Acute and Sub-Chronic Toxicity Evaluation of the Crude Methanolic Bark Extract of Bridelia micrantha (Hochst.) Baill. (Phyllanthaceae) and Its Fraction

Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F6 was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F6 induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 for 28 days at a dosage of up to 800 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 was estimated to be more than 2000 mg/kg.

聚β-胡萝卜素聚合物的急性毒性试验、亚慢性毒性试验和致突变性试验

本试验旨在通过小鼠急性毒性试验、大鼠亚慢性毒性试验和小鼠致突变性试验对聚β-胡萝卜素聚合物进行安全性评价。急性毒性试验:将50只昆明小鼠随机分为5组,每组10只。测定聚β-胡萝卜素聚合物的半数致死量(LD_(50))和95%置信区间。亚慢性毒性试验:将80只无特定病原体(SPF)级SD大鼠随机分为4组,每组20只。低、中高剂量组分别灌胃100、250和500 mg/kg BW的聚β-胡萝卜素聚合物,对照组灌胃等体积的植物油,连续灌服30 d。测定大鼠生长性能、血液生理指标、血清生化指标、脏器指数及组织病理学。致突变性试验:将50只昆明小鼠随机分为5组,每组10只。依据本试验得出聚β-胡萝卜素聚合物的LD50,低、中、高剂量组分别灌胃282.5、565.0和1130.0 mg/kg BW的聚β-胡萝卜素聚合物,阴性对照组灌胃等体积的植物油,阳性对照组腹腔注射0.4 mL/kg环磷酰胺。测定嗜多染红细胞/红细胞比值和嗜多染红细胞微核率。结果表明:1)急性毒性试验中,聚β-胡萝卜素聚合物的LD_(50)为2260 mg/kg BW,95%置信区间为2067~2470 mg/kg BW。2)亚慢性毒性试验中,试验期间内大鼠精神食欲等状况良好。与对照组相比,低、中、高剂量组的雄性大鼠和高剂量组的雌性大鼠末重、平均日增重、平均日采食量极显著升高(P<0.01),料重比极显著降低(P<0.01)。中剂量组的雄性大鼠红细胞压积显著低于低剂量组(P<0.05),各组之间大鼠的其他血液生理指标和血清生化指标均无显著差异(P>0.05)。中、高剂量组的雌性大鼠肾脏指数显著低于对照组和低剂量组(P<0.05),各组之间大鼠的脏器重和其他脏器指数均无显著差异(P>0.05)。组织病理学检查表明各组大鼠心脏、肝脏、脾脏、肾脏、肺脏无明显病理变化。3)致突变性试验中,与阴性对照组相比,阳性对照组的雄性、雌性小鼠的嗜多染红细胞微核率极显著增加(P<0.01),低、中、高剂量组的雄性、雌性小鼠的嗜多染红细胞微核率均差异不显著(P>0.05)。由此可见,聚β-胡萝卜素聚合物无明显急性毒性、亚慢性毒性和致突变性。聚β-胡萝卜素聚合物可以提高大鼠的生长性能,可作为一种安全的饲料添加剂进一步开发利用。

Evaluating the safety of forsythin from Forsythia suspensa leaves by acute and sub-chronic oral administration in rodent models

Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mice,Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0,540,1 620,and 6 480 mg/kg in SD rats.Results: In the acute toxicity study,mortality was not observed after 14 days,In addition,clinically relevant adverse effects,or variations in body weight or food consumption were not observed,Similarly,after 30 days in the sub-chronic toxicity study,no mortality or significant toxicological effects such as decreased food consumption,body weight,biochemical parameters and vital organs etc,were noticed,Conclusion: The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration,and therefore is suitable for further development and applications.

Sub-chronic Toxicity of Defoamer Used in Seawater Desalination

Objective To explore the possible long‐term health effects of the defoamer used in seawater desalination by sub‐chronic toxicity testing. Methods Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high(0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration. Results The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase(P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin(P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups(P < 0.05). All dose groups showed significant induction of alkaline phosphatase(P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices. Conclusion Long‐term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.

Effects of Sub-chronic Aluminum Exposure on Renal Pathologic Structure in Rats

A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg aluminum chloride （AlCl3） per kilogram body weight in drinking water for 120 days. Kidney coefficient and aluminum （Al） concentrations in blood and kidney were determined, and renal autopsy and histological changes were observed. The results showed that kidney coefficient in all Al-treated groups were obviously lower than that in GC （P〈0.01） and there was a dose-effect relationship. The kidneys were solid, lusterless and pale brown with white necrosis point on surface. Under electron microscope, renal cortex became thin, the renal tubule was narrowed and the epithelium dissolved; the renal glomerulus became atrophied and the glomerular became vasodilator. The Al concentrations in blood and kidney were higher in all Al-treated rats than those in GC （P〈0.01）, and there was a dose-effect relationship. The results indicated that sub-chronic Al exposure could lead to Al accumulation in kidney, restrain the development of kidney and cause the pathologic damage in rats.

Effects of Sub-chronic Intoxication of 1,8-cineole on Blood Biochemical Indexes of Mice

[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.

Effects of Sub-chronic Aluminum Exposure on Renal Structure in Rats

To investigate the effects of aluminurn （Al） exposure on renal structure of rats, 60 Wistar rats were randomly divided into four treatment groups and were orally exposed to 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg· kg^-1 BW AlCl3 in drinking water for 120 days. The body weight of different rats was recorded, the kidney pathologic structure and the ultrastructure were observed. The results showed that the body weight of different rats was markedly lower in Al-treated rats than those in GC （P〈0.05; P〈0.01）. After masson staining, the collagen was deposited in the renal interstitium and aggravated with Al dose increases in Al-treated rats. Under electron microscope, the infolding of the plasma membrane was slight swollen, the mitochondrion was abundant with different sizes, the mitochondrion cristae was fused, the microvillus was swollen and fused in GH. Our findings indicated that sub-chronic A1 exposure slowed the weight of rats and caused the kidney pathologic damage in rats.

Sub-chronic Toxicity Test of Tephrosia canadida DC. in Mice

[ Objective] To observe sub-chronic toxicity of Tephrosia canadida DC. in mice and thus to evaluate their safety to be used as protein feed resources. [ Methed]Sixty-four 6-week-old healthy Kunming mice weighing about 25 g were randomly divided into four groups （ n = 16）, half male and half female. Mass ratios of basic diet to leaf meal of Tephrosia canadida DC. in group A, group B, group C and group D were 10：0, 4：1, 3：2 and 2：3, respectively. After 35-d feeding, the effects of Tephrosia canadida DC. on growth, blood and organs of mice were observed. [ Resultl Dudng the trial, all mice had normal activities, and no death and no abnormal blood index were observed. All organs of the mice in the experimental groups had no visible pathological lesion, and organ indexes had no significant difference between the experimental groups and the control group. Except that slightly abnormal histological changes appeared in liver and kidney of the mice in the group C and D, no histological change was ob- served in other organs of the experimental mice. [ Conclusion] Tephrosia canadida DC. have no adverse effects on mice, which provides a refer- ence for research about their safety in feed of other animals.

Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B

AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.

Effect of switching from treatment with nucleos(t)ide analogs to pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients

AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.

A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats

Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent.

Interleukin-10 and chronic liver disease

Interleukin （IL）-10 is an important immunoregulatory cytokine produced by many cell populations. Numerous investigations suggest that IL-10 plays a major role in chronic liver diseases. IL-10 gene polymorphisms are possibly assodated with liver disease susceptibility or se-verity. Recombinant human IL-10 has been produced and is currently tested in clinical trials. These trials may give new insights into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a new therapeutic target.

Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

Association of promoter polymorphism of the CD14 C (-159) T endotoxin receptor gene with chronic hepatitis B

AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 patients with established diagnosis of chronic hepatitis B and 126 healthy subjects served as a control population. The CD 14 C (-159) T polymorphism was investigated using an allele specific PCR method. RESULTS: Twenty seven percent of chronic hepatitis B patients and 75% of controls were heterozygous for CT genotype. The difference between the chronic hepatitis B and control groups was statistically significant [P < 0.0001; Odds ratio (OR) = 2.887; 95% CI: 1.609-5.178]. Twenty four point six percent of chronic hepatitis B and patients 12.3% of the control group were heterozygous for TT genotype. The difference between groups was not statistically significant (P = 0.256; OR = 0.658; 95% CI: 0.319-1.358). Forty eight point four percent of chronic hepatitis B patients and 12.7% of control were homozy- gote for CC genotype (P < 0.004; OR = 0.416; 95% CI: 0.229-0.755). The frequency of allele C was 61.9% and allele T was 38.1% in hepatitis B patients group. The frequency of allele C was 55.2% and allele T was 44.8% for the control group (P = 0.179; OR = 1.319; 95% CI: 0.881-1.977). CONCLUSION: The TT heterozygous genotype was not a risk factor for chronic hepatitis B. CC homozygote genotype is protective for hepatitis B. Lack of heterozy- gosis of genotype CT is a risk factor for chronic hepatitis B. Alleles C or T were not risk factors for chronic hepatitis B. These findings show the role of a single-nucleotide polymorphism at CD14/-159 on the development ofchronic hepatitis B. Endotoxin susceptibility may play a role in the pathogenesis of chronic hepatitis B.

砷对雄性大鼠睾丸组织AQP-8及survivin蛋白表达的影响

[目的]研究亚慢性砷中毒对大鼠睾丸组织AQP-8及survivin蛋白表达的影响。[方法]将40只健康成年清洁级SD雄性大鼠随机分为对照组以及低、中、高剂量砷染毒组,每组10只;采用自由饮水方式染毒,低、中、高剂量染毒组饮水中亚砷酸钠浓度分别为2.4、12.0、60.0 mg/L,连续染毒15周,对照组饮用蒸馏水;染毒试验结束后,对各组大鼠进行精子计数,计算精子存活率;制备睾丸组织切片进行病理学观察;利用免疫组化及Western blotting法测定大鼠睾丸组织中AQP-8及survivin蛋白的表达水平。[结果]与对照组相比,中、高剂量染毒组大鼠精子计数与精子存活率均降低,且差异显著(P<0.05)。低剂量染毒组大鼠生精小管无明显变化;中剂量染毒组大鼠生精上皮层数减少,小管间隙增宽;高剂量染毒组大鼠部分生精小管出现基膜溶解,生精上皮细胞层次紊乱,细胞间隙增大,间质出现水肿、渗出。免疫组化分析结果显示,AQP-8蛋白主要表达于各级生精细胞的细胞膜和精子细胞,与对照组相比,各剂量染毒组大鼠睾丸组织中AQP-8阳性细胞平均光密度值显著(P<0.05)升高;survivin蛋白主要表达于次级精母细胞和精子细胞的胞浆,与对照组相比,各剂量染毒组大鼠睾丸组织中survivin阳性细胞平均光密度值显著(P<0.05)降低。Western blotting分析结果显示,对照组和各剂量染毒组大鼠睾丸组织中均存在AQP-8及survivin蛋白的表达;与对照组相比,低、中、高剂量染毒组AQP-8蛋白表达量显著(P=0)增加,survivin蛋白表达量显著(P=0)降低。[结论]砷暴露使睾丸组织AQP-8蛋白表达量增加,survivin蛋白表达量下降,这可能是导致其雄性生殖毒性效应的机制之一。

Interferon β-1a alone or in combination with ribavirin: A randomized trial to compare efficacy and safety in chronic hepatitis C

AIM： To compare the efficacy and safety of recombinant human IFN β-la alone or in combination with ribavirin in treatment-naive subjects with chronic hepatitis C. METHODS： Open, randomized trial was performed in 6 Italian tertiary centers： 102 of the 108 patients screened were randomized to receive 6 MIU of recombinant human IFN β-la subcutaneously daily for 24 wk, alone （Group 1, n = 51） or in combination with ribavirin 1 000 to 1 200 mg/d （Group 2, n = 51）. RESULTS： The end-of-treatment virologic response rate was 29.4% in Group 1 and 41.2% in Group 2 （nonsignificant）. Twenty-four weeks after stopping therapy, sustained virologic response rate was 21.6% in Group 1 and 27.4% in Group 2 （non-significant）. All subjects in Group 1 completed treatment, while two subjects in Group 2 stopped therapy due to treatment-related adverse events. CONCLUSION： Recombinant human IFN β-la, alone or in combination with ribavirin, has an excellent safety profile and, may represent an alternative for chronic hepatitis C patients who are unable to tolerate pegylated α-interferon.

Effect of interferon and ribavirin combined with amantadine in interferon and ribavirin non-responder patients with chronic hepatitis C (genotype 1)

AIM: To evaluate the efficacy of amantadine plus interferonalpha and ribavirin in non-responder patients with chronic hepatitis C.METHODS: Twenty-six non-responder patients received the regimen of IFN-α-2a at a dose of 6 million units three times a week, 1 000-1 200 mg of ribavirin daily, and 200 mg of amantadine daily in divided doses over 48 wk. After the end of treatment, at the 72nd wk, a sustained viral response rate was determined.RESULTS: An early (after 12 wk of therapy) response was seen in 34.6% (9/26) of patients. Response rate at the 24th wk was 42.3% (11/26). End of treatment response (ETR) was 53.8% (14/26). Sustained viral response (SVR) was 42.3% (11/26). There was a statistically significant difference between 0 and 12 wk (P = 0.04), 0 and 24 wk (P = 0.01), 0 and 48 wk (P = 0.00), and 0 and 72 wk (P = 0.001). No patient had severe adverse effects during the treatment.CONCLUSION: Combination regimen of interferon-α,ribavirin and amantadine can enhance sustained viral response on IFN-α and ribavirin non-responder patients with HCV. Triple therapy with amantadine should be evaluated in further studies.

5-lipoxygenase expression in a brain damage model induced by chronic oral administration of aluminum

A preliminary study has found that the 5-lipoxygenase inhibitor, caffeic acid, has a marked protective effect on acute brain injury induced by intracerebroventricular microinjection of aluminum. In this experiment, chronic brain injury and neuronal degeneration model was established in rats by chronic oral administration of aluminum, and then intervened using caffeic acid. Results showed that caffeic acid can downregulate chronic aluminum overload-induced 5-1ipoxygenase mRNA and protein expression, and repair the aluminum overload-induced hippocampal neuronal damage and spatial orientation impairment. It is suggested that direct intervention of 5-lipoxygenase expression has a neuroprotective role in the degeneration induced by chronic aluminum overload brain injury model.

Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus

BACKGROUND Chronic hepatitis C(CHC)is associated with type 2 diabetes mellitus.Although the pathogenesis remains to be elucidated,a growing evidence has suggested a role of pro-inflammatory immune response.Increased serum concentrations of Interleukin 6(IL-6)have been associated with insulin resistance,type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection.AIM To investigate the frequency of IL-6-174G/C(rs1800795)single nucleotide polymorphism(SNP)in CHC patients and in healthy subjects of the same ethnicity.Associations between type 2 diabetes mellitus(dependent variable)and demographic,clinical,nutritional,virological and,IL-6 genotyping data were also investigated in CHC patients.METHODS Two hundred and forty-five patients with CHC and 179 healthy control subjects(blood donors)were prospectively included.Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association.Clinical,biochemical,histological and radiological methods were used for the diagnosis of the liver disease.IL-6 polymorphism was evaluated by Taqman SNP genotyping assay.The data were analysed by logistic regression models.RESULTS Type 2 diabetes mellitus,blood hypertension and liver cirrhosis were observed in 20.8%(51/245),40.0%(98/245)and 38.4%(94/245)of the patients,respectively.The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls(P=0.81)and all alleles were in Hardy-Weinberg equilibrium(P=0.38).In the multivariate analysis,type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174(OR=0.42;95%CI=0.22-0.78;P=0.006)and positively associated with blood hypertension(OR=5.56;95%CI=2.79-11.09;P<0.001).CONCLUSION This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus.The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.

Anxiety and Depression Disorders in Chronic Non-Specific Low Back Pain in Lomé(Togo)

Chronic non-specific low back pain has an important psychological impact. Objectives: To determine the prevalence of anxiety and depressive disorders (ADD) and factors associated to their apparition in patients suffering from chronic non-specific low back pain in rheumatological consultation in Lomé. Patients and Methods: It was a cross-sectional study, conducted from October 1st, 2015 to 31st March 2016. This study focused on all patients suffering from common chronic low back pain without psychiatric history in the Rheumatology Ward at the Sylvanus Olympio’s Teaching Hospital of Lomé and who have given their consent. The psychological evaluation was carried out through Hamilton scale. The processing, the statistical treatment and analysis of our data have been carried out using Epiinfo software, version 7.1.5. The investigation was approved by the local Ethics Committee. Results: 48 (39 women and 09 men) out of 123 patients with chronic lower back pain presented anxiety and depressive disorders (ADD) accounting for a prevalence rate of 39%. Their average age was 50.3 years old. The most frequent ADD was: psychic anxiety (58.6%), depressive mood (51.3%), difficulties to feel asleep (47.9%) and disturbed or agitated sleep (43.1%). Factors associated with the anxiety and depressive disorders in common chronic low back pain were: female gender (p = 0.02), dependent children (p = 0.02), occupation (reseller (p = 0.002), liberal profession (p = 0.009), monthly financial income (p = 0.002), surroundings family (0.009), medical history (p = 0.0002) and pain’s intensity > 7 (p = 0.04). Conclusion: This study shows the high frequency of anxiety and depressive disorders in common chronic low back pain and their influence by socio-economic and demographic factors.