A tiered approach for assessing children's exposure

Recently, intense attention has been given to children's health issues, particularly in the use of consumer products. Because of this attention, researchers have been planning and initiating studies specifically aimed at developing both toxicology data and exposure data directed to improve our understanding of industrial and consumer product chemical impacts on children's health. To ensure that this research is focused on the highest priority chemicals, we present a methodology for determining and prioritizing the higher hazard chemicals and scenarios for which children could be disproportionately or highly exposed. This tiered approach includes a screening step for initial chemical selection, a hazard assessment based on no- or lowest-observed-adverse-effect levels, and a margin of exposure (MOE) calculation. The initial chemical screen focuses on the chemical presence in specific media that are special to children, such as foods children regularly eat and drink, residential or school air, products children use, and soil and dust in and around residences. Data from the literature or from models serve as the initial exposure estimate. This methodology would allow us to focus on those chemicals to which children are most exposed that are also associated with, potentially, the highest risk. Use of the MOE calculation allows for comparison among chemicals, prioritization of chemicals for evaluation and testing, and identification of significant data gaps.     

Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces

Background

HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV – DNA by Real time – PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals.

Methods

Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector

Results

Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy.

Conclusion

HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time – PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.Key Words: Real time – PCR, Chronic Hepatitis B, HBV – DNA, Antivirals     

Surveys of Norwegian youth indicated that breast feeding reduced subsequent risk of obesity

BACKGROUND AND OBJECTIVE: Breast-feeding protects against overweight in childhood, while it is uncertain if it is protective against adolescent and adult overweight. The objective of this study was to examine whether having been breast fed protects against adolescent and adult overweight and obesity. METHODS: Participants in the Oslo Youth study examined in 1979/1981 (n=635, mean age 13.1 years) and in 1999. Weight and height were measured in 1979/1981 and self-reported in 1999. Breast-feeding information was provided by the parents in 1979/1981. Potential confounders adjusted for included parents' body mass index and education, mother's smoking habits, participants' physical activity, smoking status, education and energy intake. RESULTS: Comparing those having been breast fed more than 3 months with those never breast fed, the adjusted odds ratios (95% confidence interval [CI]) between the two groups were 0.27 (0.13-0.56) for being overweight and 0.15 (0.03-0.72) for being obese in adolescent. In adulthood, the corresponding odds ratios were 0.64 (0.33-1.26) and 0.34 (0.12-1.01), respectively. CONCLUSION: Breast feeding during infancy appears to protect against adolescent overweight and obesity, while the effect on adult weight status is weaker. With increasing age, the impact of any protective physiologic mechanisms of breast feeding seen earlier in life tends to diminish.     

Plasma concentration of folate as a biomarker for the intake of fruit and vegetables: the Hordaland Homocysteine Study

BACKGROUND: Nutritional biomarkers may be used to assess dietary exposure without the errors commonly associated with self-reported dietary data. OBJECTIVE: The objective was to examine the association between plasma folate and intake of folate, fruit, and vegetables in a large cohort of healthy adults consuming foods that had not been fortified with folic acid. DESIGN: The present study population included 5533 middle-aged (47-49 y) and old (71-74 y) subjects from the Hordaland Homocysteine Study. The participants completed a food-frequency questionnaire and provided blood samples for chemical analyses. RESULTS: We observed a significant difference in plasma concentrations of folate across increasing quartiles of fruit, vegetable, and orange juice consumption. The difference in plasma folate between the highest and lowest quartiles was 1.97 (95% CI: 1.86, 2.07) nmol/L for fruit intake, 1.79 (95% CI: 1.69, 1.89) nmol/L for vegetable intake, and 2.69 (95% CI: 2.51, 2.87) nmol/L for orange juice intake. A significant inverse relation was observed across increasing quartiles of milk and bread intakes. The difference between the highest and lowest quartiles was -1.03 (95% CI: -1.13, -0.92) nmol/L for milk and -1.60 (95% CI: -1.69, -1.50) nmol/L for bread. CONCLUSION: Plasma folate concentration may be a useful biomarker for the intake of fruit and vegetables in populations consuming unfortified food products. The association can be attenuated by and should be corrected for individual intake of folic acid supplements.     

AlphaV- and beta1-integrin subunits are commonly expressed in malignant effusions from ovarian carcinoma patients

OBJECTIVE: The objective was to study expression of alphav- and beta1-integrin subunits in effusions, primary tumors, and solid metastases of ovarian carcinoma patients, as well as to evaluate its potential association with previously studied metastasis-associated molecules and clinicopathologic parameters. METHODS: Sections from 121 malignant effusions and 30 corresponding primary and metastatic lesions were evaluated for protein expression of the alphav- and beta1-integrin subunits using immunohistochemistry (IHC). A subset of effusions was additionally studied using immunoblotting (IB) and flow cytometry (FCM). mRNA in situ hybridization (ISH) was performed in 58 effusions and 30 biopsies. RESULTS: Protein expression of alphav- and beta1-integrin subunits was detected in carcinoma cells in 116/121 (96%) and 113/121 (93%) effusions, respectively. alphav protein expression was limited to carcinoma cells. IB and FCM confirmed IHC results. mRNA for alphav- and beta1-integrin subunits was detected in carcinoma cells in 37/58 (64%) and 33/58 (57%) effusions, respectively. Both protein and mRNA expression were higher in peritoneal effusions, significantly for alphav mRNA (P = 0.042) and beta1 protein (P = 0.023). beta1 protein expression in effusions was more frequently detected in better-differentiated tumors (P = 0.006). alphav-integrin subunit expression correlated with that of the previously studied matrix metalloproteinase-9 (MMP-9) (P = 0.006) and the MMP inducer EMMPRIN (P = 0.001). Expression of beta1-integrin subunit showed an association with that of EMMPRIN (P = 0.029), basic fibroblast growth factor (P < 0.001), and the MMP inhibitor TIMP-2 (P = 0.025). In carcinoma cells of solid lesions, alphav protein was uniformly present, while beta1 expression was limited to 15/30 (50%) specimens. As in effusions, protein expression of alphav subunit was cancer-specific, while beta1 protein was detected also in stromal fibroblasts and endothelial cells. CONCLUSIONS: The alphav- and beta1-integrin subunits are frequently expressed in ovarian carcinoma cells in effusions, and the alphav-integrin subunit is a powerful diagnostic marker for carcinoma cells. The reduced expression of the beta1-integrin subunit in solid lesions may be attributed to the role of other subunits at these stages, such as the beta3 subunit as part of the alphavbeta3-vitronectin receptor. The high expression of integrin subunits with a role of binding mesothelium, invasion, and angiogenesis in carcinoma cells in both peritoneal and pleural effusions suggests that cells at both sites have metastatic potential.     

Reliability,validity and psychometric properties of the Greek translation of the Major Depression Inventory

Background  

The Major Depression Inventory (MDI) is a brief self-rating scale for the assessment of depression. It is reported to be valid because it is based on the universe of symptoms of DSM-IV and ICD-10 depression. The aim of the current preliminary study was to assess the reliability, validity and psychometric properties of the Greek translation of the MDI.     

Adult cockatiels (Nymphicus hollandicus) at maintenance are more sensitive to diets containing excess vitamin A than to vitamin A-deficient diets

The purpose of this experiment was to examine the physiological responses of adult cockatiels at maintenance to dietary vitamin A (VA) concentrations, and to identify concentrations associated with deficiency and toxicity. Adult cockatiels at maintenance (n = 22, 2-3 y of age) were fed a diet of 0, 600, 3000 or 30,000 microg VA/kg (0, 2000, 10,000 or 100,000 IU), and monitored for signs of VA deficiency or toxicity for up to 706 d. The analyzed diet concentrations were 0, 835, 2815 and 24,549 microg/kg, respectively. After 269 d, birds fed the 30,000 microg/kg VA diet had greater plasma retinal concentrations, markedly intensified vocalization patterns, pancreatitis and multifocal accumulation of lymphocytes in the lamina propria of the duodenum compared to birds fed the 600 microg/kg diet (P < 0.05). The 3000 microg/kg VA diet induced increased plasma retinol, splenic hemosiderosis and altered vocalization patterns (P < 0.05), although not as striking as those induced by the 30,000 microg/kg VA diet. The secondary antibody response was reduced after 225 d and vocalization patterns were altered in birds fed 0 microg/kg VA (P < 0.05), but after almost 2 y there were no changes in body condition, plasma retinol, organ pathology or classical signs of deficiency such as squamous metaplasia of nasal epithelia. Thus, adult cockatiels at maintenance were more susceptible to VA toxicity than to VA deficiency and concentrations > or = 3000 microg VA/kg diet can cause toxicity. It is possible that disturbances in VA nutrition contribute to the widespread incidence of behavioral problems reported in companion birds.