A study of age-related IgE pathophysiological changes

The literature on immunosenescence has focused mainly on T cell impairment. However, it is well known that B function is also profoundly affected. In particular, several studies have shown age-related changes in immunoglobulin serum levels. Concerning allergic diseases, the incidence of onset of allergic symptoms, as well as their severity, seems to decrease with age. So, the decline of onset of allergic symptoms observed in ageing might result from a decrease of serum total IgE due to an unbalance of cytokines and soluble factors involved in its production. To gain insight into the mechanisms of age related incidence of onset of allergic symptoms, as well as their severity, in this study we have evaluated in a sample of young (12 females and 15 males, range 20-64 years) and old (42 females and 20, males range 70-93 years) individuals serum values of IgE and sCD23 and in vitro Type 2 cytokine production. Total serum IgE levels were quantified by CAP-system fluorescence enzyme immunoassay. Serum CD23 levels were measured by a sandwich enzyme-linked immunoassay. Enzyme immunoassay tests have been used to quantify IL-4, IL-10 and IL-13 on mitogen-stimulated cultures. Serum total IgE and sCD23 in the two groups of young and old subjects were not significantly different. No detectable levels of IL-4, IL-10 and IL-13 were observed in supernatants from unstimulated cultures in all the subjects tested. After 48 h stimulation with PHA, cytokine amounts became detectable in all subjects. However, the values of the cytokines under study were not significantly different between young and old subjects. In our study, we have not been able to show no impairment in the afferent (type 2 cytokine production) and in the central (serum IgE and sCD23 levels) branch of allergic responses. Previous studies have shown that the efferent branch, at least studied as basophil releasability and bronchial responsiveness, is not impaired in elderly. In conclusion, as suggested from the present and previous papers it is questionable whether there is sufficient information to validate the statement that the incidence of allergic diseases decreases with age.     

IL-10 and TNF-alpha polymorphisms in a sample of Sicilian patients affected by tuberculosis: implication for ageing and life span expectancy

Human longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses, in particular cytokine gene polymorphisms. In fact, modification of cytokine network is a constant report in studies on age related modification of immune response. Moreover cytokine polymorphisms studies are indicating their involvement in the reshaping of cytokines network as an integral part of the scenario related to a successful ageing. A particular role might be attributed to the influence of cytokine polymorphisms on the efficiency of immune response against infectious diseases that have been the principal selection in oldest old. Here are reported data on the evaluation of the frequency of the functional polymorphisms at genes coding for TNF-alpha (-308G-->A) and IL-10 (-1082G-->A), analysed by ARMS-PCR, in a group of Sicilian patients affected by chronic lung tuberculosis (TBC) compared to that from a group of healthy individuals living in the same region. Data obtained demonstrated a reduction of -308GG TNF homozygous individuals in TBC affected subject group. In the same group a reduction of IL-10 -1082A/* carriers was found. Our results seem to suggest that multiple genetic traits may affect the capacity to cope with an infectious agents and this might predispose to an overt disease. Moreover these data are in agreement with previous reports suggesting that a balanced interaction among pro- and anti-inflammatory molecules it is a key point for conditioning the life span expectancy.     

Antioxidant treatment with carnitines is effective in infertile patients with prostatovesiculoepididymitis and elevated seminal leukocyte concentrations after treatment with nonsteroidal anti-inflammatory compounds

OBJECTIVE: To evaluate whether the association of antioxidants and anti-inflammatory compounds may be beneficial in treatment of patients with abacterial prostatovesiculoepididymitis (PVE) and elevated seminal leukocyte concentrations. DESIGN: Open, prospective, random study. SETTING: Academic research environment. PATIENT(S): Ninety-eight patients with PVE who had increased seminal leukocyte concentrations (>1 x 10(6) cells/mL).Carnitines (group A; n = 30) or nonsteroidal anti-inflammatory drugs (group B; n = 16) for 4 months; nonsteroidal anti-inflammatory drugs for 2 months, followed by treatment with carnitines for 2 months (group C; n = 26); or nonsteroidal anti-inflammatory treatment given concomitantly with carnitines (group D; n = 26) for 4 months. MAIN OUTCOME MEASURE(S): Semen variables, production of reactive oxygen species, and pregnancy outcome were evaluated before and after treatment and following a 3-month washout period. RESULT(S): Patients in group C had the highest reduction in production of reactive oxygen species associated with increased sperm motility and viability. Groups B and D experienced intermediate effects, and group A experienced the least effect. CONCLUSION(S): Antioxidant treatment with carnitines is effective in patients with abacterial PVE and increased seminal leukocyte concentrations if these patients have been pretreated with nonsteroidal anti-inflammatory drugs.     

Magnetic resonance cholangiopancreatography in primary sclerosing cholangitis in children

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown aetiology. Diagnosis is based on clinical and laboratory data in conjunction with imaging of the biliary tree using endoscopic retrograde cholangiopancreatography (ERCP). OBJECTIVE:: To evaluate the clinical usefulness of MR cholangiopancreatography (MRCP) in the diagnosis of PSC in children. MATERIALS AND METHODS: Twenty-one children with clinical and laboratory suspicion of PSC were enrolled. MRCP was performed using a superconductive system with a phased-array coil. Rapid acquisition with relaxation enhancement (RARE) T2-weighted and half-Fourier single-shot turbo-spin-echo (HASTE) sequences were used. The distribution and extent of biliary tree changes were evaluated and classified according to Majoie's classification. A comparison between MRCP and ERCP was performed blind in all cases to evaluate the usefulness of MRI. RESULTS: In 13 cases (62%), MRCP showed abnormalities of the biliary tree which were considered positive for PSC, while in 8 cases there were no signs of PSC. Both MRCP and ERCP correctly identified changes in 13 cases and excluded abnormalities in 5. MRCP had a sensitivity of 81%, specificity of 100%, negative predictive value of 62%, positive predictive value of 100% and an accuracy of 85%. CONCLUSIONS: MRCP can be proposed as the preliminary non-invasive imaging modality for the diagnosis of PSC in children.     

Association between social class and food consumption in the Italian EPIC population

AIMS AND BACKGROUND: The objectives of the present study were to validate the social stratification variables adopted by the European Prospective Investigation into Cancer and Nutrition (EPIC) by comparing them with data from another independent source and to evaluate the geographic and social distribution of eating habits in the Italian EPIC population. METHODS: The validation of the socioeconomic data collected by the EPIC study was performed with the Turin Longitudinal Study as gold standard and using Cohen's kappa statistics to evaluate the concordance between the studies. We then analyzed food groups based on the consumption of meat and fats, carbohydrates, sweets and alcohol, and on an index of the Mediterranean diet. The standardized scores for each food group were subdivided into quartiles, which were used to compare persons in the extreme quartiles. Analysis of the differences in eating habits by center and by educational level was conducted separately for men and women, calculating the prevalence rate ratios and controlling for age, area of birth and body mass index. RESULTS: Concordance between the two data sources was high for educational level and low for the social-class index based on occupation. Most of the eating habits considered to be potentially harmful (high consumption of meat or fats and alcohol and low consumption of olive oil and fish) were more frequent in Northern than in Southern Italy. These habits were inversely correlated with educational level, especially in the South. CONCLUSIONS: A significant improvement in health could be obtained in the Italian population if culturally and socioeconomically disadvantaged individuals were to abandon their diet rich in meat and fats, as done by more advantaged persons. In the absence of preventive interventions specifically addressed to disadvantaged groups, it is likely that social inequalities in mortality and morbidity will increase.     

Biomarkers of dietary intake of micronutrients modulate DNA adduct levels in healthy adults

DNA adducts, a reliable indicator of internal dose exposure to genotoxic agents and, possibly, of cancer risk, have been shown to be modulated by diet, particularly by the consumption of fresh fruit and vegetables, and by the intake of antioxidants (Palli et al., 2000, Int. J. Cancer, 87, 444-451). We have therefore investigated the association between DNA adducts in peripheral leukocytes and plasma levels of selected micronutrients, also taking into account the role of metabolic polymorphisms and smoking history, in a large independent random sample of volunteers enrolled in the prospective study EPIC-Italy (approximately 110 subjects from each of the three main geographical study areas, Northern, Central and Southern Italy). DNA adducts and five polymorphic metabolic genotypes were determined in peripheral leukocytes using the (32)P-post-labelling technique and PCR methods. Plasma levels of six carotenoids, retinol and alpha- and gamma-tocopherol were determined in the same blood sample. Among 331 subjects, 78.3% had detectable levels of DNA adducts (mean 7.46 +/- 0.48 per 10(9) nucleotides). Vitamin supplementation was reported by only a few subjects (3.9%). Strong inverse associations emerged between levels of DNA adducts and plasma retinol (P = 0.02), alpha-tocopherol (P = 0.04) and gamma-tocopherol (P = 0.03), but not carotenoids (except a borderline inverse association with beta-carotene, P = 0.08). An inverse significant association with plasma levels of retinol and gamma-tocopherol persisted in the subgroup of non-smokers, whereas a negative association with alpha-tocopherol emerged only in smokers. DNA adduct levels did not show any significant variation according to analyzed genotypes. Stratification by GSTM1 genotype, however, showed a significant negative association between DNA adduct levels and plasma levels of alpha- (P = 0.02) and beta-carotene (P = 0.02) in subjects with the GSTM1 null genotype. Our results confirm that biomarkers of dietary intake of antioxidants significantly modulate DNA adducts and suggest specific inverse associations between DNA adduct levels and antioxidant concentrations among GSTM1 null subjects and smokers.     

Polymyalgia rheumatica and vertebral fractures: a 1-year pilot controlled study

No data exist about the possibility that vertebral fracture in PMR patients could be independent of steroid therapy. For this reason, we aimed to investigate this topic by a case cohort study with a 1-year follow-up for each patient. We selected ten consecutive patients who experienced vertebral fractures (VF-group) during the first month of 1-year follow-up period and without any other significant associated condition. As a control group we studied ten control patients, without vertebral fractures and with a follow-up of 1 year, randomly selected among a larger group of patients affected by polymyalgia rheumatica. The following data were analysed: eritrosedimention rate (ESR), visual analogical scale score (VAS), methyprednisolone daily dosage. Each patient had been monthly evaluated by the aforementioned clinical and laboratoristic parameters during the 1-year follow-up period. The VF-group resulted with a higher and statistically significant median corticosteroid 12-month total dosage [mean 3,480 mg (95%CI 2,805–3,030) vs. 2,760 mg (2,666.25–3,247.5)]. The VF-group had statistically significant higher ESR and VAS AUC when compared to control group (median ESR AUC, 484.75 vs. 288.25; P = 0.0001; median VAS AUC, 70.75 vs. 43.5 P < 0.0001); ESR at the baseline (cut-off >80 mm) showed a specificity of 90% (95%CI 56–100) and sensitivity of 70% (95%CI 35–93). VAS difference from first to second month (cut-off ≤3) showed a specificity of 90% (95%CI 56–100) and sensitivity of 80% (95% CI 44–97). Our results point out that vertebral fracture might be predicted from commonly used laboratory (ESR) and clinical (VAS) findings.     

Delayed effects of chronic cortisol treatment on brain and plasma concentrations of corticotropin (ACTH) and beta-endorphin

The effects of 2-day and 7-day cortisol treatment on immunoreactive corticotropin (ACTH) and beta-endorphin concentrations were measured in the cerebral cortex, hippocampus, hypothalamus, and cerebellum in male rats. Plasma ACTH, beta-endorphin, corticosterone, and cortisol levels were also measured in parallel. Cortisol administration by osmotic minipumps (25 mg/kg/day) maintained a constant, moderately high concentration (23.0 +/- 2.7 micrograms/100 ml) of this glucocorticoid in plasma. Two-day cortisol treatment suppressed the plasma concentration of ACTH and corticosterone, and also decreased, to a lesser degree, concentrations of beta-endorphin. ACTH and beta-endorphin levels in the brain remained unchanged after 2 days of cortisol treatment. After 7-day treatment, however, plasma concentrations of ACTH and beta-endorphin further decreased, while ACTH and beta-endorphin concentrations in the cortex and beta-endorphin concentrations in the cerebellum were also significantly decreased. Peptide concentrations in other brain areas did not change significantly with either 2-day or 7-day cortisol treatment. These data suggest that there are delayed effects of glucocorticoids on pro-opiomelanocortin peptide secretion and/or metabolism in the central nervous system. These findings are consistent with the impaired cognitive functions of patients with diseases, such as Cushing's syndrome and depression, that have long-lasting elevated cortisol secretion.