Decrease In Glycogen Research Articles

Phosphamidon induced effects on estrous cycle, ovarian, and uterine biochemical parameters in Swiss albino mice

Phosphamidon is chemically known as phosphoric acid, 2-chloro-2-diethyl carboryl-methylvenyl-0-0-dimethyl phosphate. It is a systemic and contact insecticide with broad spectrum of activity. The present investigation was carried out to evaluate its effects on estrous cycle, ovarian, and uterine biochemical contents in albino mice. Normal virgin female Swiss albino mice of 90 days old and weighing about 20–30 g were divided into five groups. Phosphamidon was orally administered at doses 1.3, 2.6, 3.9, and 5.2 mg/kg body weight/day for 30 days consecutively. The vaginal smear and body weight were recorded daily and mice were sacrificed on 31st day. Estrous cycle was affected by showing a significant decrease in the number of estrous cycle and duration of proestrus, estrus, and metestrus in all the groups except in 1.3 mg/kg body weight/day phosphamidon treated group, and with concomitant increase in the duration of diestrus in all the treated groups. However there is a significant decrease in the body weight in all the groups except 1.3 mg/kg body weight/ day phosphamidon treated group. The deleterious effects were also reflected in the loss of weights of ovary and uterus: In mice treated with 2.6, 3.9, and 5.2 mg/kg phosphamidon showed a significant decrease in total protein and glycogen in the ovary and uterus. The response of the ovary and uterus for nucleic acid (DNA) content was significantly decreased in higher doses. The observed effects of phosphamidon may be due to imbalance in the hormone or toxic effects.

Investigation on Acute Biochemical Effects of Ce(NO 3) 3 on Liver and Kidney Tissues by MAS 1H NMR Spectroscopic-Based Metabonomic Approach

High resolution magic angle spinning (MAS)- 1H nuclear magnetic resonance (NMR) spectroscopic-based meta-bonomic approach was applied to the investigation on the acute biochemical effects of Ce(NO 3) 3. Male Wistar rats were administrated with various doses of Ce(NO 3) 3(2, 10, and 50 mg·kg −1 body weight), and MAS 1H NMR spectra of intact liver and kidney tissues were analyzed using principal component analysis to extract toxicity information. The biochemical effects of Ce(NO 3) 3 were characterized by the increase of triglycerides and lactate and the decrease of glycogen in rat liver tissue, together with an elevation of the triglyceride level and a depletion of glycerophosphocholine and betaine in kidney tissues. The target lesions of Ce(NO 3) 3 on liver and kidney were found by MAS NMR-based metabonomic method. This study demonstrates that the combination of MAS 1H NMR and pattern recognition analysis can be an effective method for studies of biochemical effects of rare earths.

Study of a novel indolin-2-ketone compound Z24 induced hepatotoxicity by NMR-spectroscopy-based metabonomics of rat urine, blood plasma, and liver extracts

Antiangiogenic compound has been believed to be an ideal drug in the current cancer biological therapy, but the angiogenesis inhibitors suffer setback for unknown toxicity now. A novel synthetic indolin-s-ketone small molecular compound, 3Z-3-[((1)H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one (Z24) can inhibit angiogenesis in new blood vessels. The hepatotoxicity effects of Z24 oral administration (dosed at 60, 130 and 200 mg/kg) have been investigated in female Wistar rats by using metabonomic analysis of (1)H NMR spectra of urine, plasma and liver extracts, as well as by clinical chemistry analysis, liver histopathology and electron micrographs examination. The (1)H NMR spectra of the biofluids were analyzed visually and via pattern recognition by using principal component analysis. The metabonomic trajectory analysis on the time-related hepatotoxicity of Z24 was carried out based on the (1)H NMR spectra of urine samples, which were collected daily predose and postdose over an 8-day period. Urinary excretion of citrate, lactate, 2-oxo-glutarate and succinate increased following Z24 dosing. Increased plasma levels of lactate, TMAO and lipid were observed, with concomitant decrease in the level of glucose and phosphatidylcholine. Metabolic profiling on aqueous soluble extracts of liver tissues with the high dose level of Z24 showed an increase in lactate and glutamine, together with a decrease in glucose, glycogen and choline. On the other hand, studies on lipid soluble extracts of liver tissues with the high dose level of Z24 showed increased level in lipid triglycerides and decreased level in unsaturated fatty acids and phosphatidylcholine. Moreover, the most notable effect of Z24 on the metabolism was the reduction in the urinary levels of creatinine and TMAO and the increase in acetate, citrate, succinate and 2-oxo-glutamate with time dependence. The results indicate that in rats Z24 inhibits mitochondrial function through altering the energy and lipid metabolism, which results in the accumulation of free fatty acids and lactate because of the lack of aerobic respiration. These data show that the metabonomic approach represents a promising new technology for the toxicological mechanism study.

Effects of leptin administration on the endocrine pancreas and liver in the lizard Podarcis sicula

In this study, we investigated the presence of leptin receptor in pancreatic islets and the effect of exogenous leptin administration in Podarcis sicula on glucose metabolism. Our data show the presence of leptin receptor immunoreactivity in the endocrine pancreas suggesting that leptin may act at a peripheral level as previously postulated in mammals. The effects of short- and long-term and dose-response treatment with supraphysiological concentrations of leptin on circulating levels of insulin, glucagon and glucose in the blood have been evaluated. Taken together, our results indicate that leptin treatment was followed by an increase in insulin, glucagon and glucose in the blood, depending on the dose of leptin. Moreover, leptin treatment brought about a decrease of glycogen and the appearance of tyrosine-phosphorylated proteins in the liver. This study shows that in the lizard P. sicula leptin is involved in glucose metabolism.

Hypoxia causes glycogenolysis without an increase in percent phosphorylase a in rat skeletal muscle.

Stimulation of skeletal muscle to contract activates phosphorylase b-to-a conversion and glycogenolysis. Despite reversal of the increase in percentage of phosphorylase a after a few minutes, continued glycogen breakdown can occur during strenuous exercise. Hypoxia causes sustained glycogenolysis in skeletal muscle without an increase in percentage of phosphorylase a. We used this model to obtain insights regarding how glycogenolysis is mediated in the absence of an increase in percentage of phosphorylase a. Hypoxia caused a 70% decrease in glycogen in epitrochlearis muscles during an 80-min incubation despite no increase in percentage of phosphorylase a above the basal level of approximately 10%. Muscle Pi concentration increased from 3.8 to 8.6 mumol/g muscle after 5 min and 15.7 mumol/g after 20 min. AMP concentration doubled, attaining a steady state of 0.23 mumol/g in 5 min. Incubation of oxygenated muscles with 0.1 microM epinephrine induced an approximately sixfold increase in percentage of phosphorylase a but resulted in minimal glycogenolysis. Muscle Pi concentration was not altered by epinephrine. Despite no increase in percentage of phosphorylase a, hypoxia resulted in a fivefold greater depletion of glycogen over 20 min than did epinephrine. To evaluate the role of phosphorylase b, muscles were loaded with 2-deoxyglucose 6-phosphate, which inhibits phosphorylase b. The rate of glycogenolysis during 60 min of hypoxia was reduced by only approximately 14% in 2-deoxyglucose 6-phosphate-loaded muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological and morphological effects of genetic alterations leading to a reduced synthesis of UDP-glucose in Saccharomyces cerevisiae.

Yeast cells lacking UDP-Glc pyrophosphorylase (UGPase) encoded by UGPI are not viable. Two strategies were developed to drastically reduce the intracellular concentration of UDP-Glc in order to study the consequences of this metabolic engineering on physiology and morphology. Firstly, UGP1 was placed under the strongly regulatable THI4 promoter. This resulted in a 95% reduction of UGPase activity in the presence of thiamine. The phenotypic effects of this reduction were slightly stronger than those of glucose on the GALI0/CYC1-UGP1 gene fusion [Daran et al. (1995) Eur. J. Biochem. 230, 520-530]. A further reduction of flux towards UDP-Glc was achieved by deletion of the two phosphoglucomutase genes in the ugp1 conditional strain. The growth of this new mutant strain was hardly affected, while it was extremely sensitive to cell wall interfering drugs. Surprisingly, UDP-Glc levels were reduced only by 5-fold, causing a proportional decrease in both glycogen and beta-glucans. Taken altogether, these results indicate that a few percent of enzymatic activities leading to the formation of UDP-Glc appears sufficient to provide the UDP-Glc demands required for cell viability, and that the loss of function of UGP1 is lethal mainly because of the inability of yeast cells to properly form the cell wall.

Biochemical study of the anti-diabetic action of the Egyptian plants Fenugreek and Balanites

Fenugreek and Balanites are two plants commonly used in Egyptian folk medicine as hypoglycemic agents. In the present study, the effects of 21 days oral administration of Fenugreek seed and Balanites fruit extracts (1.5 g/kg bw) on the liver and kidney glycogen content and on some key liver enzymes of carbohydrate metabolism in STZ-diabetic rats were studied. In addition, the effects of these two plant extracts on the intestinal alpha-amylase activity in vitro and starch digestion and absorption in vivo were also examined. Results indicated that single injection of STZ (50 mg/kg bw) caused 5-folds increase in the blood glucose level, 80% reduction in serum insulin level, 58% decrease in liver glycogen and 7-folds increase in kidney glycogen content as compared to the normal levels. The activity of glucose-6-phosphatase was markedly increased, whereas, the activities of both glucose-6-phosphate dehydrogenase and phospho-fructokinase were significantly decreased in the diabetic rat liver. Administration of Fenugreek extract to STZ-diabetic rats reduced blood glucose level by 58%, restored liver glycogen content and significantly decreased kidney glycogen as well as liver glucose-6-phosphatase activity. Meanwhile, Balanites extract reduced blood glucose level by 24% and significantly decreased liver glucose-6-phosphatase activity in diabetic rats. On the other hand, our results demonstrated that both the Fenugreek and Balanites extracts were able to in vitro inhibit alpha-amylase activity in dose-dependent manner. Fenugreek was more potent inhibitor than Balanites. This inhibition was reversed by increasing substrate concentration in a pattern which complies well with the effect of competitive inhibitors. Furthermore, this in vitro inhibition was confirmed by in vivo suppression of starch digestion and absorption induced by both plant extracts in normal rats. These findings suggest that the hypoglycemic effect of Fenugreek and Balanites is mediated through insulinomimetic effect as well as inhibition of intestinal alpha-amylase activity.

Effects of reduced glycogen on structure and in vitro function of rat sarcoplasmic reticulum Ca2+-ATPase

The aim of this study was to examine the effects of reduced glycogen concentration on sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity in rat fast-twitch muscles. In the first experiment, the gastrocnemius (GAS) muscle from one leg was removed, followed by starvation for 24-72 h, after which the remaining GAS was removed. Intra-animal comparisons revealed that starvation caused a 25% reduction (P<0.05) in the glycogen concentration but no change in SR Ca(2+)-ATPase activity in the GAS. In the second experiment, the SR was purified from a mixture of the GAS and vastus lateralis muscles. In half of the samples obtained from each animal, glycogen was extracted from the SR by treatment with glucoamylase. Treatment resulted in a 94.1 and 70.2% decrease (P<0.01) in glycogen and glycogen phosphorylase, respectively, and a 41.5% increase (P<0.05) in a fluorescein isothiocyanate (FITC) binding to SR Ca(2+)-ATPase. On the other hand, SR Ca(2+)-ATPase activity and the affinity of the enzyme for ATP were unaltered. These results do not implicate depletion of muscle glycogen as a contributor to impaired SR Ca(2+)-ATPase activity as measured in vitro. Therefore, it is concluded that muscle glycogen does not influence exercise tolerance and work productivity in working muscles by modulating the structure of protein involved in Ca(2+) sequestering. Furthermore, it is suggested that the FITC binding assay may be inappropriate as a method for examining the mechanisms for the altered activity of SR Ca(2+)-ATPase.

Effects of clove oil on the stress response of matrinxã (Brycon cephalus) subjected to transport

Fish transport is one of the most stressful procedures in aquaculture facilities. The present work evaluated the stress response of matrinxã to transportation procedures, and the use of clove oil as an alternative to reduce the stress response to transport in matrinxã (Brycon cephalus). Clove oil solutions were tested in concentrations of 0, 1, 5 and 10 mg/L during matrinxã transportation in plastic bags, supplied with water and oxygen as the usual field procedures in Brazil. Clove oil reduced some of the physiological stress responses (plasma cortisol, glucose and ions) that we measured. The high energetic cost to matrinxã cope with the transport stress was clear by the decrease of liver glycogen after transport. Our results suggest that clove oil (5 mg/l) can mitigate the stress response in matrinxã subjected to transport.

In vivo biochemical changes in liver and gill of Clarias batrachus during cypermethrin exposure and following cessation of exposure

The sublethal effect of a synthetic pyrethroid, cypermethrin on total protein, amino acids, ammonia, glycogen, and enzymes like aminotransaminases (AIAT, AAT), glutamate dehydrogenase, and glycogen phosphorylases (a and ab) was studied in physiological important tissues viz; liver and gill tissues of freshwater teleost air breathing fish, Clarias batrachus. The study was conducted during exposure of 1/3 (33%) of LC 50 concentration and followed by cessation of exposure. Thirty-six fish were exposed to 0.07 mg/L cypermethrin for 10 days. After 10 days, 18 fish were released to freshwater and kept in the same for 10 days (recovery group). Thirty-six fish were kept in freshwater as control batch. Protein content in liver tissues decreased at the end of 1st and 5th day followed by slight increase at the end of 10th day. Gill tissue showed statistical significant decrease ( P < 0.001) in protein content during exposure period of 10 days. Recovery in protein content was observed to a large extent in both the tissues. Total free amino acids were increased in liver and gill tissues throughout the treatment period, recovery response was seen after cessation of exposure. Ammonia level was decrease in both the tissues throughout the exposure period except in liver tissue at the end of 1st day of exposure. Recovery response was exhibited by both the tissues. A decreased in glycogen content of liver tissue was observed during exposure period, gill tissue also showed decrease in glycogen at the end of 1st and 5th day followed by increase at the end of 10th day of exposure period. When the fish were transferred to freshwater, recovery in glycogen content was noted. The activity level of alanine, aspartate aminotransaminase, glutamate dehydrogenase, and phosphorylases (a, ab) was increased in both the tissues, followed by recovery response after released of fish into freshwater. The present study showed that cypermethrin caused alterations in certain biochemical mechanisms of C. batrachus. This fish indicated recovery response when transferred to cypermethrin free water.

Influence Of Carbohydrate/placebo On Oxidative Changes And Plasma Antioxidant Capacity Following 2.5-hours Of Intensive Cycling

Carbohydrate administration during exercise has been shown to diminish cortisol and catecholamine hormone release. These hormones may mediate oxidative stress, but this relationship has not been examined during cycling exercise. Purpose The purpose of this project was to study the effect of carbohydrate (CHO) compared to placebo (PLA) ingestion on oxidative stress following 2.5 hours of intensive cycling in 15 highly trained cyclists compared to 5 resting controls. Methods Subjects were recruited and five control subjects (non-exercise) were utilized to control for time and lab drift effects. Subjects agreed to avoid the use of large-dose vitamin/mineral supplements (above 100% of recommended dietary allowances) for one week prior to each test session. Subjects functioned as their own controls and ingested CHO or PLA beverage in a randomized, counterbalanced design. Subjects reported to the lab at 3:00 pm not having ingested energy for at least 5 hours. The two cycling bouts (75% VO2max) were 4–6 weeks apart. Subjects received CHO or PLA beverages 15–30 min pre-exercise (12 ml/kg) and during the 2.5-h cycling bout (4 ml.kg−1.15 min−1). Blood and skeletal muscle biopsy samples were collected 30 min pre-exercise, immediately post-exercise, and 12-h post-exercise and analyzed for F2-isoprostanes, ferric reducing ability of plasma (FRAP), cortisol, and epinephrine and muscle glycogen, respectively. The statistical design was a 2 (treatment) × 3 (time) repeated measures ANOVA. Results The pattern of change between groups was significant for the increase in F2-isoprostanes, cortisol, and epinephrine (P = 0.004, P = 0.012, and P = 0.02, respectively) indicating that CHO vs PLA resulted in diminished increases of these compounds. Although significant time effects were found for the increase in FRAP (P = 0.000) and the decrease in muscle glycogen (P = 0.000), interaction effects were not significant. Significant correlations were found between cortisol, muscle glycogen, FRAP, epinephrine, and F2-isoprostanes. Conclusion These findings indicate that oxidative stress during cycling exercise is influenced by stress hormones, muscle glycogen content, and plasma antioxidant potential. Supported by a grant from Gatorade.

Glycogenin activity and mRNA expression in response to volitional exhaustion in human skeletal muscle

Glycogenolysis results in the selective catabolism of individual glycogen granules by glycogen phosphorylase. However, once the carbohydrate portion of the granule is metabolized, the fate of glycogenin, the protein primer of granule formation, is not known. To examine this, male subjects (n = 6) exercised to volitional exhaustion (Exh) on a cycle ergometer at 75% maximal O2 uptake. Muscle biopsies were obtained at rest, 30 min, and Exh (99 +/- 10 min). At rest, total glycogen concentration was 497 +/- 41 and declined to 378 +/- 51 mmol glucosyl units/kg dry wt following 30 min of exercise (P < 0.05). There were no significant changes in proglycogen, macroglycogen, glycogenin activity, or mRNA in this period (P > or = 0.05). Exh resulted in decreases in total glycogen, proglycogen, and macroglycogen as well as glycogenin activity (P < 0.05). These decrements were associated with a 1.9 +/- 0.4-fold increase in glycogenin mRNA over resting values (P < 0.05). Glycogenolysis in the initial exercise period (0-30 min) was not adequate to induce changes in glycogenin; however, later in exercise when concentration and granule number decreased further, decrements in glycogenin activity and increases in glycogenin mRNA were demonstrated. Results show that glycogenin becomes inactivated with glycogen catabolism and that this event coincides with an increase in glycogenin gene expression as exercise and glycogenolysis progress.

Fluctuations of biochemical constituents and marker enzymes as a consequence of naphthalene toxicity in the edible estuarine crab Scylla serrata

The sublethal effects of naphthalene on protein, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), carbohydrates, lipids, and certain marker enzymes such as phosphatases, transaminases, and lactate dehydrogenase were studied in hepatopancreas, hemolymph, and ovary in the edible crab Scylla serrata. The results revealed that there was overall decrease in total protein, total DNA, total RNA, free sugar, glycogen, protein-bound sugars, neutral lipid, glycolipid, and phospholipid in the test samples compared to control. Similarly all the marker enzymes (acid phosphatase, alkaline phosphatase, aspartate transaminase, alanine transaminase, and lactate dehydrogenase) were decreased in hepatopancreas and ovary. On the other hand, in hemolymph, the activities of marker enzymes were increased. The results were tested statistically and interpreted accordingly.

Acute biochemical effects of La(NO 3) 3 on liver and kidney tissues by magic-angle spinning 1H nuclear magnetic resonance spectroscopy and pattern recognition

High-resolution magic-angle spinning (MAS) 1H nuclear magnetic resonance (NMR) spectroscopic and pattern recognition (PR) based methods have been applied to studies on the acute biochemical effects of La(NO 3) 3 on rats. Male Wistar rats were treated with various doses of La(NO 3) 3 (2, 10, and 50 mg/kg body weight), and MAS 1H NMR spectra of their intact liver and kidney tissues were analyzed using principal components analysis to extract metabolic information. The biochemical effects of La(NO 3) 3 were characterized by the increase of triglyceride and bile acid and the decrease of glycogen in liver tissue, together with a slight elevation of triglyceride level in kidney tissue. The target lesion of La(NO 3) 3 to liver was found by MAS NMR–PR methods. This study illustrated the power of the combination of MAS 1H NMR and pattern recognition for the analysis of biochemical effects of rare earths.

Seizures induced in immature rats by homocysteic acid and the associated brain damage are prevented by group II metabotropic glutamate receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate

The present study has examined the anticonvulsant and neuroprotective effect of group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the model of seizures induced in immature 12-day-old rats by bilateral intracerebroventricular infusion of dl-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic–tonic seizures, ∼45–50 min after infusion. Comparable time intervals were used for sacrificing the pups which had received 2R,4R-APDC. Low doses of 2R,4R-APDC (0.05 nmol/side) provided a pronounced anticonvulsant effect which was abolished by pretreatment with a selective group II mGluR antagonist LY341495. Generalized clonic–tonic seizures were completely suppressed and cortical energy metabolite changes which normally accompany these seizures were either normalized (decrease of glucose and glycogen) or markedly reduced (an accumulation of lactate). EEG recordings support the marked anticonvulsant effect of 2R,4R-APDC, nevertheless, this was only partial. In spite of the absence of obvious motor phenomena, isolated spikes or even short periods of partial ictal activity could be observed. Isolated spikes could also be seen in some animals after application of 2R,4R-APDC alone, reflecting most likely subclinical proconvulsant activity of this agonist. The neuroprotective effect of 2R,4R-APDC was evaluated after 24 h and 6 days of survival following DL-HCA-induced seizures. Massive neuronal degeneration, as revealed by Fluoro-Jade B staining, was observed in a number of brain regions following infusion of DL-HCA alone (seizure group), whereas 2R,4R-APDC pretreatment provided substantial neuroprotection. The present findings support the possibility that group II mGluRs are a promising target for a novel approach to treating epilepsy.

Integrated Metabonomic Analysis of the Multiorgan Effects of Hydrazine Toxicity in the Rat

Hydrazine is a model toxin that induces both hepatotoxic and neurotoxic effects in experimental animals. The direct biochemical effects of hydrazine in kidney, liver, and brain tissue were assessed in male Sprague-Dawley rats using magic angle spinning nuclear magnetic resonance (NMR) spectroscopy. A single dose of hydrazine (90 mg/kg) resulted in changes to the biochemical composition of the liver after 24 h including an increase in triglycerides and beta-alanine, together with a decrease in hepatic glycogen, glucose, choline, taurine, and trimethylamine-N-oxide (TMAO). From histopathology measurements of liver tissue, minimal to mild hepatocyte alteration was observed in all animals at 24 h. The NMR spectra of the renal cortex at 24 h after dosing were dominated by a marked increase in the tissue concentration of 2-aminoadipate (2-AA) and beta-alanine, concomitant with depletions in TMAO, myo-inositol, choline, taurine, glutamate, and lysine. No alteration to the NMR spectral profile of the substantia nigra was observed after hydrazine administration, but perturbations to the relative concentrations of creatine, aspartate, myo-inositol, and N-acetyl aspartate were apparent in the hippocampus of hydrazine-treated animals at 24 h postdose. No overt signs of histopathological toxicity were observed in either the kidney or the brain regions examined. Elevated alanine levels were observed in all tissues indicative of a general inhibition of alanine transaminase activity. By 168 h postdose, NMR spectral profiles of treated rats appeared similar to those of matched controls for all tissue types indicative of recovery from toxic insult.

Interactive effects of high stocking density and food deprivation on carbohydrate metabolism in several tissues of gilthead sea breamSparus auratus

The influence of high stocking density (HSD) and food deprivation was assessed on carbohydrate metabolism of several tissues of gilthead sea bream Sparus auratus for 14 days. Fish were randomly assigned to one of four treatments: (1) fed fish under normal stocking density (NSD) (4 kg m(-3)); (2) fed fish under HSD (70 kg m(-3)); (3) food-deprived fish under NSD; and (4) food-deprived fish under HSD. After 14 days, samples were taken from the plasma, liver, gills, kidney and brain for the assessment of plasma cortisol, levels of metabolites and the activity of several enzymes involved in carbohydrate metabolism. HSD conditions alone elicited important changes in energy metabolism of several tissues that in some cases were confirmatory (5-fold increase in plama cortisol, 20% increase in plasma glucose, 60% decrease in liver glycogen and 20% increase in gluconeogenic potential in the liver) whereas in others provided new information regarding metabolic adjustments to cope with HSD in the liver (100% increase in glucose phosphorylating capacity), gills (30% decrease in capacity for phosphorylating glucose), kidney (80% increase in the capacity of phosphorylating glucose) and brain (2.5-fold increase in ATP levels). On the other hand, food deprivation alone resulted in increased plasma cortisol, and metabolic changes in the liver (enhanced gluconeogenic and glycogenolytic potential of 13% and 18%, respectively) and brain (10% increase in glycolytic capacity), confirmatory of previous studies, whereas new information regarding metabolic adjustments during food deprivation was obtained in the gills and kidney (decreased lactate levels in both tissues of 45% and 55%, respectively). Furthermore, the results obtained provided, for the first time in fish, information indicating that food deprivation increased the sensitivity of gilthead sea bream to the stress induced by HSD compared with the fed controls, as demonstrated by increased plasma cortisol levels (50% increase vs. fed fish) and a further increase in the capacity to export glucose mobilized from liver glycogen stores (70% decrease vs. fed fish). These results lend support for a cumulative effect of both stressors on plasma cortisol and parameters assessed on carbohydrate metabolism in the present experiments, and provide information regarding reallocation of metabolic energy to cope with simultaneous stressors in fish.

Carbohydrate-Fat Interactions and Obesity Examined by a Two-Compartment Computer Model

A systems dynamics computer model was developed to examine how the interactions between carbohydrate and fat metabolism influence body weight regulation. It reflects the operation of a two reservoir-system: one representing the body's limited glycogen, and the other, its large fat reserves. The outflows from the reservoirs correspond to the oxidation of glucose and fat, whose relative contributions are affected by the size of the prevailing glycogen and fat reserves. Together, they meet the body's energy expenditure. Replenishments occur three times per day, in portions restoring total glycogen content to specific levels. A parameter mimicking the action of insulin is necessary to create realistic responses. The model was run for 125-day periods to establish the degree of adiposity for which rates of fat oxidation become commensurate with fat intake and the influence thereon of various dietary, environmental, lifestyle, and inherited variables. Equivalent degrees of adiposity can be sustained under a variety of conditions. For instance, the impact on steady-state body fat contents of a 10% increase or decrease in the energy provided by dietary fat is offset by a 26-gram decrease or increase in mean glycogen levels. Environmental factors such as food diversity, palatability, and availability can be expected to raise the range within which glycogen levels are habitually maintained. This restrains fat oxidation, until expansion of the fat mass is sufficient to promote fat oxidation to a rate commensurate with dietary fat intake. This metabolic leverage can explain why increased food offerings tend to raise the prevalence of obesity.

Effects of short-term fasting on energy reserves of vampire bats ( Desmodus rotundus)

Studies on metabolic responses to fasting in common vampire bats ( Desmodus rotundus) have demonstrated the susceptibility of this species when subjected to long-term fasting. We investigated the effects of short-term fasting (12 h), a period similar to what they face in the field, on their energy reserves. Blood glucose (BG) levels in fed bats were similar to other mammals, but after 12 h without food, these levels were reduced. Plasma lactate and free fatty acids levels in fed bats were higher than in other mammals, although no changes in these levels were detected in response to fasting. Liver glycogen content decreased significantly following fasting. Muscle glycogen, as well as liver and muscle lipid and protein levels, remained unaltered for up to 12 h of fasting. Although BG levels decreased after short-term fasting, body energy reserves do not seem to play an important role for maintenance of glycemic homeostasis during fasting. Despite the decrease in liver glycogen, this small reserve seems insufficient to maintain adequate levels of BG, even during short periods of fasting. Because other reserves were not decreased after fasting, it is possible that the main source of glucose for common vampire bats might be the glucose content of their blood diet.

Effect of cyclosporin A on the survival and ultrastructure of Echinococcus granulosus protoscoleces in vitro

Surgical treatment of human hydatidsosis involves the use of various scolicidal agents to kill infective Echinococcus granulosus protoscoleces that may disseminate into the peritoneal cavity during surgery and potentially re-infect the patient. Currently, no scolicidal agent is completely effective in killing intracystic protoscoleces in humans. Cyclosporin A (CsA) has previously been found to be lethal for E. granulosus protoscoleces in vitro. In this study, we further assessed the effectiveness of CsA as a scolicidal agent by testing the toxic effect of CsA at higher doses over various time-periods. Experiments were performed on activated and unactivated protoscoleces cultured in nutrient medium or sheep hydatid cyst fluid. All activated protoscoleces were killed following culture in 100 microg/ml of CsA for 3 days and 50 or 20 microg/ml for 5 days. The lethal effect of CsA on unactivated protoscoleces varied but reached 100% over 15 days in culture with 100 or 50 microg/ml of CsA. Pulse treatment of protoscoleces with 50, 20 or 10 microg/ml of CsA for 5 min or 72 h killed all parasites by day 10 and day 5 respectively. Untreated protoscoleces remained greater than 95 % viable for the duration of experiments. Changes in protoscolex ultrastructure induced by treatment with 10 microg/ml of CsA over 10 days in in vitro culture was assessed by TEM. Protoscolex alterations observed in treated parasites included an increase in cellular vacuolization, swelling of mitochondria, rounding of cells, damage to the tegument, decrease in glycogen, a breakdown of the extracellular matrix and an increase in lipid globules. The untreated protoscoleces, by comparison, had few changes during the 10-day culture period with the exception of large amounts of extracellular glycogen observed in the protoscoleces at culture days 7 and 10. From these results, CsA is clearly an effective scolicidal agent in vitro that may have potential application as a new therapeutic agent in the treatment of human hydatid disease.