Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstuffs and Cigarette Smoke

Cadmium is a cumulative nephrotoxicant that is absorbed into the body from dietary sources and cigarette smoking. The levels of Cd in organs such as liver and kidney cortex increase with age because of the lack of an active biochemical process for its elimination coupled with renal reabsorption. Recent research has provided evidence linking Cd-related kidney dysfunction and decreases in bone mineral density in nonoccupationally exposed populations who showed no signs of nutritional deficiency. This challenges the previous view that the concurrent kidney and bone damage seen in Japanese itai-itai disease patients was the result of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and calcium. Further, such Cd-linked bone and kidney toxicities were observed in people whose dietary Cd intakes were well within the provisional tolerable weekly intake (PTWI) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives of 1 mug/kg body weight/day or 70 mug/day. This evidence points to the much-needed revision of the current PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is accumulating and Cd effects on reproductive outcomes have begun to emerge.

Medication management reviews for people from the former Yugoslavia now resident in Australia

Aim: The objective of this prospective study was to conduct medication management reviews (MMR) in people from a non-English speaking background (NESB) (Bosnian/Serbian/ Croatian, from former Yugoslavia, currently residing in Australia) in their native language in order to identify medication-related problems (needs analysis) and implement appropriate therapeutic interventions, in collaboration with their general practitioners (GPs). Methods: Twenty-five participants entered the study. Each was interviewed and medication-related issues were identified by the health care team. Results: Various interventions (over 150 for the whole group, an average of 6 per participant), based on actual and potentia medication-related problems, were designed to improve the use of medicines. The MMRs introduced effective changes into the participants' health care. Psychological (e.g., feeling depressed) and sociological factors (e.g., costs of medicines, not understanding labels written in English) were identified having significant impacts on medication management. Conclusions: These data confirmed there are avoidable medication-related problems in people from a NESB. GPs and pharmacists working in health care teams with a trained interpreter could greatly improve medication use through regular review and a team approach to problem identification and solving.

Effects of chronic exposure to low-level cadmium on renal tubular function and CYP2A6-mediated coumarin metabolism in healthy human subjects

Relationships between cadmium (Cd) body burden, kidney function and coumarin metabolism were investigated using two groups of 197 and 200 healthy Thais with men and women in nearly equal numbers. A mean age of one group was 30.5 years and it was 39.3 years for the other group. Of 397, 20 subjects (5%) excreted urine Cd between 1.4 mug/g and 3.8 mug/g creatinine and these subjects faced 10-15% increase in the probability of having abnormal urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG-uria). The prevalence of NAG-uria varied with Cd body burden in a dose-dependent manner (chi(2) = 22, P < 0.008). Also NAG-nuria was one of the three kidney effect markers tested that showed the greatest strength of correlation with urine Cd in both men and women (r = 0.48 P < 0.001). In addition, urine Cd excretion of men and women showed a positive correlation (r = 0.46 to 0.54. P < 0.001) with urine 7-hydroxycoumarin (7-OHC) excretion which was used as a marker of liver cytochrome P450 2A6 (CYP2A6) enzyme activity. Urinary CA excretion accounted for 25% of the total variation in urine 7-OHC excretion (P < 0.001). These data suggest that Cd may increase the expression of CYP2A6 in liver, resulting in enhanced coumarin metabolism in subjects with high Cd body burden. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Influence of body iron store status and cigarette smoking on cadmium body burden of healthy Thai women and men

The influence of cigarette smoking, body iron store status and gender on cadmium (Cd) body burden was examined in a group of 197 healthy Thais with overall mean age of 30.5 year (19-47 year). The lowest, geometric mean, and the highest urinary Cd excretion rate was 0.04, 0.46 and 3.84 mug/g creatinine, respectively. The prevalence of low iron stores (serum ferritin

Ratiometric and nonratiometric Ca2+ indicators for the assessment of intracellular free Ca2+ in a breast cancer cell line using a fluorescence microplate reader

Transporters of Ca2+ are potential drug targets and Ca2+ is a useful signal in the assessment of G-protein-coupled receptor activation. Assays involving the assessment of intracellular Ca2+ using microplate readers most often use Ca2+ indicators which do not exhibit a spectra shift on Ca2+ binding (e.g. fluo-3). Indicators that do exhibit a spectral shift upon Ca2+ binding (e.g. fura-2) offer potential advantages for the calibration of intracellular Ca2+ levels. However, experimental limitations may limit the use of ratiometric dyes in microplate readers capable of screening. In this study, we compared the assessment of intracellular Ca2+ in adherent breast cancer cells using ratiometric and nonratiometric Ca2+ indicators. Our results demonstrate that both fluo-3 and fura-2 detect ATP dose-dependent increases in intracellular Ca2+ in the MCF-7 breast cancer cell line and that some of the limitations in the use of fura-2 appear to be overcome by the use of glass bottom microplates. The calibrated intracellular Ca2+ levels derived using fura-2 are consistent with those from microscopy and cuvette-based studies. Fura-2 may be useful in microplate studies, where cell lines with different properties are compared or where screening treatments lead to differences in the number of cells or dye loading. (C) 2003 Elsevier B.V. All rights reserved.

A commentary on the impacts of metals and metalloids in the environment upon the metabolism of drugs and chemicals

The salient feature of metals is that unlike organic compounds they do not degrade in the environment and barely move from one environmental matrix to another. Human interventions take these compounds from their stable and non-bioavailable geological matrix into situations of biological accessibility. Studies in the 1970s and the 1980s of metal bioavailability and impacts of metals and metalloids were driven by the process of abatement of lead in the environment. Humans have clear and identifiable sources of exposure from fuels, food and leaded water pipes to lead. Interventions started at that time have dramatically lowered human lead exposure. Attention has now shifted to other metals, in particular, cadmium, which has seen increasing use. It is generally accepted that food crops grown on cadmium containing soils or soils naturally rich in this metal are the major source of exposure to humans other than exposure from smoking of cigarettes. This mini-review gives a summary and commentary on early studies on effects of lead on haem metabolism that provide us the clue to why investigations of the impacts of other toxic heavy metals and metalloids such as cadmium and arsenic on different human cytochrome P450 forms have become of great interest at the current time. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Associations of location and perceived environmental attributes with walking in neighborhoods

Purpose. Ecological models highlight the importance of environmental influences. We examined associations of coastal versus noncoastal location and perceived environmental attributes with neighborhood walking, total walking, and total activity. Methods. Telephone interviews with 800 faculty and general staff of an Australian university. Results. Men were significantly more likely to walk in their neighborhood if they lived in a coastal location (odds ratio [OR] = 1.66), and they highly rated environmental aesthetics (OR = 1.91), convenience of facilities (OR = 2.20), and access to facilities (OR = 1.98). For women, neighborhood walking was associated with high ratings of convenience (OR = 3.78) but was significantly less likely if they had high ratings for access (OR = 0.48). For total walking and total physical activity, few significant associations emerged. Conclusions. Environmental attributes were related to walking in the neighborhood but not to more general activity indices. Understanding gender-specific environmental correlates of physical activity should be a priority.

Development of lipid-core-peptide (LCP) based vaccines for the prevention of the group A streptococcal (GAS) infection

Traditional vaccines consisting of whole attenuated micro-organisms. or microbial components administered with adjuvant, have been demonstrated as one of the most cost-effective and successful public health interventions. Their use in large scale immunisation programs has lead to the eradication of smallpox, reduced morbidity and mortality from many once common diseases, and reduced strain on health services. However, problems associated with these vaccines including risk of infection. adverse effects, and the requirement for refrigerated transport and storage have led to the investigation of alternative vaccine technologies. Peptide vaccines, consisting of either whole proteins or individual peptide epitopes, have attracted much interest, as they may be synthesised to high purity and induce highly specific immune responses. However, problems including difficulties stimulating long lasting immunity. and population MHC diversity necessitating multiepitopic vaccines and/or HLA tissue typing of patients complicate their development. Furthermore, toxic adjuvants are necessary to render them immunogenic. and as such non-toxic human-compatible adjuvants need to be developed. Lipidation has been demonstrated as a human compatible adjuvant for peptide vaccines. The lipid-core-peptide (LCP) system. incorporating lipid adjuvant, carrier, and peptide epitopes, exhibits promise as a lipid-based peptide vaccine adjuvant. The studies reviewed herein investigate the use of the LCP system for developing vaccines to protect against group A streptococcal (GAS) infection. The studies demonstrate that LCP-based GAS vaccines are capable of inducing high-titres of antigen specific IgG antibodies. Furthermore. mice immunised with an LCP-based GAS vaccine were protected against challenge with 8830 strain GAS.

Transdermal delivery of a tetrapeptide: Evaluation of passive diffusion

Skin penetration of the tetrapeptide Ac-Ala-Ala-Pro-Val-NH2 was assessed. This peptide sequence fits the P-P-1 subsites of elastase and inhibits human neutrophil elastase competitively. Consequently this peptide may be therapeutically useful in a variety of inflammatory disorders, including psoriasis. in which elevated levels of human neutrophil elastase have been reported. Peptide penetration was assessed across whole human skin, whole skin with the stratum corneum removed by tape stripping and epidermis, which had been removed from the dermis by heat separation. The influence of 75% aqueous ethanol as a potential penetration enhancer of the tetrapeptide across epidermis was also assessed. The tetrapeptide did not penetrate whole human skin or epidermis, even under the influence of 75% aqueous ethanol. However, when the stratum corneum was removed tetrapeptide flux of 73.39 mug cm(-2) h(-1) was achieved. The study demonstrates that the stratum corneum is the main barrier to tetrapeptide skin penetration and must be overcome if therapeutically relevant amounts of tetrapeptide are to be delivered to the skin.

Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosis

Focal biliary cirrhosis causes significant morbidity and mortality in cystic fibrosis (CF). Although the mechanisms of pathogenesis remain unclear, bile acids have been proposed as potential mediators of liver injury. This study examined bile acid composition in CF and assessed altered bile acid profiles to determine if they are associated with incidence and progression of liver injury in CF-associated liver disease (CFLD). Bile acid composition was determined by gas-liquid chromatography/mass spectrometry in bile, urine, and serum samples from 30 children with CFLD, 15 children with CF but without liver disease (CFnoLD)), and 43 controls. Liver biopsies from 29 CFLD subjects were assessed histologically by grading for fibrosis stage, inflammation, and disruption of the limiting plate. A significantly greater proportion of endogenous biliary ursodeoxycholic acid (UDCA) was demonstrated in CFnoLD subjects vs. both CFLD subjects and controls (2.4- and 2.2-fold, respectively; ANOVA, P = .04), and a 3-4 fold elevation in endogenous serum UDCA concentration was observed in both CFLD subjects and CFnoLD subjects vs. controls (ANOVA, P < .05). In CFLD, there were significant correlations between serum cholic acid and hepatic fibrosis, inflammation, and limiting plate disruption as well as the ratio of serum cholic acid/chenodeoxycholic acid to hepatic fibrosis, inflammation, and limiting plate disruption. In conclusion, elevated endogenous UDCA in CFnoLD suggests a possible protective role against liver injury in these patients. The correlation between both cholic acid and cholic acid/chenodeoxycholic acid levels with histological liver injury and fibrosis progression suggests a potential monitoring role for these bile acids in CFLD.

Understanding environmental influences on walking - Review and research agenda

Background: Understanding how environmental attributes can influence particular physical activity behaviors is a public health research priority. Walking is the most common physical activity behavior of adults; environmental innovations may be able to influence rates of participation. Method: Review of studies on relationships of objectively assessed and perceived environmental attributes with walking. Associations with environmental attributes were examined separately for exercise and recreational walking, walking to get to and from places, and total walking. Results: Eighteen Studies were identified. Aesthetic attributes, convenience of facilities for walking (sidewalks, trails); accessibility of destinations (stores, park, beach); and perceptions about traffic and busy roads were found to be associated with walking for particular purposes. Attributes associated with walking for exercise were different front those associated with walking to get to and from places. Conclusions: While few studies have examined specific environment-walking relationships, early evidence is promising. Key elements of the research agenda are developing reliable and valid measures of environmental attributes and walking behaviors, determining whether environment-behavior relationships are causal, and developing theoretical models that account for environmental influences and their interactions with other determinants. (C) 2004 American Journal of Preventive Medicine.

Perceived environment attributes, residential location, and walking for particular purposes

Background: Identifying environmental factors that can influence physical activity is a public health priority. We examined associations of perceived environmental attributes with walking for four different purposes: general neighborhood walking, walking for exercise, walking for pleasure, and walking to get to and from places. Methods: Participants (n =399; 57% women) were surveyed by mail. They reported place of residence, walking behaviors, and perceptions of neighborhood environmental attributes. Results: Men with the most positive perceptions of neighborhood aesthetics were significantly more likely (odds ratio [OR] =7.4) to be in the highest category of neighborhood walking. Men who perceived the weather as not inhibiting their walking were much more likely (OR= 4.7) to be high exercise walkers. Women who perceived the weather as not inhibiting their walking were significantly more likely to be high neighborhood walkers (OR=3.8) and those with moderate perceptions of accessibility were much more likely to do more walking for pleasure (OR=3.5). Conclusions: Different environmental attributes were associated with different types of walking and these differed between men and women. Approaches to increasing physical activity might usefully focus on those attributes of the local environment that might influence particular subsets of walking behavior.

Knowledge beliefs and attitudes of squash venue operators relating to use of protective eyewear

Sports venues are in a position to potentially influence the safety practices of their patrons. This study examined the knowledge, beliefs and attitudes of venue operators that could influence the use of protective eyewear by squash players. A 50% random sample of all private and public squash venues affiliated with the Victorian Squash Federation in metropolitan Melbourne was selected. Face-to-face interviews were conducted with 15 squash venue operators during August 2001. Interviews were transcribed and content and thematic analyses were performed. The content of the interviews covered five topics: (1) overall injury risk perception, (2) eye injury occurrence, (3) knowledge, behaviors, attitudes and beliefs associated with protective eyewear, (4) compulsory protective eyewear and (5) availability of protective eyewear at venues. Venue operators were mainly concerned with the severe nature of eye injuries, rather than the relatively low incidence of these injuries. Some venue operators believed that players should wear any eyewear, rather than none at all, and believed that more players should use protective eyewear. Generally, they did not believe that players with higher levels of experience and expertise needed to wear protective eyewear when playing. Only six venues had at least one type of eyewear available for players to hire or borrow or to purchase. Operators expressed a desire to be informed about correct protective eyewear. Appropriate protective eyewear is not readily available at squash venues. Better-informed venue operators may be more likely to provide suitable protective eyewear.

Measurement and prediction of energy expenditure in males during household and garden tasks

Participation in at least 30 min of moderate intensity activity on most days is assumed to confer health benefits. This study accordingly determined whether the more vigorous household and garden tasks (sweeping, window cleaning, vacuuming and lawn mowing) are performed by middle-aged men at a moderate intensity of 3-6 metabolic equivalents (METs) in the laboratory and at home. Measured energy expenditure during self-perceived moderate-paced walking was used as a marker of exercise intensity. Energy expenditure was also predicted via indirect methods. Thirty-six males [Xmacr (SD): 40.0 (3.3) years; 179.5 (6.9) cm; 83.4 (14.0) kg] were measured for resting metabolic rate (RMR) and oxygen consumption (V.O-2) during the five activities using the Douglas bag method. Heart rate , respiratory frequency, CSA (Computer Science Applications) movement counts, Borg scale ratings of perceived exertion and Quetelet's index were also recorded as potential predictors of exercise intensity. Except for vacuuming in the laboratory, which was not significantly different from 3.0 METs (P=0.98), the MET means in the laboratory and home were all significantly greater than 3.0 (Pless than or equal to0.006). The sweeping and vacuuming MET means were significantly higher (P