Quantitative assessment of histological changes in chronic gastritis after eradication of Helicobacter pylori.

AIMS: To evaluate the effect of 10 day triple treatment on H pylori eradication and associated gastritis. METHODS: Fifty patients with H pylori positive non-ulcer dyspepsia were treated for 10 days with amoxicillin, tinidazole, and bismuth salts. Histological examination of the antral mucosa was performed before (T0), six weeks (T1), and six months (T2) after treatment. The new Sydney classification of gastritis was used, using a score from 0 to 3 to grade degree of inflammation, atrophy, activity (intraepithelial or lamina propria damage) and H pylori. RESULTS: At T0 all patients had chronic active gastritis. Lymphoid follicules were present in 12 cases. At T1 33 patients were H pylori negative: the score showed a decrease of activity (from 2.5 to 0.54). The result was confirmed at T2 (mean score 0.22). Inflammation decreased from 1.8 to 1.4 at T2. Only one case of follicular gastritis was observed. In H pylori positive patients the scores did not show significant modifications. CONCLUSIONS: Ten day triple treatment is effective in eradicating H pylori in 69% of cases, causing a decrease of the total score for gastritis. Activity, defined by polymorph infiltration, was promptly reduced when H pylori was eradicated. There was a trend to a reduction in inflammation, but atrophy was irreversible.     

Cytotoxic activity of human lymphocytes against differentiated intestinal tumour cell lines.

The natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activity of human peripheral blood lymphocytes (PBL) against various human tumour cell lines from intestinal origin (WIDR, HT29, Caco-2) has been investigated. The differentiated Caco-2 cells were then used as a model to investigate the cytotoxic activity against enterocyte-like target cells. Caco-2 were seeded on polycarbonate filters and maintained in culture for at least 15 days to allow the differentiation and formation of tight junctions. The integrity of tight junctions was assayed by measuring [3H]mannitol flux from apical to basolateral compartment. Cytotoxic analysis showed that both differentiated and undifferentiated Caco-2 cells were similarly susceptible to NK and LAK activity. The capacity of cytotoxic lymphocytes to kill enterocyte-like cells with intact junctional complex may suggest a direct role of cytotoxic lymphocytes in causing intestinal lesions under inflammatory conditions.     

Modifications of the hydrophilicity of heterocyclic methacrylate copolymers for protein release

A series of copolymers comprising ethyl methacrylate (EM) and tetrahydrofurfuryl methacrylate (THFMA) gelled with either THFMA monomer or hydroxyethyl methacrylate (HEMA) monomer have been developed. In this paper, we examine the water uptake characteristics of the polymer systems and address the possibility of increasing the hydrophilicity of the systems by changing the ratios of the copolymers. We have investigated whether protein release from the polymers is related to the composition of the polymer systems. More protein was released from the polymers gelled with the more hydrophilic monomer (HEMA) than with THFMA. This was consistent with the calculated diffusion coefficients, which were 10 times greater for the polymers gelled with HEMA than those gelled with THFMA. Interestingly, the water uptake and protein release profiles were not dependent on the ratio of EM and THFMA in the copolymers. This is probably due to the conflicting roles of THFMA in the copolymer; it is both the more hydrophilic component as well as a cross-linking agent. In addition, it would appear that the structural and surface topography of these polymers had more significant effects on protein release than copolymer composition.     

Hepatitis C virus recurrence after liver transplantation:A 10-year evaluation

AIM: To evaluate the predictors of 10-year survival of patients with hepatitis C recurrence. METHODS: Data from 358 patients transplanted between 1989 and 2010 in two Italian transplant centers and with evidence of hepatitis C recurrence were analyzed. A χ2, Fisher's exact test and Kruskal Wallis' test were used for categorical and continuous variables, respectively. Survival analysis was performed at 10 years after transplant using the Kaplan-Meier method, and a log-rank test was used to compare groups. A P level less than 0.05 was considered significant for all tests. Multivariate analysis of the predictive role of different variables on 10-year survival was performed by a stepwise Cox logistic regression.RESULTS: The ten-year survival of the entire population was 61.2%. Five groups of patients were identified according to the virological response or lack of a response to antiviral treatment and, among those who were not treated, according to the clinical status(mild hepatitis C recurrence, "too sick to be treated" and patients with comorbidities contraindicating the treatment). While the 10-year survival of treated and untreated patients was not different(59.1% vs 64.7%, P = 0.192), patients with a sustained virological response had a higher 10-year survival rate than both the "non-responders"(84.7% vs 39.8%, P 0.0001) and too sick to be treated(84.7% vs 0%, P 0.0001). Sustained virological responders had a survival rate comparable to patients untreated with mild recurrence(84.7% vs 89.3%). A sustained virological response and young donor age were independent predictors of 10-year survival. CONCLUSION: Sustained virological response significantly increased long-term survival. Awaiting the interferon-free regimen global availability, antiviral treatment might be questionable in selected subjects with mild hepatitis C recurrence.     

Dermoscopy and Onychomycosis: guided nail abrasion for mycological samples

Mycological examination is still the cornerstone for the diagnosis ofonychomycosis for many dermatologists, but sampling technique interferes onits sensitivity and specificity. Nail abrasion may be used to reach themost proximal part of the lesion and can be easily accomplished with anelectric abrasor. We suggest nail plate dermoscopy to identify the bestlocation for localized abrasion to obtain adequate samples for mycologicalexamination.     

Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety

Background and aimTo address the paucity of randomized clinical studies assessing ginseng on long-term outcomes in type 2 diabetes, we assessed the clinical antidiabetic efficacy and safety of 12 weeks of supplementation with a Korean red ginseng (KRG) preparation, dose, and mode of administration, selected from an acute, clinical, screening model.Methods and resultsNineteen participants with well-controlled type 2 diabetes (sex: 11 M:8 F, age: 64 ± 2 years, BMI: 28.9 ± 1.4 kg/m², HbA_1c: 6.5%) completed the study. Using a double-blind, randomized, crossover design, each participant received the selected KRG preparation (rootlets) and placebo at the selected dose (2 g/meal = 6 g/day) and mode of administration (preprandial oral agent [−40 min]) for 12 weeks as an adjunct to their usual anti-diabetic therapy (diet and/or medications). Outcomes included measures of efficacy (HbA_1c and fasting- and 75-g oral glucose tolerance test [OGTT]-plasma glucose [PG], plasma insulin [PI], and insulin sensitivity index [ISI] indices); safety (liver, kidney, haemostatic, and blood-pressure function); and compliance (returned capsules, diet-records, and body-weight).There was no change in the primary endpoint, HbA_1c. The participants, however, remained well-controlled (HbA_1c = 6.5%) throughout. The selected KRG treatment also decreased 75g-OGTT-PG indices by 8–11% and fasting-PI and 75g-OGTT-PI indices by 33–38% and increased fasting-ISI (homeostasis model assessment [HOMA]) and 75g-OGTT-ISI by 33%, compared with placebo (P < 0.05). Safety and compliance outcomes remained unchanged.ConclusionsAlthough clinical efficacy, as assessed by HbA_1c, was not demonstrated, 12 weeks of supplementation with the selected KRG treatment maintained good glycemic control and improved PG and PI regulation safely beyond usual therapy in people with well-controlled type 2 diabetes. Further investigation with similarly selected KRG treatments may yield clinical efficacy.     

Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1

The calcium activated K⁺ channel KCa3.1 plays an important role in T lymphocyte Ca²⁺ signaling by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca²⁺ influx. We previously showed that nucleoside diphosphate kinase beta (NDPK-B), a mammalian histidine kinase, is required for KCa3.1 channel activation in human CD4 T lymphocytes. We now show that the mammalian protein histidine phosphatase (PHPT-1) directly binds and inhibits KCa3.1 by dephosphorylating histidine 358 on KCa3.1. Overexpression of wild-type, but not a phosphatase dead, PHPT-1 inhibited KCa3.1 channel activity. Decreased expression of PHPT-1 by siRNA in human CD4 T cells resulted in an increase in KCa3.1 channel activity and increased Ca²⁺ influx and proliferation after T cell receptor (TCR) activation, indicating that endogenous PHPT-1 functions to negatively regulate CD4 T cells. Our findings provide a previously unrecognized example of a mammalian histidine phosphatase negatively regulating TCR signaling and are one of the few examples of histidine phosphorylation/dephosphorylation influencing a biological process in mammals.     

HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells

HIV infection is characterized by a brisk immune activation that plays an important role in the CD4 depletion and immune dysfunction of patients with AIDS. The mechanism underlying this activation is poorly understood. In the current study, we tested the hypothesis that this activation is the net product of two distinct pathways: the inflammatory response to HIV infection and the homeostatic response to CD4 T cell depletion. Using ex vivo BrdU incorporation of PBMCs from 284 patients with different stages of HIV infection, we found that CD4 proliferation was better predicted by the combination of CD4 depletion and HIV viral load (R² = 0.375, P < 0.001) than by either parameter alone (CD4 T cell counts, R² = 0.202, P < 0.001; HIV viremia, R² = 0.302, P < 0.001). Interestingly, CD8 T cell proliferation could be predicted by HIV RNA levels alone (R² = 0.334, P < 0.001) and this predictive value increased only slightly (R² = 0.346, P < 0.001) when CD4 T cell depletion was taken into account. Consistent with the hypothesis that CD4 T cell proliferation is driven by IL-7 as a homeostatic response to CD4 T cell depletion, levels of phosphorylated STAT-5 were found to be elevated in naive subsets of CD4 and CD8 T cells from patients with HIV infection and in the central memory subset of CD4 T cells. Taken together these data demonstrate that at least two different pathways lead to immune activation of T cells in patients with HIV infection and these pathways differentially influence CD4 and CD8 T cell subsets.     

Use of dissecting sealer may affect the early outcome in patients submitted to hepatic resection

Background. Many technological devices have been used to avoid intraoperative bleeding during hepatic parenchymal transection and to avoid morbidity and mortality, but until now none is complete. The aim of this work is to prospectively analyze hepatic resection patients treated with a water-cooled high frequency monopolar device in order to evaluate its effectiveness. Patients and methods. All consecutive patients who underwent liver resection by use of this device, between January 2003 until December 2007, were analyzed prospectively. The following variables were considered: age, sex, kind of disease, kind of liver resection, number of major/minor resections, total operative time and transection time, number and time of clamping, blood loss, time of hospitalization, morbidity, and mortality. Results. Between January 2003 and December 2007, 26 patients were analyzed prospectively (69% women, 31% men). Ages ranged from 18 to 84 years. Sixty-five percent of patients had a malignant disease; 35%, a benign disease. The procedures performed were two major hepatectomies (7.6%) and 24 minor hepatectomies (92.4%). Hepatic transection was performed in 35 to 150 min. Total operative time range was 120–480 min. The average blood loss was 325 ml (range 50–600 ml). The mean postoperative stays were nine days for all the patient and six days for non-cirrhotic patients. Conclusion. The water-cooled high frequency monopolar device is useful for reducing ischemia–reperfusion damage due to the Pringle maneuver and for reducing the risk of morbidity. However, the Kelly forceps remains the only inexpensive instrument really essential for liver surgery.