Virus dynamics and immune responses during treatment in patients coinfected with hepatitis C and HIV

Mathematical modeling of the biological effect of interferon on virus decay permits the quantification of the efficacy (epsilon) of blocking virion production in different patient populations. The viral dynamic and immunologic responses of hepatitis C virus (HCV) infection to daily interferon therapy were characterized in twelve patients co-infected with human immunodeficiency virus (HIV). Three out of the twelve patients (25%) achieved an early viral response, a two-log reduction in HCV RNA by week 12. The mean epsilon of IFN-alpha in blocking HCV and HIV production were 72% and 74%, respectively. For HCV epsilon was highest (97%) in the one patient who had a sustained viral response, while it was reduced in the other two patients (68% and 77%). Baseline HCV RNA and the number of CD3+CD56+16+ cells were inversely related (r = -0.89, p = 0.03), and baseline HCV-specific immune responses were significantly higher in the three patients with 2-log viral load reductions. These data suggest that: 1) interferon efficacy at blocking virion production is correlated with treatment outcome in HIV/HCV co-infected patients, 2) that immunodeficient patients can respond to standard IFN-alpha, 3) that both innate and adaptive immune responses may be important determinants of HCV RNA decline in response to interferon.     

The interplay between the statistical correlations of gamma-ray emission probabilities and efficiency calibration.

The procedure to determine the statistical correlations between gamma-ray intensities is described here, as well as that required to take these correlations into account. The advantages of using branching-ratios and feeding fractions instead of gamma-ray intensities in the gamma-ray standards are discussed.     

Galactose-specific adhesin and cytotoxicity of Entamoeba histolytica

We examined the molecular mechanisms of the cytotoxicity of Entamoeba histolytica, using the loss of transepithelial electrical resistance (TER) of monolayers of Madin-Darby canine-kidney (MDCK) cells on their incubation with axenic trophozoites of the HM1-IMSS strain. Such loss of TER occurs very early (in 2–5 min) and is caused by the opening of tight junctions and the detachment of cells. We used specific inhibitors for three of the four molecules currently accepted as being responsible for cytotoxicity: galactose-specific adhesin(s), phospholipase A, and cysteine proteinases. We also used inhibitors of calcium channels. Axenic trophozoites of E. histolytica strain HM1-IMSS were preincubated with the different inhibitors for 1 h prior to their coincubation with MDCK-cell monolayers. The only inhibitor that effectively blocked the loss of TER caused by the parasite was galactose. We suggest that in this experimental model, galactose-specific adhesin(s) are essential for amebic cytotoxicity. Received: 8 June 1999 / Accepted: 21 July 1999     

Successful treatment in the patient with serum sodium level greater than 200 mEq/L

Hypernatremia developing in nonhospitalized adults is predominantly a disease of the elderly and mentally handicapped patients, possibly revealing inadequate nursing care of these patients. It has long been claimed that the duration of hypernatremia and its rate of correction are correlated with improvement in patients' neurologic status. Since there are only a handful of cases with serum sodium levels greater than 200 mEq/L until recently, it is not clear at what rate plasma sodium concentration can be safely normalized in severe hypernatremic patients. We report a case of severe hypernatremia with survival. This patient underwent rapid correction of serum sodium concentration during the management of this metabolic derangement using isotonic solution.     

Immunosuppressive activity of proteases in cervical carcinoma

OBJECTIVE: The host immune response is essential for restraining both HPV infections and HPV-related cervical cancer. We previously reported a direct correlation between proteolytic activity and malignant progression from precursor lesions to invasive cervical carcinoma. The present study was undertaken to investigate whether proteinases from cervical carcinoma extracts and representative purified proteinases involved in tumor progression could regulate lymphocyte proliferation to phytohemagglutinin (PHA) mitogen. METHODS: Extracts were prepared from tissue samples obtained from patients with invasive cervical squamous carcinoma, squamous intra-epithelial lesions or women with normal cervix. Lymphocytes obtained from a single healthy donor were pre-incubated with one of these extracts in the presence or absence of proteinase inhibitors, and stimulated with PHA during 72 h. The proliferative response was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method (re-validated with thymidine uptake). RESULTS: Lymphocyte proliferation was significantly decreased by cervical carcinoma extracts, while only slightly decreased by squamous intra-epithelial lesions or normal extracts. Inhibitor assays indicated that proteinases from cervical carcinoma were responsible for 53.30% of total suppressive activity. We found that purified enzymes such as trypsin, cathepsin B, uPA and type IV collagenase suppressed the proliferative response in a dose-dependent fashion. CONCLUSIONS: Our data suggest that in addition to the classic role in tumor invasion, proteases could represent an immune evasion mechanism in cervical carcinoma.     

Interactions between the -514C->T polymorphism of the hepatic lipase gene and lifestyle factors in relation to HDL concentrations among US diabetic men

BACKGROUND: Low plasma HDL-cholesterol concentrations are a hallmark of diabetic dyslipidemia. A common polymorphism (-514C-->T) of the hepatic lipase gene (LIPC), which accounts for up to 30% of the variation in hepatic lipase activity, has been associated with low hepatic lipase activity and high HDL-cholesterol concentrations. OBJECTIVE: We examined the association between this polymorphism and plasma HDL-cholesterol concentrations and evaluated whether this association was modified by adiposity and dietary fat intake. DESIGN: We followed men aged 40-75 y who participated in the Health Professionals Follow-Up Study in 1986. Among 18 159 men who returned blood samples by 1994, 780 had confirmed type 2 diabetes at blood drawing or during follow-up to 1998 and were free of cardiovascular disease at blood drawing. RESULTS: After adjustment for age, smoking, alcohol consumption, fasting status, glycated hemoglobin concentration, physical activity, and body mass index, HDL-cholesterol concentrations were significantly higher in men with the C/T or T/T genotype than in those with the C/C genotype (adjusted x: 40.9 and 38.8 mg/dL, respectively; P = 0.01). We observed significant LIPC -514 polymorphism x body mass index and LIPC -514 polymorphism x saturated fat intake interactions for HDL-cholesterol concentrations (P = 0.003 for both). The T allele was associated with higher HDL-cholesterol concentrations only in men who were not overweight or who had higher saturated fat intake. CONCLUSION: Our study suggests that the effects of -514C-->T of the LIPC gene on HDL concentrations were modified by saturated fat intake and obesity.     

Anti-oxidants reduce the acute adverse effects of residual oil fly ash on the frog palate mucociliary epithelium

There is evidence indicating that oxidants play a pivotal role in determining air pollution-dependent lung injury. In the present study we explored the role of oxidants present in ambient particles in causing damage to the mucociliary epithelium. We explored the protective effects of pretreatment with three substances (n-propyl gallate, DL-alpha-tocopherol acetate, and EDTA) on the frog palate exposed to residual oil fly ash (ROFA). The parameters analyzed were mucociliary transport (MCT) and ciliary beating frequency (CBF) after 0, 10, 20, 30, 60, and 120 min of exposure. MCT was decreased significantly by ROFA (P < 0.001), with a significant interaction effect (P = 0.02) between the duration of exposure and treatment with antioxidants. The inhibitory effects on MCT of the substances tested were significantly different (P = 0.002); vitamin E was similar to control (Ringer) and different from all other groups. CBF showed no significant effect of duration of exposure (P = 0.465), but a significant interaction between duration of exposure and treatments was observed (P = 0.011). Significant differences were detected among treatments (P < 0.001), with ROFA and n-propyl gallate at concentrations of 50 microM presenting a short-lived increase in CBF, which was not observed in the remaining groups. The results showed that both MCT and CBF were affected within a short period (100 min) of exposure to ROFA and that the presence of antioxidant substances, such as vitamin E (4 mg/mL) and n-propyl gallate (300 microM), protected against the mucociliary impairment induced by ROFA on the frog palate.     

Situation of endemic pemphigus foliaceus in Mato Grosso do Sul, Brazil, 1990-1999

307 cases were examined to characterize epidemiological aspects of endemic pemphigus foliaceus. The disease was predominantly identified in rural workers between 10 and 42 years old. Incidence was higher in the December, January, February, March and May (average: 30.7 cases/year). Our findings identified a corridor, coinciding with the state watershed.