, consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Energy expenditure and substrate utilization were assessed using indirect calorimetry at baseline and during the 10th week of intervention. RESULTS: Consumption of fructose, but not glucose, led to significant decreases of net postprandial fat oxidation and significant increases of net postprandial carbohydrate oxidation (P<0.0001 for both). Resting energy expenditure (REE) decreased significantly from baseline values in subjects consuming fructose (P=0.031) but not in those consuming glucose. CONCLUSIONS: Increased consumption of fructose for 10 weeks leads to marked changes of postprandial substrate utilization including a significant reduction of net fat oxidation. In addition, we report that REE is reduced compared with baseline values in subjects consuming fructose-sweetened beverages for 10 weeks.

Assessment of the potential of a boron-fructose additive in counteracting the toxic effect of Fusarium mycotoxins.

Trichotecenes are mycotoxins produced by Fusarium sp., which may contaminate animal feeds and human food. A feeding trial was conducted to evaluate the effect of a fusarotoxin-contaminated diet, and to explore the counteracting potential of a calcium fructoborate (CFrB) additive on performance, typical health biochemistry parameters and immune response in weaned pigs. A naturally contaminated maize, containing low doses of deoxynivalenol, zearalenone, fumonisins and T-2/HT-2 toxins (1790, 20, 0·6 and 90 parts per billion), was included in a maize-soyabean meal diet, and given ad libitum to eight weaned piglets (two groups: four pigs/group) for a period of 24 d. CFrB was administered to one of the contaminated groups and to another four piglets as a daily supplement, following the manufacturer's recommendation. A decrease in performance was observed in contaminated animals at this concentration of feed toxins, which was ameliorated by the dietary CFrB supplementation. Fusarium toxins also altered the pig immune response by increasing (P < 0·05) the ex vivo peripheral blood mononuclear cell proliferation (111·7 % in comparison with control), the respiratory burst of porcine granulocytes (15·4 % for responsive cells v. 5·1 % for unstimulated cells and 70·95 v. 22·65 % for stimulated cells, respectively), the percentage of peripheral T, CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) subsets and the synthesis of IL-1ß, TNF-α and IL-8 (123·8, 217·1 and 255·1 %, respectively). The diet containing the CFrB additive reduced these exacerbated cellular immune responses induced by Fusarium toxins. However, consumption of CFrB did not counteract the effect of mycotoxins on biochemistry parameters, and increased plasma IgM and IgG of contaminated pigs.

Biotechnological valorization of low-cost sugar-based media for bacteriocin production by Leuconostoc mesenteroides E131.

The aim of the present study was to evaluate the suitability of low-cost carbon sources for bacteriocin production by Leuconostoc mesenteroides strain E131. For this purpose, inexpensive sugars derived from a sugar refinery plant (glucose, fructose and sucrose) as well as waste molasses were utilized as carbon sources in submerged shake-flask experiments and the kinetic response of the microorganism was evaluated. Interestingly, in the case of molasses, non-negligible decolorization-detoxification (up to ∼27%) of the residue was performed together with the production of bacteriocin. In all instances the initial concentration of sugars employed was adjusted at 20 and 30 g/L, therefore the effect of both the nature and the initial quantity of sugar upon the growth of the microorganism was assessed. All media proved to be suitable for both biomass and bacteriocin production by L. mesenteroides, whereas variable quantities of lactate, acetate and ethanol were detected into the medium. Employment of fructose, sucrose or molasses as carbon sources resulted in the accumulation of mannitol (in some cases in significant quantities) into the medium; remarkable portion thus of the available or released fructose acted as electron acceptor instead of carbon source by the microorganism. The highest bacteriocin production achieved (=640 AU/mL) was obtained when initial glucose at 30 g/L was used as substrate. Finally, utilization of waste molasses as carbon source by L. mesenteroides resulted in satisfactory bacteriocin production (up to 320 AU/mL) besides the decolorization of the residue.

Topiramate: a review of its use in the treatment of epilepsy.

Topiramate (Topamax) is a structurally novel broad-spectrum antiepileptic drug (AED) with established efficacy as monotherapy or adjunctive therapy in the treatment of adult and paediatric patients with generalised tonic-clonic seizures, partial seizures with or without generalised seizures, and seizures associated with Lennox-Gastaut syndrome. The incidence and severity of many adverse events, including CNS-related events, may be reduced through the use of slow titration to effective and well tolerated dosages. It is associated with few clinically significant interactions with other drugs, is effective when used with other AEDs, is not associated with drug-induced weight gain and, at lower dosages, does not interfere with the effectiveness of oral contraceptives. Therefore, topiramate is a valuable option as monotherapy or adjunctive therapy in the treatment of epilepsy in adult and paediatric patients.

Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport.

PURPOSE: Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using (125)I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. METHODS: Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. RESULTS: Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p<0.05; heart, p<0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p<0.001; muscle, p<0.001; heart, p<0.01) whereas no significant changes were observed in fructose-fed rats. CONCLUSION: This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging.

[Topiramate and epilepsy in the light of Das-Naglieri Cognitive Assessment System]. / Topiramato y epilepsia a la luz del Das-Naglieri Cognitive Assessment System.

INTRODUCTION: Cognitive side effect is a possible effect of topiramate. Cognitive function is not unanimously defined and a test measures according to the concept is based on. On the other hand, behavioral dysfunction is frequent in epileptics and the euthimic effect of topiramate on impulsive dysfunction is known. AIMS: To asses the cognitive effect of topiramate with a modern battery, Das-Naglieri Cognitive Assessment System (DN:CAS), which diagnoses mental programs, but not only achievement. Also, to test the influence of topiramate on behavior. PATIENTS AND METHODS: As a prospective study, 35 patients with idiopathic or cryptogenic epilepsies were administered DN:CAS battery, and, simultaneously, patients and parents were given behavioral questionnaires at baseline, and after 6 and 12 months on topiramate. Cognitive scores were compared to those of a group of healthy controls at baseline, and baseline scores were compared to 6 and 12 months follow-up scores within the patient group. t-Student was applied. RESULTS: Patient scores were lower in successive processing before treatment as compared to controls (p < 0.001). After 6 months no change was noted. After 12 months of treatment, patients scored significantly better in planning processing than before treatment (p = 0.04) and, moreover, improved behavioral scores were noted. CONCLUSIONS: The patients showed a successive processing dysfunction not related with topiramate. An improved planning processing and behavioral pattern were observed 12 months after treatment. According to the euthimic effect of topiramate and the neurocognitive-neuroimpulsive interaction, a positive effect of topiramate on DN:CAS cognition and behavior can be postulated.

Fate of fructose supplied to leaf sheaths after defoliation of Lolium perenne L.: assessment by 13C-fructose labelling.

The role of fructans from leaf sheaths for the refoliation of Lolium perenne after severe defoliation was assessed by following the fate of (13)C-fructose supplied to leaf sheaths at the time of defoliation. At the end of the 4 h labelling period on defoliated plants, 77% of the (13)C incorporated was still located in leaf sheaths. Only 4% and 0.9% were, respectively, allocated to stem and roots, while 18% was imported by the growing leaves where (13)C was allocated first to the proximal part of the leaf growth zone (0-10 mm). In all tissues, the most highly (13)C-labelled carbohydrates was not fructose but sucrose. In leaf sheaths, (13)C-loliose was produced. In the leaf growth zone (0-20 mm), fructans were simultanously synthesized from (13)C entering the leaves and degraded. The export of (13)C from leaf sheaths continued during the first day of regrowth but stopped afterwards. There was no net loss of C from (13)C-fructose over the first 2 d of regrowth. The role of fructans and loliose is discussed as well as the physiological mechanisms contributing to defoliation tolerance in L. perenne.

Antiepileptic efficacy of topiramate: assessment in two in vitro seizure models.

The antiepileptic efficacy of topiramate (TPM) has been demonstrated in both whole animal seizure models and clinical trials; however, there is no consensus concerning its mechanism of action. We determined first whether the antiepileptic effect of TPM generalized to in vitro seizure models. Epileptiform discharges, recorded extracellularly, were evoked by repeated tetanic stimulation of Schaffer collaterals and layer III association fibers in entorhinal cortex/hippocampus and piriform cortex slices, respectively. TPM was applied at concentrations of 20 or 100 microM. Whole cell recordings were made from CA1 pyramidal neurons and the effect of TPM was assessed on a variety of intrinsic membrane properties including resting membrane potential, input resistance and postspike potentials. TPM (20 microM) was without effect in entorhinal cortex/hippocampus (N=6); however, 100 microM TPM decreased significantly the Coastline Burst Index from 358.3+/-65.8 to 225. 5+/-77.1 (N=4), the frequency of spontaneous epileptiform discharges to 44.6+/-21.8 (N=5) and the duration of primary afterdischarge (PAD) to 65.9+/-10.1 (N=10) percent of control. In contrast, phenytoin (50 microM, N=7; 100 microM, N=8) reduced PAD to 96.9+/-14. 8 and 86.5+/-17.3 percent of control, respectively. TPM (100 microM) did not reduce significantly the frequency of spontaneous discharges in piriform cortex (85.4+/-12.3 percent of control; N=5). TPM (100 microM) was without significant effect on intrinsic membrane properties in CA1 pyramidal neurons. Likely candidate mechanisms underlying the antiepileptic effect produced by TPM include enhancement of chloride-mediated GABA(A) currents and reduction of kainate and L-type calcium currents.

An assessment of the ability of insulin-stimulated cyclic AMP phosphodiesterase to decrease hepatocyte intracellular cyclic AMP concentrations.

Treatment of hepatocytes with either NH4Cl (10mM) or fructose (10mM) blocks insulin's activation of the 'dense-vesicle' cyclic AMP phosphodiesterase. The ability of insulin (10 nM) to decrease intracellular cyclic AMP concentrations raised by glucagon (10 nM) was unaffected by pre-treatment with either NH4Cl (10 mM) or fructose (10 mM). It is concluded that the 'dense-vesicle' enzyme does not play a significant role in this action of insulin and that as yet unidentified cyclic AMP phosphodiesterase(s) must be activated by insulin. Treatment of hepatocytes with either NH4Cl or fructose appeared to increase, reversibly, cyclic AMP phosphodiesterase activity. When N6-(phenylisopropyl)adenosine was used to prevent glucagon from blocking insulin's activation of the plasma-membrane cyclic AMP phosphodiesterase activity, insulin's ability to decrease intracellular cyclic AMP concentrations in glucagon-treated hepatocytes was increased markedly. Insulin's activation of the plasma-membrane cyclic AMP phosphodiesterase activity can exert a potent effect in decreasing intracellular cyclic AMP concentrations elevated by glucagon.

Use of fructose in the treatment of acute alcoholic intoxication.

The literature concerning the use of fructose to lower ethanol blood levels in acute alcoholic intoxication is reviewed. Studies indicate that 500 ml of a 40% infusion of fructose solution given over a 30-minute period can increase the rate of decline of ethanol blood levels by 25%. The recommended daily dosage is one to three liters of a 10% solution. Lactic acidosis is a potentially serious side effect of large doses of fructose. The lack of controlled clinical studies or other convincing evidence makes the routine use of fructose to treat acute alcoholic intoxication inadvisable.