Tetrathiomolybdate protects against cardiac damage by doxorubicin in mice

Cardiac toxicity is the limiting factor in therapy with doxorubicin, an otherwise useful cancer drug. In this article we detail our study of a mouse model of doxorubicin-induced cardiac toxicity in which, after 4 days' treatment, doxorubicin caused marked increases in plasma concentrations of creatine kinase, lactic dehydrogenase, and troponin I, indicators of cardiac injury; marked increases in the plasma concentrations of tumor necrosis factor-alpha and interleukin-1(beta), both inflammatory cytokines; and a marked increase in the plasma concentration of interleukin-2, an indicator of cytotoxic T-cell activation. Therapy with tetrathiomolybdate, designed to limit copper availability, eliminated almost all of the increases of these six parameters in plasma. The marked protection against cardiac injury by doxorubicin in tetrathiomolybdate-treated animals suggests that tetrathiomolybdate would be of use clinically in helping prevent doxorubicin toxicity in patients. In other preclinical work, it has been shown that tetrathiomolybdate potentiates the chemotherapeutic effect of doxorubicin in cancer, so a double benefit might accrue clinically from the combined use of tetrathiomolybdate and doxorubicin. The mechanism by which tetrathiomolybdate protects against doxorubicin toxicity is of considerable interest. Our working hypothesis, based on the inhibition of interleukin-2 by tetrathiomolybdate as shown here, is that tetrathiomolybdate interrupts the inflammatory cascade at the activated-T-lymphocyte stage.     

吸毒人群HBV、HCV感染状况及吸毒合并两种病毒感染对ALT异常的影响

目的 :为评估湛江市吸毒人群 HCV、HBV的感染状况 ,以及吸毒合并 HCV、HBV感染对血清 AL T异常的影响。方法 :收集 2 0 0 2 - 0 2～ 2 0 0 3- 0 3湛江市吸毒人群资料 ,并对调查对象进行血清 HCV、HBV和 AL T的检测。结果 :湛江市静脉吸毒人群的 HBs Ag阳性率、HCV感染率和 HBV感染率分别为 2 4 .6 1%、5 7.87%、6 7.32 % ,明显高于对照组(11.0 3%、0 .91%、5 1.96 % ) ,有显著性差异 ,非静脉吸毒组此 3项与对照组比较无显著性差异 ;HBV单项、HCV单项、HBV和 HCV混合项 ,这 3种组合感染的静脉吸毒者 ,他们血清中的 AL T异常率分别为 15 .6 9%、33.33%、4 5 .5 0 % ,这3种 AL T异常率分别与未感染 HBV、HCV的静脉吸毒者的 AL T异常率 (9.84 % )比较 ,前者无显著性差异 ,后两者有显著性差异。结论 :静脉吸毒是吸毒者感染 HBV、HCV的重要途径 ;HCV感染对静脉吸毒者血清 AL T的异常起重要作用     

Efficiency of combined methotrexate/chloroquine therapy in adjuvant-induced arthritis

The present study evaluates the effects of methotrexate (MTX) and chloroquine (CQ), and of combined MTX + CQ treatment, on the inflammatory response and on plasma and liver phosphatase and transaminase activities, employing an adjuvant-induced arthritis model in rats. Arthritis was induced by the intradermal injection of a suspension of Mycobacterium tuberculosis in mineral oil into the plantar surface of the hind paws. Development of the inflammatory response was assessed over a 21-day period. Animal groups received either: (i) MTX, administered i.p., weekly, in 0.15, 1.5, 3, 6 or 12 mg/kg doses; (ii) CQ, given intragastrically, in daily 25 or 50 mg/kg doses; or (iii) MTX + CQ, administered in two combinations (MTX1.5 mg/kg + CQ50 mg/kg, or MTX6 mg/kg + CQ50 mg/kg). At the end of the experimental period, the animals were anesthetized and killed, blood and liver samples were collected and prepared for measurement of acid and alkaline phosphatase (AP, ALP), and aspartate (AST) and alanine aminotransferase (ALT) activities. MTX at 6 and 12 mg/kg reduced the inflammatory response while CQ had no effect. MTX6 mg/kg + CQ50 mg/kg reduced the inflammatory response similar to MTX12 mg/kg, without affecting the bone marrow. Plasma AP and liver ALP activities were very elevated in the arthritic rats. While MTX treatment partially reduced both plasma AP and liver ALP activities at all doses used in the arthritic rats, CQ treatment reduced plasma AP, but increased liver AP activity. MTX + CQ treatment decreased plasma AP and liver ALP activities in the arthritic rats to control values. Plasma and liver AST activities were unaltered in the arthritic rats, and were unaffected by treatment. However, plasma and liver ALT activities were significantly reduced in the arthritic rats. While MTX or CQ treatment did not alter plasma transaminase activity in the arthritic rats, after MTX + CQ treatment, plasma ALT activity returned to normal values. In conclusion, the present data suggest that MTX + CQ treatment provides more effective anti-inflammatory protection against adjuvant-induced arthritis than does MTX alone, reverting the alterations in enzyme activities induced by this inflammatory disease in rats.     

Comparison of biliary atresia with and without intracranial hemorrhage

Background/Purpose

Intracranial hemorrhage (ICH) is a severe complication of biliary atresia (BA). We aimed to compare the clinical data of BA patients with and without ICH.

电针联合游泳训练对脊髓全横断大鼠脊髓神经营养因子-3及血清谷丙转氨酶、谷草转氨酶的影响

目的:探讨电针联合游泳训练对脊髓全横断大鼠脊髓神经营养因子-3(NT-3)及血清谷丙转氨酶(ALT)、谷草转氨酶(AST)的影响。方法:雌性成年SD大鼠180只,随机分为6个组(正常组,假手术组,损伤组,游泳组,电针组,联合组),每组30只。制作脊髓T10全横断损伤模型。术后第5天开始电针及游泳训练(电针每天30min,电流1m A,频率为2/100Hz,波型为疏密波。游泳第1周游一组,以后每周加一组,一组时间为4min。每周治疗7次)。对照组不进行治疗。术后7d、14d、21d、28d、35d进行运动功能评估(BBB评分),治疗结束时取材。用免疫组化及生化来检测相关因子的表达。结果:(1)各治疗组的运动功能评分较损伤组均有提高(除第1周(P0.05)),并随时间的延长效果更为明显;在各干预组中,联合组运动功能的恢复最为突出(P0.01)。(2)治疗组大鼠脊髓损伤区NT-3表达较损伤组均有提高(P0.05),并随时间的延长而提高,治疗组之间联合组NT-3的表达更为突出(P0.01)。(3)各治疗组中血清ALT、AST的表达水平较损伤组均有下降(P0.05),联合组下降最为明显(P0.01)。结论:游泳训练及电针能够促进脊髓损伤后运动功能的恢复,将两者联合应用效果更为明显。     

Pattern of liver function and clinical profile in COVID-19: A cross-sectional study of 91 patients

Background– COVID-19 caused by SARS-CoV-2 leads to myriad range of organ involvement including liver dysfunction.AimTo analyse the liver function in patients with COVID-19 and their association with respect to age, sex, severity of disease and clinical features.Materials and methodsThis study was a cross-sectional study done at Rajendra Institute of Medical Sciences, Ranchi. 91 patients admitted with confirmed SARS-CoV-2 infection were included in this study and divided into asymptomatic, mild, moderate and severe groups. Liver function tests were compared among different severity groups.ResultsOf 91 patients with COVID-19, 70 (76.9%) had abnormal liver function. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin levels was 1–2 × ULN in 33(36.3%), 34(37.3%), 12(13.2%), 6(6.6%) cases and >2 × ULN in 20(22%), 18(19.8%), 7(7.7%) and 2 (2.2%) cases respectively. Mean AST and ALP levels among different severity groups of COVID-19 was statistically significant (p < 0.05) whereas mean ALT and total bilirubin levels was statistically non-significant (p > 0.05). There was no statistical difference between males and females with regard to abnormal liver function. Liver injury was seen in 64.3% cases of hypertension and 73.3% cases of diabetes. Fever, myalgia, headache and breathlessness were found to be correlated significantly with severity of disease.ConclusionLiver injury is common in SARS-CoV-2 infection and is more prevalent in the severe disease group. Aspartate transaminase and alkaline phosphatase are better indicators of covid-19 induced liver injury than alanine transaminase and total bilirubin.     

Oral toxicological studies of black soybean (Glycine max) hull extract: Acute studies in rats and mice, and chronic studies in mice

Black soybean (Glycine max) has been used for traditional medicine and food in Asian countries, but safety of its hull has not been studied. We conducted acute and chronic oral toxicity studies. For the acute study, an extract of black soybean hull (BE; 2.5 g/kg body weight) was administered singly by intragastric intubation to Sprague–Dawley rats and C57BL/6 mice. There was no death or significant decrease in body weight in rats and mice, and the oral LD₅₀ of BE was >2.5 g/kg body weight. In the chronic study, BE was administered at dietary levels of 0% (control), 2.0%, and 5.0% to male and female C57BL/6 mice for 26 weeks. No mortality or toxicologically significant clinical changes were observed through the experimental period. Although body weights, as well as abdominal fat, blood levels of triglyceride and total cholesterol in 5.0% males were significantly lower than that in control and 2.0% groups, these changes were considered not to be adverse. Hematology and histopathological observation revealed no toxicologically significant changes. The no-observed adverse-effect-level of BE was estimated to be 5.0% in the diet (5074.1 mg/kg body weight/day for males and 7617.9 mg/kg body weight/day for females).     

Protective effect of gallic acid against lindane induced toxicity in experimental rats

Lindane is an organochlorine pesticide that persists in the environment, bioaccumulate through food chain and has a risk of causing adverse effects to human health and the environment. It induces cell damage by producing free radicals and reactive oxygen species. The aim of the present study is to investigate the protective effect of gallic acid (a plant derived polyphenol) against lindane induced hepatic and renal toxicity in rats. Liver damage was assessed by hepatic serum marker enzymes like SGOT, SGPT and ALP and histopathological observation. Renal damage was observed by histopathological examination and serum markers like creatinine and urea. Treatment with lindane increased the levels of lipid peroxidation, serum marker enzyme activity with a concomitant decrease in GSH, CAT, SOD, GPx and GST. Histological alterations were also observed in kidney and liver tissue with lindane treatment. Co-treatment of gallic acid significantly prevented the lindane induced alterations in kidney and liver tissues with a decrease in LPO, serum marker enzyme activity and a significant increase in antioxidant levels. These results suggest that gallic acid has protective effect over lindane induced oxidative damage in rat liver and kidney.     

常州地区单采血小板献血者抗丙型肝炎病毒以及输血传播病毒-DNA的调查及相关研究

目的了解常州地区单采献血人群中的抗丙型肝炎病毒(HCV)以及输血传播病毒(TTV)-DNA感染的状况,探讨TTV-DNA对单采血小板献血者对丙氨酸转氨酶(ALT)的影响。方法应用酶联免疫吸附试验(ELISA)法检测单采献血小板以及单一献全血人群中的抗-HCV;应用荧光定量聚合酶链反应(FQ-PCR)检测单采血小板献血者以及献全血者TTV-DNA;并应用全自动生化速率法检测TTV-DNA阳性及阴性献血者血清ALT。结果单采献血者抗-HCV、TTV-DNA的阳性率分别为0.15%、14.16%,普通献全血者则分别为0.43%、5.83%;和单一献全血者相比,单采血小板献血者抗-HCV阳性率低于献全血者(χ2=10.22,P<0.01);TTV-DNA阳性率则高于献全血者(χ2=6.57,P<0.05);单采献血者中TTV-DNA阳性和阴性献血者ALT水平分别为(22±7)、(17±10)U/L,两者比较差异无统计学意义(t=0.63,P>0.05)。结论单采献血小板者感染者抗-HCV低于单一献全血者,可能与其反复多次的检验有关;而单采献血者TTV-DNA感染者高于献全血者,可能和其频繁采血有关;单采献血者TTV-DNA阳性对单采献血者ALT无影响,其机制有待进一步的研究。     

慢性乙型肝炎患者外周血Th17细胞的表达及临床意义

目的探讨慢性乙型肝炎(CHB)患者外周血Th17细胞频率、血清IL-17水平及其与临床指标的相关性。方法采集29例CHB患者(CHB组)及17例健康体检者(对照组)外周血,采用流式细胞仪分析外周血Th17细胞频率;酶联免疫吸附测定(ELISA)法检测血清IL-17水平及HBV标志物;荧光实时定量聚合酶链反应(RT-PCR)检测血清HBV DNA载量,同时进行肝功能检测。结果 CHB组患者外周血Th17细胞频率、血清IL-17水平高于对照组(P<0.05);CHB组患者外周血Th17细胞频率与其血清ALT水平正相关(r=0.582,P<0.01),而与血清HBV DNA载量无明显相关(r=-0.213,P>0.05)。结论 Th17细胞可能参与了CHB的发生、发展。