Subhepatotoxic exposure to arsenic enhances lipopolysaccharide-induced liver injury in mice

Exposure to arsenic via drinking water is a serious health concern in the US. Whereas studies have identified arsenic alone as an independent risk factor for liver disease, concentrations of arsenic required to damage this organ are generally higher than found in the US water supply. The purpose of the current study was to test the hypothesis that arsenic (at subhepatotoxic doses) may also sensitize the liver to a second hepatotoxin. To test this hypothesis, the effect of chronic exposure to arsenic on liver damage caused by acute lipopolysaccharide (LPS) was determined in mice. Male C57Bl/6J mice (4-6 weeks) were exposed to arsenic (49 ppm as sodium arsenite in drinking water). After 7 months of exposure, animals were injected with LPS (10 mg/kg i.p.) and sacrificed 24 h later. Arsenic alone caused no overt hepatotoxicity, as determined by plasma enzymes and histology. In contrast, arsenic exposure dramatically enhanced liver damage caused by LPS, increasing the number and size of necroinflammatory foci. This effect of arsenic was coupled with increases in indices of oxidative stress (4-HNE adducts, depletion of GSH and methionine pools). The number of apoptotic (TUNEL) hepatocytes was similar in the LPS and arsenic/LPS groups. In contrast, arsenic pre-exposure blunted the increase in proliferating (PCNA) hepatocytes caused by LPS; this change in the balance between cell death and proliferation was coupled with a robust loss of liver weight in the arsenic/LPS compared to the LPS alone group. The impairment of proliferation after LPS caused by arsenic was also coupled with alterations in the expression of key mediators of cell cycle progression (p27, p21, CDK6 and Cyclin D1). Taken together, these results suggest that arsenic, at doses that are not overtly hepatotoxic per se, significantly enhances LPS-induced liver injury. These results further suggest that arsenic levels in the drinking water may be a risk modifier for the development of chronic liver diseases.     

Clinical safety evaluation of marine oil derived from Calanus finmarchicus

Marine oils are rich in polyunsaturated fatty acids (PUFAs), including docosahexaenoic and eicosapentaenoic acid. These PUFAs are associated with health benefits and additional sustainable sources of marine oils are desirable. One of the source organisms is Calanus finmarchicus, a copepod endemic to the North Atlantic. PUFAs in the lipid fraction of this organism are largely in the form of wax esters. To assess the safety of these wax esters as a source of PUFAs, a randomized, double-blinded, placebo-controlled clinical trial was conducted whereby 64 subjects consumed 2 g Calanus oil in capsule form daily for a period of one year. A group of 53 subjects consumed placebo capsules. At baseline, 6-, and 12-months, series of evaluations were conducted, including: vital signs, clinical chemistry and hematological evaluations, and adverse event reporting. Food intake and physical exercise were controlled by means of a questionnaire. There were no effects on Calanus oil treatment on any of the safety parameters measured. A slight increase in the incidence of eczema was reported in the Calanus oil group, but the response was minor in nature, not statistically significant after controlling for multiple comparisons, and could not be attributed to treatment.     

原发性胆汁性胆管炎25-(OH)维生素D、AMA-M2、ALP、IgM相关性研究

目的 分析原发性胆汁性胆管炎与25-(OH)维生素D、抗线粒体抗体M2(AMA-M2)、碱性磷酸酶(ALP)、免疫球蛋白M(IgM)间的相关性.方法 收集2018年1月至2019年12月28例本院原发性胆汁性胆管炎患者(A组)、20例肝硬化患者(B组)、20例健康体检(C组)进行研究,均检测抗线粒体抗体、25-(OH)...     

Variants of self-assembling peptide,KLD-12 that show both rapid fracture healing and antimicrobial properties

KLD-12 (KLD) is a 12-residue self-assembling peptide that can adopt nano-structures and is known for its tissue-engineering properties. Our objective was to introduce antimicrobial attribute to KLD which would help in preventing secondary infection associated with external application of such tissue engineering materials. Considering the net charge of KLD-12, varying number of cationic arginine residues were added to its N-terminus. KLD variants showed appreciable bactericidal properties without any significant increase in cytotoxicity against tested mammalian cells. Further, these variants adopted β-sheet structures and self-assembled into nano-structures comparable to that of KLD. Interestingly, the KLD variants with two (KLD-2R) and three (KLD-3R) arginine residues added to its N-terminus showed significant osteogenic effect which was comparable or better than the original peptide as evident from the alkaline phosphatase activity assay, mineralized nodule formation and expression of different osteogenic genes. Particularly, application of KLD-2R in rats to the site of a drill-hole (0.8 mm diameter) that was created in the femur metaphysis displayed significantly higher bone regeneration compared to that of KLD. The results demonstrate a simple way to improve biological property of a self-assembling peptide with tissue engineering property.     

血清5'-核苷酸酶与肝功能生化酶的联合检测在胆道良恶性疾病中的诊断价值

目的 探讨5'-核苷酸酶(5'NT)与肝功能生化酶的联合检测在胆道良恶性病变中的诊断价值.方法 采用速率法检测经手术及病理证实的胆道恶性肿瘤74例,慢性胆囊炎70例,胆结石+慢性胆囊炎68例及正常健康人70例血清中5'-核苷酸酶水平,同时检测肝功能相关的血清总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)、γ-谷氨酰氨转肽酶(GGT)、碱性磷酸酶(ALP).结果 胆囊癌+胆管癌的血清5'NT水平明显高于慢性胆囊炎、胆结石+慢性胆囊炎组及正常健康人群(P＜0.05),而胆囊癌+胆管癌(伴梗阻)组与胆囊癌+胆管癌(未梗阻)组差异无统计学意义(P＞0.05),胆道良性疾病与健康人群之间差异也无统计学意义(P＞0.05).胆道恶性疾病中5'NT与ALP、GGT呈高度正相关(r=0.665,r=0.519;F=57.16,F=26.588,P＜0.05).血清5'NT、ALP、GGT联合检测的特异性、敏感度分别为95.65%和94.59%.结论 5'NT与肝功能生化酶类指标联合应用,可作为诊断胆道良恶性疾病的较为敏感、有效的生化指标,有助于胆道良恶性疾病的鉴别.     

Safety assessment of lutein and zeaxanthin (Lutemax™ 2020): Subchronic toxicity and mutagenicity studies

Lutein and zeaxanthin, naturally occurring carotenoids, have shown to reduce the risk of cataracts and age-related macular degeneration. Lutemax™ 2020 is a lutein and zeaxanthin (including meso-isomer) enriched product obtained from Marigold flowers (Tagetes erecta L). The objective of the present study was to investigate adverse effects, if any, of Lutemax 2020™ in acute and subchronic toxicity, and mutagenicity studies. In acute toxicity study in rats no lethality was noted at 2000 mg Lutemax 2020™/kg body weight (bw). In the subchronic study, Wistar rats (10/sex/group) were administered (gavage) lutein/zeaxanthin concentrate at dose levels of 0, 4, 40 and 400 mg/kg bw/day for 90-days. Compared with the control group, administration of lutein/zeaxanthin concentrate did not result in any toxicologically significant treatment-related changes in clinical observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No toxicologically relevant findings were noted in urinalysis, hematology or clinical biochemistry parameters at the end of the treatment or recovery period. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. The results of mutagenicity testing in Salmonella typhimurium did not reveal any genotoxicity. The no observed-adverse-effect level (NOAEL) for lutein/zeaxanthin concentrate was determined as 400 mg/kg bw/day, the highest dose tested.     

原发性肝癌患者血清酶类指标变化的临床价值

目的:探讨血清a-L-岩藻糖苷酶(AFU)、γ-谷氨酰转移酶(GGT)、碱性磷酸酶(ALP)和胆碱酯酶(CHE)对原发性肝癌(primary hepatocarcinoma,PHC)的诊断价值.方法:使用全自动生化分析仪对107例原发性肝癌患者血清中AFU、GGT、ALP和CHE进行检测.结果:原发性肝癌患者血清AFU、GGT、ALP和CHE水平及阳性率均明显高于正常对照组及良性肝病组(P＜0.01);联合检测的敏感性和诊断准确性均比单项检测高.结论:联合检测血清中AFU 、GGT、ALP和CHE对原发性肝癌诊断具有重要临床价值.     

儿童锌缺乏敏感指标的评价

为评价反映儿童锌缺乏的敏感指标.方法 我们对300名3～6岁儿童进行膳食调查与体格检查,同时测定了锌缺乏组和对照组儿童的尿锌与尿肌酐比值,血清ALP活性,血清胆固醇水平及锌缺乏儿童补锌治疗前后上述指标的变化.结果 锌缺乏组与对照组尿锌与尿肌酐比值,血清ALP活性有显著性差异.锌缺乏组儿童血浆锌,尿锌与尿肌酐比值,血清ALP活性,血清胆固醇水平在补锌治疗前后有显著性差异.结论 血浆锌和血清ALP同时降低可以预示儿童体内锌缺乏,需要补锌治疗;尿锌与尿肌酐比值能较敏感地反映儿童的锌营养状况;胆固醇与锌营养之间的关系值得进一步研究.     

Selective impairment of drug-metabolizing enzymes in pig liver during subchronic dietary exposure to aflatoxin B1.

Consequences of subchronic exposure to aflatoxin B1 (AFB1) on liver monooxygenase and transferase enzymes were compared in control pigs and pigs given 385, 867 or 1,807 microg AFB1/kg of feed for 4 weeks. Animals exposed to the highest dose of toxin developed clinical signs of aflatoxicosis, like liver fibrosis, hepatic dysfunction and decreased weight gain. This group had significantly lower levels of liver cytochrome P450, ethoxyresorufin O-deethylase (EROD) activity, testosterone metabolism, P450 1A and P450 3A protein expression. By comparison, mild degenerative hepatic changes, no hepatic dysfunction but a similar pattern of liver P450 enzymes activity without changes in P450 3A expression were observed in pigs exposed to 867 microg AFB1/kg of feed. Benzphetamine and aminopyrine N-demethylase activities were increased in pigs exposed to 867 or 1,807microg AFB1/kg of feed. Pigs exposed to 385 microg AFB1/kg of feed had low levels of EROD activity and all other biotransformation and clinical parameters remained at control levels. Aniline hydroxylase activity, P450 2C protein expression, UDP-glucuronosyl and glutathione S-transferase activities were unaffected at all doses of AFB1. In conclusion, P450 1A and P450 3A appear to be specific targets of AFB1 even if pig did not display clinical sign of liver toxicosis.