铅 镉对小鼠肝脏毒性作用的形态学观察

目的长期定时定量经口灌胃对小鼠重金属铅、镉用药,观察小鼠肝脏的形态学变化及其毒性机制。方法取30只小鼠分为三组,分别为氯化镉给药组、醋酸铅给药组和生理盐水组（阴性对照组）各10只,每天定时定量连续灌胃给药40d后,取小鼠肝脏经甲醛固定液固定、石蜡包埋、苏木精一伊红染色,制成切片,在显微镜下观察小鼠肝脏的组织形态学改变。结果经显微镜下观察,氯化镉给药组小鼠肝脏肝小叶有点片状坏死病变及大量肝细胞的水样变性;醋酸铅给药组小鼠肝脏肝小叶在中央静脉周围有炎症细胞聚集现象;阴性对照组小鼠肝细胞正常,无炎症细胞聚集现象。结论重金属铅、镉同等条件下对小鼠用药,对小鼠肝脏均有毒性作用,但病变部位、严重程度有所不同。     

Reversibility of the toxic effect of lead on the male reproductive axis

The present study investigates the reversibility of the toxic effects of lead on the hypothalamic-pituitary-testicular axis in prepubertal and pubertal male rats. Male Wistar rats, 27 days and 52 days old, were given ad libitum access to 0.0% or 0.6% lead acetate containing water. Groups of animals were sacrificed at the end of 30 days of exposure or after a 30-day recovery period. Blood lead and free erythrocyte porphyrin (FEP) levels in the lead-treated groups were significantly higher than in the control animals (P less than 0.001). The animals in the recovery groups had lower, albeit not normal, blood lead and FEP levels 30 days after discontinuing treatment. Serum testosterone, intratesticular sperm counts, and sperm production rates were suppressed in the lead-treated groups (P less than 0.001). Serum testosterone and sperm parameters normalized at the end of the recovery period in the prepubertal animals but not in the pubertal animals.     

铅诱发大鼠脂质过氧化作用及毒作用机制研究

本研究表明，醋酸铅染毒大鼠肝和脑组织中氧自由基的信号随着染毒剂量的增高而增高，表明铅染毒可诱发大鼠体内氧自由基产生；血、肝、和脑组织中ＭＤＡ水平升高程度与染毒剂量呈极显著正相关性；红细胞内ＳＯＤ活性下降和ＧＳＨ－Ｐｘ酶活性轻度升高，使得机体清除自由基和抗氧化的能力下降，造成体内的氧自由基蓄积，从而诱发脂质过氧化作用，推测这可能是铅的毒作用机制之一。     

Light and electron microscopic study of the toxic effect of prolonged lead exposure on the seminiferous tubules of albino rats and the possible protective effect of ascorbic acid

Background

Lead has been long recognized as an occupational toxicant. Now, lead is considered to be one of the major environmental pollutants which have serious potential threat to human health. Reports of declining male fertility have renewed interest in the role of environmental and occupational exposures in the etiology of human infertility.

Objectives

The aim of the present work was to investigate the toxic effect of prolonged exposure to lead on albino rat’s seminiferous tubules and the possible protective effect of ascorbic acid (vitamin C) on lead toxicity.

Methods

The study was carried out on 40 adult male albino rats divided into three groups: a control group which comprised three subgroups; negative control which received no treatment and two positive controls receiving an oral daily dose of distilled water or ascorbic acid, respectively. Lead acetate - intoxicated group received lead acetate orally in a dose of 25 mg/kg b.w dissolved in distilled water for 3 months. While the protected group received ascorbic acid orally in a dose of 100 mg/kg b.w daily for 3 months, simultaneously with lead acetate in a similar dose to that of the intoxicated group. By the end of the experimental period, blood samples were collected for estimation of blood lead level. Fresh specimens were taken from the testis and processed for light and electron microscopic examination.

Results

Biochemical analysis demonstrated significant increase in the blood lead level in lead intoxicated group compared to the control group, while ascorbic acid - protected group revealed significant decrease in the blood lead level. Light microscopic examination of lead treated group revealed loss of normal archicture of the testicular tissue in the form of thin walled seminiferous tubules with wide lumen and vacuolations in the spermatogenic epithelium mostly separating primary spermatocytes from spermatogonia and surrounding nuclei of Sertoli cells. Apoptotic bodies were found among the basal part of the spermatogenic epithelium. Ultrastructural examination of the same group revealed degenerating cells with cytoplasmic vacuolations, apoptotic cells with heterochromatic nuclei and dense cytoplasm, irregularities in the basal lamina with increased collagen deposition and shrunken myoid cells. Late differentiating spermatids showed deformed head with widening of the subacrosomal space and redundant acrosome, in addition to the abnormalities in the tail of developing sperms. On the other hand, ascorbic acid - protected group showed amelioration of most of the degenerative changes depicted in the lead intoxicated group.

Conclusion

Lead had an injurious effect on the testis of the exposed animals. Simultaneous administration of ascorbic acid was efficient in preventing most of such toxic effect and decreasing the blood lead level. Therefore, ascorbic acid can be recommended for protection against lead intoxication.     

Comparative study of chronic toxic effects of daunorubicin and doxorubicin in rabbits

This study compares the chronic toxicity of two anthracyclines--daunorubicin and doxorubicin, commonly used for induction of anthracycline cardiomyopathy in the rabbit model. Such a comparative study has not been published until now. Both drugs were administered intravenously to male Chinchilla rabbits in doses at 3 mg/kg (50 mg/m2) once weekly for 10 weeks. Selected biochemical, haematological and cardiovascular parameters and body weights were regularly monitored; additionally, a histological evaluation of heart, kidney and liver was performed at the end of the experiment. In the daunorubicin group, there were marked signs of the progressive development of heart failure, like the significant increases of the pre-ejection period/left ventricular ejection time index values (up to 134%)--and histological changes within the myocardium were also observed. On the other hand, the 10-week doxorubicin administration did not cause these changes that are typical for heart injury. Haematotoxicity, manifested particularly by aplastic anaemia, was apparent in both the experimental groups. Significant body weight loss (by 45.2%) and high premature mortality (100% versus 36.4%) reflected a greater general toxicity, especially nephrotoxicity of doxorubicin in comparison with daunorubicin. Further studies are necessary to find a possible explanation for these findings.     

Comparative study on two freshwater invertebrates for monitoring environmental lead exposure

Two freshwater invertebrate organisms, Biomphalaria glabrata and Lumbriculus variegatus, were tested as potential experimental animal models to assess Pb exposure using acute laboratory bioassays. Since long, the enzyme delta-aminolevulinic acid dehydratase (ALA-D) has been recognised as a useful biomarker of Pb exposure and effect. Therefore, determinations of ALA-D activity were performed in the whole body soft tissues of pigmented and non-pigmented gastropods B. glabrata and in the oligochaete L. variegatus. The organisms were exposed to varying concentrations of Pb for 48 h. Levels of Pb in the invertebrates were also analysed. Highly significant negative correlations were found between the enzymatic activity and the levels of Pb exposure, and also between the enzymatic activity and the metal incorporated by the invertebrates. No significant differences were found in the enzyme activity nor in the resulting metal accumulation based on gastropod pigmentation. The values of Pb concentration that produce 50% of inhibition on the enzyme activity (EIC50) were 0.023 and 0.029 mg Pb/L for pigmented and non-pigmented B. glabrata, respectively. A much higher value was found for L. variegatus (0.703 mg Pb/L). The non-observed effect concentration (NOEC) on enzyme activity for the oligochaetes was 0.05 mg Pb/L, about twice the EIC50 calculated for the gastropods. These data showed that both pigmented and non-pigmented B. glabata were much more sensitive organisms than the oligochaetes. The differences in enzyme inhibition could be attributed, at least partly, to differences in the metal body burden found between the organisms, since levels of Pb accumulated by B. glabrata were approximately three times higher compared to those observed in L. variegatus. Therefore B. glabrata showed to be a more suitable and reliable bioindicator organism for assessing Pb contamination in aquatic ecosystems, especially at low levels of metal exposure.     

Comparative study on sensitivity of higher plants and fish to heavy fuel oil

Laboratory tests were conducted on higher plants [garden cress (Lepidium sativum), great duckweed (Spirodela polyrrhiza), and Tradescantia clone BNL 02] and fish [rainbow trout (Oncorhynchus mykiss) at all stages of development: eggs, larvae and adults] to estimate their sensitivity to heavy fuel oil (HFO). A number of biological indices (survival, growth, and physiological and morphological parameters) as well as the genotoxic impact (Tradescantia) of HFO was evaluated by acute and chronic toxicity tests. Fish were found to be more sensitive to the toxic effect of HFO than were higher plants. EC(50) values obtained for higher plants ranged from 8.7 g/L (L. sativum) to 19.8 g/L (Tradescantia), and maximum-acceptable-toxicant concentration (MATC) values ranged from 0.1 to 1.0 g/L of total HFO for L. sativum and Tradescantia, respectively. The 96-h LC(50) values ranged from 0.33 g/L, for larvae, to 2.97 g/L, for adult fish, and the MATC value for fish was found to be equal to 0.0042 g/L of total HFO. To evaluate and predict the ecological risk of the overall effects of oil spills, studies should be performed using a set of acute and chronic bioassays that include test species of different phylogenetic levels with the most sensitive morphological, physiological, and genotoxic indices.     

Comparative study of glycosylated haemoglobin and serum fructosamine values in children with protein-energy malnutrition.

Serum fructosamine, glycosylated haemoglobin (HbAic), fasting blood glucose and serum proteins were determined in 50 malnourished children aged 1-5 years and in 25 healthy and nutritionally normal children of the same age group. It was observed that both HbAic and fructosamine values correlated well with the blood glucose values of the patients. It was also observed that the patients had significantly elevated values of HbAic, indicating the existence of glucose intolerance in them. In contrast, the fructosamine values were significantly reduced in the patients and this was attributed to the hypoproteinaemia in such patients. It was concluded that while both HbAic frustosamine correlate well with blood glucose values, HbAic gives a better reflection of the glycaemic status of malnourished children because its level is not significantly altered by hypoproteinaemia. HbAic measurement may, therefore, be a more reliable indicator of glucose status than serum fructosamine in children with protein-energy malnutrition.     

原位脾切除术与托出式脾切除术的疗效比较

目的对比分析原位脾切除术与托出式脾切除术的疗效。方法人选的62例脾切除患者为2009年1月～2012年1月在我院进行手术治疗的患者,其中行原位脾切除术治疗的患者32例设立为A组,行托出式脾切除术治疗的患者30例设立为B组,观察比较两组患者术中出血量、术后引流量、下床活动时间、手术时间及术后住院时间等手术指标,以及应用统计学方法对两组患者出现脾窝脓肿、脾热、感染（泌尿系感染、肺部感染）、胰瘘等并发症发生率进行比较分析。结果B组患者的术中出血量、术后引流量、下床活动时间、手术时间均明显短于A组,组问比较差异均有统计学意义（P〈0．05）。B组术后住院时间与A组比较,差异无统计学意义（P〉0．05）。B组患者无一例发生脾窝脓肿,发生脾热、感染、胰瘘等并发症发生率合计13．3％,虽然低于A组并发症的发生率（15．6％）,但组间比较差异无统计学意义（P〉0．05）。结论托出式脾切除术的疗效明显优于原位脾切除术,具有操作迅速、手术时间短、患者恢复快等优点,且并发症少,值得广泛推广和应用,但要求严格掌握好手术适应证。     

鱼油逆转癌性恶病质的实验研究

目的探讨促炎细胞因子IL-6、TNF-α在癌性恶病质（CC）中形成的作用,并研究鱼油对小鼠恶病质状态的改善情况及生存时间的影响,初步探讨鱼油在预防用药中的价值及其可能机制。方法将鼠结肠腺癌26细胞株皮下接种于BALB/c小鼠,构建癌性恶病质模型。将50只BALB/c小鼠随机分成健康对照组（A组）、荷瘤＋等渗生理盐水组（B组）、荷瘤＋鱼油组（C组）、荷瘤＋吲哚美辛组（D组）。监测各组小鼠一般情况,去瘤体质量、血清IL-6、TNF-α的水平及各生化指标浓度变化。结果CC小鼠去瘤体质量明显下降（P〈0.05）,血清各生化指标不同程度的出现代谢消耗状态（P〈0.05）,血清IL-6、TNF-α水平明显升高（P〈0.05）。C、D组IL-6、TNF-α水平均低于B组（P〈0.05）,各生化指标亦有不同程度的改善（P〈0.05）,但C、D2组指标比较差异无统计学意义（P〉0.05）。结论炎性细胞因子IL-6、TNF-α与CC的发生、密切相关,鱼油具有显著的逆转CC作用,鱼油的早期干预对CC的发生发展有着重要作用。     

Time-dependent oxidative stress responses after acute exposure to toxic cyanobacterial cells containing microcystins in tilapia fish (Oreochromis niloticus) under laboratory conditions

Microcystins (MCs) have been reported to induce oxidative stress in aquatic organisms including fish. The effect of acute exposure to toxic cyanobacterial material containing MCs on antioxidant enzymes and lipid peroxidation has been studied in liver, kidney and gills of tilapia fish (Oreochromis niloticus). Fish were orally exposed to a single dose of cyanobacterial cells containing 120 microg/fish MC-LR and sacrificed at 24 and 72 h. The activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) enzymes in the studied organs decreased in general 24 and 72 h after the dose application, although elevation of CAT and GR was found in liver at 72 h post exposure in comparison to 24h values. In contrast, the lipid peroxidation level increased significantly in all the studied organs with the liver (3.6-fold) proving to be the most affected. Protein oxidation was also increased 1.5-fold in the liver. However, recovery in these parameters was observed in liver 72 h after exposure. The results show that an acute dose of MCs does not induce an adaptative response of the antioxidant enzymes, as a sub-chronic exposure to MCs in tilapia fish does, but a general decrease in them with an initial recovery of the oxidative damage after 72 h, expressed as enhancement of CAT and GR activities and a reduction of LPO and protein oxidation in comparison to 24h values.     

贝那普利与卡托普利降压效果的对比研究

目的 对比观察贝那普利与卡托普利治疗轻、中度高血压患者的临床疗效与安全性.方法 将120例高血压患者随机平分为两组,分别给予贝那普利和卡托普利治疗,均加用小剂量氢氯噻嗪, 治疗8周, 于治疗前及治疗8周末行血压监测, 评定各组降压效果.结果 贝那普利组患者降压有效率高于卡托普利组,组间比较差异有统计学意义(P<0.05);不良反应发生率两组间差异无统计学意义(P>0.05).结论 贝那普利对轻、中度原发性高血压病有较好的降压效果,联合应用小剂量利尿剂可提高疗效.     

Vitapex与根管糊剂疗效的比较研究

目的　探讨2种不同根管充填剂的临床疗效。方法　164例根尖周炎、牙髓炎病人随机分两组分别采用Vitapex与根管榴剂进行根管充填。结果　经2年临床观察，Vitapex组成功率为96．4％，根管榴剂对照组成功率为88．1％，两组差异有显著意义(P＜0．05)。结论　Vitapex用于根充临床疗效优于根管榴糊剂。     

Comparative study on the effect of staphylococcal alpha-toxin on erythrocytes and thrombocytes

The effect of staphylococcal alpha-toxin on the release of haemoglobin from rat erythrocytes, and serotonine from rat thrombocytes, has been measured and expressed in ₅₀ values. The Hb depletion is dose-dependent and appears after a latency period. Higher doses produce complete haemolysis. Diluted and full plasma decreases the toxin potency in this respect. 5-HT release from thrombocytes starts immediately after toxin administration and is dose-dependent. However, even after 60 min of incubation with plasma, high toxin doses release only about 50 per cent of 5-HT. Diluted plasma somewhat enhances the releasing effect.     

Cocaine toxic effect on endothelium-dependent vasorelaxation: an in vitro study on rabbit aorta

Effects of cocaine on vascular endothelium relaxing properties and the related mechanism were investigated in vitro in rabbit aorta. Several vasorelaxing agents with different mechanisms, i.e. acetylcholine, substance P, calcium ionophore A23187, 2,5-di-tert-butylhydroquinone, or sodium nitroprusside, were employed. Cocaine effects on the vascular response to relaxing agents in cumulative (acetylcholine, substance P, or A23187) or single dose (2,5-di-tert-butyl-hydroquinone) were performed in endothelium-intact aortic rings precontracted with phenylephrine. Relaxing activity of cumulative doses of sodium nitroprusside was evaluated in endothelium-denuded aortic rings, in the presence of cocaine. Cocaine significantly reduced endothelium-dependent relaxations induced by acetylcholine, or substance P. By contrast A23187 endothelium-mediated relaxation as well as endothelium-independent relaxation by sodium nitroprusside were unaffected by cocaine. Furthermore, cocaine significantly increased endothelium-dependent relaxation response to 2,5-di-tert-butylhydroquinone, a sarcoplasmic Ca2+-ATPase pump inhibitor, in the aortic rings. These findings indicate that cocaine reduces nitric oxide release from vascular endothelium apparently through the inhibiting action of Ca2+-ATPase pump.     

Paralytic shellfish poisoning toxins accumulation in purple clam Hiatula rostrata and toxic effect on milkfish Chanos chanos larval fish.

In an attempt to feed purple clams (Hiatula rostrata) with dinoglagellate Alexandrium minutum, the maximal accumulation toxicity of paralytic shellfish poisoning (PSP) toxins reached 40.6 MU/g on day 5 of feeding. Subsequently, the toxicity increased no further, although purple clams ingested more toxic algae. Furthermore, when milkfish (Chanos chanos) larvae were treated with toxic, nontoxic A. minutum or PSP toxin-containing extract in the water medium, it was found that the mortality of fish increased with the increasing concentrations of toxic algae. PSP toxin-containing extract did not show any toxic effect on milkfish larvae.     

Experimental study of pharmacotherapeutic effect of phytoecdisteroids and nerobol in toxic liver damage

Phytoecdysteroids ecdysteron and turkesteron isolated from Ajuga turkestanica (Rgl.) Brig. decrease the manifestations of uremic intoxication in rats with experimental renal pathology induced by a nephrotoxic mixture (containing uranyl acetate and glycerol). Injected in a dose of 5 mg/kg, the drugs restore glomerular filtration level, favor the disappearance of the albuminuria and normalize urinary sediments. The nephroprotector effect of the phytoecdysteroids studied resembles the action of a steroidal anabolic drug nerobol.     

Sublethal effects of profenofos on locomotor behavior and gill architecture of the mosquito fish, Gambusia affinis

Subacute studies of profenofos on mosquito fish, Gambusia affinis, were carried out for 20 days to assess the locomotor behavior and structural integrity of gill in relation to bioaccumulation and targeted enzyme acetylcholinesterase (AChE; EC 3.1.1.7). The sublethal concentration of 0.13 mg/L (1/5 of LC50) altered locomotor behavior such as distance traveled and swimming speed in exposed fish. This could be due to inhibition in the activity of acetylcholinesterase and deformities in the primary and secondary lamella of gill. The bioaccumulation values indicated that the accumulation of profenofos was highest in viscera followed by head and body. The average bioconcentration factor values are 254.83, 6.18, and 2.52 microg/g for viscera, head, and body. The findings revealed that profenofos is highly toxic even at sublethal concentrations to the mosquito fish, Gambusia affinis.