[Analysis of liver function injury associated with 2019-nCoV Omicron mutant strains].

Objective: To investigate the clinical features and influencing factors of liver function injury in patients with 2019-nCoV/SARS-CoV-2 Omicron mutant strains. Methods: 1 183 confirmed imported cases of SARS-CoV-2 who were admitted at Shanghai Public Health Clinical Center (affiliated to Fudan University) from July 1, 2021 to January 15, 2022 were collected. Clinical data, viral genotyping and laboratory test results were collected to retrospectively analyze the basic condition and clinical characteristics of liver function injury. Statistical analysis was performed using t-test or Wilcoxon rank-sum test, χ2 test or Fisher's exact test, Pearson correlation test and logistic regression analysis. Results: 125 (10.6%) cases had raised baseline ALT level and 60 (5.1%) cases had abnormal baseline AST level. Among them, 33 cases (2.8%) had received hepatoprotective drugs. Liver function injury was generally mild in SARS-CoV-2 infection and minimal in Omicron mutant strains. Leukocyte count was increased in patients with raised alanine aminotransferase (ALT) [(6.96±1.78)×109/L vs. (6.41±1.96)×109/L, P=0.005 2], CT scan showed the proportion of liver hypodensity was significantly increased (2.4% vs. 0.3%, P=0.018 0). High-sensitivity C-reactive protein [(7.83±22.36) mg/L vs. (2.68±6.21) mg/L, P=0.007 8] and D-dimer [(0.34±0.39) µg/ml vs. (0.31±0.75) µg/ml, P=0.047 5] levels were higher in patients with raised AST than normal group. 26 cases had normal liver function at hospital admission; however, abnormal liver function was occurred during the course of the disease. Another 8 patients had abnormal liver function at hospital admission, and reduced liver function further during the course of treatment. Recovery time and length of hospital stay was significantly affected in patients with worsened liver function. Baseline body mass index value [odds ratio (OR)]=1.80, P=0.047), non-Omicron strains (OR=12.63, P=0.046), D-dimer (OR=2.36, P=0.047) and interleukin-6 levels (OR=1.03, P=0.009), and those who used glucocorticoids and/or ulinastatin after hospital admission (OR=6.89, P=0.034) had a higher risk of worsening liver function. Conclusions: Liver dysfunction could be observed among COVID-19 patients. Patients infected with omicron variant generally showed mild liver injury. Dynamic monitoring of liver function is necessary, especially among those with baseline elevated IL-6, D-Dimer level and use of antiinflammation medication during treatment.

Urinary biomarkers of early renal injury in antiretroviral-naïve HIV-positive persons in Shanghai, China: comparison with the general population.

OBJECTIVES: People living with HIV (PLWH) have a high risk of kidney injury. Measurement of serum creatinine, along with proteinuria, is not sensitive to detect early kidney injury. Here, we investigated novel urinary biomarkers of early renal injury in PLWH. METHODS: We performed a cross-sectional study of 166 antiretroviral-naïve PLWH and 99 HIV-negative persons who all had an estimated glomerular filtration rate > 90 mL/min/1.73 m2 . We compared the levels of seven urinary biomarkers between the two groups using the propensity score matching (PSM) approach and explored the risk factors associated with elevated urinary biomarkers in PLWH. RESULTS: Eighty-three pairs were successfully matched based on PSM. Compared with the HIV-negative group, the HIV-positive group had higher ratios of N-acetyl-ß-D-glucosaminidase (NAG) to urine creatinine (UCr), alpha1-microglobulin (α1-M) to UCr, kidney injury marker-1 (KIM-1) to UCr, neutrophil gelatinase-associated lipocalin to UCr, and epidermal growth factor to UCr, whereas the Tamm-Horsfall protein to UCr ratio and the abnormal albumin to UCr ratio were not significantly different. Positive correlations were observed between HIV RNA level and NAG: UCr (rs  = 0.32; P < 0.001) and α1-M:UCr (rs  = 0.24; P = 0.002) ratios, and negative correlations were observed between CD4 cell count and NAG:UCr (rs  = -0.34; P < 0.001), KIM-1:UCr (rs  = -0.16; P = 0.042) and α1-M:UCr (rs  = -0.36; P < 0.001) ratios. In multivariate linear regression analyses, older age, lower total cholesterol and higher HIV RNA were independently associated with higher NAG:UCr; older age, lower total cholesterol and lower CD4 cell count were independently associated with higher α1-M:UCr. CONCLUSIONS: In comparioson with HIV-negative participants, PLWH were more likely to have tubular injury. Early antiretroviral treatment might mitigate the development of kidney injury.

A retrospective cohort study of early mortality among patients with HIV/TB co-infection in Shanghai municipality.

OBJECTIVES: Tuberculosis (TB) is the most common and fatal opportunistic co-infection among HIV-infected individuals. While TB-associated mortality predominantly occurs in the first 90 days after admission, such a correlation remains unclear in HIV/TB co-infected patients. Thus, we aimed to investigate the 90-day mortality and associated risk factors among HIV/TB co-infected patients in China. METHODS: Adult patients with HIV and a newly confirmed TB diagnosis admitted to the Shanghai Public Health Clinical Center between September 2009 and August 2017 were enrolled. Clinical and laboratory characteristics, key treatments and outcomes were collected retrospectively. The associations between different factors and early mortality were analysed. RESULTS: Of the 485 laboratory-confirmed HIV/TB patients [median (range) age = 39 (19-79) years], 413 (85.15%) were male. Diagnosis was confirmed by culture, pathology and acid-fast bacilli smear alone in 362 (74.6%), 6 (1.2%) and 117 (24.1%) patients, respectively. Multiple drug-/rifampin-resistant TB was detected in 21 (5.8%) of the 367 patients with a positive culture. Rifampin or rifabutin was administered to 402 (82.9%) patients. Additionally, 66 (13.6%) and 86 (17.7%) died within 90 days and 1 year of admission, respectively. Of the 64 TB-related deaths, 59 (92.2%) occurred within 90 days of admission. In Cox regression, central nervous system (CNS) TB [odds ratio (OR) = 2.49, 95% confidence interval (CI): 1.46-4.23, P < 0.001], no antiretroviral therapy (ART) within 3 months after admission (OR = 11, 95% CI: 6.4-18.9, P < 0.001), and plasma albumin level < 25 g/L (OR = 1.91, 95% CI: 1.07-3.40, P = 0.021) were associated with early death. CONCLUSIONS: Tuberculosis co-infection was prevalent and fatal in HIV-infected patients, with most deaths occurring within 90 days of admission. Early mortality was associated with CNS-TB, no ART, and serum albumin level < 25 g/L.

Effects of arginase inhibition via jugular infusion of Nω-hydroxy-nor-l-arginine on metabolic and immune indices in lactating dairy cows.

Transformation of Arg to nitric oxide and ornithine (Arg-Orn) constitutes the main route of Arg metabolism in mammals. The primary objective of this work was to determine the effects of inhibiting the Arg-Orn pathway via Nω-hydroxy-nor-l-arginine (nor-NOHA) on health of lactating cows. Furthermore, we also explored the effect of Arg-Orn inhibition on the efficiency of nitrogen utilization to find support for previous research that showed the inhibition of Arg-Orn inhibited milk protein synthesis. Six healthy Chinese Holstein cows of similar body weight (550.0 ± 20 kg), parity (4.0 ± 0), body condition score (3.0 ± 0), milk yield (21.0 ± 1.0 kg), and days in milk (80 ± 2 d) were selected and randomly assigned to 3 treatments in a replicated 3 × 3 Latin square design with 22 d for each period (7 d for infusion and 15 d for washout). The treatments were (1) saline infusion (control); (2) infusion of 125 mg/L of nor-NOHA; and (3) infusion of 125 mg/L of nor-NOHA with 9.42 g/L of Arg. Dry matter intake, apparent digestibility of nutrients, urinary N, N in milk, and blood indices of metabolism and immune function were determined. Compared with the control, the infusion of nor-NOHA had no effect on the concentrations of cholesterol, high-density lipoproteins, IgA, IL-1ß, tumor necrosis factor-α, and alanine transaminase. In addition, the dry matter intake, apparent digestibility of N, and the concentration of milk protein N in the Nor-NOHA did not differ from the control; however, the infusion of nor-NOHA and Arg resulted in greater concentrations of high-density lipoprotein, IgA, IL-1ß, and tumor necrosis factor-α, and lower concentrations of cholesterol in serum compared with the control. Moreover, the addition of Arg to cows infused with nor-NOHA increased the concentration of nitrate (the indicator of nitric oxide) in serum and was associated with greater milk protein N production due to greater milk yield compared with those infused with nor-NOHA. Overall, the results indicated important roles of Arg in immunity and mammary N utilization, whereas a minor role of the Arg-Orn pathway in these physiologic processes was found.

Jugular arginine infusion relieves lipopolysaccharide-triggered inflammatory stress and improves immunity status of lactating dairy cows.

The objective of this study was to evaluate the effects of jugular l-Arg infusion on performance and immune function during lipopolysaccharide (LPS)-induced inflammation of lactating dairy cows. Eight Holstein cows (multiparous, 608.8 ± 31.5 kg) at mid-lactation were randomly assigned to 5-d jugular infusions of control (saline), Arg (3 g/h), LPS (0.033 µg/kg per h), and LPS + Arg (0.033 µg/kg per h of LPS and 3 g/h of Arg) in a replicated 4 × 4 Latin square design with 4 infusion periods separated by 10-d noninfusion periods. Jugular solutions of saline, Arg, LPS, and LPS + Arg were continuously infused using peristaltic pumps for approximately 6 h/d during infusion periods. Milk yield was measured on each day of the infusion period. Milk samples were obtained on the last 2 d of each infusion period, and blood samples were obtained on the last day of each infusion period before infusion (0 h) and at 3 and 6 h. We found that the jugular LPS infusion significantly increased serum concentrations of IL-1ß, IL-6, tumor necrosis factor, inducible nitric oxide synthase, and lipopolysaccharide binding protein, whereas Arg attenuated the increase in IL-6 and inducible nitric oxide synthase levels and tended to decrease the lipopolysaccharide binding protein level. Arginine alleviated the decrease in dry matter intake and milk fat yield and the increase of somatic cell count induced by LPS. Total casein in milk was decreased during the LPS-induced inflammation period, and jugular Arg infusion significantly increased the content of total casein. In contrast, lactalbumin in milk increased during the LPS-induced inflammation period, whereas jugular Arg infusion significantly decreased the content of lactalbumin. The concentrations of plasma Gly, Thr, Ile, Leu, Arg, Phe, and total free AA were significantly decreased by LPS treatment, but Arg attenuated this tendency. These results indicated that jugular Arg infusion (18 g/d) has protective effects on relieving inflammatory stress and improving immunity status triggered by LPS. In conclusion, Arg could attenuate inflammatory stress and improve milk performance of lactating dairy cows. This protective effect may be due to the ability of Arg to suppress LPS effects and improve immunity status.

Amoxicillin and clavulanate potassium in treating children with suppurative tonsillitis.

To evaluate clinical effects of amoxicillin and clavulanate potassium in the treatment of children with suppurative tonsillitis, 146 children with suppurative tonsillitis were randomly divided into a ceftezole sodium group and an amoxicillin and clavulanate potassium group. The two groups were given anti-infection treatment using different drugs. Symptomatic treatment was carried out once symptoms such as fever appeared. Five to seven days were taken as one treatment course. Blood routine examination and the detection of C-reactive protein (CRP) were performed three days after treatment. Indexes such as the time to the relief of symptoms, the count of white blood cells, the proportion of neutrophil and CRP levels and the incidence of adverse reactions were compared between groups to evaluate the curative effect. The overall response rate of the amoxicillin and clavulanate potassium group was 94.52%, while that of the ceftezole sodium group was 78.08%; the difference was statistically significant (P<0.05). The improvement of white blood cells and CRP levels of the amoxicillin and clavulanate potassium group was more obvious than that of the ceftezole sodium group (P<0.05). The difference of the time to the improvement of symptoms between the two groups had statistical significance; the amoxicillin and clavulanate potassium group was superior to the ceftezole sodium group (P<0.05). No severe drug-related adverse reactions were observed. Amoxicillin and clavulanate potassium dispersible tablet is effective in treating children with suppurative tonsillitis as it can rapidly relieve the clinical symptoms without increasing incidence of adverse reactions.

[Comparative study of two rounds of colorectal cancer screening in 80, 000 targeted population in Haining].

Objective: To compare the results of two rounds of colorectal cancer screening in Haining, explore the long-term mechanism and interval time of screening during the prevention and control of colorectal cancer, and establish practical basis for the rational prevention and control strategies. Methods: Between 2007 to 2010 and 2013 to 2015, a total of 80, 000 cases who had completed two rounds of tumor screening were enrolled and analyzed. All cases comes from five towns in Haining. Results: The first round of screening was performed in 80 603 cases and 12.92% (n=10 417) were identified as high-risk population. Colonoscopy were completed in 7 796 subjects and 22.05%(n=1 719) of them were found at least one neoplastic lesions (polyps, adenoma or carcinoma). The population detection rate of all neoplasia was 21.33 per thousand. The detection rate of advanced neoplasia was 4.58% per colonoscopy and 4.43‰ in the population. A total of 357 advanced neoplasia including 296 advanced adenomas and 61 colorectal cancers were found, 330 of whom were applied to early treatment (92.44%). A total of 89 403 subjects participated the second round of screening. The detection rate of high-risk population in the second round (20.81%) was significantly higher than that in the first round (P<0.05). A total of 12 917 subjects completed colonoscopy and 31.97% (n=4 129) of them were found as least one neoplastic lesion. The population detection rate of all neoplasia was 46.18 ‰. Both in the subjects completed colonoscopy and in the screened population, the detection rate of all neoplasia were significantly (P<0.01) higher than that of the first round. The detection rate of advanced neoplasia (n=851) in both the subjects completed colonoscopy (6.59‰)and the total screened population (9.52‰) in the second round were also significantly (P<0.01) higher than that of the first round. The difference of early detection rates for the first (92.44%) and the second (97.53%) round screening were not statistically significant(P>0.05). Conclusions: The main technical indicators of the second round of colorectal cancer screening were significantly better than that of the first round, with significant screening effect. A screening interval of 5 years was suggested for the next round of colorectal cancer screening.

Serological survey of viral hepatitis markers among newly diagnosed patients with HIV/AIDS in China.

OBJECTIVES: The aim of the study was to determine the seroprevalence and epidemiological features of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among patients newly diagnosed with HIV/AIDS in China. METHODS: Two thousand and forty patients newly diagnosed with HIV/AIDS from 10 provinces in China were selected during 2009 to 2010. Serum samples obtained from each individual were screened for HBV and HCV serum markers [HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), HBV envelope antigen (HBeAg), HBV envelope antibody (HBeAb), HBV core antibody (HBcAb) and HCV antibody (HCVAb)]; liver function tests were also performed. Demographics and medical histories were collected. RESULTS: Of the 2040 patients, 741 (36.3%) were positive for at least one HBV and HCV serum marker; 300 (14.71%) were HCVAb positive, and 248 (12.16%) were isolated HCVAb positive; 222 (10.9%) were positive for HBsAg; 19 (0.93%) were positive for both HBsAg and HCVAb. The highest prevalence of HBsAg positivity was found in Guangxi (15.31%), followed by Guangdong (15.19%) and Shanghai (14.36%). The highest prevalence of HCVAb positivity was found in Xinjiang (43.18%), followed by Henan (39.06%) and Yunnan (27.36%). The proportion of patients with abnormal liver function in patients positive for HCVAb and/or HBsAg was significantly higher than that in those who were negative for both HCVAb and HBsAg (P < 0.001). CONCLUSIONS: The seroprevalence of HBV and HCV among patients newly diagnosed with HIV/AIDS in China is high. HBsAg and HCVAb positivity prevalences were found to vary significantly in different provinces in China. Patients newly diagnosed with HIV/AIDS and coinfected with HBV and HCV are at higher risk of abnormal liver function. It is necessary to routinely screen for HBV and HCV infection among patients newly diagnosed with HIV/AIDS.

Behavioural and physiological responses of Small Tail Han sheep to predators.

Prey animals modify their behaviour and physiology in the presence of predators. Domestic animals differ from wild animals in having less exposure to wild predators, but whether they still retain an antipredator instinct is frequently unknown. In this study, we used domesticated Small Tail Han sheep as a model prey animal to gauge their response to the presence of predators, in the form of odours from the faeces of lion, tiger, and leopard. The faeces of male sheep and male rabbit (as a heterogeneous non-predator) were used as control. We found that the frequency and time of feeding, exploration, moving, watching, and lying down behaviours were significantly affected by predator odour, and that there was an interaction between odour sources and sex. When exposed to predator odour, sheep reduced their frequency and time of feeding, and increased their exploratory, moving, and watching behaviours. Female sheep showed greater motivation towards frequent and lengthy exploration, moving, watching, and lying down behaviours than male sheep, and less motivation towards feeding and drinking behaviours. Serum cortisol levels were lowest in response to tiger stimuli. These results illustrated that Small Tail Han sheep could recognise predator odour and adjust their behaviour to display antipredator strategies, and displayed some physiological responses, although only changing in serum cortisol could be significantly attributed to the odour of predators.

[Effectiveness of FibroTouch combined with four hepatic fibrosis biomarkers for evaluation of the liver fibrosis degree among patients with chronic schistosomiasis-induced liver disorders].

OBJECTIVE: To evaluate the performance of FibroTouch in combination with four hepatic fibrosis biomarkers for assessment of the degree of hepatic fibrosis among patients with chronic schistosomiasis-induced liver disorders. METHODS: A total of 63 patients with chronic schistosomiasis-induced liver diseases admitted to The Third People's Hospital of Kunshan City from January to March 2021 were enrolled as the observation group, while 50 healthy volunteers receiving health examinations in the hospital during the study period were randomly selected as the control group. The liver stiffness measurement (LSM) was determined using the FibroTouch technique, and the serum levels of four hepatic fibrosis biomarkers were detected using chemilumi-nescence immunoassay, including type IV collagen (IV-C), type III procollagen (PC-III), hyaluronidase (HA) and laminin (LN). The receiver operating characteristic (ROC) curves of LSM and four hepatic fibrosis biomarkers alone and in combination for assessing the degree of hepatic fibrosis among patients with chronic schistosomiasis-induced liver disorders were plotted and the area under the ROC curve (AUC) was estimated to examine the value of LSM and four hepatic fibrosis biomarkers alone and in combination for assessing the degree of hepatic fibrosis. RESULTS: There were 63 subjects in the observation group, including 28 men and 35 women, and the participants had a mean age of (65.34 ± 12.56) years and a mean body mass index (BMI) of (24.47 ± 11.05) kg/m2. There were 50 subjects in the control group, including 22 men and 28 women, and the participants had a mean age of (64.28 ± 13.10) years and a mean BMI of (25.12 ± 11.64) kg/m2. There were no significant differences between the observation and control groups in terms of gender ratio (χ2 = 0.002, P > 0.05), age (t = 0.437, P > 0.05) or BMI (t = 0.303, P > 0.05). The LSM [(8.65 ± 5.22) vs. (3.24 ± 1.10) kPa; t = 8.013, P < 0.05], IV-C [(51.80 ± 9.45) vs. (30.10 ± 10.34) ng/L; t = 11.506, P < 0.05], PC-III [(77.28 ± 17.22) vs. (48.62 ± 9.54) ng/L; t = 11.224, P < 0.05], HA [(39.55 ± 5.32) vs. (84.89 ± 10.34) ng/L; t = 30.158, P < 0.05] and LN [(99.47 ± 7.37) vs. (61.93 ± 9.80) ng/L; t = 22.496, P < 0.05] were significantly greater in the observation group than in the control group, and Spearman correlation analysis showed that the degree of liver fibrosis positively correlated with LSM (rs = 0.675, P < 0.01), IV-C (rs = 0.421, P < 0.01), PC-III (rs = 0.517, P < 0.01), HA (rs = 0.550, P < 0.01) and LN (rs = 0.539, P < 0.01) among patients with chronic schistosomiasis-induced liver diseases. ROC curve analysis revealed that the AUC of LSM for assessment of the hepatic fibrosis degree was 0.884 (P < 0.001), and the LSM cutoff, sensitivity and specificity were 11.75 kPa, 71.43% and 84.00% at the highest Youden index, respectively. In addition, the AUC of four hepatic fibrosis biomarkers for assessment of the hepatic fibrosis degree was 0.577 to 0.670, with 70.174 to 115.237 ng/L cutoff values, 17.46% to 68.25% sensitivity and 71.01% to 96.00% specificity. In addition, the sensitivity and specificity of LSM combined with four hepatic fibrosis biomarkers were 92.06% and 95.07% for assessment of the hepatic fibrosis degree among patients with chronic schistosomiasis-induced liver diseases. CONCLUSIONS: FibroTouch in combination with detection of four hepatic fibrosis biomarkers has a high sensitivity and specificity for assessing the degree of hepatic fibrosis among patients with chronic schistosomiasis-induced liver diseases, which deserves widespread clinical uses.

MiR-186 promotes the apoptosis of glioma U87 cells by down-regulating the expression of Smad6.

OBJECTIVE: MiRNA family gene is an evolutionarily conserved non-coding small RNA that directly participates in a variety of physiological processes and cancer development via regulating gene expression in the biological level of transcription. To research the specific mechanism by which miR-186 regulates apoptosis within gliomas. PATIENTS AND METHODS: RT-qPCR was performed to verify the transcriptional level of miR-186 within glioma tissues and glioma cells. miRanda and Dual-Luciferase assay were performed to predict and confirm that Smad6 gene is an effective target of miR-186 within glioma. The expression of Smad6 protein was tested by Western blot following cell effective transfection. Apoptosis of gliomas was analyzed by inverted fluorescence microscopy and flow cytometry. RESULTS: The mRNA level of miR-186 was suppressed within glioma tissues and glioma U87 cells. MiR-186 is associated with apoptosis in glioma. Overexpression of miR-186 promoted U87 cell apoptosis, whereas suppression of miR-186 had the opposite effect. Besides, miR-186 directly targeted Smad6 and suppress its expression in glioma. The expression of Smad6 affected the regulation of miR-186 on glioma cell apoptosis, restoration of Smad6 rescued apoptosis of glioma U87 cells induced by miR-186 mimics, whereas inhibition of Smad6 promoted apoptosis. CONCLUSIONS: As noted above, miR-186 exerts a tumor-suppressing effect by targeting Smad6. We propose that miR-186 can be used as a novel biomarker for glioma diagnosis in the future, or as a new pharmacy target in the cure of gliomas.

Effects of intravenous arginine infusion on inflammation and metabolic indices of dairy cows in early lactation.

Enhancing the supply of arginine (Arg), a semi-essential amino acid, has positive effects on immune function in dairy cattle experiencing metabolic stress during early lactation. Our objective was to determine the effects of Arg supplementation on biomarkers of liver damage and inflammation in cows during early lactation. Six Chinese Holstein lactating cows with similar BW (508 ± 14 kg), body condition score (3.0), parity (4.0 ± 0), milk yield (30.6 ± 1.8 kg) and days in milk (20 ± days) were randomly assigned to three treatments in a replicated 3 × 3 Latin square design balanced for carryover effects. Each period was 21 days with 7 days for infusion and 14 days for washout. Treatments were (1) Control: saline; (2) Arg group: saline + 0.216 mol/day l-Arg; and (3) Alanine (Ala) group: saline + 0.868 mol/day l-Ala (iso-nitrogenous to the Arg group). Blood and milk samples from the experimental cows were collected on the last day of each infusion period and analyzed for indices of liver damage and inflammation, and the count and composition of somatic cells in milk. Compared with the Control, the infusion of Arg led to greater concentrations of total protein, immunoglobulin M and high density lipoprotein cholesterol coupled with lower concentrations of haptoglobin and tumor necrosis factor-α, and activity of aspartate aminotransferase in serum. Infusion of Ala had no effect on those biomarkers compared with the Control. Although milk somatic cell count was not affected, the concentration of granulocytes was lower in response to Arg infusion compared with the Control or Ala group. Overall, the biomarker analyses indicated that the supplementation of Arg via the jugular vein during early lactation alleviated inflammation and metabolic stress.

Feeding corn grain steeped in citric acid modulates rumen fermentation and inflammatory responses in dairy goats.

Cereal grains treated with organic acids were proved to increase ruminal resistant starch and can relieve the risk of ruminal acidosis. However, previous study mainly focussed on acid-treated barley, the effects of organic acid-treated corn is still unknown. The objectives of this study were to evaluate whether feeding ground corn steeped in citric acid (CA) would affect ruminal pH and fermentation patterns, milk production and innate immunity responses in dairy goats. Eight ruminally cannulated Saanen dairy goats were used in a crossover designed experiment. Each experimental period was 21 day long including 14 days for adaption to new diet and 7 days for sampling and data collection. The goats were fed high-grain diet contained 30% hay and 70% corn-based concentrate. The corn was steeped either in water (control) or in 0.5% (wt/vol) CA solution for 48 h. Goats fed CA diet showed improved ruminal pH status with greater mean and minimum ruminal pH, and shorter (P<0.05) duration of ruminal pH<5.6 and less area of ruminal pH<5.6, 5.8 and 6.0. Concentration of total volatile fatty acid and molar proportion of propionate were less but the molar proportion of acetate was greater (P<0.05) in goats fed the CA diet than the control diet. Concentration of ruminal lipopolysaccharide (LPS) was lower (P<0.05) and that of lactic acid also tended (P<0.10) to be lower in goats fed CA than the control. Although dry matter intake, actual milk yield, yield and content of milk protein and lactose were not affected, the milk fat content and 4% fat-corrected milk tended (P<0.10) to be greater in goats fed CA diet. For the inflammatory responses, peripheral LPS did not differ, whereas the concentration of LPS binding protein and serum amyloid A tended (P<0.10) to be less in goats fed CA diet. Similarly, goats fed CA diet had less (P<0.05) concentration of haptoglobin and tumour necrosis factor. These results indicated that feeding ground corn treated with CA effectively improved ruminal pH status, thus alleviated the risk of ruminal acidosis, reduced inflammatory response, and tend to improve milk yield and milk fat test.

Pathologic features of initial adenomas as predictors for metachronous adenomas of the rectum.

BACKGROUND: Colorectal cancer is the third most common cancer in the world, arising mostly from pre-existing adenomatous polyps (adenomas) of the large bowel. Patients with colorectal adenomas are at increased risk of colorectal cancer because of a high recurrence rate for adenomas. We followed a cohort of 1490 patients with rectal adenomas to determine whether recurrence might be related to pathologic characteristics of the initial adenomas. METHODS: The patients were identified in Haining County, China, from 1977 through 1978 by means of examination with a 15-cm rigid sigmoidoscope. They were followed by endoscopic examination at years 2, 4, 6, 11, and 16 after their initial polypectomy. New adenomas in the rectum were identified in 280 patients in these follow-up examinations. RESULTS: Statistically significant twofold to threefold elevated risks of metachronous (recurrent) adenomas were observed for patients who had more than two initial adenomas or whose most advanced initial adenoma was more than 1.0 cm in size, was of villous/tubulovillous type, or showed moderate to severe dysplasia. Much stronger associations were observed for advanced metachronous neoplasms, which are defined as cancers or adenomas with severe dysplasia, with multivariate adjusted relative risks (95% confidence interval) of 4.2 (1.8-9.9) for a large initial adenoma (>1.0 cm), 8.1 (4.2-15.6) for villous/tubulovillous architecture, and 14.4 (5.0-41.3) for severe dysplasia. In particular, patients who had a large (>1.0 cm) adenoma with severe dysplasia at baseline had a relative risk of 37 (7.8-174.7) of developing advanced metachronous neoplasms compared with patients who had small adenoma(s) with mild dysplasia. CONCLUSIONS: The risk of metachronous adenomas is closely related to the pathology of initial adenomas, thus allowing identification of a high-risk group of adenoma patients for close surveillance after their initial polypectomy.

Genetic heterogeneity in three Chinese children with Fukuyama congenital muscular dystrophy.

Three Chinese patients, two boys and one girl, were afflicted with the typical clinical, myopathological and neuroradiological findings of Fukuyama congenital muscular dystrophy (FCMD). Polymorphism analysis of our patients did not reveal the founder haplotype (138-192-147-183 in D9S2105-D9S2170-D9S2171-D9S2107) of Japanese FCMD, even though one patient was descended from Japanese ancestry. Full mutational analysis of the fukutin gene revealed that there is neither 3 kb insertion nor point mutation. These findings suggest genetic heterogeneity between Chinese and Japanese FCMD patients.

Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy.

Magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy were used to evaluate the therapeutic effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid. Systemic administration of 3-nitropropionic acid (15 mg/kg per day) to two-month-old Sprague-Dawley rats (n = 10 for each group) for five consecutive days induced selective striatal and hippocampal lesions and specific behavioral change. Pretreatment with lamotrigine (10 mg/kg or 20 mg/kg per day) or MK-801 (2 mg/kg per day) attenuated the lesions and behavioral change. There were no significant differences in T2 values of the striatum and hippocampus among rats pretreated with MK-801, lamotrigine (20 mg/kg) and sham controls. Significant elevations of succinate/creatine and lactate/creatine ratios and decreases of N-acetylaspartate/creatine and choline/creatine ratios were observed after 3-nitropropionic acid injections (P < 0.001). The changes were nearly prevented after pretreatment with lamotrigine (20 mg/kg). However, the N-acetylaspartate/creatine in rats pretreated with lamotrigine (10 mg/kg) (P < 0.01) and MK-801 (P < 0.05) still showed significant reduction as compared with sham controls. Thus we conclude that both lamotrigine and MK-801 are effective in attenuation of brain lesions induced by 3-nitropropionic acid. A higher dose of lamotrigine provides a better neuroprotective effect than MK-801. With a better therapeutic effect and fewer side effects, lamotrigine is more promising for potential clinical application.

The mechanisms of neuronal death produced by mitochondrial toxin 3-nitropropionic acid: the roles of N-methyl-D-aspartate glutamate receptors and mitochondrial calcium overload.

Previous studies showed that 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase, produced neuronal death secondary to perturbed intracellular calcium homeostasis. However, the response of intramitochondrial calcium ([Ca(2+)](m)) to 3-nitropropionic acid remains unknown. In this study, we investigated the roles of and relationships among [Ca(2+)](m) overload, mitochondrial reactive oxygen species, and mitochondrial membrane depolarization in 3-nitropropionic acid-induced neuronal death. Following 1 mM 3-nitropropionic acid treatment on primary rat neuronal cultures, there was a gradual increase of [Ca(2+)](m) beginning at 2-4 h post 3-nitropropionic acid application, and a twofold increase of mitochondrial reactive oxygen species at 4 h. These were followed by mitochondrial membrane depolarization at 6-8 h post-treatment. By inhibiting [Ca(2+)](m) uptake, Ruthenium Red attenuated the production of reactive oxygen species, and prevented the 3-nitropropionic acid-induced mitochondrial membrane depolarization and 70% of apoptotic neuronal death (P<0.001). Inhibition of caspase activation attenuated the elevation of [Ca(2+)](m) (P<0.001), indicating that caspase activation plays a role in the elevation of [Ca(2+)](m). MK-801, an antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors, prevented 3-nitropropionic acid-induced [Ca(2+)](m) elevation, caspase-3 activation, mitochondrial depolarization, and neuronal death. We conclude that the activation of NMDA glutamate receptor contributes to mitochondrial alterations induced by 3-nitropropionic acid. Inhibition of its activation and [Ca(2+)](m) overload with subsequent mitochondrial membrane depolarization can therefore attenuate the neuronal death induced by 3-nitropropionic acid.

Cancellation of low-frequency stimulation-induced long-term depression by docosahexaenoic acid in the rat hippocampus.

The effects of docosahexaenoic acid (DHA) on low-frequency stimulation (LFS)-induced long-term depression (LTD) were investigated in the CA 1 subfield of rat hippocampal slices. LTD was routinely produced by LFS of 900 pulses at 1 Hz. The field excitatory postsynaptic potential (fEPSP) 40 min after LFS was 59 +/- 4% (n = 18) of baseline response. However, in experiments from 18 neurons pretreated with DHA (50 microM), fEPSP returned to baseline levels within 20 min after LFS in eight cells and was slightly potentiated in three cells. Only in seven cells was LTD induced. The effect of DHA on LTD was concentration dependent. The slopes of fEPSP 40 min after LFS were 67 +/- 4% (n = 6), 72 +/- 7% (n = 7) and 80 +/- 5% (n = 18) of baseline response, with pretreatment of 1, 10 and 50 microM DHA, respectively. The blockade of LTD induction suggests that DHA may play a role in learning and memory.

Epileptic seizures and electroencephalographic evolution in genetic leukodystrophies.

The purpose of this study is to explore and compare epileptic seizures and EEG evolution in the various types of genetic leukodystrophy (GL). The authors reviewed the medical records and analyzed 69 serial EEGs in 27 patients with GLs: 13 with late infantile metachromatic leukodystrophy, one with juvenile metachromatic leukodystrophy, one with globoid cell leukodystrophy, six with X-linked childhood adrenoleukodystrophy, one with neonatal adrenoleukodystrophy, four with classic Pelizaeus-Merzbacher disease (PMD), and 1 with connatal Pelizaeus-Merzbacher disease. The diagnoses were made by biochemical and molecular studies. Two or more EEG studies with both awake and sleep traces were recorded during the varying clinical stages for each patient. At the beginning of the GLs, the EEGs were normal or showed mild slowing of background activity. Clinical seizures, mainly of focal origin, with progressive slowing and paroxysmal discharges on EEGs, usually appeared during the later stages of metachromatic leukodystrophy, X-linked childhood adrenoleukodystrophy, and classic Pelizaeus-Merzbacher disease. However, intractable seizures, mainly generalized in nature, and more severe slowing and abundant paroxysmal discharges on EEGs, with commensurate neurologic deterioration, were observed during the earlier course of globoid cell leukodystrophy, neonatal adrenoleukodystrophy, and connatal Pelizaeus-Merzbacher disease. These results indicate that GLs involve not only white matter, but gray matter as well. In all types of GL, there is good correlation between the severity of EEG changes, the severity of the diseases, and the clinical state of the patient.

Effect of valproate on the pharmacokinetics of free and total plasma bilirubin in experimental hyperbilirubinemia in guinea pigs.

The effects of valproate (VPA) on free and total bilirubin concentrations in plasma were studied in guinea pigs. Steady-state hyperbilirubinemia (around 2.5-3.0 mg/100 mL) was induced by constant intravenous (i.v.) infusion of bilirubin followed by an i.v. bolus dose of sodium valproate (VPA-Na) of 50 (n = 4) or 200 (n = 5) mg/kg. Steady-state plasma total bilirubin concentration was lowered by 40% and 55% and the unbound fraction (fu) increased by 1.9- and 4.9-fold at the respective doses of 50 mg/kg and 200 mg/kg VPA-Na. Free bilirubin was not significantly changed by 50 mg/kg VPA-Na, but did show a significant transient elevation with the 200 mg/kg dose. In another experiment, guinea pigs (n = 3) were given a constant i.v. infusion of VPA-Na to maintain a steady-state plasma concentration (58 micrograms/mL), followed by an i.v. bolus dose of bilirubin (2 mg/kg). A control study (n = 3) was performed simultaneously using normal saline instead of VPA. Free bilirubin was detectable only following induction of hyperbilirubinemia in either group. A higher volume of distribution and lower elimination rate constant of bilirubin were observed in the VPA-treated than in the control animals. The displacement effect of VPA on bilirubin-plasma binding in vitro was studied by adding serial concentrations of VPA-Na to bilirubin-plasma solution. VPA displaced bilirubin from the high-affinity plasma protein binding site, with a binding constant (KD) of 5.7 x 10(-2)/microM. Similar displacement of bilirubin plasma protein binding was observed in vivo. These results suggest that VPA reduces plasma protein binding and slows the elimination rate of bilirubin. The principal mechanism for decreased plasma concentrations of total bilirubin by administration of VPA is caused by decreased plasma binding, as opposed to metabolic induction.