Modulation of intestinal gene expression by dietary zinc status: effectiveness of cDNA arrays for expression profiling of a single nutrient deficiency.

Mammalian nutritional status affects the homeostatic balance of multiple physiological processes and their associated gene expression. Although DNA array analysis can monitor large numbers of genes, there are no reports of expression profiling of a micronutrient deficiency in an intact animal system. In this report, we have tested the feasibility of using cDNA arrays to compare the global changes in expression of genes of known function that occur in the early stages of rodent zinc deficiency. The gene-modulating effects of this deficiency were demonstrated by real-time quantitative PCR measurements of altered mRNA levels for metallothionein 1, zinc transporter 2, and uroguanylin, all of which have been previously documented as zinc-regulated genes. As a result of the low level of inherent noise within this model system and application of a recently reported statistical tool for statistical analysis of microarrays [Tusher, V.G., Tibshirani, R. & Chu, G. (2001) Proc. Natl. Acad. Sci. USA 98, 5116-5121], we demonstrate the ability to reproducibly identify the modest changes in mRNA abundance produced by this single micronutrient deficiency. Among the genes identified by this array profile are intestinal genes that influence signaling pathways, growth, transcription, redox, and energy utilization. Additionally, the influence of dietary zinc supply on the expression of some of these genes was confirmed by real-time quantitative PCR. Overall, these data support the effectiveness of cDNA array expression profiling to investigate the pleiotropic effects of specific nutrients and may provide an approach to establishing markers for assessment of nutritional status.

Integrative noetic therapies as adjuncts to percutaneous intervention during unstable coronary syndromes: Monitoring and Actualization of Noetic Training (MANTRA) feasibility pilot.

BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) for unstable coronary syndromes have substantial emotional and spiritual distress that may promote procedural complications. Noetic (nonpharmacologic) therapies may reduce anxiety, pain and distress, enhance the efficacy of pharmacologic agents, or affect short- and long-term procedural outcomes. METHODS: The Monitoring and Actualization of Noetic Training (MANTRA) pilot study examined the feasibility of applying 4 noetic therapies-stress relaxation, imagery, touch therapy, and prayer-to patients in the setting of acute coronary interventions. Eligible patients had acute coronary syndromes and invasive angiography or PCI. Patients were randomized across 5 treatment groups: the 4 noetic and standard therapies. Questionnaires completed before PCI reflected patients' religious beliefs and anxiety. Index hospitalization end points included post-PCI ischemia, death, myocardial infarction, heart failure, and urgent revascularization. Mortality was followed up for 6 months after hospitalization. RESULTS: Of eligible patients, 88% gave informed consent. Of 150 patients enrolled, 120 were assigned to noetic therapy; 118 (98%) completed their therapeutic assignments. All clinical end points were available for 100% of patients. Results were not statistically significant for any outcomes comparisons. There was a 25% to 30% absolute reduction in adverse periprocedural outcomes in patients treated with any noetic therapy compared with standard therapy. The lowest absolute complication rates were observed in patients assigned to off-site prayer. All mortality by 6-month follow-up was in the noetic therapies group. In patients with questionnaire scores indicating a high level of spiritual belief, a high level of personal spiritual activity, a low level of community-based religious involvement, or a high level of anxiety, noetic therapies appeared to show greater reduction in absolute in-hospital complication rates compared with standard therapy. CONCLUSIONS: Acceptance of noetic adjuncts to invasive therapy for acute coronary syndromes was excellent, and logistics were feasible. No outcomes differences were significant; however, index hospitalization data consistently suggested a therapeutic benefit with noetic therapy. Of all noetic therapies, off-site intercessory prayer had the lowest short- and long-term absolute complication rates. Definitive demonstration of treatment effects of this magnitude would be feasible in a patient population about 4 times that of this pilot study. Absolute mortality differences make safety considerations a mandatory feature of future clinical trials in this area.

Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D.

We conducted a study to determine whether increasing vitamin D intake above the recommended dietary allowance (RDA) of 5.0 micrograms (200 IU)/d reduces bone loss in healthy postmenopausal women residing at latitude 42 degrees N. In this double-blind, randomized 2-y trial, we enrolled 247 healthy ambulatory postmenopausal women who consumed an average of 2.5 micrograms (100 IU) vitamin D/d in their usual diets. The women were given either 2.5 micrograms (100 IU) or 17.5 micrograms (700 IU) vitamin D/d. All women received 500 mg supplemental calcium per day as citrate malate. Duplicate hip and spine and single whole-body scans were performed by dual-energy x-ray absorptiometry at 6-mo intervals selected to flank the periods when 25-hydroxycholecalciferol (calcidiol) concentrations are highest (summer/fall) and lowest (winter/spring). Plasma calcidiol and serum osteocalcin were measured in these seasons in year 1. Both treatment groups lost bone mineral density from the femoral neck, but the 17.5-micrograms group lost less than (-1.06 +/- 0.34%; mean +/- SE) the 2.5-micrograms group (-2.54 +/- 0.37%, P = 0.003). Seventy percent of the benefit each year occurred in winter/spring and 30% in summer/fall. Changes in spinal and whole-body bone densities did not differ by treatment group and were minimal after 2 y. Serum osteocalcin and plasma calcidiol (2.5-micrograms group only) fluctuated with season. In conclusion, in healthy, calcium-supplemented, postmenopausal women residing at latitude 42 degrees N, an intake of 5.0 micrograms (200 IU) vitamin D/d is sufficient to limit bone loss from the spine and whole body but it is not adequate to minimize bone loss from the femoral neck.(ABSTRACT TRUNCATED AT 250 WORDS)

Looking into a deaf child's future. A brief treatment approach.

This article describes the brief psychotherapeutic treatment of a hearing mother who reported obsessional thoughts about her deaf child's future. The article was written jointly by the therapist and the client. Clinical hypnosis was used to modify the mother's negative images of her child's future. Structured meetings between the mother, a vocational counselor, and deaf adults affirmed and expanded the more positive images. Theoretical descriptions and personal sentiments are offered.

Verapamil but not nifedipine impairs left ventricular function during exercise in hypertensive patients.

Calcium antagonists are popular therapeutic agents in the treatment of systemic hypertension. Although these agents have similar antihypertensive efficacy, they have varied effects on left ventricular function at rest in hypertensive patients. The effect of different calcium antagonists on left ventricular function during exercise and on exercise performance in patients with hypertension, however, is less clear. Fifteen patients with essential hypertension (diastolic blood pressure = 95 to 110 mm Hg) were enrolled in a placebo-controlled, single-blinded crossover study comparing nifedipine with verapamil for rest/exercise heart rate and blood pressure, exercise performance, and rest/exercise left ventricular function. Each drug was titrated to achieve resting diastolic pressures less than 90 mm Hg. All patients underwent maximal exercise testing and rest/exercise gated radionuclide ventriculography at the end of 3-week placebo, nifedipine, and verapamil treatment periods. Both calcium antagonists significantly reduced blood pressure at rest and during exercise compared with placebo. Neither calcium antagonist altered resting heart rate; however, both verapamil and nifedipine significantly reduced heart rate at maximal exercise. Verapamil but not nifedipine impaired left ventricular peak emptying rate and left ventricular peak filling rate during exercise but not at rest. Neither verapamil nor nifedipine, however, significantly altered rest or exercise global left ventricular ejection fraction (LVEF) compared with placebo. There was a trend, however, for impairment in the LVEF response to exercise (delta LVEF) in the verapamil treatment group. Exercise capacity was not significantly altered by either calcium antagonist compared with placebo. Thus verapamil but not nifedipine impairs left ventricular function during exercise in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)