Diabetic foot syndrome:Immune-inflammatory features as possible cardiovascular markers in diabetes

Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality. Diabetic foot syndrome(DFS), as defined by the World Health Organization, is an "ulceration of the foot(distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection". Pathogenic events able to cause diabetic foot ulcers are multifactorial.Among the commonest causes of this pathogenic pathway it's possible to consider peripheral neuropathy, foot deformity, abnormal foot pressures, abnormal joint mobility, trauma, peripheral artery disease. Several studies reported how diabetic patients show a higher mortality rate compared to patients without diabetes and in particular these studies under filled how cardiovascular mortality and morbidity is 2-4 times higher among patients affected by type 2 diabetes mellitus. This higher degree of cardiovascular morbidity has been explained as due to the observed higher prevalence of major cardiovascular risk factor, of asymptomatic findings of cardiovascular diseases, and of prevalence and incidence of cardiovascular and cerebrovascular events in diabetic patients with foot complications. In diabetes a fundamental pathogenic pathway of most of vascular complications has been reported as linked to a complex interplay of inflammatory, metabolic and procoagulant variables. These pathogenetic aspects have a direct interplay with an insulin resistance, subsequent obesity, diabetes, hypertension, prothrombotic state and blood lipid disorder. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects as reported by Tuttolomondo et al confirmed the pathogenetic issue of the a "adipo-vascular" axis that may contribute to cardiovascular risk in patients with type 2 diabetes. This "adipo-vascular axis" in patients with type 2 diabetes has been reported as characterized by lower plasma levels of adiponectin and higher plasma levels of interleukin-6 thus linking foot ulcers pathogenesis to microvascular and inflammatory events. The purpose of this review is to highlight the immune inflammatory features of DFS and its possible role as a marker of cardiovascular risk in diabetes patients and to focus the management of major complications related to diabetes such as infections and peripheral arteriopathy.

Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis

AIM: To investigate the effects of troglitazone (TGZ), an anti-diabetic drug which activates peroxisome proliferatoractivated receptor-γ (PPAR-γ), for liver tissue repair, and the development of ductular reaction, following common bile duct ligation (BDL) in rats.METHODS: Rats were supplemented with TGZ (0.2% w/w in the pelleted food) for 1 wk before BDL or sham operation.Animals were killed at 1, 2, or 4 wk after surgery.RESULTS: The development of liver fibrosis was reduced in rats receiving TGZ, as indicated by significant decreases of procollagen type Ⅰ gene expression and liver hydroxyproline levels. Accumulation of α-smooth-muscle actin (SMA)-expressing cells surrounding newly formed bile ducts following BDL, as well as total hepatic levels of SMA were partially inhibited by TGZ treatment, indicating the presence of a reduced number and/or activation of hepatic stellate cells (HSC) and myofibroblasts. Development of the ductular reaction was inhibited by TGZ, as indicated by histochemical evaluation and hepatic activity of γ-glutamyltransferase (GGT).CONCLUSION: Treatment with thiazolidinedione reduces ductular proliferation and fibrosis in a model of chronic cholestasis, and suggests that limiting cholangiocyte proliferation may contribute to the lower development of scarring in this system.

Surveillance for early diagnosis of hepatocellular carcinoma: How best to do it?

Surveillance for hepatocellular carcinoma(HCC)is considered a standard of care for patients with chronic liver disease who are at risk of developing this malignancy.Several studies have shown that surveillance can improve the prognosis of patients diagnosed with HCC through an increased likelihood of application of curative or effective treatments.Repetition of liver ultrasonography(US)every 6 mo is the recommended surveillance program to detect early HCCs,and a positive US has to entrain a well-defined recall policy based on contrast-enhanced,dynamic radiological imaging or biopsy for the diagnosis of HCC.Although HCC fulfills the accepted criteria regarding cost-effective cancer screening and surveillance,the implementation of surveillance in clinical practice is defective and this has a negative impact on the cost-effectiveness of the procedure.Education of both physicians and patients is of paramount importance in order to improve the surveillance application and its benefits in patients at risk of HCC.The promotion of specific educational programs for practitioners,clinicians and patients is instrumental in order to expand the correct use of surveillance in clinical practice and eventually improve HCC prognosis.

Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease

AIM: To evaluate the role of genetic factors in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), we investigated the single nucleotide poly- morphisms (SNPs) of NOD2/CARD15 (R702W, G908R and L1007fi nsC), and Toll-like receptor 4 (TLR4) genes (D299G and T399I) in a selected inflammatory bowel disease (IBD) population coming from Southern Italy. METHODS: Allele and genotype frequencies of NOD2/ CARD15 (R702W, G908R and L1007finsC) and TLR4 (D299G and T399I) SNPs were examined in 133 CD pa-tients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS: NOD2/CARD15 R702W mutation was sig-nificantly more frequent in CD (9.8%) than in controls (2.4%, P = 0.001) and in UC (2.3%, P = 0.03). No sig-nificant difference was found between UC patients and control group (P > 0.05). In CD and UC patients, no signifi cant association with G908R variant was found. L1007f insC SNP showed an association with CD (9.8%) compared with controls (2.9%, P = 0.002) and UC patients (2.3%, P = 0.01). Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort (allele frequencies: D299G-controls 3.9%, CD 3.7%, UC 3.4%, P > 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P > 0.05). CONCLUSION: These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with in-creased risk of CD.

Multiple immune disorders in unrecognized celiac disease:a case report

We reported a female patient with unrecognized celiac disease and multiple extra intestinal manifestations, mainly related to a deranged immune function, including macroamilasemia, macrolipasemia, IgA nephropathy,thyroiditis, and anti-b2-glicoprotein-1 antibodies, that disappeared or improved after the implementation of a gluten-free diet.

Peliosis hepatis as an early histological finding in idiopathic portal hypertension: A case report

紫癜 hepatis 是肝窦状隙和充满血的空格的膨胀在主要在暴露于有毒的物质或雌激素的题目观察的肝描绘的一个稀罕条件，它经常是无征状的。仅仅当门静脉高血压的出血性的复杂并发症发生时，非肝脏硬化症的自发的门静脉高血压(NCIPH ) 也是很少在欧洲国家观察的肝的脉管的疾病，它通常被诊断。我们在与肝紫癜被诊断的年轻白种人男性报导 NCIPH 的一个案例，显示出 ultrasonographic 和门静脉高血压四年的内视镜的符号在以后。第二活体检视为 NCIPH 是诊断的。就算致病仍然保持阴暗，紫癜 hepatis 能被看作肝的脉管的疾病的一个早符号，它可以进行到更明确的条件。

Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study

AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis Disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel Disease Questionnaire(IBDQ), Crohn's Disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo L.RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earliest(6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES.CONCLUSION Ada treatment, upon multidisciplinary(gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQo L in patients affected by ES.

Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption

The etiology of most cases of idiopathic bile acid malabsorption (IBAM) is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR) and peroxisome proliferator activated receptor alpha (PPARa). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine (SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7a-hydroxy-4-cholesten-3-one (C4). The ASBT, FXR, and PPARa genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate withthe bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARa genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.

Serum SCCA-IgM as a predictor of hepatocellular carcinoma in patients with liver cirrhosis

Aberrant Squamous Cell Carcinoma Antigen (SCCA) expression is an early hepatocarcinogenetic event and circulating SCCA-IgM complexes are elevated in most HCC patients. We evaluated whether serum SCCA-IgM levels can identify HCV +ve cirrhotic patients at low HCC risk. In this retrospective study we enrolled 29 cirrhotic patients in whom serum SCCA-IgM was measured 8 - 69 months (median 31) before HCC diagnosis, and 28 cirrhotic patients who remained HCC- free, with SCCA-IgM measured 15 - 68 months (median 48) before the study end. The best discriminating value of SCCA-IgM was calculated and tested in predicting HCC diagnosis within 12, 24 and 36 months. Sensitivity analysis, considering different HCC incidence, was conducted to identify the patient subgroup with an annual cancer risk below the threshold of a cost-effective semiannual surveillance with ultrasound. Cumulative HCC incidence at 12, 24 and 36 months was 7.0%, 15.7% and 26.3%, respectively. SCCA-IgM levels were higher in HCC than in cirrhotic patients [median: 381 (95% C.I.: 50 - 5289) vs. 100 (70 - 493) AU/mL, P = 0.005]. The SCCA-IgM value ≤ 200 AU/mL accurately identified patients at low risk of HCC development in the subsequent year (sensitivity 75%, specificity 62%, positive predictive value 13% and negative predictive value 97%). Considering an annual HCC incidence ≤ 3%, patients with SCCA-IgM ≤ 200 AU/mL (60% of the whole patients) had an HCC risk below the accepted threshold of a cost-effective surveillance (1.5%). In conclusion, provided that our provocative results are confirmed in larger studies, SCCA-IgM serum measurement could permit implementation of a two step (with different costs) surveillance: an initial serological surveillance, based on the annual monitoring of this biomarker, and the conventional surveillance by semiannual US when SCCA-IgM becomes >200 AU/mL. This could improve the cost/effectiveness of surveillance of HCV infected patients at risk of HCC.

Chlamydia pneumoniae replicates in Kupffer cells in mouse model of liver infection

AIM: To develop an animal model of liver infection with Chlamydia pneumoniae (C. pneumoniae) in intraperito-neally infected mice for studying the presence of chlamy-diae in Kupffer cells and hepatocytes.METHODS: A total of 80 BALB/c mice were inoculated intraperitoneally with C. pneumoniae and sacrificed at various time points after infection. Chlamydiae were looked for in liver homogenates as well as in Kupffer cells and hepatocytes separated by liver perfusion with collagenase. C. pneumoniae was detected by both isola-tion in LLC-MK2 cells and fluorescence in situ hybridiza-tion (FISH). The releasing of TNFA-α by C. pneumoniae in vitro stimulated Kupffer cells was studied by enzyme-linked immunosorbent assay.RESULTS: C. pneumoniae isolation from liver homoge-nates reached a plateau on d 7 after infection when 6 of 10 animals were positive, then decreased, and became negative by d 20. C. pneumoniae isolation from sepa-rated Kupffer cells reached a plateau on d 7 when 5 of 10 animals were positive, and became negative by d 20. The detection of C. pneumoniae in separated Kupffer cells by FISH, confirmed the results obtained by culture. Isolated hepatocytes were always negative. Stimula-tion of Kupffer cells by alive C. pneumoniae elicited high TNF-α levels. CONCLUSION: A productive infection by C. pneumo-niae may take place in Kupffer cells and C. pneumoniae induces a local pro-inflammatory activity. C. pneumoniae is therefore, able to act as antigenic stimulus when local-ized in the liver. One could speculate that C. pneumoniaeinfection, involving cells of the innate immunity such as Kupffer cells, could also trigger pathological immune re-actions involving the liver, as observed in human patients with primary biliary cirrhosis.

Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy:A randomized controlled trial

AIM: To assess the efficacy of different schedules of consensus interferon (CIFN) plus ribavirin in retreating chronic hepatitis C patients who relapsed after recombinant interferon (rIFN) monotherapy. METHODS: Forty-five patients (34 males and 11 females) with chronic hepatitis due to hepatitis C virus (HCV) genotype 1 who relapsed after a previous course of rIFN monotherapy were randomized to receive 9 μg CIFN three times per week for 52 wk (group A, n = 22) or 18 μg CIFN three times per week for 52 wk (group B, n = 23) in combination with ribavirin 800 to 1200 mg daily for 52 wk (according to body weight). Virological response was evaluated at week 24 (EVR), at the end of treatment (ETR) and at 76 wk (SVR). RESULTS: By intention-to-treat analysis, subjects in group A had an EVR in 35% of cases, an ETR in 35% and a SVR in 27.3% of cases. Subjects in group B had an EVR in 32% of cases, an ETR in 35% and a SVR in 26.1% of cases. Treatment was stopped because of adverse effects (mostly intolerance) in 15 patients (6 in group A and 9 in group B). IFN dose reduction was needed in 2 patients (1 in group A and 1 in group B). Ribavirin dose was reduced in 2 patients in group A and 1 in group B respectively. Among the 15 subjects who received at least 80% of the intended schedule, the rate of SVR was 80% (6 in group A and 6 in group B). CONCLUSION: CIFN in combination with ribavirin when given to HCV genotype 1 relapsers after rIFN monotherapy obtains an unsatisfactory rate of sustainedviral clearance independently of dosage of the drug. This may be due to its scarce tolerability.

Clinical and economic impact of infliximab one-hour infusion protocol in patients with inflammatory bowel diseases:A multicenter study

AIM To assess the impact of short infliximab(IFX) infusion on hospital resource utilization and costs.METHODS All inflammatory bowel diseases(IBD) patients who received IFX 1 h infusion from March 2007 to September 2014 in eight centers from Southern Italy were included in the analysis. Demographic, clinical and infusion related data were collected. The potential benefits related to the short infusion protocol were assessed both in terms of time saving and increased infusion unit capacity. In addition, indirect patient-related cost savings were evaluated.RESULTS One hundred and twenty-five patients were recruited(64 with ulcerative colitis and 61 with Crohn's disease). Median duration of disease was of 53 mo and mean age of pts at diagnosis was of 34 years(SD: ± 13). Adverse infusion reactions were reported in less than 4% both before and after short infusion. The total number of infusions across the selected centers was of 2501(30.5% short infusions). In the analyzed cohort, 1143 h were saved(762 in the infusion and 381 in observation phases) through the rapid IFX infusion protocol. This time saving(-15% compared to the standard protocol in infusion phase) represents, from the hospital perspective, an opportunity to optimize infusion unit capacity by allocating the saved time in alternative cost-effective treatments. This is the case of opportunity cost that represents the value of forgone benefit which could be obtained from a resource in its next-best alternative use. Hence, an extra hour of infusion in the case of standard 2-h IFX represents a loss in opportunity to provide other cost effective services. The analysis showed that the short infusion increased the infusion units capacity up to 50% on days when the IFX infusions were scheduled(infusion phase). Furthermore, the analysis showed that the short IFX infusion protocol leads to time savings also in the post-infusion phase(observation) leading to a time saving of 10% on average among the analyzed centers. Finally, the short infusion protocol has been demonstrated to lead to indirect cost savings of €138/patient(average-€17.300 on the whole cohort).CONCLUSION A short IFX infusion protocol can be considered time and cost saving in comparison to the standard infusion protocol both from the hospital's perspective, as it contributes to increase infusion units capacity, and the patients' perspective, as it reduces indirect costs and the impact of treatment on everyday life and work productivity.

Biochemical mechanisms in drug-induced liver injury:Certainties and doubts

Drug-induced liver injury is a significant and still unresolved clinical problem.Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development.Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites.Aging,preexisting liver disease,enzyme induction or inhibition,genetic variances,local O2 supply and,above all,the intrinsic molecular properties of the drug may affect this process.Necrotic death follows antioxidant consumption and oxidation of intracellular proteins,which determine increased permeability of mitochondrial membranes,loss of potential,decreased ATP synthesis,inhibition of Ca2+-dependent ATPase,reduced capability to sequester Ca2+ within mitochondria,and membrane bleb formation.Conversely,activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis.Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage.Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis,in which different HLA genotypes might play a major role.This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage.Future perspectives including new frontiers for research are discussed.

Metabolic syndrome in hypertensive patients:An unholy alliance

For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.

Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux

AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER.METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry.Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM).Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed.RESULTS: Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagus,5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis.After 3 mo of therapy, 13/15 patients (86.7%, P＜0.01)showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months,complete recovery of DIS and heartburn were achieved in one.CONCLUSION: Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.

Asthma and metabolic syndrome: Current knowledge and future perspectives

Asthma and obesity are epidemiologically linked; however, similar relationships are also observed with other markers of the metabolic syndrome, such as insulin resistance and dyslipidemia, which cannot be accounted for by increased body mass alone. Obesity appears to be a predisposing factor for the asthma onset, both in adults and in children. In addition, obesity could make asthma more difficult to control and to treat. Although obesity may predispose to increased Th2 inflammation or tendency to atopy, othermechanisms need to be considered, such as those mediated by hyperglycaemia, hyperinsulinemia and dyslipidemia in the context of metabolic syndrome. The mechanisms underlying the association between asthma and metabolic syndrome are yet to be determined. In the past, these two conditions were believed to occur in the same individual without any pathogenetic link. However, the improvement in asthma symptoms following weight reduction indicates a causal relationship. The interplay between these two diseases is probably due to a bidirectional interaction. The purpose of this review is to describe the current knowledge about the possible link between metabolic syndrome and asthma, and explore potential application for future studies and strategic approaches.

Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis

Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with increased cardiovascular risk and higher mortality in respect to general population.Beyond joint disease,inflammation is the major determinant of accelerated atherosclerosis observed in rheumatoid arthritis.We review the relationship between inflammation,atherosclerosis and cardiovascular risk in rheumatoid arthritis,focusing on the assessment of subclinical atherosclerosis by functional and morphological methods.These tools include flow mediated dilatation,carotid intima-media thickness,ankle/brachial index,coronary calcium content,pulse wave analysis and serum biomarker of subclinical atherosclerosis.

Liver angiogenesis as a risk factor for hepatocellularcarcinoma development in hepatitis C virus cirrhotic patients

AIM: To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients. METHODS: One hundred-five patients (69 males, 36 females; age range, 51-90 year; median 66 year) with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 mo. Angiogenesis was assessed by using microvessel density (MVD), hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies. RESULTS: Forty six patients (43.8%) developed HCC after a median time of 55 (6-120) mo while 59 (56.2%) did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low (median MVD = 3; range 0-20) and high (median MVD = 7; range 1-24) MVD was statistically significant (χ2 = 22.06; P < 0.0001) which was not the case for MIB1 or PCNA (MIB-1: χ2 = 1.41; P = 0.2351; PCNA: χ2 = 1.27; P = 0.2589). The median MVD was higher in patients who developed HCC than in those who did not. HCC-free interval was significantly longer in patients with the MVD ≤ 4 (P = 0.0006). No relationship was found between MIB1 or PCNA and MVD (MIB-1 r2 = 0.00007116, P = 0.9281; PCNA: r2 =0.001950; P = 0.6692). MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk. CONCLUSION: Liver angiogenesis has a role for in HCV- related liver carcinogenesis and for defining patients at higher risk.

Ileal lesions in patients with ulcerative colitis after ileo-rectal anastomosis:Relationship with colonic metaplasia

AIM:To assess whether in ulcerative colitis (UC) patients with ileo-rectal anastomosis (IRA), ileal lesions may develop in the neo-terminal-ileum and their possible relation with phenotypic changes towards colonic epithelium. METHODS: A total of 19 patients with IRA under regular follow up were enrolled, including 11 UC and 8 controls (6 Crohn’s disease, CD; 1 familial adenomatous polyposis, FAP; 1 colon cancer, colon K). Ileal lesions were identifi ed by ileoscopy with biopsies taken from the ileum (involved and uninvolved) and from the rectal stump. Staining included HE and immunohistochemistry using monoclonal antibodies against colonic epithelial protein CEP (Das-1) and human tropomyosin isoform 5, hTM5 (CG3). Possible relation between development of colonic metaplasia and ileal lesions was investigated.RESULTS: Stenosing adenocarcinoma of the rectal stump was detected in 1 UC patient. The neo-terminal ileum was therefore investigated in 10/11 UC patients. Ileal ulcers were detected in 7/10 UC, associated with colonic metaplasia in 4/7 (57.1%) and Das-1 and CG3 reactivity in 3/4 UC. In controls, recurrence occurred in 4/6 CD, associated with colonic metaplasia in 3/4 and reactivity with Das-1 and CG3 in 2/3. CONCLUSION: Present fi ndings suggest that in UC, ileal lesions associated with changes towards colonic epithelium may develop also after IRA. Changes of the ileal content after colectomy may contribute to the development of colonic metaplasia, leading to ileal lesions both in the pouch and in the neo-terminal ileum after IRA.

Production of reactive oxygen species and expression of inducible nitric oxide synthase in rat isolated Kupffer cells stimulated by Leptospira interrogans and Borrelia burgdorfen

瞄准：为了评估反应的氧种类(ROS ) 和可诱导的氮的氧化物的表示的生产，在老鼠的 synthase (i NOS ) 孤立肾脏钩端螺旋体和包柔氏螺旋体属 burgdorferi 刺激的 Kupffer 房间(KC ) 。方法：老鼠 Kupffer 房间被肝的灌注用 0.05% 胶原酶分开，并且由 Percoll 坡度净化了。净化的 Kupffer 房间是有活着的 L 的测试在试管内。interogans 和 B。burgdorferi 准备。ROS 的生产被化合光决定，而 i NOS 蛋白质表达式被西方的污点试金用 anti-iNOS 抗体计算。结果：B。burgdorferi 并且到一更少的程度 L。interrogans 与一座山峰导致了 ROS 生产在感染以后的 35 min。化合光信号日益增多地减少了并且由孵化的 180 min 是无法发现的。Leptospirae 和 borreliae 在在 6 个小时达到顶点并且仍然是明显的 Kupffer 房间导致了增加的 i NOS 表情在感染以后的 22 h。结论：螺旋菌的两个类在老鼠 Kupffer 细胞导致了 ROS 和 i NOS 生产。自从在 leptospiral 以及在 borrelial 感染的肝损坏的原因，仍然是未知的，我们建议那螺旋体和肝的包柔氏螺旋体属损坏能被氧激进分子开始调停，并且然后被氮的氧化物部分地至少维持。