An assessment of the developmental,reproductive, and neurotoxicity of endosulfan

BACKGROUND : Endosulfan has been used for over 50 years. Although most analogs have been discontinued, endosulfan has less environmental persistence. Nevertheless, pressure groups are lobbying for a worldwide ban. The reasons are: possible rodent male reproductive toxicity, other endocrine effects and cancer; human epidemiology, and exposure studies; residues appearing in remote areas of the world, e.g., the Arctic. METHODS : The endosulfan toxicology database is described and risks of its use assessed. RESULTS : Endosulfan is an antagonist at the GABA_A receptor Cl^? ionophore in mammalian CNS. Rat acute toxicity is moderate, LD₅₀=48 (M) or 10 mg/kg/d (F), oral gavage; 130 (M), 70 mg/kg/d (F) dermal; LC₅₀=34.5 µg/L (M), 12.6 µg/L (F), inhalation. Critical NOELs for risk assessment: acute oral (gavage)=0.7 mg/kg/d (rabbit developmental); Subchronic oral (diet)=1.2 mg/kg/d (rat reproduction); Chronic oral (diet)=0.6 mg/kg/d. There were no acceptable dermal toxicity studies. The critical acute and subchronic inhalation NOELs=0.001 mg/L, chronic inhalation=0.0001 mg/L (estimated). Toxicity to rat sperm occurred at doses causing neurotoxicity. Endocrine effects, resulting from P450 oxygenase(s) induction, were reversible. Increased cancer, genotoxicity, or histopathology in rodents was not observed in any organ. Possible effects on brain biogenic amine levels were probably secondary. CONCLUSIONS : Epidemiology and rodent studies suggesting autism and male reproductive toxicity are open to other interpretations. Developmental/ reproductive toxicity or endocrine disruption occurs only at doses causing neurotoxicity. Toxicity to the fetus or young animals is not more severe than that shown by adults. Birth Defects Res (Part B)86:1‐28, 2009. © 2009 Wiley‐Liss, Inc.     

Boron exhibits hepatoprotective effect together with antioxidant,anti-inflammatory,and anti-apoptotic pathways in rats exposed to aflatoxin B1

BackgroundAflatoxins are one of the important environmental factors that pose a risk to living organisms. On the other hand, it has been indicated in research that boron intake has beneficial effects on organisms. In this study, the effect of boron was disclosed in rats exposed to aflatoxin B1 (AFB1), which poses a toxicological risk.MethodsA total of 36 male Sprague Dawley rats were separated into 6 groups and 0.125 mg/kg bw AFB1 and 5, 10, or 20 mg/kg bw doses of boron were given orally for 21 days. End of the experiment, biochemical, molecular, and histopathological analyses were performed.ResultsAFB1 treatment increased liver enzyme activities (AST, ALT, and ALP) and malondialdehyde level; on the other hand, it caused a decrease in glutathione level, superoxide dismutase and catalase activities. In addition, the mRNA expression levels of apoptotic (Bax, Caspase-3, Caspase-8, Caspase-9, and p53) and pro-inflammatory (TNF-α and NFκB) genes increased and the mRNA expression of the anti-apoptotic gene (Bcl-2) decreased in liver tissue. Also, AFB1 treatment increased DNA damage and caused histopathological alterations in the liver tissue. Additionally, boron applications at doses of 5, 10, and 20 mg/kg bw given with AFB1 reversed these negative changes.ConclusionsAs a result, boron exhibited hepatoprotective effect together with antioxidant, anti-inflammatory, and anti-apoptotic effects against AFB1-induced liver damage.     

Mutagenic adaptive response to high-LET radiation in human lymphoblastoid cells exposed to X-rays

The ability of cells to adapt low-dose or low-dose rate radiation is well known. High-LET radiation has unique characteristics, and the data concerning low doses effects and high-LET radiation remain fragmented. In this study, we assessed in vitro the ability of low doses of X-rays to induce an adaptive response (AR) to a subsequent challenging dose of heavy-ion radiation. Lymphoblastoid cells (TK6, AHH-1, NH32) were exposed to priming 0.02-0.1Gy X-rays, followed 6h later by challenging 1Gy heavy-ion radiation (carbon-ion: 20 and 40keV/μm, neon-ion: 150keV/μm). Pre-exposure of p53-competent cells resulted in decreased mutation frequencies at hypoxanthine-guanine phosphoribosyl transferase locus and different H2AX phosphorylation kinetics, as compared to cells exposed to challenging radiation alone. This phenomenon did not seem to be linked with cell cycle effects or radiation-induced apoptosis. Taken together, our results suggested the existence of an AR to mutagenic effects of heavy-ion radiation in lymphoblastoid cells and the involvement of double-strand break repair mechanisms.     

Anticonvulsant activity of aqueous extract of Leonotis leonurus.

Water extract of Leonotis leonurus was tested for anticonvulsant activity against seizures produced in mice by pentylenetetrazole, picrotoxin, bicuculline and N-methyl-DL-aspartic acid (intraperitoneal injections). L. leonurus extract in the doses of 200 and 400 mg/kg respectively protected 37.5% and 50% of animals used and significantly (p < 0.05; Student's t-test) delayed pentylenetetrazole (90 mg/kg)-induced tonic seizures. Similarly, the same doses of L. leonurus extract significantly (p < 0.05; Student's t-test) delayed the onset of tonic seizures produced by picrotoxin (8 mg/kg) and N-methyl-DL-aspartic acid (400 mg/kg). However, all the doses of aqueous extract of L leonurus used did not alter the seizures induced by bicuculline (20 mg/kg) to any significant extent. The data suggest that the extract of L. leonurus has anticonvulsant activity and may probably be acting through non-specific mechanisms, since it affects both gabaergic and glutaminergic systems. High performance liquid chromatography (HPLC) and phytochemical tests carried out respectively show a spectrum profile, characteristic of L. leonurus and the presence of alkaloids, saponins and tannins in the extract.     

Immune priming and pathogen resistance in ant queens

Growing empirical evidence indicates that invertebrates become more resistant to a pathogen following initial exposure to a nonlethal dose; yet the generality, mechanisms, and adaptive value of such immune priming are still under debate. Because life‐history theory predicts that immune priming and large investment in immunity should be more frequent in long‐lived species, we here tested for immune priming and pathogen resistance in ant queens, which have extraordinarily long life span. We exposed virgin and mated queens of Lasius niger and Formica selysi to a low dose of the entomopathogenic fungus Beauveria bassiana, before challenging them with a high dose of the same pathogen. We found evidence for immune priming in naturally mated queens of L. niger. In contrast, we found no sign of priming in virgin queens of L. niger, nor in virgin or experimentally mated queens of F. selysi, which indicates that immune priming in ant queens varies according to mating status and mating conditions or species. In both ant species, mated queens showed higher pathogen resistance than virgin queens, which suggests that mating triggers an up‐regulation of the immune system. Overall, mated ant queens combine high reproductive output, very long life span, and elevated investment in immune defense. Hence, ant queens are able to invest heavily in both reproduction and maintenance, which can be explained by the fact that mature queens will be protected and nourished by their worker offspring.     

Short time priming of pig cumulus-oocyte complexes with FSH and forskolin in the presence of hypoxanthine stimulates cumulus cells to secrete a meiosis-activating substance

This study evaluated the effect of forskolin and FSH on pig oocyte maturation when cultured in a maturation inhibiting system. Ovaries from prepubertal gilts were collected at a local slaughterhouse. Oocytes were cultured in a hypoxanthine (HX 4 mM) containing M 199 for 24 or 40 h with or without forskolin and FSH treatment. After the culture, we examined germinal vesicle breakdown (GVBD) and polar body (PB) formation. Two experiments were designed. (1) Cumulus enclosed oocytes (CEO) were cultured for 24 or 40 h with or without different doses of forskolin and FSH. (2) CEO were primed by forskolin and FSH for different times and then transferred into an HX-medium for a further culture. The total culture period was 24 h. The results revealed that 4 mM HX markedly prevented pig CEO from undergoing GVBD. After 24 and 40 h culture, FSH (50-200 U/L) stimulated oocytes to resume meiosis by overcoming the inhibition of HX. Both GVBD and PB formation were increased (P < 0.002 and 0.01 respectively) after 40 h exposed to FSH. Forskolin showed a biphasic effect on CEO maturation. Within 24 h forskolin, in combination with HX, inhibited oocytes maturation. The GVBD percentage was significantly decreased compared to HX alone group (2% to 20%, P < 0.01), whereas no inhibition was observed after 40 h of culture. The second experiment showed that forskolin (3 microM) and FSH (100 U/L) priming CEO could time-dependently induce oocyte maturation by overriding the inhibition of HX. After 30 and 60 min priming by FSH or forskolin, the GVBD and PB percentage was significantly increased (P < 0.002 and 0.01 respectively). No difference of GVBD percentage was observed between FSH short time priming group and FSH long time presentation group. In conclusion, we found that forskolin and FSH in vitro can stimulate pig cumulus cells to secrete a meiosis-activating substance which induces the oocyte to overcome the inhibition of hypoxanthine and undergo GVBD.     

天麻素对CUS大鼠抑郁样行为和海马BDNF/GDNF水平的影响

目的:探讨天麻素对慢性不可预见应激(CUS)大鼠抑郁样行为的改善作用及对海马脑源性神经营养因子(BDNF)及胶质原纤维酸性蛋白(GDNF)表达的影响。方法:将64只SD大鼠随机分为对照组(Sham),Sham+天麻素低、中、高剂量组,模型组(CUS),模型(CUS)+天麻素低、中、高剂量组,每组8只。对照组每天腹腔注射生理盐水(1 m L/kg),连续14天;Sham+天麻素低、中、高剂量组每天腹腔注射不同剂量的天麻素(50、100或者200 mg/kg),连续14天;模型组接受CUS造模,并且在造模结束后每天腹腔注射生理盐水(1 m L/kg),连续14天;模型+天麻素低、中、高剂量组在CUS造模结束后每天腹腔注射不同剂量的天麻素(50、100或者200 mg/kg),持续14天。随后,通过糖水偏好实验和强迫游泳实验检测各组大鼠的抑郁样行为,在行为学检测结束后处死大鼠,通过Elisa检测海马GFAP和BDNF的表达情况。结果:(1)慢性不可预见应激(CUS)可以导致明显的抑郁样行为,包括糖水偏好减少(P0.05)和强迫游泳不动时间增加(P0.01),CUS组大鼠海马GFAP和BDNF水平下降(P0.01)。(2)一定剂量(100和200 mg/Kg)天麻素干预可以缓解CUS大鼠的抑郁行为,CUS与CUS+GAS(M)组(P0.05)以及CUS与CUS+GAS(H)组之间(P0.01)存在显著性差异。(3)中高剂量的天麻素可以恢复CUS大鼠海马的BDNF和GDNF水平,CUS与CUS+GAS(M)组(P0.05)以及CUS与CUS+GAS(H)组之间(P0.05)的BDNF和GDNF水平存在显著性差异。结论:天麻素可以缓解CUS模型大鼠抑郁样行为,恢复CUS模型大鼠海马的BDNF和GDNF水平。     

Effect of Age,Duration of Exposure,and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague–Dawley Rat

Atrazine (ATZ) was administered daily by gavage to pregnant female Sprague Dawley rats at doses of 0, 6.25, 25 or 50 mg/kg/day, either during gestation, lactation and post‐weaning (G/L/PW cohort) to F₁ generation female offspring or only from postnatal day (PND 21) until five days after sexual maturation (vaginal opening) when the estrogen‐primed, luteinizing hormone (LH) surge was evaluated (PW cohort). Additional subgroups of F₁ females received the vehicle or ATZ from PND 21–133 or from PND 120–133. Slight reductions in fertility and the percentage of F₁ generation pups surviving to PND 21 in the gestationally exposed 50 mg/kg dose group were accompanied by decreased food intake and body weight of dams and F₁ generation offspring. The onset of puberty was delayed in of the F₁ generation G/L/PW females at doses of 25 and 50 mg/kg/day. F₁ generation females in the PW high‐dose ATZ group also experienced a delay in the onset of puberty. ATZ had no effect on peak LH or LH AUC in ovariectomized rats 5 days after sexual maturation, irrespective of whether the F₁ generation females were treated from gestation onward or only peripubertally. There was no effect of ATZ treatment on the estrous cycle, peak LH or LH AUC of F₁ generation females exposed from gestation through to PND 133 or only for two weeks from PND 120–133. These results indicate that developing females exposed to ATZ are not more sensitive compared to animals exposed to ATZ as young adults     

Morpho-functional alterations in lymphocytes and erythrocytes of Japanese quail due to prolonged in vivo exposure to heavy metal complexes

BackgroundLead and cadmium are significant environmental pollutants that cause pathophysiological responses in many organs. Heavy metal absorption into many tissues is very fast due to a pronounced affinity for metallothioneins.MethodJapanese quail were exposed to different concentrations of metals (cadmium 0.20 mg/L and lead 0.25 and 0.50 mg/L) for 20 days. Erythrocytes (normal and hemolyzed) and lymphocytes (normal and altered) were monitored in this study. The analysis observed the percentage of normal and altered cells, as well as erythrocyte surface area. Cell counts were analyzed using light microscopy, while surface area and cytological changes in cells and nuclei were analyzed using licensed software.ResultsDifferent concentrations of metals have caused erythrocyte hemolysis as well as structural and morphological alterations in lymphocytes. Destruction of cell and nucleus membrane, changes in cell size, erythrocyte denucleation and reduced erythrocyte surface area were observed. Cadmium has caused erythrocyte hemolysis (29.30 %) and lymphocyte damage (92.10 %). Higher doses of lead resulted in greater damage to lymphocytes (63 %). Also, treatment with higher dose of lead produced a higher percentage of hemolyzed erythrocytes (19.20 %) in comparison to lower dose (9.90 %).ConclusionThe toxicity of heavy metals leads to reduced maturation of the blast, which causes the appearance of immature cells in peripheral circulation and severe destruction of blood cell membranes. Erythrocyte hemolysis can lead to anemia, while lymphocyte damage can lead to lymphocytopenia.     

Phytotoxicity of Sodium Fluoride and Uptake of Fluoride in Willow Trees

The willow tree (Salix viminalis) toxicity test and a cress seed germination test (Lepidium sativum) were used to determine uptake of F and phytotoxicity of NaF. Concentrations in hydroponic solutions were 0–1000 mg F/L and 0–400 mg F/L in the preliminary and definitive test. A third test was done with soils collected from a fluoride-contaminated site at Fredericia, Denmark. The EC₁₀, EC₂₀ and EC₅₀-values for inhibition of transpiration were determined to 38.0, 59.6 and 128.7 mg F/L, respectively. The toxicity test with soil showed strong inhibition for the sample with the highest fluoride concentration (405 mg free F per kg soil, 75 mg F per L soil solution). The seed germination and root elongation test with cress gave EC₁₀, EC₂₀ and EC₅₀-values of 61.4, 105.0 and 262.8 mg F/L, respectively. At low external concentrations, fluoride was taken up more slowly than water and at high external concentrations at the same velocity. This indicates that an efflux pump becomes overloaded at concentrations above 210 mg F/L. Uptake kinetics were simulated with a non-linear mathematical model, and the Michaelis-Menten parameters were determined to half-saturation constant K_M near 2 g F/L and maximum enzymatic removal rate v_max at 9 g/(kg d).     

Within and transgenerational immune priming in an insect to a DNA virus

Invertebrates mount a sophisticated immune response with the potential to exhibit a form of immune memory through ‘priming’. Increased immune protection following early exposure to bacteria has been found both later in life (within generation priming) and in the next generation (transgeneration priming) in a number of invertebrates. However, it is unclear how general immune priming is and whether immune priming occurs in response to different parasites, including viruses. Here, using Plodia interpuctella (Lepidoptera) and its natural DNA virus, Plodia interpunctella granulosis virus, we find evidence for both within generation and transgeneration immune priming. Individuals previously exposed to low doses of virus, as well as the offspring of exposed individuals, are subsequently less susceptible to viral challenge. Relatively little is known about the mechanisms that underpin viral immunity but it is probable that the viral immune response is somewhat different to that of bacteria. We show that immune priming may, however, be a characteristic of both responses, mediated through different mechanisms, suggesting that immune memory may be a general phenomenon of insect immunity. This is important because immune priming may influence both host–parasite population and evolutionary dynamics.     

Protective effect exerted by soil phosphorus on soybean subjected to arsenic and fluoride

Objetive: Arsenic (As) and fluoride (F) are found in groundwater and soils around the world, causing different problems to crops. Because these elements compete against phosphorus (P) in soils and plants, their relationship is complex. The aim of this work was to study the oxidative stress of soybean plants subjected to different concentrations of As and F, and the effect of P.

Methods: The following 10 treatments were carried out in each of two soils with different P content: three As levels (low 10?mg?As?kg^-1, medium 50?mg?As?kg^?1 and high 100?mg As kg^?1), three F levels (low 160?mg?F?kg^?1, medium 250?mg?F?kg^?1 and high 500?mg?F?kg^?1) and three As?+?F levels (same concentrations), and the control treatment (soil with the background As and F concentrations) Lipid peroxidation, chlorophyll, gluthatione contents and antioxidant enzymes activities were determination.

Results: Increased lipid peroxidation and alterations in glutathione content, catalase, superoxide dismutase and peroxidase activities as well as in chlorophyll content revealed that As causes higher oxidative stress in plants grown in soils with low P content.

Conclusion: Stress parameters in F treatments were less affected. Plants grown in soils enriched with P revealed a decrease in the toxic effects caused by As and F.     

Differential modulation of natural and adaptive immunity in fischer rats exposed for 6 weeks to 60 Hz linear sinusoidal continuous-wave magnetic fields

Two separate, independent experiments were conducted to evaluate the effect of 60 Hz linearly polarized, sinusoidal, continuous-wave magnetic fields (MFs) on immune system performances in rats born and raised under these fields. Each experiment lasted for 6 weeks. A total of 96 animals, divided into groups of eight animals each, was exposed for 20 h/day to MFs of different intensities, i.e., sham (<0.02 μT) and 2, 20, 200, and 2000 μT. Another group of animals, which was housed in a separate room, served as cage controls (CC). These animals were exposed to ambient MFs of <0.02 μT. The following immune responses were evaluated in both experiments: total T and B cells; CD4⁺ and CD8⁺ subpopulation and natural killer (NK) cell activity in splenic lymphocytes; hydrogen peroxide (H₂O₂), nitrous oxide (NO), and tumor necrosis factor (TNF) production by peritoneal macrophages. Our results show that a 6 week exposure to MFs induced a significant decrease in the number of CD5⁺, CD4⁺, and CD8⁺ populations. These changes were even more significant in rats that were exposed to fields of 2000 μT. A lower, although significant, decrease in the CD5⁺ population was also observed in animals that were exposed to fields of 200 μT. Linear regression analysis demonstrated a dose effect with MF intensity. B lymphocyte (Ig⁺ cell) populations also showed a 12% decrease (P < .05) in the groups that were exposed to fields of 20 and 200 μT. However, these results were not significant, and no relation with MF intensities could be demonstrated. In contrast, evaluation of splenic NK cell activity revealed a 50% increase (P < .05) in animals that were exposed to fields of 2000 μT. No significant results were obtained from the evaluation of TNF activity and NO secretion in peritoneal macrophages. Phorbol 12-myristate 13-acetate (PMA)-stimulated and net H₂O₂ productions for a minor subpopulation of peritoneal cells showed positive dose-response correlations by linear regression analysis. Taken together, our results suggest that an in vivo exposure of rats for 6 weeks to 60 Hz MFs can induce significant immunological perturbations on effector cells of both natural and adaptive immunity in a dose-dependent fashion. © 1996 Wiley-Liss, Inc.     

Decreased paraoxonase 2 enzymatic activity in monocyte/macrophages cells. A comparative in vivo and in vitro study for diabetes

Aim: To investigate peripheral blood monocytes/macrophages (Mo/M?) paraoxonase 2 (PON2) in diabetes and the factors modulating its activity.

Methods: One hundred and eighteen patients with newly diagnosed uncomplicated type 2 diabetes mellitus were compared regarding clinical, biochemical and oxidative stress parameters with 80 healthy subjects. The capacity of the peripheral blood mononuclear cells (PBMNC) to release pro-oxidants and to neutralise them was determined by measuring the respiratory burst (RB) and the intracellular antioxidant enzyme PON2. In vitro experiments were conducted on a differentiated monocytes cell line (dU937) that was exposed to serum deprivation followed by addition of isolated lipoproteins (VLDL or LDL).

Results: Paraoxonase 2 activity in Mo/M? was significantly lower in type 2 diabetes patients (0.042?±?0.044 vs 0.165?±?0.133U lactonase activity/mg protein in controls, p?1c) and insulin resistance (HOMA-IR). In multivariate regression models, 15–34% of the PON2 variance was explained by diabetes. The in vitro addition of VLDL normalised the RB of serum deprived dU937 cells, S? (to 82?±?18% of the cells incubated with serum, S+) and PON2 activity (from 0.524?±?0.061 in S???to 0.298?±?0.048?U/mg protein). In contrast, when LDL was added, the RB remained lower (61?±?12% of S+, p?=?.03) and PON2 higher (0.580?±?0.030?U/mg protein, p?=?.003).

Conclusions: The decrease in monocyte/macrophage PON2 enzymatic activity observed in type 2 diabetes cannot be totally explained by abdominal obesity and insulin resistance. The underlying molecular mechanisms need to be identified.     

Neuropharmacological and molecular docking studies of xanthones from Swertia corymbosa

Anxiety represents a public health problem consistently found to be the most prevalent class of mental disorders among people of all ages. Xanthones possess many biological properties, including neuroprotective, antioxidant or antidepressant-like. In this study, we aimed to investigate anxiolytic-like antidepressant and anticonvulsant properties of isolated xanthones from Swertia corymbosa. We evaluated anxiolytic-like activity of compounds 1–3 in the mouse elevated plus maze (EPM) and open field test (OF). We examined the influence on locomotor activity in mouse to determine if the effect observed in the actophotometer specific. We used step-through rotarod tests to evaluate the motor function and muscle grip. Compounds 1–3 significantly induced an increase in the number of entries into open arms and a decrease in time spent into closed arms at the dose of 50?mg/kg body weight (BW). The compounds also induced increase of rearing and decrease grooming at the doses of 25 and 50?mg/kg BW during the OF test. In addition, compounds induced a significant increase of time taken to enter at the center of the experimental set at the dose of 50?mg/kg BW during the open field test. The compounds 1–3 significantly delayed the onset as well as decreased the pentylenetetrazole and isoniazid-induced seizure tests. Compound 3 pretreatment significantly improved survivals in pentylenetetrazole and isoniazid-induced seizure tests. In silico studies reveal its possible mechanism of action shed on light to develop novel drugs against CNS disorders.     

The role of thiamine inYersinia kristensenii resistance to antibiotics and heavy metals

The resistance to divalent metal ions, antibiotics and H₂O₂ was investigated inYersinia kristensenii strains 13, 15, 18 by performing subcultivations with CdSO₄ (20 and 100mg/L) in nutrient agar (NA) and M9 medium with thiamine. Metal resistance of all three strains in NA was the same and decreased in the following sequence: Ni>Zn=Co>Cd. The chloramphenicol (Cmp) resistance ranged between 32 and 256 mg/L and the H₂O₂ sensitivity was very low or even zero. In the presence of thiamine the metal resistance sequence changed to Zn=Cd>Ni, Co, Ni and Co tolerance being 10–20 mg/L. Cmp resistance of all strains increased to 256 mg/L and H₂O₂ sensitivity also rose. In Cd-treated cultures, the ratio of glucose to thiamine in culture medium affected Cd resistance. At normal content of glucose and thiamine (5 g/L and 5mg/L), Cd resistance markedly decreased coincident with thiamine exhaustion in these slowly-growing cultures. The Cmp resistance decreased to 16 mg/L, Ni and Co intolerance and H₂O₂ hypersensitivity appeared. At lowered glucose or thiamine levels (5 g/L and 2.5 mg/L or 2.5 g/L and 5 mg/L) a marginal decrease of Cd resistance took place in response to limited glucose uptake. Low thiamine or low-glucose cultures were resistant to H₂O₂, and exhibited a small decrease in Cmp resistance and a low Ni, Co tolerance. The adaptation of strain 15 to Cd induced only a small decrease of Cd resistance. Lowered glucose-to-thiamine ratio in culture medium probably induced in Cd-treated cultures a response triggering Cd resistance.     

Toxicity of silver nanoparticles on the brain of Oreochromis niloticus and Tilapia zillii

BackgroundSilver nanoparticles (Ag-NPs) are widely used nowadays in a variety of commercial applications including medical, health care, textiles and household supplies.ObjectivesThe current study was designed to determine the median lethal dose (LC₅₀) of Ag-NPs on Oreochromis niloticus and Tilapia zillii.MethodsAcute and sub-acute toxicity study of the Ag-NPs on brain tissues was carried out using different concentrations of the NPs at 2 mg L and 4 mg L. These concentrations were dispersed in deionized water with the exception of the control groups in the experiments. Biochemical and molecular analysis were conducted on tissue homogenates in order to evaluate the potential effects of NPs on the antioxidant system.ResultsThe Ag-NP acute toxicity (96 h LC₅₀) values of 19.5 ± 2 and 20 ± 2.4 mg/L were reported for O. niloticus and T. zillii respectively. Fish exposed to 2 mg/L Ag-NPs did not show any significant change in the levels of reduced glutathione (GSH), total glutathione (tGSH) levels, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activity or genes expression and malondialdehyde (MDA) level. In contrary, a dose of 4 mg/L showed a significant reduction in the levels all the above-mentioned parameters except in MDA level where it was significantly induced.ConclusionResults indicate that exposure of O. niloticus and T. zillii to Ag-NPs (4 mg/L) has deleterious effects on brain antioxidant system, whereas a dose of 2 mg/L has no effects.     

耐高浓度氨氮的异养硝化好氧反硝化菌株U1的鉴定及其脱氮特性

【背景】城市垃圾渗滤液是一种成分复杂的有机废水,含氮量高,如果未经处理直接排放到环境中会造成严重的环境污染。【目的】筛选可以耐受垃圾渗滤液中高浓度氨氮并高效去除污水中氮素的异养硝化好氧反硝化菌株,为解决垃圾渗滤液的氮素污染提供功能菌株。【方法】从垃圾渗滤液中筛选分离能耐受高氨氮浓度的菌株,通过测定各菌株的脱氮能力,筛选到一株脱氮能力最强的菌株,命名为U1,通过测定16S rRNA基因序列和生理生化特性确定该菌株为铜绿假单胞菌。进一步研究了菌株U1在不同初始氨氮浓度、碳源、转速、初始pH、碳氮比等单因素变量下的脱氮能力,并结合L₉（3⁴）正交试验研究了菌株U1的最佳脱氮条件。【结果】分离出一株铜绿假单胞菌并命名为U1。该菌株的最优脱氮条件为:初始氨氮浓度为1 000 mg/L,红糖和柠檬酸三钠的混合碳源,pH 6.0,C/N为10,转速为130 r/min,菌株U1的最大总氮去除率为64.37%,最大氨氮去除率为76.73%。对于总氮和氨氮含量分别是2 345 mg/L和1 473.8 mg/L的垃圾渗滤液,菌株U1最大总氮去除率为27.86%...     

The occurrence of cross-tolerance between morphine and ethyl-ketocyclazocine using the tail-flick test: Lack of effect of diazepam,phenobarbital, or amphetamine

Experiments were designed to test for short-term tolerance to morphine and ethyl-ketocyclazocine (EKC), mu and kappa agonists, respectively, and cross-tolerance between the two drugs. Mice were primed with one of the drugs, using doses that did not affect the tail-flick response when tested at a time 1 or 3 hours later, when the same or alternate test drug was administered. All animals were injected with the priming drug IP. In one series of experiments, the test drugs were given SC, and in the other, the test drugs were injected ICV under brief halothane anesthesia. Priming with morphine (30 or 100 mg/kg) significantly raised the ED₅₀ for ICV morphine. Priming with EKC (2 or 6 mg/kg) similarly elevated the ED₅₀'s for SC and ICV EKC. Symmetrical cross-tolerance was produced in experiments where the test drugs were administered SC when tested at 3 hrs. The effects of priming with EKC on morphine analgesia was evident when the interval between priming and test drugs was 1 hour. When the test drugs were given ICV, cross-tolerance was also symmetrical: priming with EKC significantly raised the ED₅₀ for morphine and priming with morphine raised the ED₅₀ for EKC when tested at 3 hrs. These data suggest that both agonists act on a common site to produce analgesia as similar pA₂ values for naloxone antagonism were determined. The occurrence of short-term tolerance and cross-tolerance to the opiates was unaltered by chronic pretreatment with diazepam, phenobarbital, or amphetamine.     

Pentoxifylline with metformin treatment improves biochemical parameters in patients with nonalcoholic steatohepatitis

BackgroundThe progression of the nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) is multifactorial, and there is still a lack of approved medications for its treatment. The study aimed to evaluate the impact of combined treatment with Pentoxifylline and Metformin on biochemical parameters in patients with Nash. Setting: Outpatient hepatology clinic.MethodsA prospective trial was conducted. The first cohort included patients with biopsy-proven Nash, while the second cohort consisted of patients with biopsy-confirmed NAFLD. Blood tests were checked at baseline and every three months. Pentoxifylline at a dosage of 400 mg t.i.d. and Metformin at the dosage of 500 mg t.i.d. were introduced for six months in Nash group. The impact of the treatment was assessed based on biochemical results after combined treatment with low-cost medications.ResultsAll 33 Nash patients completed 24 weeks of treatment. We observed significant improvement (p<0.05) of median values after treatment for the following parameters: serum uric acid levels decreased by 51.0 mmol/L, calcium decreased for 0.27 mmoL/L, magnesium showed an increase of 0.11 mmoL/L. Insulin resistance improved as a reduction of HOMA - IR by 1.3 was detected. A significant decrease of median in liver enzymes, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase by 24.0 U/L, 9.1 U/L, 10.8 U/L respectively, was noted.ConclusionsPentoxifylline and Metformin may provide possible treatment option in Nash. Some new potential benefit of the therapy in improving liver function whilst decreasing cardiovascular risk was perceived.