IL-4 in vitro production is upregulated in Alzheimer's disease patients treated with acetylcholinesterase inhibitors

Cytokines appear to be involved in the pathogenesis of Alzheimer's Disease (AD). Their modulation by treatment has been investigated only in a few studies. The aim of our study was to evaluate the effect of acetylcholinesterase inhibitors (AChEI) on Interleukin-4 (IL-4) production in AD patients. IL-4 levels were measured by ELISA on peripheral blood mononuclear cell cultures in the presence or absence of Concanavalin A or Phytohaemagglutinin. Linear regression analysis shows that patients who have been treated, have higher levels of IL-4 independently from age, gender and comorbidity. The increased production of IL-4 in AChEI treated patients might represent an additional mechanism through which AChEI act on AD progression.     

Blood pressure and contributing factors in inhabitants of Estonia: 15-year trends

AIM: To study the 15-year trends of blood pressure (BP) values in inhabitants of Estonia, three independent random samples of the population of Tallinn aged 20-54 years were examined in 1984/86, 1992/94 and in 1999/2001. RESULTS: A substantial decrease in BP values was observed in the population of Tallinn by the early 1990s; it continued to a smaller extent during the late 1990s. An improvement in some factors contributing to the development of arterial hypertension: decrease in body mass index (BMI) mean values and positive dietary changes were observed during this period. In the late 1990s, the changes in contributing factors were less synonymous. In men, the BMI mean values, intake of calories and alcohol increased but smoking rates dropped substantially; physical activity and P/S ratio increased. In women, the BMI mean values, which decreased considerably between the 1980s and early 1990s, remained stable, as well as smoking rates; physical activity increased and positive changes in nutrition were more pronounced than in men. The BP values also decreased in women to a greater extent than in men. CONCLUSION: Favourable trends in BP and contributing factors were found in Estonia during the transition period accompanied by a cardiovascular disease mortality decline since 1995.     

Prevalence of rheumatoid arthritis in Tucumán,Argentina

OBJECTIVE: To ascertain the prevalence of rheumatoid arthritis (RA) in Tucumán, Argentina. METHODS: The study was conducted between January 1, 1998, and December 31, 1999, in Tucumán province in northwest Argentina. Outpatient and hospitalization medical records for all patients with RA aged > or = 16 years were reviewed. Diagnosis was by 1987 American College of Rheumatology (ACR) criteria for RA and the population data were based on the 1991 national census. Prevalence rates, with 95% CI, were calculated using the number of San Miguel de Tucumán residents who fulfilled the 1987 ACR criteria for RA as numerator, and the city population aged > or = 16 as denominator. Crude and age-specific prevalence rates were calculated as number of cases/1,000 inhabitants. RESULTS: We identified 695 cases of RA. Sex-specific and overall prevalence rates (per 1,000) were 1.97 (95% CI 1.8-2) for all, 0.6 (95% CI 0.49-0.73) for men, 3.2 (95% CI 2.9-3.5) for women. CONCLUSION: Prevalence of RA is low in residents of Tucumán, Argentina, and comparable with rates observed in epidemiological surveys from Southern European countries.     

A pilot study of capsule endoscopy after a standard meal for the detection and grading of oesophageal varices in cirrhotic patients

Background

Capsule endoscopy has been proposed as an alternative to fibreoptic endoscopy for oesophageal varices evaluation in cirrhotics. However, it shows only moderate sensitivity compared to fibreoptic endoscopy.

Aim

To compare post-meal capsule endoscopy to fibreoptic endoscopy, based on the hypothesis that meal-induced increase of portal pressure can enhance its sensitivity.

Methods

Twenty-five patients were submitted to fibreoptic endoscopy and, after a standard meal, capsule endoscopy.

Results

Post-meal capsule endoscopy detected varices in the 18 patients in whom fibreoptic endoscopy detected varices plus 3 more subjects (sensitivity 100%, specificity 70%); large varices in the 4 patients in whom fibreoptic endoscopy graded varices as large, plus 5 more subjects; red markers in the 5 patients in whom fibreoptic endoscopy detected red markers, plus 3 more subjects. High-risk varices were identified in 11 patients by post-meal capsule endoscopy and in 10 by fibreoptic endoscopy (sensitivity 100%, specificity 93.8%).

Conclusions

Post-meal capsule endoscopy identified more varices, large varices and red markers than fibreoptic endoscopy. The two methods detected similar proportions of high-risk varices. These data suggest that a standard meal can enhance the sensitivity of capsule endoscopy in the detection and grading of oesophageal varices in cirrhotics.     

Gadoxetic acid magnetic-enhanced resonance imaging in the diagnosis of cholangiocarcinoma

The use of liver magnetic resonance imaging is increasing thanks to its multiparametric sequences that allow a better tissue characterization, and the use of hepatobiliary contrast agents. This review aims to evaluate gadoxetic acid enhanced magnetic resonance imaging in the diagnosis and staging of cholangiocarcinoma and its different clinical and radiological classifications proposed in the literature. We also analyze the epidemiology, risk factors in correlation with clinical findings and laboratory data.     

Distinct roles of the photosystem II protein PsbS and zeaxanthin in the regulation of light harvesting in plants revealed by fluorescence lifetime snapshots

The photosystem II (PSII) protein PsbS and the enzyme violaxanthin deepoxidase (VDE) are known to influence the dynamics of energy-dependent quenching (qE), the component of nonphotochemical quenching (NPQ) that allows plants to respond to fast fluctuations in light intensity. Although the absence of PsbS and VDE has been shown to change the amount of quenching, there have not been any measurements that can detect whether the presence of these proteins alters the type of quenching that occurs. The chlorophyll fluorescence lifetime probes the excited-state chlorophyll relaxation dynamics and can be used to determine the amount of quenching as well as whether two different genotypes with the same amount of NPQ have similar dynamics of excited-state chlorophyll relaxation. We measured the fluorescence lifetimes on whole leaves of Arabidopsis thaliana throughout the induction and relaxation of NPQ for wild type and the qE mutants, npq4, which lacks PsbS; npq1, which lacks VDE and cannot convert violaxanthin to zeaxanthin; and npq1 npq4, which lacks both VDE and PsbS. These measurements show that although PsbS changes the amount of quenching and the rate at which quenching turns on, it does not affect the relaxation dynamics of excited chlorophyll during quenching. In addition, the data suggest that PsbS responds not only to ΔpH but also to the Δψ across the thylakoid membrane. In contrast, the presence of VDE, which is necessary for the accumulation of zeaxanthin, affects the excited-state chlorophyll relaxation dynamics.Plants regulate light harvesting by photosystem II (PSII) in response to changes in light intensity. One way that plants are able to regulate light harvesting is through turning on and off mechanisms that dissipate excess energy. This energy dissipation is assessed via nonphotochemical quenching (NPQ) measurements of chlorophyll fluorescence. Energy-dependent quenching (qE) is the NPQ process with the fastest kinetics. It turns on and off in seconds to minutes, allowing plants to respond to rapid fluctuations in light intensity, which is thought to reduce photodamage (1, 2).Illumination causes the formation of gradients of electrical potential (Δψ) and of proton concentration (ΔpH) across the thylakoid membrane. Although it has been suggested that Δψ may play a role in qE (3), only ΔpH is thought to trigger different proteins and enzymes to induce qE (4). The major known factors involved in induction of qE are the enzyme violaxanthin deepoxidase (VDE) (5) and the PSII protein PsbS (6). The mutant npq1, which lacks VDE and cannot convert violaxanthin to zeaxanthin, has a phenotype with lower qE compared with the wild type (7). Transient absorption measurements suggest that zeaxanthin may quench excited chlorophyll (8). The npq4 mutant, which lacks PsbS, shows no rapidly reversible quenching of chlorophyll fluorescence, suggesting that PsbS is required for qE in vivo (6). PsbS is pH sensitive (9) but is not thought to bind pigments, and thus is likely not the site of quenching (10). It has therefore been hypothesized that PsbS plays an indirect role in quenching, perhaps facilitating a rearrangement of proteins within the grana (11–13). In this paper, we examine the fluorescence lifetime of chlorophyll throughout the induction and relaxation of quenching in intact leaves with and without PsbS and zeaxanthin to examine whether PsbS and zeaxanthin change the type of quenching that occurs in plants.The amount and dynamics of qE are generally measured by changes in the chlorophyll fluorescence yield. One limitation of the chlorophyll fluorescence yield is that it can only inform on the amount of quenching, not on excited-state chlorophyll relaxation dynamics, which reflect how chlorophyll is quenched. Despite this issue, the amount of quenching is commonly used as a proxy for the type of quenching by separating components of quenching based on kinetics, mutants, and the effects of chemical inhibitors. By artificially increasing ΔpH in isolated chloroplasts from npq4, Johnson and Ruban (14, 15) have been able to increase the amount of quenching in npq4 plants to levels observed in wild type plants, suggesting that PsbS may catalyze qE. One potential complication with these studies is that the use of the chemical mediators of cyclic electron transport often necessitates studying isolated chloroplasts rather than intact leaves. In addition, the observation of equivalent amounts of quenching still does not prove that the type of quenching in npq4 is the same as in wild type.In contrast with fluorescence yield measurements, fluorescence lifetime measurements can be used to determine whether the relaxation dynamics of excited chlorophyll are modified by different mutations, informing on the role of a protein or molecule during quenching. The relaxation dynamics of excited chlorophyll during NPQ depends on many variables, including the distance to a quencher, the interactions between the orbitals of chlorophyll and the quencher, and the number of quenchers (16). The shape of the fluorescence lifetime decay curve can be used to determine whether two samples have similar excited chlorophyll relaxation dynamics. Our results show that, although the presence of PsbS does not alter excited chlorophyll relaxation dynamics, the absence of VDE does. These measurements are performed in intact leaves without any chemical treatments, and the data strongly suggest that PsbS plays a catalytic role in vivo.