辛伐他汀对大鼠肺纤维化及其内皮间质变过程的影响*

目的: 观察辛伐他汀对大鼠肺纤维化及其内皮间质变(EnMT )过程中VE-钙粘素(VE-cad)、波形蛋白(VIM)、α-平滑肌蛋白(α-SMA)表达的影响。方法: 健康雄性SD大鼠60只,随机分为对照组(A组)、造模组(B组)、辛伐他汀5 mg治疗组(C组)、辛伐他汀10 mg治疗组(D组),每组各15只。博来霉素(BLM)按5 mg/kg剂量一次性气管内灌注复制博莱霉素致大鼠肺纤维化模型,从造模第1日起C、D 组每天分别胃内灌注辛伐他汀混悬液5 mg /(kg·d)及辛伐他汀混悬液10 mg /(kg·d),A组和B 组每天胃内灌注等体积生理盐水10 ml /(kg·d)。于造模第7、14和28 日随机处死各组大鼠5只。Masson染色观察大鼠肺组织形态变化;碱性水解法检测肺组织中羟脯氨酸(HYP)含量;免疫组化法测定各组大鼠肺组织血管新生微血管密度(MVD);免疫组化和逆转录-聚合酶链反应法测定各组肺组织中VE-Cad、VIM及α-SMA蛋白和mRNA的表达水平。结果: ①与A组相比,B、C、D组各时间点肺组织HYP和MVD水平、VIM、α-SMA的mRNA和蛋白表达水平均明显升高(P均＜0.05),且以28 d达最高;而相应时间点VE-Cad 的mRNA和蛋白表达水平均明显降低(P均＜0.05),且以28 d达最低。②与B组相比,C、D组HYP和MVD水平、VIM、α-SMA的mRNA和蛋白表达水平均有降低(P均＜0.05),以D组28 d下降最明显;而相应时间点VE-Cad 的mRNA和蛋白表达水平均有升高(P均＜0.05),以D组28 d升高最明显。结论: 辛伐他汀可减轻大鼠肺纤维化,其机制可能与增强VE-cad表达,降低VIM及α-SMA表达,减少EnMT 发生有关。     

Preventive role of gallic acid on alcohol dependent and cysteine protease-mediated pancreas injury

In order to investigate an association between alcohol consumption and lysosomal cysteine protease induced pancreatic injury and preventive effect of gallic acid as dose-dependent, we determined myeloperoxidase and malondialdehyde levels, serum amylase activities and cathepsin B and L activities in the cytosolic and lysosomal fractions of pancreatic tissue in the ethanol (8?g/kg) and ethanol plus gallic acid (at different doses 50, 100 and 200?mg/kg) given rats. Absolute ethanol (8?g/kg) was given by oral gavage. Gallic acid was dissolved in the saline (2?ml/kg) and administered before 30?min the oral administration of ethanol. Pancreatic myeloperoxidase and also malondialdehyde levels and serum amylase activities were measured. Besides, histological investigations were made. Cathepsin B activities in the cytosolic fraction were decreased by gallic acid (200?mg/kg) and increased in ethanol given rats. Cytosolic/lysosomal ratio of cathepsin B and L were found to be low in the all doses of gallic acid as compared to ethanol group. Serum amylase, pancreatic myeloperoxidase activities and malondialdehyde levels in the ethanol group were higher than in the control group. These were not statistically significant for myeloperoxidase and malondialdehyde. Also, our histopathologic results indicated that ethanol administration increased pancreatic tissue injury. Gallic acid especially at 200?mg/kg improved ethanol-mediated pancreatic tissue damage.In conclusion, gallic acid treatments were decreased release of lysosomal cathepsin B and L enzymes into cytoplasmic fraction and prevented alcohol mediated pancreatic tissue injury. Preventive effect of gallic acid might be dose-dependent.     

糖尿病肾病患者血浆NGAL和血清CysC水平改变及其早期诊断价值

目的:研究糖尿病肾病(DN)患者血浆中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和血清胱抑素C(CysC)水平变化,分析其对DN的早期诊断价值。方法:选取160例糖尿病(DM)患者按尿微量白蛋白排泄率(UAER)分为DN前期组58例(A组),DN早期组52例(B组)及DN临床组50例(C组),同期选择健康体检者61例为对照组(D组)。比较四组受试者血中NGAL、CysC、尿素氮(BUN)和血肌酐(CREA),及尿中微量清蛋白(UMA)水平的差异,分析血NGAL、CysC与UMA之间的相关关系。结果:(1)A、B、C组受试者NGAL、CysC及UMA水平显著高于D组,且CBA,差异均有统计学意义(P0.05);C组BUN和CREA水平均明显高于A、B、D三组,差异均有统计学意义(P0.05),而A、B组较D组均无统计学差异(P0.05)。(2)血NGAL、CysC与尿UMA均存在正相关关系(r=0.59,0.64;P均0.05)。结论:DN早期患者血浆NGAL与血清CysC水平显著升高,且二者均与尿UMA水平存在正相关关系,可作为评价肾脏损害程度及DN早期诊断的较敏感的生物学标志物,临床推荐应用。     

Effects of administration of probiotic strains on GALT of larval gilthead seabream: Immunohistochemical and ultrastructural studies

Two bacterial strains Lactobacillus fructivorans (AS17B), isolated from adult seabream (Sparus aurata L.) gut, and Lactobacillus plantarum (906), isolated from human faeces, were administered contemporaneously during seabream development using Brachionus plicatilis and/or Artemia salina and dry feed as vectors. Experimental group A received the probiotic strains already via rotifers from day 5 post-hatch (ph), whereas treatment of group B began with Artemia feeding from day 27 ph. Fish were sampled at day 28 ph (group A and control) and day 99 ph (groups A, B and control) for electron microscopy, histology and immunohistochemistry with the polyclonal antiserum ORa against homologous serum Ig and the mAb G7 specific for seabream acidophilic granulocytes. In all groups, timing and pattern of differentiation of the digestive tract did not differ. Furthermore, neither tissue damage nor manifest inflammation was provoked by probiotic administration. At day 28 ph, the developing GALT already housed mucosal leucocytes, including Ig(+) cells but no acidophilic granulocytes. No differences were seen between experimental groups. At day 99 ph, the density of Ig(+) cells (+51%) and acidophilic granulocytes (+284%) was significantly higher (p<0.05) in group A than in controls. Also group B had a higher density of Ig(+) cells (+17%) and acidophilic granulocytes (+130%) compared with controls, although less pronounced. Light and electron microscopy observations detailed the occurrence of heterogeneous populations of lymphocytes and granulocytes in the developing intestinal mucosa, and highlighted the net expansion of G7(+) acidophilic granulocytes (A +536%, B +292% vs. control) due to probiotic administration. Evidence is provided that early feeding with probiotic-supplemented diet increased the number of Ig(+) cells and acidophilic granulocytes in seabream gut and that the effects were more pronounced when administration started during gut metamorphosis. These results point to a stimulatory effect of probiotics on the gut immune system that correlates with improvement of fry survival.     

Taurine: Protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats

Summary Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not to affect the urinary excretion of taurine (a non-invasive marker of liver damage), levels of serum and liver taurine were markedly raised in animals receiving alcohol + taurine compared to animals given taurine alone. The ethanol-inducible form of cytochrome P-450 (CYP2E1) was significantly induced by alcohol; the activity was significantly lower than controls and barely detectable in animals fed the liquid alcohol diet containing taurine. In addition, alcohol significantly increased homocysteine excretion into urine throughout the 28 day period of ethanol administration; however, taurine did not prevent this increase. There was evidence of slight cholestasis in animals treated with alcohol and alcohol + taurine, as indicated by raised serum bile acids and alkaline phosphatase (ALP). The protective effects of taurine were attributed to the potential of bile acids, especially taurine conjugated bile acids (taurocholic acid) to inhibit the activity of some microsomal enzymes (CYP2E1). Thesein vivo findings demonstrate for the first time that hepatic steatosis and lipid peroxidation, occurring as a result of chronic alcohol consumption, can be ameliorated by administration of taurine to rats.     

The effect of probiotic BioPlus 2B on feed efficiency and metabolic parameters in swine

The purpose of our work was to observe the influence of probiotic preparation BioPlus 2B on average daily gains of weaned pigs, feed efficiency and to evaluate some metabolic indices. The weaned pigs, at the age of 42 days, were included into the trial and divided into four groups. Pigs in groups A (n = 5) and B (n = 4) received BioPlus 2B also before weaning. Only group A received BioPlus 2B, at the concentration of 3.2 × 10⁹ CFU per kg of feed, after weaning continually. Groups C (n = 5) and D (n = 4) did not receive BioPlus 2B until the start of the trial, but group C was given BioPlus 2B at the same concentration as group A during the experiment. Blood samples for determination of metabolic indices were collected at the start of experiment, i.e. on 42^nd day of pigs life, and then on 56^th, 70^th, 84^th and 91^st days of pigs life. The following biochemical indices were evaluated within the trial: serum levels of total proteins, albumin, urea, total cholesterol and total lipids. Total serum protein level (p < 0.0001) and serum albumin level (p = 0.0024) in groups A and B were significantly higher in comparison with groups C and D on day 56 of pigs life. Serum urea level in group D was significantly (p = 0.049) higher than in group A on 70^th day of pigs life. Serum level of total cholesterol in group B on day 56 and 84 of pigs life was significantly (p = 0.0004) higher than in groups C and D. Total serum lipid level was significantly (p < 0.05) higher in B group compared to other groups on 56^th, 70^th, 84^th days of pigs life. Average daily gains (ADG) in A group, even if non-significantly, were about 10% better than in groups B, C, D between 57^th and 77^th days of pigs life. ADG in groups A and B were 14% better in comparison with that in groups C and D between 78^th and 91^st days of pigs life (p = 0.036). The best feed efficiency in the trial was in group A, approximately 13%, 16% and 21% better than that in the groups B, C and D, repectively. Presented at the Second Probiotic Conference, Košice, 15–19 September 2004, Slovakia.     

The interactive effect of alcohol and folic acid on genome stability in human WIL2-NS cells measured using the cytokinesis-block micronucleus cytome assay

Chromosomal mutations are commonly found in cancer cells, and can be caused by several factors including dietary insufficiency and exposure to environmental and life-style genotoxins. Folate (vitamin B9), one of the essential micronutrients, is required for DNA repair and synthesis and to maintain genome stability. Since excessive alcohol (ethanol) consumption may alter folate status and low folate might alter susceptibility to alcohol toxicity, a study was performed to investigate the individual and interactive impacts of folic acid (FA) and ethanol on genome stability in vitro. The experiments were performed using WIL2-NS cells cross-tested at three FA (20, 200 and 2000 nM) and four ethanol concentrations (0, 0.09, 0.36 and 1.34%, v/v) over a two-week culture time. Chromosomal damage and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. The present study showed dose-related genotoxic effects of both decreasing folic acid concentration and increased ethanol on day 15 resulting in significant induction of micronuclei, nuclear buds and nucleoplasmic bridges which are biomarkers of chromosome breakage or loss, gene amplification and chromosomal rearrangement, respectively. Increased ethanol and FA deficiency interacted to further significantly increase micronuclei and nucleoplasmic bridges. However there was no evidence showing alcohol's ability to cleave FA. The findings from this study suggest a protective effect of FA against alcohol-induced DNA damage and that FA deficiency in the physiological range has a stronger impact on genome stability than exposure to cytotoxic doses of ethanol achievable in binge drinking.     

外源金属硫蛋白对奶牛抗热应激调控及SOD基因表达的影响

将28头泌乳奶牛随机分成A、B、C、D 4组,分别按每头0 (对照)、6.0、12.0和16.0 mg剂量静脉注射经生理盐水溶解的Zn-MT,以探讨外源性金属硫蛋白(MT)对奶牛抗热应激的调控作用及其机理.结果表明：B、C和D组的脉搏、呼吸频率及血清MDA含量均显著(P＜0.05或P＜0.01)低于A组;4%标准乳产量、血液GSH-PX活性、红细胞SOD活性、血清MT含量、奶MT含量及SOD基因表达水平均显著(P＜0.05或P＜0.01)高于A组;C和D组的上述各项指标又优于(P＜0.05或P＞0.05)B组;外源性MT的调控效果以注射后第30天表达最佳.说明MT是一种能够有效调控奶牛热应激能力的生理活性物质,且在奶牛体内表现出一定的剂量效应和时间效应.     

In-vivo and in-vitro effects of ethanol on mouse preimplantation embryos

In Exp. 1A, hybrid mice (N = 10) were provided with food and 25% (v/v) ethanol as the only source of liquid for 72 h, beginning at the detection of the copulatory plug (08:00 h, Day 1). Control mice received food and tap water. Food consumption (P less than 0.001) but not total caloric intake (P greater than 0.05) was less for the alcohol-treated mice than the controls. Ethanol-derived calories averaged 35% of caloric intake during the 72 h of treatment. Alcohol-treated animals showed a dramatic weight loss until Day 5 while controls gained weight (P less than 0.05). Ethanol consumption did not influence pregnancy rate, litter size or litter weight. In Exp. 1B, animals were treated as in Exp. 1A, but were killed at various times between 24:00 h, Day 1, and 08:00 h, Day 4. Trunk blood was used to determine haematocrit and serum to determine alcohol concentration. Haematocrit was greater (P less than 0.05) for all alcohol-treated mice than for controls at all time periods sampled except one. Dehydration was therefore probably responsible for the weight loss seen in Exps 1A and 1B. Average blood alcohol concentrations fluctuated with time of day and day of treatment. Average maximum concentration was 91.4 mg ethanol/100 ml serum. In Exp. 2, hybrid mouse 2-cell embryos were cultured in vitro in 0 or 0.1% ethanol (Exp. 2A) and 0 or 1.0% ethanol (Exp. 2B) for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hydrochlorothiazide, amiloride and tolmetin in the treatment of diabetes insipidus of Brattleboro rats

To test the effects of hydrochlorothiazide (HCTZ) alone and in combination with amiloride or tolmetin in the treatment of nephrogenic diabetes insipidus, metabolic studies of 12 days each were carried out in 36 male, Brattleboro rats. They were divided into five groups as follows: (A) controls; (B) high dose HCTZ at 6 mg/rat/day; (C) low dose HCTZ at 3 mg/rat/day; (D) HCTZ identical to (C) but with addition of amiloride at 0.6 mg/rat/day; (E) HCTZ identical to (C) but with addition of tolmetin at 40 mg/rat/day. The immediate response to treatment was a significant increase in urinary sodium excretion from mean values (mEq/kg/day) of less than 11 to values higher than 13, except group E with mean value of 12. There was marked increase in urinary potassium excretion (mEq/kg/day), from mean control value of 15.5 to 21.5, 20.8, 18.5 and 17.7 in groups B, C, D and E, respectively. During the last three days of the study, mean urine osmolality (Uosm) and free water reabsorption (TCH2O) increased significantly: [formula: see text]. These indices were higher in groups B, D and E than in group C. Serum osmolality decreased only in groups B, C and D but not in the HCTZ-tolmetin groups. Similarly, serum sodium concentration was significantly lower in groups B, C and D compared to the control and the HCTZ-tolmetin groups. Serum potassium concentration was reduced in all the treated groups, but in both the groups treated with HCTZ-amiloride and HCTZ-tolmetin, the reduction was smaller than the one observed in the high-HCTZ treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of H. pylori Infection on Cytokine Profiles and Oxidative Balance in Subjects with Chronic Alcohol Ingestion

Different amounts of ingested alcohol can have distinct effects on the human body. However, there is limited research on chronic alcohol consumption with Helicobacter pylori infection. We sought to investigate the relationship between the cytokine profile, oxidative balance and H. pylori infection in subjects with chronic alcohol consumption. A total of 142 subjects were divided into three groups: 59 subjects with chronic alcohol ingestion and H. pylori infection (group A); 53 subjects with chronic alcohol ingestion without H. pylori infection (group B); and 30 control subjects (group C). The serum levels of CagA, interleukin (IL)-10, E-selectin, TNF-α, malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by enzyme-linked immunosorbent assay (ELISA). We found that the ages and serum H. pylori CagA levels among the three groups, as well as both the mean drinking age and the mean daily alcohol consumption between groups A and B, were matched and comparable. Comparing the BMIs among the three groups, the BMI differences were found to be statistically significant (F=3.921, P<0.05). Compared with group C, the BMIs in groups A and B were significantly higher (P<0.001 and P<0.01, respectively); however, the BMI differences between group A and group B were not statistically significant (P>0.05). Additionally, no differences in the serum CagA levels were found in comparisons among the groups (all P>0.05). The serum IL-10 and E-selectin levels in group A were significantly lower than those in group B (serum IL-10: P<0.05; E-selectin: P<0.05). The serum IL-10 in group A was significantly higher than that in group C (P<0.01); the serum E-selectin levels in group A did not significantly differ compared with those in group C (P>0.05). Furthermore, the serum IL-10 and E-selectin levels in group B were significantly higher than those in group C (serum IL-10: P<0.001; E-selectin: P<0.05); however, the serum TNF-α levels did not differ among groups (all P>0.05). Although the serum levels of MDA and SOD in groups A and B were slightly lower than those in group C, there were no significant differences among groups (all P>0.05). In conclusion, we believe that H. pylori infection might cause a significant inhibition of certain cytokine profiles in subjects with chronic alcohol ingestion. Moreover, chronically ingested alcohol may exert an adjusted inflammatory effect, but there was no association between H. pylori infection, chronic alcohol consumption and oxidative balance.     

Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes

Concanavalin A (ConA) induces natural killer T (NKT) cell-mediated liver damage. Glucocerebroside (GC) is a naturally occurring glycolipid. Our aims were to determine the effect of GC in a murine model of ConA-induced hepatitis. Mice in groups A and B were treated with GC 2 h before and 2 h following administration of ConA, respectively; group C mice were treated with ConA; group D mice was treated with GC; group E mice did not receive any treatment. Liver damage was evaluated by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver histology. The immune effect of GC was determined by fluorescence-activated cell sorter analysis of intrahepatic and intrasplenic NKT lymphocytes, measurement of cytokine levels, and Western blot analysis for STAT 1, 4, 6, and NF-kappaB expression. The effect of GC on NKT cell proliferation was assessed in vitro. Serum AST and ALT levels were markedly reduced in GC-treated group A mice compared with nontreated group C animals, and histological damage was markedly attenuated in group A. The beneficial effect of GC was associated with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of serum IFN-gamma levels, and decreased STAT1 and STAT6 expression. In vitro administration of GC led to a 42% decrease of NKT cell proliferation in the presence of dendritic cells but not in their absence. Intraperitoneally administered radioactive GC was detected in the liver and bowel. Administration of GC led to amelioration of ConA hepatitis associated with an inhibitory effect on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.     

The membrane attack complex in complement-mediated glomerular epithelial cell injury: formation and stability of C5b-9 and C5b-7 in rat membranous nephropathy

Using a model of rat membranous nephropathy (MN), we examined the relationship between the development of glomerular epithelial cell injury and the formation and stability of the membrane attack complex (MAC) of complement. Isolated rat kidneys were perfused with buffered bovine albumin (BSA) or various plasmas (complement source). Kidneys containing nephritogenic amounts of complement-fixing sheep antibody to glomerular epithelial antigens (aFx1A) perfused with BSA (n = 5), and normal kidneys perfused with normal human plasma in BSA (50% v/v, n = 6) excreted 0.30 +/- 0.02 mg protein/min/g during 90 min perfusion (control groups). When normal plasma was added to the perfusate of aFx1A kidneys at concentrations of 12.5, 25, and 50% v/v, protein excretion rose in a time- and concentration-dependent manner. Perfusions with 25% plasma resulted in baseline proteinuria from 0 to 20 min that increased to 2.8 +/- 0.9 mg/min/g at 20 to 40 min and 8.6 +/- 2.1 at 40 to 60 min (n = 4, p less than 0.01 vs control groups). Removal of plasma at 20 min did not prevent this rise in protein excretion (3.9 +/- 2.4 and 5.8 +/- 2.6 mg/min/g at 30 to 40 and 55 to 65 min respectively, p less than 0.01, n = 4). Perfusion of aFx1A kidneys with C8-deficient (C8D) human plasma (25% v/v, n = 4) or C6D rabbit serum (25% v/v, n = 2) independently produced low levels of proteinuria comparable with BSA, but in combination, the two reagents restored enhanced protein excretion (n = 2). In aFx1A kidneys containing C5b-7, addition of C8 and C9 (C6D serum) after intervals of 20, 60, or 90 min immediately reconstituted heavy proteinuria. Thus, the magnitude of MAC-induced glomerular epithelial injury in rat MN is related to the complement dose. Altered glomerular permeability is delayed with respect to the onset of complement activation. Once sufficient C5b-9 is formed, proteinuria can develop despite cessation of new MAC assembly, implying that C5b-9 persists after formation. Moreover, the C5b-7 MAC intermediate is not eliminated rapidly in this model.     

Effect of dietary calcium on serum BGP (osteocalcin).

The present study was designed to clarify the effects of dietary calcium (Ca) intake on serum BGP (osteocalcin) levels. Twelve women with a mean age of 21.2 years participated in the study. After one week of normal Ca intake (mean +/- SE, 535 +/- 2 mg/day), a low-Ca diet (163 +/- 1 mg/day) was given for one further week. Additional asparagine Ca (3 g as Ca/day) was also given to half of the subjects. Serum total and ionized Ca concentrations as well as BGP, PTH and 1,25(OH)2D3 were measured at the end of each period. Amounts of Ca and hydroxyproline excreted in urine were also determined. The plasma level of ionized Ca was significantly increased without any change in total Ca in either group. Low and high Ca intake decreased and increased urinary Ca excretion by 28% and 56%, respectively. Serum levels of BGP and 1,25(OH)2D3 were significantly augmented along with a transient increase in urinary hydroxyproline excretion after Ca deprivation. These results suggest that serum BGP is increased after one week of Ca restriction in healthy subjects.     

Ethanol consumption and serum lipid profiles in Sinclair (S-1) miniature swine

Ethanol consumption was correlated with changes in acyl group profiles of phosphatidylcholine and triacylglycerols in serum of Sinclair(S-1) miniature boars. Serum triacylglycerols in the control pigs were high in linoleate (18:2) (48%) and low in stearate (18:0 (3%). Upon feeding with 10% (w/v) ethanol $\text{ad lib}$ for two weeks, the proportion of 18:2 in serum triacylglycerols decreased to 12–15% with a concomitant increase in 16:0, 18:0 and 18:1. Similar, but less extensive, acyl group changes were observed in the serum phosphatidylcholine. In addition, there was a decrease in the proportion of 20:3 (n?6), but a biphasic change was shown in 20:4 (n?6) with respect to ethanol consumption. In general, the high ethanol consumers (7.0 g/kg/day) indicated a more rapid rate of acyl group change than the low consumers (3.8 g/kg/day). Upon withdrawal of ethanol, acyl groups of triacylglycerols rapidly returned towards the control values, whereas only small changes were observed for the recovery in phospholipids. In this situation, the low-consumer group indicated a more rapid recovery than the high-consumer group. Results indicate that with the swine model, serum lipid changes can be a useful parameter for correlating biological changes upon ethanol consumption.     

Effects of neonatal allopregnanolone manipulations and early maternal separation on adult alcohol intake and monoamine levels in ventral striatum of male rats

Changes in endogenous neonatal levels of the neurosteroid allopregnanolone (AlloP) as well as a single 24 h period of early maternal separation (EMS) on postnatal day (PND) 9 affect the development of the central nervous system (CNS), causing adolescent/adult alterations including systems and behavioural traits that could be related to vulnerability to drug abuse. In rats, some behavioural alterations caused by EMS can be neutralised by previous administration of AlloP. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP could increase adult alcohol consumption, and if EMS could change these effects. We administered AlloP or finasteride, a 5α-reductase inhibitor, from PND5 to PND9, followed by 24 h of EMS at PND9. At PND70 we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v) + glucose 3% (w/v), and glucose 3% (w/v)) for 15 days. Ventral striatum samples were obtained to determine monoamine levels. Results revealed that neonatal finasteride increased both ethanol and glucose consumption, and AlloP increased alcohol intake compared with neonatal vehicle-injected animals. The differences between neonatal groups in alcohol consumption were not found in EMS animals. In accordance, both finasteride and AlloP animals that did not suffer EMS showed lower levels of dopamine and serotonin in ventral striatum. Taken together, these results reveal that neonatal neurosteroids alterations affect alcohol intake; an effect which can be modified by subsequent EMS. Thus, these data corroborate the importance of the relationship between neonatal neurosteroids and neonatal stress for the correct CNS development.     

Inhibition of ethanol-induced changes in rats by Padma 28

In male Wistar rats the protective effect of Padma 28 against changes induced by prolonged treatment with ethyl alcohol was investigated. Exposure of the animals to prolonged ethyl alcohol consumption caused a significant increase in AspAT (by 32%), A1AT (by 50%) and alkaline phosphatase (by 372%) activities as well as an increase in the levels of bilirubin (by 98%) and lipids in the blood serum and lipids in the liver homogenate. Padma 28 administration was found to exert a protective action against these changes: a significant reduction of blood total lipid, triacylglycerol, total cholesterol and bilirubin concentrations as well as in the activity of the liver enzymes was observed.     

Acute and chronic dose of alcohol affect the load carrying capacity of long bone in rats

In the present investigation, the effects of acute and chronic dose of alcohol were evaluated on mechanical properties of long bones of Sprague Dawley rats. In "acute study", 18 animals were divided into three groups containing six animals each, i.e. Group A: control animals, normal saline was given to them intraperitoneally for the period of 5 days; Group B: treated animals, given 20% (v/v) absolute alcohol and Group C: treated animals, given 30% (v/v) absolute alcohol, by same route and time duration. In "chronic study", also, 18 animals were divided into three groups containing six animals each, i.e. Group A: control animals, normal saline was given to them intraperitoneally for the period of 6 weeks; Group B: treated animals, given 20% (v/v) absolute alcohol and Group C: treated animals, given 30% (v/v) absolute alcohol by same route and time duration. A significant increase was observed in bone weight of animals taking 20% alcohol but there was decrease in the same for 30% alcohol in case of acute study. For chronic study, there was a decrease in bone weight for both treated groups. During acute study, breaking strength of bone was increased in case of 20% alcohol administration but a slight decrease was shown in the same for 30% alcohol group as compared to control animals. Breaking strength of long bone in the case of chronic study was decreased in case of both groups taking alcohol, i.e. 20% and 30%. The present document is useful in understanding the functional load carrying capacity of bone during alcoholism.     

蝉棒束孢菌子实体对大鼠肾小管上皮细胞的影响

对蝉棒束孢菌子实体（0.75g/kg）重复灌胃SD雄性大鼠90d及恢复28d的早期肾损伤生物标记物肾损伤分子-1（KIM-1）和中性粒细胞明胶酶相关载脂蛋白（NGAL）进行测定,评估蝉棒束孢菌子实体对肾小管上皮细胞的影响;研究不同剂量蝉棒束孢菌子实体（0.25g/kg、0.5g/kg、1.0g/kg）对肾小管上皮细胞增殖和增生能力的影响。给药30、60、90d及恢复28d时,SD大鼠血清中KIM-1浓度与对照组相比均无显著差异（P>0.05）,给药30d、60d时,SD大鼠血清中NGAL浓度与对照组相比均无显著差异（P>0.05）,给药90d及恢复28d时,SD大鼠血清中NGAL浓度低于对照组（P<0.05）,且给药90d组与对照组相比有显著性差异（P<0.01）;免疫组化检测增殖细胞核抗原法（PCNA）及四甲基偶氮唑盐微量酶反应比色法（MTT）表明：与对照组相比,蝉棒束孢菌子实体能使肾小管上皮细胞增生能力增强,未导致肾小管上皮细胞凋亡。     

Vitamin C or Vitamin B6 supplementation prevent the oxidative stress and decrease of prostacyclin generation in homocysteinemic rats

We hypothesize that homocysteinemia causes oxidative stress, decreases the aortic ability to generate prostacyclin and that antioxidants have a protective role. Four groups of eight rats each were fed for 8 weeks the control diet (group A), control diet with folic acid omitted and excess methionine (Me) added to drinking water (group B), diet B + 500 mg/kg of Vitamin C (group C) or diet B + 60 mg/kg Vitamin B6 (group D). The three groups of rats fed folic acid deficient (FD) diets (groups B, C and D) were homocysteinemic as indicated by the significant increase in their serum homocysteine (HC) concentration. Rats fed diet B had oxidative stress as indicated by an increase in serum thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein products (AOPP) and urinary isoprostanes and had a decreased ability of their aortas to generate prostacyclin. Homocysteinemic rats fed a FD diet + Vitamin C (group C) or Vitamin B6 (group D) also had high levels of serum homocysteine but the oxidative stress markers and the ability of their aortas to generate prostacyclin returned to normal. This indicates that the homocysteinemic effect is through an oxidative mechanism and that Vitamin C as a free radical scavenger prevents these effects. Serum Vitamin C and liver glutathione concentrations significantly increased in rats fed excess Vitamin B6 compared to the control or FD rats. This may explain why Vitamin B6 has an antioxidative effect.