Neonatal exposure to bisphenol A advances pubertal development in female rats

Neonatal exposure to bisphenol A (BPA) is hypothesized to advance pubertal development. However, the effects of neonatal BPA exposure on pubertal development has not been described. In this study, female Sprague‐Dawley rats were exposed to 0.05, 0.5, 5, or 10 mg·kg^?1·day^?1 BPA, or corn oil vehicle alone from postnatal day 1 (PND1) to PND10 via subcutaneous injection. We evaluated day of vaginal opening (DVO), ovarian morphology, serum hormone concentrations, and hypothalamic expression of Gnrh1 and Kiss1 in female rats at PND35. DVO was significantly advanced in rats exposed to 5 and 10 mg·kg^?1·day^?1 BPA. Serum hormone concentrations increased as BPA dose increased. Additionally, hypothalamic Gnrh1 and Kiss1 expression were increased with BPA exposure; rats exposed to 10 mg·kg^?1·day^?1 BPA had significantly upregulated hypothalamic Gnrh1 and Kiss1 expressions in terms of both messenger RNA and protein levels. Our results suggest that exposure to a 10 mg·kg^?1·day^?1 dose of BPA might advance pubertal development significantly. In addition, within the range of 0 to 10 mg·kg^?1·day^?1, neonatal exposure to BPA may affect pubertal development in a dose‐dependent manner.     

Protective effects of antioxidant combination against D‐galactosamine‐induced kidney injury in rats

The protective effects of an antioxidant combination in kidney injury induced by the injection of D‐galactosamine (D‐GaIN) were examined in the present study. Sprague Dawley female rats were used and divided into four groups as follows: (1) animals injected physiological saline solution, intraperitoneally, (2) animals treated with the combination of ascorbic acid (100 mg kg^?1 day^?1), β‐carotene (15 mg kg^?1 day^?1), α‐tocopherol (100 mg kg^?1 day^?1), and sodium selenate (0.2 mg kg^?1 day^?1) for three days orally, (3) rats injected D‐GaIN (500 mg kg^?1) intraperitoneally as a single dose, and (4) animals treated with the antioxidant combination for three days, then injected D‐GaIN. The tissue and blood samples of animals were collected for morphological and biochemical evaluations. Histopathological injury in kidney tissues was observed together with a significant increase in tissue lipid peroxidation (LPO) level, myeloperoxidase (MPO), lactate dehydrogenase, catalase and superoxide dismutase (SOD) activities, and serum creatinine and urea levels, and a significant decrease in glutathione level and glutathione peroxidase activity in D‐GaIN injected rats. However, a decrease in the degenerative changes was detected in the kidney tissue of D‐GaIN + antioxidant group, and biochemical results showed reversed effects. In conclusion, it seems reasonable to conclude that the treatment of the antioxidant combination has a protective effect on D‐GaIN‐induced kidney injury of rats. Copyright © 2010 John Wiley & Sons, Ltd.     

Montelukast abrogates prednisolone‐induced hepatic injury in rats: Modulation of mitochondrial dysfunction,oxidative/nitrosative stress,and apoptosis

The aim of this study was to investigate the protective effect of montelukast (MTK) against prednisolone‐induced hepatic injury in rats. Twenty‐eight male albino rats were categorized into four equal groups. Group I served as the control group; group II: rats orally received prednisolone (5 mg·kg^?1·d^?1) for 30 days; groups III and IV: rats orally received MTK at 10 and 20 mg·kg^?1·d^?1, respectively, simultaneously with prednisolone for 30 days. Serum liver enzymes, hepatic mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic markers were evaluated, and the results were confirmed by histopathological examination. MTK showed significant hepatic protection evidenced by alleviated histological lesion and improvement of mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic changes induced by prednisolone, with more profound protection in higher MTK dose (20 mg·kg^?1). In view of these findings, we can conclude that MTK may have hepatoprotective potential, beyond its therapeutic value for asthmatic patients during their course of corticosteroid therapy.     

Methylmercury toxicity: amelioration by selenium and water‐soluble chelators as N‐acetyl cysteine and dithiothreitol

The protective potential of chelators, i.e. N‐acetyl cysteine (0.6 mg /kg, intraperitoneally) and dithiothreitol (15.4 mg kg^?1, intraperitoneally) with selenium (0.5 mg kg^?1, pre‐oral) were evaluated individually and in combination against methylmercury‐induced biochemical alterations and oxidative stress consequences. Forty‐two male Sprague–Dawley rats were exposed with methylmercury (1.5 mg kg^?1, pre‐oral) daily for 21 days followed by different treatments for five consecutive days. Administration of methylmercury caused significant enhancement in the release of transaminases, alkaline phosphatases and lactate dehydrogenases in serum. A significant increased was observed in lipid peroxidation level with a concomitant decreased in glutathione content after methylmercury exposure in liver, kidney and brain. Hepatic microsomal drug metabolizing enzymes (aniline hydroxylase and amidopyrine N‐demethylase) of cytochrome p4502E₁ showed sharp depletion after methylmercury exposure. Alterations in histological changes in liver, kidney and brain were also noted in methylmercury administered group. All treated groups showed recovery pattern, but the combined treatments with N‐acetyl cysteine and dithiothreitol in combination with selenium were more effective than that with either alone treatments in recovering blood biochemical changes after methylmercury toxicity. In conclusion, the results demonstrated that combination therapy may recover all blood biochemical alterations and offer maximum protection against methylmercury‐induced toxicity. Copyright © 2014 John Wiley & Sons, Ltd.     

Novel action of 3,4-DAA ameliorating acute liver allograft injury

The anti‐allergic drug, N‐(3,4‐dimethoxycinnamonyl) anthranilic acid (3,4‐DAA), is a synthetic anthranilic acid derivative that has been used therapeutically in Japan for many years. In this study, to investigate the effects of 3,4‐DAA in allograft immunorejection model, liver orthotopic transplants were performed using inbred male Dark Agouti donors and Lewis rat recipients (allografts). The levels of indoleamine 2,3‐dioxygenases (IDO) enzymic activities in five groups, allografts (control), dimethyl sulphoxide‐treated group (vehicle control), 200 mg·kg^–1·day^–1 of 3,4‐DAA‐treated group and 200 mg·kg^–1·day^–1 of 3,4‐DAA + 5 mg·ml^–1 of 1‐methyl‐D‐tryptophan (1‐MT)‐treated group were confirmed by determination of L‐kynurenine (L‐Kyn) concentrations. The serum alanine aminotransferase levels in 3,4‐DAA‐treated rats significantly decreased compared with those in mock and control group, whereas treatment of 1‐MT in allografts led to the opposite effect. Administration of 3,4‐DAA reduced histological severity of allograft immunorejection, decreased serum levels of cytokines tumour necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ), and raised serum levels of interleukin‐10 (IL‐10), suggesting that 3,4‐DAA has both anti‐inflammatory and anti‐immunorejection properties through IDO in immune regulation and may therefore be useful in filling an unmet need, in the treatment of allograft immunorejection. Copyright © 2011 John Wiley & Sons, Ltd.     

L‐NAME co‐treatment prevent oxidative damage in the lung of adult Wistar rats treated with vitamin A supplementation

Based on the fact that vitamin A in clinical doses is a potent pro‐oxidant agent to the lungs, we investigated here the role of nitric oxide (NO^?) in the disturbances affecting the lung redox environment in vitamin A‐treated rats (retinol palmitate, doses of 1000–9000 IU·kg^?1·day^?1) for 28 days. Lung mitochondrial function and redox parameters, such as lipid peroxidation, protein carbonylation and the level of 3‐nytrotyrosine, were quantified. We observed, for the first time, that vitamin A supplementation increases the levels of 3‐nytrotyrosine in rat lung mitochondria. To determine whether nitric oxide (NO ?) or its derivatives such as peroxynitrite (ONOO‐) was involved in this damage, animals were co‐treated with the nitric oxide synthase inhibitor L‐NAME (30 mg·kg^?1, four times a week), and we analysed if this treatment prevented (or minimized) the biochemical disturbances resulting from vitamin A supplementation. We observed that L‐NAME inhibited some effects caused by vitamin A supplementation. Nonetheless, L‐NAME was not able to reverse completely the negative effects triggered by vitamin A supplementation, indicating that other factors rather than only NO? or ONOO‐ exert a prominent role in mediating the redox effects in the lung of rats that received vitamin A supplementation. Copyright © 2011 John Wiley & Sons, Ltd.     

Caffeine antagonizes several central effects of diazepam

In spinal cats, caffeine (3–30 mg·kg^?1 i.v.) reduced the increase of dorsal root potentials (DRPs) caused by diazepam (0.1–1 mg·kg^?1 i.v.) without affecting the prolongation of DRPs evoked by phenobarbitone (10–20 mg·kg^?1 i.v.). Caffeine antagonized the depression by diazepam, but not that by phenobarbitone, of the ventral root-evoked Renshaw cell discharge. In unrestrained cats, 50 mg·kg^?1 caffeine i.p. abolished the elevation induced by 1 mg·kg^?1 diazepam i.p. of the threshold for eliciting a rage reaction by stimulation of the lateral hypothalamus, but was ineffective against the threshold increase caused by 20 mg·kg^?1 phenobarbitine i.p. In the horizontal wire test in mice, caffeine was more potent in reversing the depression of performance induced by diazepam that that by phenobarbitone (ED50 1.8 mg·kg^?1 and 139 mg·kg^?1 p.o., respectively). The reduction of skeletal muscle tone in mice produced by diazepam was antagonized by low doses of caffeine (ED50 0.53 mg·kg^?1 p.o.). While caffeine at low doses (0.3-3 mg·kg^?1 p.o.) abolished the anticonflict effect of diazepam in rats, high doses (ED50 160 mg·kg^?1 p.o.) were necessary to antagonize the anticonvulsant effect of diazepam on pentylene-tetrazole-induced seizures in mice. The interaction between caffeine and diazepam is not due to a competition at the benzodiazepine receptors but may involve purinergic mechanisms.     

The Protective Effect of N-Acetylcysteine on Oxidative Stress in the Brain Caused by the Long-Term Intake of Aspartame by Rats

Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione (GSH) homeostasis. N-Acetylcysteine provides the cysteine that is required for the production of GSH, being effective in treating disorders associated with oxidative stress. We investigated the effects of N-acetylcysteine treatment (150 mg kg^?1, i.p.) on oxidative stress biomarkers in rat brain after chronic aspartame administration by gavage (40 mg kg^?1). N-Acetylcysteine led to a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, and carbonyl protein levels, which were increased due to aspartame administration. N-Acetylcysteine also resulted in an elevation of superoxide dismutase, glutathione peroxidase, glutathione reductase activities, as well as non-protein thiols, and total reactive antioxidant potential levels, which were decreased after aspartame exposure. However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration. Furthermore, catalase and glutathione S-transferase, whose activities were reduced due to aspartame treatment, remained decreased even after N-acetylcysteine exposure. In conclusion, N-acetylcysteine treatment may exert a protective effect against the oxidative damage in the brain, which was caused by the long-term consumption of the acceptable daily dose of aspartame by rats.     

The Combined Effects of Iron Excess in the Diet and Chromium(III) Supplementation on the Iron and Chromium Status in Female Rats

Inadequate iron supply has significant consequences to health. There are some relations between the metabolism of different trace elements, such as iron, zinc, copper and chromium. However, the direction of these interactions can be antagonistic or synergistic, and it depends on many factors. The aim of the study was to evaluate the combined effects of supplementary of chromium(III) propionate complex (Cr3) with iron excess on the Cr and Fe status in healthy female rats. The 36 healthy female Wistar rats were divided into six experimental groups (six animals in each) with different Fe levels—adequate (45 mg kg^?1—100% RDA) and high (excessive—180 mg kg^?1—400% RDA). At the same time, they were supplemented with Cr(III) at doses of 1, 50 and 500 mg kg^?1 of diet: C1—control (Fe 45 mg kg^?1, Cr 1 mg kg^?1); C50 (Fe 45 mg kg^?1, Cr 50 mg kg^?1); C500 (Fe 45 mg kg^?1, Cr 500 mg kg^?1); H1 (Fe 180 mg kg^?1, Cr 1 mg kg^?1); H50 (Fe 180 mg kg^?1, Cr 50 mg kg^?1); H500 (Fe 180 mg kg^?1, Cr 500 mg kg^?1). The serum iron level and total iron binding capacity (TIBC) were measured with colorimetric methods. The serum ferritin level was measured by means of electrochemiluminescence immunoassay. The serum transferrin level was measured with the ELISA method. Haematological measurements were made with an automated blood analyser. The Cr and Fe tissular levels were measured with the AAS method. The exposure to a high level of Fe(III) alone or in combination with Cr caused Fe accumulation in tissues, especially in the liver and kidneys, but there were no significant changes in the TIBC, transferrin, ferritin concentration in the serum and most haematological parameters. Moreover, the serum, hepatic and renal Cr concentrations decreased. The doses of supplementary Cr(III) given separately or in combination with high level of Fe(III) disturbed the Cr content in the liver and kidneys of healthy female rats. However, they did not change most of the parameters of Fe metabolism, except the Fe kidney concentration. Supplementary Cr3 decreased the renal Fe level in groups with adequate Fe content in the diet. However, the renal Fe levels increased along with a higher Cr level in the diet in groups with high Fe content. The findings proved a relationship between Fe(III) and Cr(III) metabolism in healthy female rats. However, the direction of change varied and depended on relative amounts of these elements in the diet.     

Temporal-spatial distribution,environmental significance and release risks of phosphorus in the sediments of a tropical mountain’s deep drinking water reservoir in southeastern China

In this study, the fractionation and distribution of phosphorus (P) in the core sediments of the Shanmei reservoir were investigated by using the chemical extraction method in directions for the first time in order to understand its bio-availability, adsorption characteristics, potential release and environmental significance. The results of the study showed that P in the sediments mainly consisted of inorganic phosphorus (IP) and that IP mainly consisted of non-apatite phosphorus (NAIP). The horizontal and temporal distributions of the P fractions were different from each other, but the vertical distribution was similar, which indicated a trend of stabilization after falling. The content of total phosphorus (TP), IP, organic phosphorus (OP), NAIP, apatite phosphorus (AP), and bio-available phosphorus (BAP) in the sediments during the three seasons ranged from 193.85 to 1664.05 mg·kg^?1, 126.90 to 1127.70 mg·kg^?1, 43.74 to 669.29 mg·kg^?1, 57.62 to 937.07 mg·kg^?1, 32.58 to 250.71 mg·kg^?1, and 41.06 to 871.82 mg·kg^?1, respectively. NAIP contents in the sediments accounted for more than 50% of TP. Using an analysis from three aspects, the eutrophication risk index (ERI) could be used to assess the potential release of P in the sediments, and there was a high release risk of P in the sediments in the Shanmei reservoir.     

Induced anti-oxidant activity in soybean alleviates oxidative stress under moderate boron toxicity

The effect of B toxicity on antioxidant responses of soybean (Glycine max) cv. Athow was investigated by growing plants for 43 days at 0.2 (control), 2 and 12 mg B kg^?1. At the end of the treatment period, shoot growth, lipid peroxidation level, the activities of antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POX), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR), and their isoenzymes in leaves were measured. Boron concentration in leaves was significantly increased by the increasing levels of B treatment from 43 to 522 mg kg^?1, and shoot dry matter was depressed at 12 mg B kg^?1. Significant increases in SOD, CAT, and APX activities were determined in leaves under 12 mg B kg^?1; however, GR activities were decreased while POX activity was unchanged. Increased enzymic antioxidant activity arose from a combination of newly formed isoenzymes and activation of existing isoenzymes. By contrast, SOD and GR activities were decreased by 2 mg B kg^?1 concentration as compared to the control groups while POX activity was increased and the activity of CAT did not change. Malondialdehyde content increased under 2 mg B kg^?1 but decreased under 12 mg B kg^?1. These results suggest that higher antioxidant activity observed under 12 than at 2 mg B kg^?1 provided higher free radical-scavenging capacity, and thus a lower level of lipid peroxidation in Athow. While the induction of increased antioxidant activity was related to internal boron levels, the signaling and coordination of responses remain unclear.     

Effects of Long-Term Treatment with Quercetin on Cognition and Mitochondrial Function in a Mouse Model of Alzheimer’s Disease

Amyloid-β (Aβ)-induced mitochondrial dysfunction has been recognized as a prominent, early event in Alzheimer’s disease (AD). Therefore, therapeutics targeted to improve mitochondrial function could be beneficial. Quercetin, a bioflavanoid, has been reported to have potent neuro-protective effects, but its preventive effects on Aβ-induced mitochondrial dysfunction and cognitive impairment have not been well characterised. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two quercetin (either 20 or 40 mg kg^?1 day^?1) groups, or an Aricept (2 mg kg^?1 day^?1) group. After 16 weeks of treatment, we observed beneficial effects of quercetin (40 mg kg^?1 day^?1), including lessening learning and memory deficits, reducing scattered senile plaques, and ameliorating mitochondrial dysfunction, as evidenced by restoration of mitochondrial membrane potential, reactive oxygen species and ATP levels in mitochondria isolated from the hippocampus compared to control. Furthermore, the AMP-activated protein kinase (AMPK) activity significantly increased in the quercetin-treated (40 mg kg^?1 day^?1) group. These findings suggest that a reduction in plaque burden and mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms by which quercetin improves cognitive functioning in the APPswe/PS1dE9 transgenic mouse model of AD.     

Changes in amino acid composition in the tissues of African catfish (Clarias gariepinus) as a consequence of dietary L-carnitine supplements

A study was undertaken to examine the effect of different amounts of dietary lysine (13 and 21 g kg^?1 diet), lipid (80 and 160 g kg^?1 diet) and L ‐carnitine (0.2 and 1.0 g kg^?1 diet) on growth performance, proximate composition and amino acid metabolism of the African catfish (Clarias gariepinus). Juvenile African catfish (23 ± 1.5 g/fish) were stocked into 70‐L aquaria (16 aquaria, 28 fish/aquarium) connected to a recirculation system during a maximum period of 74 days. All groups were fed at a level of 24 g kg^?0.8 day^?1 in an experiment run at pair feeding. Animals receiving 1.0 g carnitine accumulated up to six times more carnitine in their tissues than animals receiving 0.2 g (P < 0.05). Acyl‐carnitine and free L ‐carnitine levels increased in the whole body and in tissues. Dietary L ‐carnitine supplements increased protein‐to‐fat ratios in the body, but did not affect growth rate. Protein‐to‐fat ratios were only affected when the biosynthesis capacity of L ‐carnitine was restricted due to low lysine levels and when there was a shortage of dietary fat. When lysine was offered at 21 g kg^?1 feed, dietary L ‐carnitine supplements did not affect the amino acid concentrations of body tissues. Dietary L ‐carnitine supplements raised the concentration of glutamic acid > aspartic acid > glycine > alanine > arginine > serine > threonine in skeletal muscle tissue (P < 0.05). Total amino acid concentration in muscle and liver tissues (dry‐matter basis) increased from 506 to 564 and from 138 to 166 mg g^?1, respectively, when diets were offered with high L ‐carnitine, low lysine and low fat levels. These data suggest that dietary L ‐carnitine supplementation may increase fatty acid oxidation and possibly decrease amino acid combustion for energy.     

Seagrass feeding choices and digestive strategies of the herbivorous fish Sarpa salpa

This is the first study investigating the plant–herbivore interaction between Sarpa salpa, which has overgrazed seagrass transplants in Portugal, and the seagrasses Cymodocea nodosa, Zostera marina and Zostera noltii, which have been considered for restoration. When offered the choice between the three seagrasses in outdoor tanks, adult S. salpa clearly preferred Z. noltii. Testing the seagrasses separately, mean ± s.d. feeding rates ranged from 21 ± 11 g seagrass fresh mass kg^?1 fish mass day^?1 for Z. marina to 32 ± 9 g seagrass fresh mass kg^?1 fish mass day^?1 for C. nodosa and 40 ± 11 g seagrass fresh mass kg^?1 fish mass day^?1 for Z. noltii (temperature = 16° C). Food‐processing rate in S. salpa did not differ between seagrasses, and there was no evidence of a regulation of processing rate according to food intake. Seagrasses differed substantially in nitrogen content and C:N, with C. nodosa containing the highest nitrogen content and lowest C:N (2·5 ± 0·1% and 14·0 ± 1·0), followed by Z. noltii (2·1 ± 0·1% and 17·0 ± 1·0) and Z. marina (1·4 ± 0·1% and 26·0 ± 2·0). Food‐processing rate in S. salpa and the nutritional value of the seagrasses were not correlated with the observed feeding preference and rate. The study suggests that C. nodosa and Z. marina are less at risk of overgrazing by S. salpa and might thus be preferable to Z. noltii for seagrass restoration in areas with noticeable abundances of this fish.     

The relative efficacy of aminoguanidine and pentoxifylline in modulating endotoxin-induced cardiac stress

This study investigates the effect of aminoguanidine (AG), a selective inducible nitric oxide synthase (iNOS) inhibitor, and pentoxifylline (PTX), a tumour necrosis factor–alpha (TNF‐α) inhibitor, on lipopolysaccharide (LPS)‐induced cardiac stress. Rats were divided into four groups: group I served as a control, group II (LPS) received a single intraperitoneal injection of LPS (10 mg·kg^–1), group III (LPS+AG) and group IV (LPS+PTX) were injected with either AG (100 mg·kg^–1) or PTX (150 mg·kg^–1) intraperitoneally 10 days prior to LPS administration. Normalization of cardiac levels of nitrite/nitrate (NO_X), malondialdehyde (MDA), glutathione (GSH), heme oxygenase‐1 (HO‐1), glutathione peroxidase (GPx) and Na⁺, K⁺‐ATPase activities was evident in the AG group. Both AG and PTX decreased the elevated serum TNF‐α levels, the activities of lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac myeloperoxidase (MPO). The levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and phosphocreatine (PCr) were enhanced following AG and PTX pretreatments. Calcium (Ca²⁺) levels were altered, and the histopathological observations supported the described results. Conclusively, the study highlights the cardioprotective potential of AG and PTX with superior results from AG. These findings reveal the relative contribution of nitric oxide and TNF‐α to oxidative stress and energy failure during endotoxemia. Copyright © 2011 John Wiley & Sons, Ltd.     

Effects of desipramine on the antioxidant status in rat tissues at carrageenan‐induced paw inflammation

The pathogenesis of many diseases and different pathological conditions, including inflammation, is associated with excess production of reactive oxygen species (ROS). The present study aimed to investigate the effects of the antidepressant desipramine (DES) on carrageenan (CG)‐induced inflammation, as well as on the endogenous levels of cell enzyme and non‐enzyme antioxidants in rat liver and spleen, 4 and 24 h after CG injection. The intra‐plantar CG injection into the right hind paw resulted in a time‐dependent increase in the paw volume; the maximum of CG‐induced edema peak was in 2–4 h. A single DES dose of 20 mg·kg^?1, administered 30 min before CG, had no effect on paw edema, whereas the higher drug dose used (50 mg·kg^?1) suppressed the edematous response to CG. The latter drug dose protected CG‐induced decrease of glutathione (non‐enzyme antioxidant) in the liver; it did not affect CG‐unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose‐6‐phosphate dehydrogenase (enzyme, important for the activity of glutathione‐conjugated antioxidant enzymes) in both liver and spleen. The drug showed an efficient antioxidant capacity in ROS‐generating chemical systems; it was higher than that of fluoxetine (another type of antidepressant). The present results suggest that the good antioxidant activity of DES might contribute to its beneficial effects in liver injuries. Copyright © 2011 John Wiley & Sons, Ltd.     

Bacterial community analysis in chlorpyrifos enrichment cultures via DGGE and use of bacterial consortium for CP biodegradation

The organophosphate pesticide chlorpyrifos (CP) has been used extensively since the 1960s for insect control. However, its toxic effects on mammals and persistence in environment necessitate its removal from contaminated sites, biodegradation studies of CP-degrading microbes are therefore of immense importance. Samples from a Pakistani agricultural soil with an extensive history of CP application were used to prepare enrichment cultures using CP as sole carbon source for bacterial community analysis and isolation of CP metabolizing bacteria. Bacterial community analysis (denaturing gradient gel electrophoresis) revealed that the dominant genera enriched under these conditions were Pseudomonas, Acinetobacter and Stenotrophomonas, along with lower numbers of Sphingomonas, Agrobacterium and Burkholderia. Furthermore, it revealed that members of Bacteroidetes, Firmicutes, α- and γ-Proteobacteria and Actinobacteria were present at initial steps of enrichment whereas β-Proteobacteria appeared in later steps and only Proteobacteria were selected by enrichment culturing. However, when CP-degrading strains were isolated from this enrichment culture, the most active organisms were strains of Acinetobacter calcoaceticus, Pseudomonas mendocina and Pseudomonas aeruginosa. These strains degraded 6–7.4 mg L^?1 day^?1 of CP when cultivated in mineral medium, while the consortium of all four strains degraded 9.2 mg L^?1 day^?1 of CP (100 mg L^?1). Addition of glucose as an additional C source increased the degradation capacity by 8–14 %. After inoculation of contaminated soil with CP (200 mg kg^?1) disappearance rates were 3.83–4.30 mg kg^?1 day^?1 for individual strains and 4.76 mg kg^?1 day^?1 for the consortium. These results indicate that these organisms are involved in the degradation of CP in soil and represent valuable candidates for in situ bioremediation of contaminated soils and waters.     

Dose-dependent inhibitory and non-inhibitory action of somatostatin on insulin release in rats

The dose-dependent effect of intravenously infused synthetic somatostatin-14 on basal and postprandial insulin and gastrin release was assessed in anesthetized rats.Infusion of 1 ng · kg^?1 · min^?1 elicited a significant reduction of basal and postprandial insulin levels compared to the saline control group. At 15 ng · kg^?1 · min^?1 basal insulin was not affected but postprandial insulin levels were still significantly reduced. At 30 ng · kg^?1 · min^?1 neither basal nor stimulated insulin levels were affected. At the highest concentration of 120 ng · kg^?1 · min^?1 basal and postprandial insulin levels were suppressed similar to the lowest infusion rate of 1 ng · kg^?1 · min^?1. Basal gastrin levels were significantly reduced only at the highest rate of 120 ng · kg^?1 · min^?1. A significant reduction of postprandial gastrin levels was observed at 15 ng · kg^?1 · min^?1 and all higher infusion rates employed. Measurements of plasma somatostatin-like immunoreactivity (SLI) demonstrated that plasma SLI levels during the lowest infusion rate of 1 ng · kg^?1 · min^?1 were not different from the controls. No significant rise of plasma SLI levels was observed in response to the test meal. The higher infusion rates elicited a dose-dependent increase in plasma SLI levels. These data demonstrate that in rats somatostatin exerts a biological effect on insulin release at very low doses while certain greater infusion rates have no suppressive effect. Gastrin secretion is inhibited in a more linear pattern.     

Z‐FA.FMK activates duodenal epithelial cell proliferation through oxidative stress,NF‐κB and IL‐1β in d‐GalN/TNF‐α‐administered mice

This study was designed to evaluate the effect of Z‐FA.FMK (benzyloxycarbonyl‐l ‐phenylalanyl‐alanine‐fluoromethylketone), a pharmacological inhibitor of cathepsin B, on the proliferation of duodenal mucosal epithelial cells and the cellular system that controls this mechanism in these cells in vivo. For this investigation, BALB/c male mice were divided into four groups. The first group received physiological saline, the second group was administered Z‐FA.FMK, the third group received d ‐GalN (d ‐galactosamine) and TNF‐α (tumour necrosis factor‐α) and the fourth group was given both d ‐GalN/TNF‐α and Z‐FA.FMK. When d ‐GalN/TNF‐α was administered alone, we observed an increase in IL‐1β‐positive and active NF‐κB‐positive duodenal epithelial cells, a decrease in PCNA (proliferative cell nuclear antigen)‐positive duodenal epithelial cells and an increase in degenerative changes in duodenum. On the other hand, Z‐FA.FMK pretreatment inhibited all of these changes. Furthermore, lipid peroxidation, protein carbonyl and collagen levels were increased, glutathione level and superoxide dismutase activity were decreased, while there was no change in catalase activity by d ‐GalN/TNF‐α injection. On the contrary, the Z‐FA.FMK pretreatment before d ‐GalN/TNF‐α blocked these effects. Based on these findings, we suggest that Z‐FA.FMK might act as a proliferative mediator which is controlled by IL‐1β through NF‐κB and oxidative stress in duodenal epithelial cells of d ‐GalN/TNF‐α‐administered mice.