Metallothionein isoforms (I+II and III) and interleukin-6 in the hippocampus of old rats: may their concomitant increments lead to neurodegeneration?

Metallothionein (MT)-III isoform is a brain metal-binding protein that, like the MT-I + II isoform, binds zinc with high affinity. In the young-adult age, MT-III isoform increases during transient stress while MT-I + II isoform decreases, suggesting compensatory phenomena between the two isoforms and a protective role of MT-III against oxidative damage. This role may be questioned during ageing, because the stress-like condition is chronic in ageing due to high persistent levels of interleukin-6. In the present study, high expression of MT-III and MT-I + II genes (examined by RT-PCR and in situ hybridisation) was found in the hippocampus of old rats. These results indicate that a large amount of free zinc ions can be sequestered by MT isoforms, leading to impaired zinc-dependent functions in the ageing brain. In addition, zinc (tested with the Timm's method) was found to be low in mossy fibres from the old hippocampus. As this method tests bound and unbound zinc, we also investigated free zinc ion bioavailability based on the ratio active thymulin/total thymulin. We found that zinc ion bioavailability was low in old rats, together with increased interleukin-6 mRNA, high expression of both MT isoforms and reduced number of synapses whose function is zinc-dependent, in the old hippocampus. The results indicate that concomitant increments of both MT isoforms may provoke detrimental synergistic effects leading to reduced free zinc ion bioavailability for synapses. As a consequence, compensatory phenomena between MT isoforms may not occur in the old hippocampus due to chronic stress-like condition elicited by high persistent levels of interleukin-6.     

Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals

BACKGROUND: The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism. AIM: To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. Design: A randomized double-blind sequential cross-over study. SUBJECTS AND METHODS: Thirty subjects of both genders (20 M/10 F), mean age 45.5+/-9.9 years (M+/-SD), BMI 26.6+/-2.2 kg/m(2), with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight) (10.6g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1h after the administration of 5.3g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated. RESULTS: No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47+/-0.70 and 6.44+/-0.78 mmol/l (n.s.) and plasma triglycerides were 1.53+/-0.71 and 1.56+/-0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37+/-38 vs. 33+/-35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14,490+/-7416 vs. 17,760+/-7710 pmol/l x 300 min; P<0.02). CONCLUSIONS: A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.     

Humor and health in early adolescents: perceived field motion as a mediating variable

The purpose of this study was to test a mediational model, developed within the science of unitary human beings, by examining the relationship between humor and eudaimonistic health conception in early adolescents and by examining the extent to which perceived field motion mediated this relationship. The sample consisted of 136 adolescents, aged 12 to 14, who responded to instruments measuring humor, perceived field motion, and eudaimonistic health conception in classroom settings. Correlational analysis supported the three hypothesized relationships. Regression analyses indicated that perceived field motion was one mediator of the relationship between humor and eudaimonistic health conception.     

The study of reproductive outcome and the health of offspring of UK veterans of the Gulf war: methods and description of the study population

Background

The aim of this study is to determine whether Gulf war veterans and their partners are at increased risk of adverse reproductive events and whether their children have increased risk of serious health problems. Methods and response to the study are reported here.

Methods

This was a retrospective cohort study of reproduction among UK Gulf war veterans, with a comparison cohort of Armed Service personnel who were not deployed to the Gulf. Reproductive history and details of children's health was collected by means of a validated postal questionnaire. A separate study of non-responders was conducted.

Results

Questionnaires were returned by a total of 25,084 Gulf war veterans (24,379 men) and 19,003 (18,439 men) subjects in the comparison group. After adjusting for undelivered mail the response rate was 53% for Gulf war veterans and 42% for non-Gulf veterans among men, 72% and 60% among women. Data from the non-responder study suggests that failure to respond to the main survey was largely unrelated to reproduction. 11,155 (46%) male Gulf war veterans and 7,769 (42%) male non-Gulf war veterans had conceived, or attempted to conceive, since the Gulf war. They reported 16442 and 11517 pregnancies respectively in that period. For women, 313 (44%) Gulf veterans and 235 (42%) non-Gulf veterans reported 484 and 377 pregnancies respectively conceived since the Gulf war.

Conclusions

This survey enabled collection of information on a range of reproductive outcomes from veterans of the Gulf war and a suitably matched comparison cohort. Although the response rate for men was disappointing, selection bias related to reproduction does not appear to be strong in these data.

     

The role of choice in health education intervention trials: a review and case study

Although the randomized, controlled trial (RCT) is considered the gold standard in research for determining the efficacy of health education interventions, such trials may be vulnerable to "preference effects"; that is, differential outcomes depending on whether an individual is randomized to his or her preferred treatment. In this study, we review theoretical and empirical literature regarding designs that account for such effects in medical research, and consider the appropriateness of these designs to health education research. To illustrate the application of a preference design to health education research, we present analyses using process data from a mixed RCT/preference trial comparing two formats (Group or Self-Directed) of the "Women take PRIDE" heart disease management program. Results indicate that being able to choose one's program format did not significantly affect the decision to participate in the study. However, women who chose the Group format were over 4 times as likely to attend at least one class and were twice as likely to attend a greater number of classes than those who were randomized to the Group format. Several predictors of format preference were also identified, with important implications for targeting disease-management education to this population.     

Utilization of care during pregnancy in rural Guatemala: does obstetrical need matter?

This study examines factors associated with the use of biomedical care during pregnancy in Guatemala, focusing on the extent to which complications in an ongoing or previous pregnancy affect a woman's decisions to seek care. The findings, based on multilevel models, suggest that obstetrical need, as well as demographic, social, and cultural factors, are important predictors of pregnancy care. In contrast, measures of availability and access to health services have modest effects. The results also suggest the importance of unobserved variables–such as quality of care–in explaining women's decisions about pregnancy care. These results imply that improving proximity to biomedical services is unlikely to have a dramatic impact on utilization in the absence of additional changes that improve the quality of care or reduce barriers to access. Moreover, current efforts aimed at incorporating midwives into the formal health-care system may need to extend their focus beyond the modification of midwife practices to consider the provision of culturally appropriate, high-quality services by traditional and biomedical providers alike.     

Prostate cancer--prevalence-based healthcare costs

OBJECTIVE: To calculate the total costs of in- and outpatient healthcare for patients with prostate cancer based on an episode-of-care approach. The cost analysis includes costs incurred during the first year of diagnosis, a longitudinal 3-year analysis and the incremental cost of prostate cancer during the first year of diagnosis. MATERIAL AND METHODS: Patients registered with prostate cancer between 1998 and 2000, according to the data files of the Southern Swedish Regional Tumour Registry, were given encrypted identifiers that could also be used in the Patient Administrative System of the Region Sk?ne County Council, making it possible to identify consumption of healthcare on an episode-of-care basis. Itemized costs for resources used by each individual patient were calculated from the complete accounting system of the County Council. RESULTS: Healthcare costs for prostate cancer during the first year varied between 45 000 and 51 000 SEK per patient. The second- and third-year costs were progressively lower, with an estimated total cost of 114 000 SEK over a period of 3 years. The age-standardized incremental cost of prostate cancer corresponded to 33 000 SEK during the first year, compared to the average cost per inhabitant. CONCLUSIONS: The episode-of-care approach, based on encrypted identifiers for the identification of the diagnoses of individual patients and their utilization of healthcare, gives a unique opportunity to estimate the healthcare costs of specific diseases. The incremental healthcare cost per patient with prostate cancer corresponded to 33 000 SEK during the first year.