Immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in strains of mice with different susceptibility to induction of aryl hydrocarbon hydroxylase

Mouse strains with different susceptibility to aryl hydrocarbon hydroxylase (AHH) induction and with different levels and/or affinity for a specific cytosolic binding protein (“receptor”) were used to investigate the immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Humoral antibody production was strongly inhibited in $\text{C57B1}\text{6}$ and $\text{C3H}\text{HeN}$ mice (more susceptible strains) with very low, single doses of TCDD (1.2 μg/kg), while other strains ($\text{DBA}\text{2}$ and AKR) required higher doses (at least 6 μg/kg) to be partially suppressed. Longer exposure (8 weeks) did not increase the sensitivity of $\text{DBA}\text{2}$ mice. A good correlation between the degree of enzyme inducibility and immunosuppression was observed in studies with B6D2F1 mice and backcrosses. Similar results were obtained with 2,3,7,8-tetrachlorodibenzo-furan (TCDF), the most powerful competitor for TCDD “receptor” in vitro and in vivo. TCDD immnotoxic effects appeared to be associated with the presence of a specific cytosolic binding protein which mediates AHH induction.     

De novo HCV infection among dialysis patients: a prospective study by HCV core antigen ELISA assay

BACKGROUND: Dialysis patients remain a high-risk group for hepatitis C virus infection. The current diagnosis of hepatitis C virus in dialysis patients includes serological measurement of anti-hepatitis C virus antibody; however, nucleic acid amplification technology for assessing hepatitis C virus viraemia is commonly used in other populations. An enzyme-linked immunosorbent assay test for detecting antibody to hepatitis C nucleocapsid core antigen (hepatitis C virus core antigen) in human serum has been recently developed (hepatitis C virus Core Antigen enzyme-linked immunosorbent assay test). It is conceived for screening of donor blood products to significantly reduce the 'serologic window' occurring before seroconversion during acute hepatitis C virus. AIM AND METHODS: A cohort (n = 72) of patients on maintenance haemodialysis in a single unit in the years 2000-2003 was included. Study patients were tested monthly by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay in a prospective, clinical trial. Routine results obtained by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay test were confirmed by assessing hepatitis C virus viraemia by branched-chain DNA (bDNA) signal amplification assay. RESULTS: De novo hepatitis C virus infection was identified in three patients during the study period; the hepatitis C virus incidence was 1.38% (95% confidence intervals, 1.31-4.09) per year. In each patient, hepatitis C virus core antigen testing allowed the serological identification of acute hepatitis C virus before anti-hepatitis C virus seroconversion. Hepatitis C virus RNA testing confirmed the results obtained by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay in all cases. The time from initial hepatitis C virus detection by hepatitis C virus Core Antigen Assay and anti-hepatitis C virus seroconversion was not greater than four weeks. Two (67%) of three patients with de novo hepatitis C virus acquisition were HBsAg negative; both these patients underwent an initial phase of hepatitis C virus viraemia that was associated with an increase in alanine aminotransferase activity and preceded the seroconversion to anti-hepatitis C virus antibody. Nosocomial transmission of hepatitis C virus between haemodialysis patients was implicated in at least two (67%) of these three patients. CONCLUSIONS: Serological testing for hepatitis C virus core antigen can identify acute hepatitis C virus infection before anti-hepatitis C virus seroconversion. The time from initial hepatitis C virus detection by hepatitis C virus core antigen assay and anti-hepatitis C virus seroconversion was not >4 weeks. De novo acquisition of hepatitis C virus in haemodialysis was associated with a rise in alanine aminotransferase levels. Hepatitis C virus core antigen enzyme-linked immunosorbent assay test results can be obtained in routine laboratories without the need of special equipment or training. Hepatitis C virus core antigen testing among anti-hepatitis C virus negative patients on maintenance dialysis is suggested in order to early assess de novo hepatitis C virus within dialysis units.     

Increased QT dispersion: a negative prognostic finding in chronic obstructive pulmonary disease

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a highly prevalent syndrome, deeply affecting the cardiovascular system as well as the lungs. We investigated the prognostic role of the QT interval and QT dispersion (QTD) in predicting all-cause, respiratory and cardiovascular mortality in COPD, and the relationship between these electrocardiographic parameters and pulmonary function in a prospective longitudinal study. METHODS: We studied 246 COPD patients without significant co-morbidities, with a mild to moderate functional impairment, admitted to the Department of Internal Medicine from January 1995 to December 2001, performing a 5-year mean follow-up (5-116 months) up to August 2004. After clinical stabilisation, an electrocardiogram and functional respiratory tests were obtained, allowing measurement of the QT interval and QTD, forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), inspiratory capacity, FEV1/FVC ratio, partial oxygen pressure and partial carbon dioxide pressure in arterial blood. RESULTS: At the end of the follow-up period, 81 patients were dead, 165 still alive; 36 died because of respiratory causes, 23 because of cardio-cerebrovascular events, 21 because of cancer (mainly lung cancer). A significant high incidence of sudden cardiac death was observed. QTD and QTcD showed a significant relationship with respiratory functional parameters. Maximal QT interval, QTcD and QTD appear to be independent predictors of all-cause, cardiovascular and respiratory mortality (relative risk 1.94, 3.22, 2.88, respectively). Age > 65 years, partial oxygen pressure < 60 mmHg and inspiratory capacity < 80% of the predicted value were the only other independent predictive parameters. CONCLUSIONS: Maximal QT interval, QTD and QTcD are independent predictors of mortality. A significant incidence of cardiac sudden death was observed. These findings suggest the need for a global and multidisciplinary risk assessment in COPD patients. Intriguing relationships between the QTD and functional respiratory parameters were also observed.     

Use of systemic cyclosporin A in a case of severe Toxocara uveitis

The report describes the case of an adult patient presenting a severe, serologically proven, Toxocara endophthalmitis, unresponsive to the common surgical and medical approach (vitrectomy, anti-parasitic treatment followed by high-dose corticosteroids). The association of oral cyclosporin A to a lower dose of prednisone was successful in achieving a long-term control of the ocular inflammation without systemic side effects.     

Assessment of anti-prothrombin antibodies in thrombosis complicating inflammatory bowel diseases

Purpose

In inflammatory bowel diseases (IBD), risk of thrombosis and production of antibodies are increased. In autoimmune and inflammatory disorders, a role of anti-prothrombin (aPT) antibodies in developing thrombosis has been hypothesised. The aim of the study is to evaluate the prevalence of aPT antibodies in IBD patients, with and without thrombosis.

Methods

Thirty-three IBD patients with thrombosis, 33 IBD patients without thrombosis matched for sex, age, diagnosis and disease activity and 66 sex- and age-matched healthy controls were enrolled. Thrombosis was considered recent when blood sample was obtained within 3 months from the event.

Results

Prevalence of aPT antibodies in thrombotic IBD patients (3/33, 9.1 %), non-thrombotic IBD patients (4/33, 12.1 %) and in healthy subjects (3/66, 4.5 %) did not result significantly different (p?=?0.377). The prevalence of aPT antibodies was more frequent in ulcerative colitis (6/32, 18.7 %) than in Crohn’s disease (1/34, 2.9 %) and healthy controls (p?=?0.022). Among thrombotic IBD patients, the prevalence of aPT antibodies was higher in those with recent (2/9, 22.2 %) than in those with previous thrombosis (1/24, 4.2 %) (p?=?0.103). All thrombotic IBD patients with aPT antibodies were affected by ulcerative colitis with previous history of deep venous thrombosis.

Conclusions

aPT antibodies do not appear to play a relevant role in thrombosis complicating IBD course. A possible association in ulcerative colitis patients with DVT could not be excluded.