A delicate balance: homeostatic control of copper uptake and distribution.

The cellular uptake and intracellular distribution of the essential but highly toxic nutrient, copper, is a precisely orchestrated process. Copper homeostasis is coordinated by several proteins to ensure that it is delivered to specific subcellular compartments and copper-requiring proteins without releasing free copper ions that will cause damage to cellular components. Genetic studies in prokaryotic organisms and yeast have identified membrane-associated proteins that mediate the uptake or export of copper from cells. Within cells, small cytosolic proteins, called copper chaperones, have been identified that bind copper ions and deliver them to specific compartments and copper-requiring proteins. The identification of mammalian homologues of these proteins reveal a remarkable structural and functional conservation of copper metabolism between bacteria, yeast and humans. Furthermore, studies on the function and localization of the products of the Menkes and Wilson's disease genes, which are defective in patients afflicted with these diseases, have provided valuable insight into the mechanisms of copper balance and their role in maintaining appropriate copper distribution in mammals.     

Plutonium fecal and urinary excretion functions: derivation from a systemic whole-body retention function.

Liver-bile secretion directly influences the content of plutonium in feces. To assess the reliability of plutonium metabolic models and to improve the accuracy of interpreting plutonium fecal data, we developed a compartmental model that simulates the metabolism of plutonium in humans. With this model, we can describe the transport of plutonium contaminants in the systemic organs and tissues of the body, including fecal and urine excretions, without using elaborate kinetic information. The parameter values of the models, which describe the translocation rates and recycling of plutonium in the body, can be derived from a multi-term exponential systemic function for whole-body retention. The analytical derivations and algorithms for solving translocation parameter values are established for the model and illustrated by applying them to the biokinetics and bioassay of plutonium. This study describes how to (1) design a physiological model for incorporating liver biliary secretion and for obtaining a fecal-excretion function, (2) develop an analytical solution for identifying the translocation-parameter values incorporating the recycling of plutonium in the body, and (3) derive a set of urinary and fecal excretion-functions from a published systemic whole-body retention function, generally acknowledged to be accurate, as a real and practical example.     

Lumbar vertebral angles and back muscle loading with belts.

The study examined belt effects on the change of lumbosacral angle (LSA) and back muscle activity in postures of standing, erect sitting, and slump sitting. We thought that the resulting changes of LSA and back muscle activity when wearing belts with different mechanical characteristics should be different. Eighteen healthy male subjects participated in this study. Though we failed to identify a significant belt effect on the back muscle EMG, the radiographic data revealed an interactive effect of postures and belts on the change of LSA. In standing, the belts increased LSA by increasing almost every lumbar vertebral angle. In erect sitting, the lumbar belt had no effect but the pelvic belt decreased LSA through a decrease in the L1/L3. While sitting slump with a trunk flexion of 15 degrees, both belts increased LSA by restricting the movement of the pelvis. Belt effect on LSA was accompanied with a change of pelvic angle. Significant correlation was found between the backward rotation angles of the pelvis and the angles of LSA (r = 0.692, p < 0.0001), also between the decrease of pelvic angles and the increase of back muscle EMG (r = -0.4, p = 0.017). A change in LSA and pelvic angle after wearing a belt along with posture change seems lead to an increase of the myoelectric activities on the back.     

Review of animal models in carotenoid research

Foods containing provitamin A carotenoids are the primary source of vitamin A in many countries, despite the poor bioavailability of carotenoids. In addition, epidemiologic studies suggest that dietary intake of carotenoids influences the risk for certain types of cancer, cardiovascular disease and other chronic diseases. Although it would be ideal to use humans directly to answer critical questions regarding carotenoid absorption, metabolism and effects on disease progression, appropriate animal models offer many advantages. This paper will review recent progress in the development of animal models with which to study this class of nutrients. Each potential model has strengths and weaknesses. Like humans, gerbils, ferrets and preruminant calves all absorb beta-carotene (betaC) intact, but only gerbils and calves convert betaC to vitamin A with efficiency similar to that of humans. Mice and rats efficiently convert betaC to vitamin A but absorb carotenoids intact only when they are provided in the diet at supraphysiologic levels. Mice, rats and ferrets can be used to study cancer, whereas primates and gerbils are probably more appropriate for studies on biomarkers of heart disease. No one animal model completely mimics human absorption and metabolism of carotenoids; thus the best model must be chosen with consideration of the specific application being studied, characteristics of the model, and the available funding and facilities.     

Evaluation of Developmentally Appropriate Programs for Adolescent Tobacco Cessation

Despite introduction of numerous smoking prevention programs in schools, tobacco use has not declined among adolescents. Schools face the dilemma of what to do with students who smoke and are not ready to quit. This study evaluated two programs based on the stages of change model. The educational program, the Tobacco Education Group (TEG), was designed for adolescents not yet thinking about quitting. The cessation program, the Tobacco Awareness Program (TAP), was intended for adolescents who want to quit. Evaluation was completed on 351 students at six public high schools. Compared to a control group of adolescent smokers not assigned to programs, both intervention groups significantly decreased tobacco use. Self-reported use was validated biochemically. Self-efficacy for quitting increased in both programs. Posttest use was predicted by posttest self-efficacy, peer support, and parental support, after controlling for initial use and initial self-efficacy.     

Linking Clients from HIV Antibody Counseling and Testing to Prevention Services

The effectiveness of HIV antibody counseling and testing as a prevention intervention is limited: persons testing seronegative do not usually change their risk behaviors, some actually increase their risk behaviors, and decreases in risk behaviors are usually short-lived. Referrals to additional prevention and other needed services are therefore recommended, although the extent and determinants of referral provision for persons testing seronegative are unknown. We assessed the prevalence of referrals and the association between risk behaviors and prevention referrals among seronegatives. We reviewed HIV testing and referral data on all persons receiving confidential seronegative test results in San Francisco (SF) in the first 10 months of 1995 (n = 5,595), and gathered more detailed referral information at the municipal STD clinic from November 1995 through May 1996 (n = 747). The overall prevalence of referrals was low: a referral was given to 19.1% of the SF sample and 10.6% of the STD clinic sample; 15.4% of the SF sample and 5.9% of the STD clinic sample received a prevention referral. Injection drug users (IDUs) were the most likely to receive a prevention referral (48.5% of SF IDUs, 36.4% of STD clinic IDUs); men having sex with men and women with high-risk partners were also more likely to get a prevention referral than others. For SF IDUs, unsafe sex and needle sharing were not associated with an increased likelihood of receiving a prevention referral. Opportunities to link high-risk clients from counseling and testing to HIV prevention services are being missed. The referral component of HIV counseling and testing should be improved.     

Preclinical evaluation of prototype products

Preclinical evaluation of medical devices (prototype products) offers the opportunity to investigate and study the intended use of device materials. Preclinical evaluation programs are designed to determine the efficacy, safety, and biocompatibility of biomaterials, prostheses, and medical devices. The purpose of safety testing is to determine if a material presents potential harm to the human; it evaluates the interaction of the material with the in vivo environment and determines the effect of the host on the implant. Preclinical evaluation is the determination of the ability of the prototype product to perform with appropriate host response in a specific application, considered from the perspective of human clinical use. Therefore, preclinical data should include materials science and engineering, biology, biochemistry, medicine, host reactions and their evaluation, the testing of biomaterials, and the degradation of materials in a biological environment.     

The role of radiotherapy in the treatment of aggressive fibromatosis

Aggressive fibromatosis is a rare benign soft tissue tumor that is difficult to cure because of its infiltrative nature and high tendency to recur locally. The authors retrospectively analyzed 20 patients with histologically-confirmed fibromatosis. All patients underwent surgery with a wide or marginal margin. Five (25%) cases with histologically-negative margins had recurred. External beam radiotherapy was administered to patients whose margins were positive or who had local recurrence. However, out of concern for safety, radiotherapy was not given to two babies and a reproductive-aged woman. The average dose was 5,020 cGy. During the follow-up (mean 32.6 months), all the patients undergoing radiotherapy showed no evidence of local recurrence. A wide local excision has traditionally been the treatment of choice. However, postoperative radiotherapy could be an effective measure for preventing local recurrence in patients with a histologically-positive surgical margin and recurrence independent of any signs of relapse.     

Protective effects of garlic juice against embryotoxicity of methylmercuric chloride administered to pregnant Fischer 344 rats

In order to investigate the beneficial effects of 0.5 or 1.0 g/kg Korean garlic juice against the embryotoxicity of 20 mg/kg methylmercury chloride (MMC, CH3HgCl), pregnant Fisher 344 rats were simultaneously orally administered on day 7 of gestation. On day 20 of gestation the dams were laparotomized under ether anesthesia, and the fetuses were removed and examined for toxicity of methylmercury. Garlic juice depressed the toxicity in terms of some parameters. In the case of simultaneous treatment with 0.1 g/kg garlic juice and MMC, rates of increase were 17.5% in maternal body weight, 13.2% and 41.9% in fetal and litters' weight respectively, and 37.0% in fetal survival rate. Decreasing rates were 10.0% in maternal death rate, and 6.9% and 31.3% in pre- and post-implantation loss respectively. Decreasing rates of mercury levels in dams were 67.2% in liver, 57.6% in brain, 47.2% in kidney, 42.1% in spleen and 40.9% in blood. As well, decreasing rates of mercury level in fetuses were 54.9% in all body burden, 55.9% in liver, 46.7% in kidney and 37% in brain, respectively. The number of fetal ossification centers were reduced by 23.8% to 58.0% following simultaneous treatment with 1.0 g/kg garlic juice. These findings indicated that garlic juice effectively inhibited the embryotoxicity of methylmercury in pregnant Fischer 344 rats.