Fasting, adrenalectomy, and gluconeogenesis in the chicken and a carnivorous bird

Previous studies showed that livers from carnivorous birds have a higher gluconeogenic capacity and higher levels of gluconeogenic enzymes than livers from granivorous birds. In this work we compare the effects of fasting and adrenalectomy on gluconeogenesis. Fasting in the chicken elicited increased rates of incorporation of 14C from alanine into blood glucose, increased gluconeogenesis in liver slices, and increased activities of four gluconeogenic enzymes: glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, alanine aminotransferase, and aspartate aminotransferase. These responses in the chicken resemble those observed in fasted rodents. In marked contrast, fasting in black vultures induced decreased rates of incorporation of alanine label into circulating glucose, decreased gluconeogenesis in liver slices, and no change in any of the four enzymes studied. This unusual response to fasting in the carnivorous bird is probably related to the high-protein-low-carbohydrate content of the diet. Fasted adrenalectomized birds (granivorous and carnivorous) had reduced rates of in vivo glucose synthesis, decreased liver gluconeogenesis, and lower activity of glucose-6-phosphatase and aspartate aminotransferase, without change in phosphoenolpyruvate carboxykinase and alanine aminotransferase activities.

Effect of non-steroidal anti-inflammatory drugs (NSAID) on the histamine release induced by compound 48/80 and cardiac anaphylaxis in guinea-pig isolated heart

Histamine release from guinea pig heart treated with compound 48/80 was potentiated by the cyclooxygenase inhibitors indomethacin and piroxicam but not by aspirin or phenylbutazone. This differential effect suggests that the potentiation is not merely due to an inhibition of prostaglandin synthesis. Piroxicam potentiated the histamine release induced by cardiac anaphylaxis whereas indomethacin reduced this effect. The SRS-A antagonist FPL 55712 inhibited histamine release induced by cardiac anaphylaxis, but not that evoked by compound 48/80, and also prevented the potentiation due to indomethacin and piroxicam. In total, these data suggest that the potentiation of histamine release by piroxicam and indomethacin is probably due to a diversion of arachidonic acid metabolism from the cyclooxygenase to the lipoxygenase pathways. The resulting lipoxygenase products may then regulate histamine release, with the secretion due to antigen being more sensitive to such modulation than that evoked by compound 48/80.

Heparin, heparin plus ASA and dipyridamole, and arteriovenous fistula as adjuvant methods to prevent rethrombosis after venous thrombectomy. Experimental study in rabbits

Venous rethrombosis following thrombectomy is a common event. The aim of the present study was to verify the action of heparin, heparin plus acetyl salicylic acid (ASA) and dipyridamole, and of an arteriovenous fistula (AVF) in the prevention of this complication. Thrombosis was induced in 48 male rabbits by the injection of thrombin in a segment of the left jugular vein, in which the blood flow was arrested for 10 minutes. After 48 hours, the animals were randomly allocated into one of 4 groups of treatment: (1) control, (2) subcutaneous heparin (600 S.I. Units/kg - 8/8 hours), (3) heparin, in the same dose, plus ASA (10 mg/kg/once a day), and dipyridamole (0.5 mg/kg thrice a day), (4) an AVF was surgically constructed between the left carotid after and the left maxillar vein. After 30 minutes, thrombectomy was performed. The venous blood flow, the hematocrit, activated partial thromboplastin time and thrombin time tests were performed before, right after the thrombectomy and 48 hours after thrombectomy. Venography was performed after thrombectomy and at the end of the experiment. The animals were killed 48 hours after thrombectomy and the veins were examined macroscopically. Venous rethrombosis was significantly prevented only in the AVF group (9/12), when compared to control group (0/12), heparin group (1/12) and heparin plus antiaggregating agents group (2/12). These results validate further clinical and experimental investigations with the use of AVF to prevent rethrombosis after venous thrombectomy, when a reduction of venous flow is present.

Toxicologic evaluation of acute and subacute oral administration of Cucurbita maxima seed extracts to rats and swine

The extract prepared from dried seeds of Cucurbita maxima was administered to rats and pigs. Following a single dose or 4 weeks of daily oral administration, the extract produced no changes in serum glucose, urea, creatinine, total protein, uric acid, GOT, GPT, LDH or blood counts. Urine analysis (urea, uric acid, creatinine, total protein, Na and K), as well as histopathological investigation, showed no abnormalities. These results taken as a whole indicate that the seeds of C. maxima as used in Brazilian folk medicine are not toxic for rats and swine.

Structure and catalytic mechanism of glucosamine 6-phosphate deaminase from Escherichia coli at 2.1 Å resolution

Background: Glucosamine 6-phosphate deaminase from Escherichia coli is an allosteric hexameric enzyme which catalyzes the reversible conversion of D-glucosamine 6-phosphate into D-fructose 6-phosphate and ammonium ion and is activated by N-acetyl-D-glucosamine 6-phosphate. Mechanistically, it belongs to the group of aldose-ketose isomerases, but its reaction also accomplishes a simultaneous amination/deamination. The determination of the structure of this protein provides fundamental knowledge for understanding its mode of action and the nature of allosteric conformational changes that regulate its function. Results: The crystal structure of glucosamine 6-phosphate deaminase with bound phosphate ions is presented at 2.1 Å resolution together with the refined structures of the enzyme in complexes with its allosteric activator and with a competitive inhibitor. The protein fold can be described as a modified NAD-binding domain. Conclusions: From the similarities between the three presented structures, it is concluded that these represent the enzymatically active R state conformer. A mechanism for the deaminase reaction is proposed. It comprises steps to open the pyranose ring of the substrate and a sequence of general base-catalyzed reactions to bring about isomerization and deamination, with Asp72 playing a key role as a proton exchanger.

Acute, subchronic and chronic 2,4-dichlorophenoxyacetic acid (2,4-D) intoxication in rats

The acute, subchronic and chronic toxicities of 2,4- dichlorophenoxyacetic acid (2,4-D) were studied in rats. Animals were exposed acutely (600 mg/kg), subchronically (200 ppm for 30 d) and chronically (200 ppm for 180 d) to 2,4-D by the oral route. Clinical, laboratory and histopathological methods were used as indicators of toxicity. After acute exposure, the herbicide decreased locomotor activity and induced ataxia, sedation, muscular weakness (mainly of the hind quarters) and gasping for breath; increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), amylase activities and creatinine levels; decreased total protein (TP) and glucose levels; and increased hematocrit values. Subchronic and chronic 2,4-D exposures did not induce overt clinical signs or symptoms of intoxication. However, subchronic herbicide exposure increased AST activity and albumin and hematocrit values, and chronic exposure increased AST, AP and LDH activities, decreased amylase and glucose levels, but did not change hematocrit values. Chromatographic analysis of the serum of chronically exposed rats showed the presence of the herbicide; the amount found (3.76 ± 1.16 mg/ml) suggested the absence of 2,4-D accumulation within the body. Although macroscopic or histopathological lesions were not observed in acutely, subchronically or chronically 2,4-D exposed rats, the laboratory data obtained suggest tissue injuries after dosing, since the results are considered early indicators of primarily hepatic and muscle tissue damage.

Efficacy, safety and tolerability of terbinafine for Tinea capitis in children: Brazilian multicentric study with daily oral tablets for 1, 2 and 4 weeks

Background: Tinea capitis is a common skin disease seen predominantly in children. The standard therapies for this disease are griseofulvin and ketoconazole. Nevertheless, these drugs have drawbacks in that they are only fungistatic and require treatment for at least 6 weeks. Previous studies with oral terbinafine for the treatment of Tinea capitis have shown that this agent is effective when given for 4 weeks, comparable to an 8-week regimen with griseofulvin. To date there is no data on the use of oral terbinafine in Brazilian children. Objectives: To assess the efficacy, safety and tolerability of oral terbinafine in short-term treatments (1-, 2- and 4-week treatment) of Tinea capitis in children. Patients and methods: One hundred and thirty-two children aged 1-14 years were enrolled in this study, but only 107 were considered for the final efficacy analysis. Diagnosis included clinical assessment and examination by Wood's light. Confirmation was obtained by direct microscopy and culture for fungus. Terbinafine dosage (125 or 250 mg/day) was adjusted according to patient weight. Efficacy was evaluated both by clinical and mycological assessment. Safety and tolerability variables included data on adverse reaction and clinical laboratory evaluations. Results: Mycological evaluation in the follow-up visit at week 12 showed negative direct microscopy and culture results in 48.6, 60.5 and 69.7% patients in groups 1-, 2- and 4-week, respectively (n.s.). At week 12, 84.8% patients in group 4-week achieved clinical cure with a significant difference compared to groups 1- and 2-week, 54.3 and 60.5%, respectively (P < 0.01). Adverse reactions were present in 4.8, 6.8 and 10.9% of patients in groups 1-, 2- and 4-week, respectively. Terbinafine was not associated with clinically relevant increases in liver function tests. Conclusions: Terbinafine is an effective, well tolerated and safe antifungal agent for the treatment of Tinea capitis m children. The shorter duration of treatment resulted in lower cure rates. However, it is important to note that depending on the severity of the disease, a 1-week-only treatment can also be effective in this indication.

Efeitos de diferentes doses de tenoxicam sobre a medula espinhal e as meninges. Estudo experimental em caes

Background and Objectives. The analgesic actions of nonsteroidal anti-inflammatory drugs (NSAID) result from the inhibition of the peripheral synthesis of prostaglandins. In spite of the emphasis on the peripheral action, several studies have shown the potential central action of such drugs. In rats, NSAID doses insufficient to block pain when systemically administered were effective when intrathecally injected. This effect could be mediated by interaction with descending serotoninergic ways together with neurotransmission modulation of glycine or N-methyl-D-aspartate receptors. Our goal was to study the effect of different tenoxican doses in the histology of dogs spinal cord and meninges. Methods. Thirty two dogs (7 to 17 kg) were randomly distributed in four groups: G1 - Control with distilled water (DW); G2 - 2 mg tenoxican diluted in DW; G3 - 4 mg tenoxican diluted in DW; G4 - 10 mg tenoxican diluted in DW in a constant volume of 1 ml. Anesthesia was induced with etomidate and fentanyl and dural puncture was performed with a 25G spinal needle in interspace L6-7. Animals were observed for 72 hours and subsequently euthanized by electrocution. Lumbar and sacral spinal cord segments were removed for further histologic examination. Results. All animals were clinically normal during the observation period and there has been no histologic alteration of the nervous system and meninges. Conclusions. In our experimental model intrathecal tenoxican doses up to 10 mg have not triggered nervous tissue or meningeal injuries in dogs.

Toxic mechanism of cadmium exposure on cardiac tissue

The presence of toxic substances in the workplace environment requires systematic evaluation of exposure and health status in exposed subjects. Cadmium is a highly toxic element found in water. Although free mediated cellular damage and reactive oxygen species (ROS), had been theorized as contributing to the cadmium mechanism of toxicity, and recent investigations have established that free radicals may be important contributors to cardiac dysfunction, there is little information on the effect of cadmium exposure on markers of oxidative stress in cardiac tissue. Cadmium exposure (Cd2+ - 100 mg/1-from CdCl2) in drinking water, during 15 days, significantly increased lipoperoxide and decreased the activities of superoxide dismutase and glutathione peroxidase. No alterations were observed in catalase activity in heart of rats with cadmium exposure. We also observed decreased glycogen and glucose concentration and increased total lipid content in cardiac tissue of rats with cadmium exposure. The decreased activities of alanine transaminase and aspartate transaminase reflected decreased metabolic protein degradation, and increased lactate dehydrogenase activity was related with increases in capacity of glycolysis. Since the metabolic pathways were altered by cadmium exposure, we can conclude that Cd2+ exposure induced ROS and initiate some series of events that occur in the heart and resulted in metabolic pathways alterations.

Enzymatic activity of hypopharyngeal gland extracts from workers of Apis mellifera (Hymenoptera, Apidae, Apinae)

This research presents a comparative study of enzymatic activity of the hypopharyngeal gland extracts from workers of Apis mellifera in three physiologic stages: newly emerged, nurse and forager workers, with the objective of contributing to the comprehension of the gland function. In order to determinate the enzymes present in the extracts, the Api Zym kit (Bio Mérieux) was used to test the activity of 19 different enzymes. The enzymes found in larger amounts only in the hypopharyngeal glands from certain individuals were the following: in newly emerged workers, the N-acetyl-down double arrow sign-glucosaminidase that may be digesting the chitin of some food ingested by the bee; in forager workers, the acid phosphatase that is likely acting in authophagic processes, the a-glucosidase, in the processing of nectar into honey, and the down double arrow sign-glucosidases, in the pollen digestion.

Effect of hydrated sodium calcium aluminosilicate on the prevention of the toxic effects of ochratoxin

We studied the efficacy of hydrated sodium calcium aluminosilicate (HSCAS) as an inhibitor of the toxic effects of ochratoxin in broilers from 1 to 42 d of age. A total of 288 broilers was distributed into four treatments with four replicates of 18 birds each: T1, control; T2, 0.25% HSCAS; T3, 2 ppm of ochratoxin; T4, 0.25% HSCAS + 2 ppm ochratoxin. The parameters evaluated were feed intake; weight gain; feed conversion; relative weights of the liver, kidneys, and bursa; and serum levels of Ca, P, total protein (TP), aspartate aminotransferase (AST) and γ-glutamiltransferase (GGT). Ochratoxin in the diet negatively affected (P < 0.05) all performance parameters evaluated when the birds were 21 and 42 d of age. However, HSCAS did not affect performance, and there was no interaction between HSCAS and dietary ochratoxin. The liver and the kidneys of birds fed ochratoxin with or without HSCAS were relatively heavier (P < 0.05) than those of the control birds, demonstrating the influence of ochratoxin, but not of HSCAS, on the relative weight of these organs. Although the bursa of birds exposed to ochratoxin with or without HSCAS had a lower relative weight as compared to control birds, the difference was not significant. Ca, P, and TP serum levels were lower (P < 0.05) in birds exposed to ochratoxin, whereas AST and GGT levels were higher (P < 0.05) in these birds. These results reflect that ochratoxin in the diet impaired the productivity indexes and that HSCAS did not improve these parameters.

Dietary restriction: Metabolic shifting for cardiac health

Purpose: To determine the effect of dietary restriction on metabolic pathways and the relationship of the metabolic shifting on antioxidant enzymes in cardiac tissue. Design: Randomized, controlled study. Male rats at 60 days old were randomly divided into four groups. Materials and Methods: The rats of control groups C30 and C60 were given free access to the diet over 30 and 60 days. The rats of the DR30 group were fed 60% of the chow consumed by the control groups over 30 days. The animals of the DR60 group ate 60% of the amount consumed by the C60 group over 60 days. Serum was used for total protein, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Protein, glycogen, total lipids, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), LDH, AST and ALT were determined in cardiac tissue. Results: Dietary restriction induced diminished serum and cardiac LDH activities. AST activities were lower in the serum and cardiac muscle of the DR60 animals. Dietary restriction induced elevated total lipid concentrations in cardiac muscle. No significant differences were observed in total protein and glycogen content among the groups. Antioxidant enzyme determinations demonstrated increased cardiac GSH-Px activities in the DR60 animals and increased SOD activities in the cardiac tissue of both feed-restricted groups. Conclusions: Dietary restriction was protective against oxidative stress in the heart by improving cardiac endogenous antioxidant defences and shifting the metabolic pathway for energy production.

Progression of liver fibrosis in blood donors infected with hepatitis C virus

Background/Aims. Chronic hepatitis by HCV is progressive towards cirrhosis, with variable rate. We evaluated the rate of fibrosis progression (RFP), risk factors associated with advanced fibrosis (F3 and F4), and estimated the evolution time to cirrhosis. Methods. We transversely selected 142 blood donors infected only with HCV, with a known route of infection, submitted to liver biopsy at admission. RFP= ratio between stage of fibrosis (METAVIR)/estimated duration of infection in years. Non-parametric tests and logistic regression analysis, with significance level of 5% were used. Results. Median RFP was 0.086 U/year (0.05 - 0.142). Ten patients had F4 and 25 had F3. Median RFP values were significantly different (p=0.001) from one age group at contamination to the others and ALT and AST levels. There were no differences in the expected evolution to cirrhosis between intermediate fibrosers (F2) and the rapid fibrosers (F3 and F4). The independent variables associated with advanced fibrosis were ALT (OR 7.2) and GGT (OR 6.4) and age at inclusion (OR 1.12). Conclusion. This study suggests that RFP is extremely variable, it is exponential with age, and mainly influenced by host characteristics, especially age at contamination and possibly ethnical group. These asymptomatic patients had high percentage of fibrosis F2, F3 and F4.

Effect of Brazilian propolis on experimental hepatotoxicity in rats

Propolis (bee glue) is one of the major hive products of bees and is rich in flavonoids, which are known for their antioxidant activities. The aim of this study was to evaluate the hepatoprotective effects of the ethanolic extract of propolis (EEP) against experimental carbon tetrachloride (CCl 4)-induced liver toxicity in rats by means of biochemical indices. The animals were divided into 4 groups: GI= received mineral oil; GII= CCl 4(4mL/kg; Lp., single dose) treated; GIII= CCl4 (4mL/kg; i.p., single dose) treatment followed by ethanolic extract of propolis (100mg/kg) for gavage from the species Tetragonisca angustula, daily for 3 days and GIV= CCl4 (4mL/kg; i.p., single dose) treatment followed by ethanolic extract of propolis (100mg/kg) for gavage from the species Nannotrigonea testaceicornes, daily, for 3 days. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cholesterol and triacylglycerols were estimated after 3 days. CCl 4 caused a maximum increase (p<0,01) above biochemical parameters. As compared to CCl4 group (GII), the EEP (GIII and GIV) showed reduction in cholesterol, triacylglycerol, ALT, AST and alkaline phosphatase activity in the serum. In conclusion, these data indicate that EEP improved the dyslipidaemia, moreover, significantly attenuated increases in serum ALT and AST activities in rats with liver damage induced by carbon tetrachloride.

Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of anesthesia with isoflurane and halothane in horses undergoing arthroscopic surgery

Objective - To compare hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of halothane and isoflurane in horses undergoing arthroscopic surgery. Animals - 8 healthy adult horses. Procedure - Anesthesia was maintained with isoflurane or halothane (crossover study). At 6 intervals during anesthesia and surgery, cardiopulmonary variables and related derived values were recorded. Recovery from anesthesia was assessed; gastrointestinal tract motility was subjectively monitored for 72 hours after anesthesia. Horses were administered chromium, and fecal chromium concentration was used to assess intestinal transit time. Venous blood samples were collected for clinicopathologic analyses before and 2, 24, and 48 hours after anesthesia. Results - Compared with halothane-anesthetized horses, cardiac index, oxygen delivery, and heart rate were higher and systemic vascular resistance was lower in isoflurane-anesthetized horses. Mean arterial blood pressure and the dobutamine dose required to maintain blood pressure were similar for both treatments. Duration and quality of recovery from anesthesia did not differ between treatments, although the recovery periods were somewhat shorter with isoflurane. After isoflurane anesthesia, gastrointestinal motility normalized earlier and intestinal transit time of chromium was shorter than that detected after halothane anesthesia. Compared with isoflurane, halothane was associated with increases in serum aspartate transaminase and glutamate dehydrogenase activities, but there were no other important differences in clinicopathologic variables between treatments. Conclusions and clinical relevance - Compared with halothane, isoflurane appears to be associated with better hemodynamic stability during anesthesia, less hepatic and muscle damage, and more rapid return of normal intestinal motility after anesthesia in horses undergoing arthroscopic procedures.