Distribution of nitric oxide synthase positive neurons in the substantia nigra of rats with liver cirrhosis

BACKGROUND：Nitrogen monoxide plays an important role in the physiological activity and pathological process of striatum in substantia nigra, and the nitric oxide synthase in substantia nigra may have characteristic changes after liver cirrhosis.OBJECTIYE： To observe the distribution and forms of nitric oxide synthase （NOS） positive neurons and fibers in substantia nigra of rats with liver cirrhosis.DESIGN： A comparative observational experiment.SETTINGS： Beijing Friendship Hospital; Capital Medical University.MATERIALS： Twenty 4-month-old male Wistar rats （120 - 150 g） of clean grade, were maintained in a 12-hour light/dark cycle at a constant temperature with free access to standard diet and water. Cryostat microtome （LEICA, Germany）; All the reagents were purchased from Sigma Company.METHODS： The experiment was carried out in the Department of Anatomy （key laboratory of Beijing city）,Capital Medical University from July 2000 to March 2002. The rats were randomly divided into normal group （n=10） and liver fibrosis group （n=10）. Rats in the liver fibrosis group were subcutaneously injected with 60% CCl4 oil at a dose of 5 mL/kg for the first time, and 3 mL/kg for the next 14 times, twice a week,totally 15 times. Liver fibrosis of grades 5 - 6 was taken as successful models. Whereas rats in the normal group were not given any treatment. Four months after CCl4 treatment, all the rats were anesthetized to remove brain, and frontal frozen serial sections were prepared. The expressions of nitric oxide synthase positive neurons in substantia nigra of rats were observed under inverted microscope. The number and gray scale of cell body of nitric oxide synthase positive neurons in substantia nigra were detected with NADPH-diaphorase staining.MAIN OUTCOME MEASURES： ①Number and gray scale of cell body of nitric oxide synthase positive neurons in substantia nigra; ②Expressions of nitric oxide synthase positive neurons in substantia nigra.RESULTS： All the 20 rats were involved in the analysis of results. ①The nitric oxide synthase positive neurons in substantia nigra were obviously fewer in the liver cirrhosis group than in the normal group （P〈0.01）, and the gray scale of the positive cell body was higher in the liver cirrhosis group than in the normal group （P〈0.05）. ② Abundant nitric oxide synthase positive neurons were observed in substantia nigra of neurons in substantia nigra were obviously fewer in the liver cirrhosis group than in the normal group （P〈0.01）, and the gray scale of the positive cell body was higher in the liver cirrhosis group than in the normal normal rats, the cell body of nitric oxide synthase positive neurons was clear and transparent, with short own cloudy processes. In substantia nigra of rats with liver cirrhosis, the body of nitric oxide synthase positive neurons were observed shrink obviously, less fibrin than normal.CONCLUSION： Rats with liver cirrhosis may suffer from the physiological dysfunction of neurons due to lack of fibers. The nitric oxide synthase positive neurons in substantia nigra can shrink and reduce.

Attenuation of portal hypertension by natural taurine in rats with liver cirrhosis

AIM： To investigate the inhibitory effect of natural taurine （NTau） on portal hypertension （PHT） in rats with experimentally-induced liver cirrhosis （LC）. METHODS： Experimentally-induced LC Wistar rats （20 rats/group） were treated with either oral saline or oral NTau for 6 consecutive weeks. Evaluation parameters included portal venous pressure （PVP）, portal venous resistance （PVR）, portal venous flow （PVF）, splanchnic vascular resistance （SVR） and mean arterial pressure （NAP）. Vasoactive substance levels including nitric oxide （NO）, nitric oxide synthase （NOS） and cyclic guanosine monophosphate （cGMP） were also measured. Histological investigation of type Ⅰ and Ⅲ collagen （COL Ⅰ and Ⅲ） and transforming growth factor-β1 （TGF-β1） was also performed. RESULTS： Treatment with NTau （1） significantly decreased PVP, PVR and PVF, and increased MAP and SVP; （2） markedly increased the vascular compliance and reduced the zero-stress of the portal vein; （3） markedly decreased the amount of NO and cGMP and activity of NOS; and （4） improved the pathological status of the liver tissue and reduced the expression of COL Ⅰ, COL Ⅲ and TGF-β1. CONCLUSION： NTau inhibited the LC-induced PHT by improving hyperdynamic circulation, morphology of liver and biomechanical properties of the portal vein in experimentally-induced LC rats.

Atorvastatin and rosuvastatin do not prevent thioacetamide induced liver cirrhosis in rats

AIM:To examine whether the administration of atorvastatin and rosuvastatin would prevent experimentallyinduced hepatic cirrhosis in rats.METHODS:Liver cirrhosis was induced by injections of thioacetamide(TAA).Rats were treated concurrently with TAA alone or TAA and either atorvastatin(1,10 and 20 mg/kg) or rosuvastatin(1,2.5,5,10 and 20 mg/kg) given daily by nasogastric gavage.RESULTS:Liver fibrosis and hepatic hydroxyproline content,in the TAA-treated group was significantly higher than those of the controls [11.5 ± 3.2 vs 2.6 ± 0.6 mg/g protein(P = 0.02)].There were no differences in serum aminotransferase levels in the TAA controls compared to all the groups treated concomitantly by statins.Both statins used in our study did not prevent liver fibrosis or reduce portal hypertension,and had no effect on hepatic oxidative stress.Accordingly,the hepatic level of malondialdehyde was not lower in those groups treated by TAA + statins compared to TAA only.In vitro studies,using the BrdU method have shown that atorvastatin had no effect of hepatic stellate cells proliferation.Nevertheless,statin treatment was not associated with worsening of liver damage,portal hypertension or survival rate.CONCLUSION:Atorvastatin or rosuvastatin did not inhibit TAA-induced liver cirrhosis or oxidative stress in rats.Whether statins may have therapeutic applications in hepatic fibrosis due to other etiologies deserve further investigation.

Effect of spleen on immune function of rats with liver cancer complicated by liver cirrhosis

OBJECTIVE: To establish a rat model of liver cancer complicated by liver cirrhosis and explore the effects of the spleen on immune function in this model. METHODS: Liver cirrhosis was inflicted in rats by percutaneous injection of 40% CCl_4 on the back. Walker-256 tumor cells were inoculated in the cirrhotic liver and splenectomy was performed. Two weeks later, the growth and metastasis of tumor were observed and the amount of ascites and the activity of NK cells and CD25 cells were investigated. RESULTS: The amount of ascites and tumor volume were significantly higher in splenectomy group than in controls (P<0.O1). Two weeks after inoculation, the activity of NK cells in both groups was decreased as compared with that before the inoculation (P<0.01). There was no significant difference between the two groups before and after the inoculation (P>0.05). The number of CD25 in both groups was higher than that before the inoculation (P<0.01). However, there was no significant difference between the two groups before and after the inoculation (P>0.05). CONCLUSIONS: Splenectomy in early stage of tumor inoculation can stimulate the tumor growth and metastasis. The activity of NK cells and the number of CD25 are inhibited by tumor itself, not by splenectomy.

Fat necrosis of liver in a patient with mixed type liver cirrhosis

To the Editor: Fatty liver diseases, including nonalcoholic fatty liver disease and alcohol related fatty liver disease, have become a major public health concern [ 1, 2 ]. Fatty liver diseases have been shown to progress through various stages, from steatosis or necrosis with inflammation and hepatocyte damage to the development of fibrosis and eventual cirrhosis with an increased risk of carcinoma [ 2, 3 ].

Clinical study on the relationship between liver cirrhosis,ascites,and hyponatremia

BACKGROUND Cirrhosis is a common liver disease,and ascites is one of the common clinical conditions.However,the clinical manifestations of ascites combined with hyponatremia as a high-risk condition and its relationship to patient prognosis have not been fully studied.AIM To explore the clinical manifestations,prognostic factors,and relationships of ascites with hyponatremia in patients with cirrhosis to provide better diagnostic and treatment strategies.METHODS In this study,we retrospectively analyzed the clinical data of 150 patients diagnosed with cirrhosis and ascites between 2017 and 2022.Patients were divided into two groups:ascites combined with hyponatremia group and ascites group.We compared the general characteristics,degree of hyponatremia,complications,treatment,and prognosis between the two groups.RESULTS In the study results,patients in the ascites combined with hyponatremia group showed an older average age(58.2±8.9 years),64.4%were male,and had a significantly longer hospitalization time(12.7±5.3 d).Hyponatremia was more severe in this group,with a mean serum sodium concentration of 128.5±4.3 mmol/L,which was significantly different from the ascites group of 137.6±2.1 mmol/L.Patients with ascites and hyponatremia were more likely to develop hepatic encephalopathy(56.2%vs 39.0%),renal impairment(45.2%vs 28.6%)and infection(37.0%vs 23.4%).Regarding treatment,this group more frequently used diuretics(80.8%vs 62.3%)and salt supplements(60.3%vs 38.9%).Multiple logistic regression analysis identified older age[Odds ratio(OR)=1.06,P=0.025]and male gender(OR=1.72,P=0.020)as risk factors for hyponatremia combined with ascites.Overall,patients with ascites and hyponatremia present a clear high-risk status,accompanied by severe complications and poor prognosis.CONCLUSION In patients with cirrhosis,ascites with hyponatremia is a high-risk condition that is often associated with severe complications.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis

BACKGROUND Liver cirrhosis patients admitted to intensive care unit(ICU)have a high mortality rate.AIM To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.METHODS We extracted demographic,etiological,vital sign,laboratory test,comorbidity,complication,treatment,and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV(MIMIC-IV)and electronic ICU(eICU)collaborative research database(eICU-CRD).Predictor selection and model building were based on the MIMIC-IV dataset.The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors.The final predictors were included in the multivariate logistic regression model,which was used to construct a nomogram.Finally,we conducted external validation using the eICU-CRD.The area under the receiver operating characteristic curve(AUC),decision curve,and calibration curve were used to assess the efficacy of the models.RESULTS Risk factors,including the mean respiratory rate,mean systolic blood pressure,mean heart rate,white blood cells,international normalized ratio,total bilirubin,age,invasive ventilation,vasopressor use,maximum stage of acute kidney injury,and sequential organ failure assessment score,were included in the multivariate logistic regression.The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases,respectively.The calibration curve also confirmed the predictive ability of the model,while the decision curve confirmed its clinical value.CONCLUSION The nomogram has high accuracy in predicting in-hospital mortality.Improving the included predictors may help improve the prognosis of patients.

Contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis patients

This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis(LC)patients according to the current guidelines.Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients.Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology.According to the current guidelines,in the absence of clinically significant portal hypertension,etiological and nonetiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding,whereas its presence serves as an indication for the administration of non-selectiveβ-blockers,among which carvedilol is the drug of choice.Non-selectiveβ-blockers,as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding.Pharmacotherapy with vasoactive drugs(terlipressin,somatostatin,octreotide),endoscopic variceal ligation,endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding.Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management,avoiding the first and further decompensation in LC,which will improve the prognosis and survival of patients suffering from it.

Causal association between 731 immunocyte phenotypes and liver cirrhosis: A bidirectional two-sample mendelian randomization analysis

BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis.AIM To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization(MR)study.METHODS Data on 731 immunocyte phenotypes were obtained from genome-wide assoc-iation studies.Liver cirrhosis data were derived from the Finn Gen dataset,which included 214403 individuals of European ancestry.We used inverse variable weighting as the primary analysis method to assess the causal relationship.Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.RESULTS The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis[P<0.05,odds ratio(OR)>1]and that 9 immu-nocyte phenotypes were negatively correlated with liver cirrhosis(P<0.05,OR<1).Liver cirrhosis was positively linked to 9 immune cell phenotypes(P<0.05,OR>1)and negatively linked to 10 immune cell phenotypes(P<0.05;OR<1).None of these associations showed heterogeneity or horizontally pleiotropy(P>0.05).CONCLUSION This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis.These findings offer new directions for the treatment of liver cirrhosis.

Pituitary stalk interruption syndrome complicated with liver cirrhosis:A case report

BACKGROUND Pituitary stalk interruption syndrome(PSIS)is a rare disorder,often characterized by delayed growth and development,short stature,and hypogonadism as the main clinical manifestations.It is not clear whether PSIS can lead to liver cirrhosis.CASE SUMMARY This paper reported a case of liver cirrhosis of unknown origin.The patient was admitted to Beijing Ditan Hospital Affiliated to Capital Medical University in November 2023.The diagnosis of PSIS complicated with liver cirrhosis was established after a series of blood tests and pituitary magnetic resonance imaging examination.CONCLUSION We also reviewed the literature from both domestic and international sources to deepen the clinical understanding of PSIS in conjunction with liver cirrhosis among medical practitioners.

Dapagliflozin as an oral antihyperglycemic agent in the management of diabetes mellitus in patients with liver cirrhosis

BACKGROUND The use of dapagliflozin in patients with cirrhosis has been relatively restricted due to concerns regarding its overall safety and pharmacological profile in this population.AIM To determine the safety and effectiveness of dapagliflozin in the co-management of diabetes mellitus and cirrhosis with or without ascites.METHODS The patients studied were divided into two groups:100 patients in the control group received insulin,while 200 patients received dapagliflozin.These patients were classified as Child A,B,or C based on the Child–Pugh classification.Child A or B and Child C were administered doses of 10 mg and 5 mg of dapagliflozin,respectively.RESULTS The rate of increased diuretics dose was markedly elevated in the group that received insulin compared to the group that received dapagliflozin.In addition,dapagliflozin treatment substantially reduced weight,body mass index,and fasting blood glucose compared to the insulin group during follow-up.However,there were no significant differences in hemoglobin A1c,liver function,or laboratory investigations between both groups during the follow-up period.The incidence of hypoglycemia,hepatic encephalopathy,variceal bleeding,and urinary tract infection was significantly higher in the insulin group compared to the dapagliflozin group.In contrast,the dapagliflozin group experienced significantly higher rates of frequent urination and dizziness.In addition,the insulin group exhibited a marked worsening of ascites compared to the dapagliflozin group.CONCLUSION Dapagliflozin demonstrated safety and efficacy in the treatment of diabetic patients who have cirrhosis with or without ascites.This resulted in an improvement of ascites,as well as a decrease in diuretic dose and Child–Pugh score.

Effects of glycyrrhetinic acid on collagen metabolism of hepatic stellate cells at different stages of liver fibrosis in rats

INTRODUCTIONLiver fibrosis is a dynamic course leading tocirrhosis from a various chronic liver diseases. Thepathological basis of fibrosis is the disturbance ofproduction and degradation of the extracellularmatrix (ECM), which causes accumulation of ECMin the liver[1,2].

Safe upper limit of intermittent hepatic inflow occlusion for liver resection in cirrhotic rats

AIM: To evaluate the effects of varying ischemic durations on cirrhotic liver and to determine the safe upper limit of repeated intermittent hepatic inflow occlusion. METHODS: Hepatic ischemia in cirrhotic rats was induced by clamping the common pedicle of left and median lobes after non-ischemic lobes resection. The cirrhotic rats were divided into six groups according to the duration and form of vascular clamping: sham occlusion (SO), intermittent occlusion for 10 (IO-10), 15(IO-15), 20(IO-20) and 30(IO-30) minutes with 5 minutes of reflow and continuous occlusion for 60 minutes (CO-60). All animals received a total duration of 60 minutes of hepatic inflow occlusion. Liver viability was investigated in relation of hepatic adenylate energy charge (EC). Triphenyltetrazollum chloride (TTC) reduction activities were assayed to qualitatively evaluate the degree of irreversible hepatocellular injury. The biochemical and morphological changes were also assessed and a 7-day mortality was observed. RESULTS: At 60 minutes after reperfusion following a total of 60 minutes of hepatic inflow occlusion, EC values in IO-10 (0.749 +/- 0.012) and IO-15 (0.699 +/- 0.002) groups were rapidly restored to that in SO group (0.748 +/- 0.016), TTC reduction activities remained in high levels (0.144 +/- 0.002 mg/mg protein, 0.139 +/- 0.003 mg/mg protein and 0.121 +/- 0.003 mg/mg protein in SO, IO-10 and IO-15 groups, respectively). But in IO-20 and IO-30 groups, EC levels were partly restored (0.457 +/- 0.023 and 0.534 +/- 0.027) accompanying with a significantly decreased TTC reduction activities (0.070 +/- 0.005 mg/mg protein and 0.061 +/- 0.003 mg/mg protein). No recovery in EC values (0.228 +/- 0.004) and a progressive decrease in TTC reduction activities (0.033 +/- 0.002 mg/mg protein) were shown in CO-60 group. Although not significantly different, the activities of the serum aspartate aminotransferase (AST) on the third postoperative day (POD(3)) and POD(7) and of the serum alanine aminotransferase (ALT) on POD(3) in CO-60 group remained higher than that in intermittent occlusion groups. Moreover, a 60% animal mortality rate and more severe morphological alterations were also shown in CO-60 group. CONCLUSION: Hepatic inflow occlusion during 60 minutes for liver resection in cirrhotic rats resulted in less hepatocellular injury when occlusion was intermittent rather than continuous. Each period of 15 minutes was the safe upper limit of repeated intermittent vascular occlusion that the cirrhotic liver could tolerate without undergoing irreversible hepatocellular injury.

Experimental models of non-alcoholic fatty liver disease in rats

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings,ranging from simple fatty liver through non-alcoholic steatohepatitis(NASH)to fibrosis and ultimately cirrhosis,which may progress to hepatocellular carcinoma.The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance.Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models.The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages.Within the past several years,great emphasis has been placed on the development of an appropriate model for human NASH.This paper reviews the widely used experimental models of NAFLD in rats.We discuss nutritional,genetic and combined models of NAFLD and their pros and cons.The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies.Considering the legislative,ethical,economical and health factors of NAFLD,animal models are essential tools for the research of this disease.

Preliminary Investigation on Regulating Effects of Different TCM Treatments on Transcription of the Correlated Genes of Liver Cancer in Rats

The regulating effects of TCM treatments including clearing away heat and toxic materials,promoting blood circulation and removing blood stasis,and strengthening the spleen and regulating qi on the oncogene transcription were observed in the liver cancer model rats.The preliminary results indicated that the mRNA levels of H-ras N-ras and K-ras,and signal molecules correlated with the ras/MAPK signal transduction pathway were down-regulated by the different TCM treatments in varying degrees.Also,the regulating effects of the treatments on differently-displayed genes were discrepant.It is suggested that the molecular mechanisms of the TCM treatments for liver cancer was complex with different target genes.

Intestinal expressions of eNOSmRNA and iNOSmRNA in rats with acute liver failure

AIM: To observe the gene expression change of eNOSmRNA and iNOSmRNA in the small and large intestines with acute liver failure (ALF), and to reveal the biological function of NO on the pathogenesis of ALF and multiple organs dysfunction at the molecular level. METHODS: Sixty male Wistar rats were selected, weighing from 250g to 350g, and divided into 5 groups randomly: SO, ALF (6h, 12h), L-Arg, L-NAME, L-Arg and L-NAME, each group with 10 rats. The dose of L-Arg was 300mg.kg(-1), and L-NAME was 30mg.kg(-1), the reagents diluted by normal saline were injected through tail vein 30 minutes pre and post operation. The rats in the ALF group were respectively sacrificed postoperatively at 6h, 12h, and the rats in the other groups were sacrificed postoperatively at 6h. The tissues of small and large intestines were harvested in 4% paraforaldehyde containing the reagent of DEPC and fixed at 6h, embedded in paraffin, and 4 microm section was cut. The expression of eNOSmRNA and iNOSmRNA in these tissues was determined with in situ hybridization, and analyzed with the imaging analysis system of CMM-3 and SPSS statistical software. RESULTS: The expression of eNOSmRNA in the large intestine and iNOSmRNA in the small and large intestines increased significantly at 6h after ALF, but the expression of iNOSmRNA in the small and large intestines reduced notably at 12h after ALF (P【0.05); the expression of eNOSmRNA in the large intestine and iNOSmRNA in the small and large intestines decreased significantly with the reagents of L-Arg at 6h ALF, but the expression of eNOSmRNA and iNOSmRNA in the small and large intestines decreased totally with the reagents of L-NAME or association with L-Arg 6h ALF. CONCLUSION: The expression of eNOSmRNA in the large intestine increased notably at the early stage of ALF, NO induced by the enzyme of eNOS from the transplantation of eNOSmRNA can protect the function of the large intestine, the high expression of iNOSmRNA is involved in the damaged function of the small and large intestines. NO precursor can reduce the expression of iNOSmRNA in the small and large intestines and the damage to intestines; NOS inhibitor or association with NO pre-cursor can totally lower the expression of eNOSmRNA and iNOSmRNA in the small and large intestines, it cannot notably influence the NOS inhibitor in the gene expression of eNOSmRNA and iNOSmRNA to supply the additional NO precursor.

Japanese herbal medicine, Saiko-keishi-to, prevents gut ischemia/reperfusion-induced liver injury in rats via nitric oxide

AIM:To determine whether Saiko-keishi-to(TJ-10),a Japanese herbal medicine,could protect liver injury induced by gut ischemia/reperfusion(I/R),and to investigate the role of NO. METHODS:Male Wistar rats were exposed to 30-min gut isohemia followed by 60 min of reperfusion.Intravital microscopy was used to monitor leukocyte recruitment.Plasma tumor necrosis factor(TNF)levels and alanine aminotransferase (ALT)activities were measured.TJ-10 1 g/(kg.d)was intragastrically administered to rats for 7 d.A NO synthase inhibitor was administered. RESULTS:In control rats,gut I/R elicited increases in the number of stationary leukocytes,and plasma TNF levels and ALT activities were mitigated by pretreatment with TJ-10.Pretreatment with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver,and the increase of plasma TNF levels and ALT activities.Pretreatment with TJ-10 increased plasma nitrite/nitrate levels. CONCLUSION:TJ-10 attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.

Hematotesticular barrier is altered from early stages of liver cirrhosis:Effect of insulin-like growth factor 1

AIM:The pathogenesis of hypogonadism in liver cirrhosis is not well understood.Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis.The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis. The aim of this study was to establish the historical progression of the described alterations in the testes, explore testicular morphology,histopathology,cellular proliferation,integrity of testicular barrier and hypophyso- gonadal axis in rats with no ascitic cirrhosis. METHODS:Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride(CCI_4)for 11 wk, were allocated into two groups(n=12,each)to receive recombinant IGF-1(2 μg/100 gd,sc)for two weeks or vehicle.Healthy rats receiving vehicle were used as control group(n=12). RESULTS:Compared to controls,rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities. However,these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression.In addition,pituitary-gonadal axis was altered,with significant higher levels of FSH(P<0.001 vscontrols)and increased levels of LH in untreated cirrhotic animals.Interestingly,IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH(P=ns vs controls,and P<0.01 vs untreated cirrhotic group). CONCLUSION:The testicular barrier is altered from an early stage of cirrhosis,shown by a reduction of transferrin expression in Sertoli cells,a diminished cellular proliferation and an altered gonadal axis.The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.

Effect of anti-fibrosis compound on collagen expression of hepatic cells in experimental liver fibrosis of rats

INTRODUCTIONLiver fibrosis is mainly characterized by theexcessive synthesis and decreased degradation ofextracellular matrix(ECM),especially the synthesisand deposition of collagen.Almost all kinds of cellsin the liver have participated in the production ofcollagen.The most important ones are hepaticstellate cells(HSC)and hepatocytes.We