Elucidation of reaction scheme describing malondialdehyde-acetaldehyde-protein adduct formation

Malondialdehyde and acetaldehyde react together with proteins and form hybrid protein conjugates designated as MAA adducts, which have been detected in livers of ethanol-fed animals. Our previous studies have shown that MAA adducts are comprised of two distinct products. One adduct is composed of two molecules of malondialdehyde and one molecule of acetaldehyde and was identified as the 4-methpl-1,4-dihydropyridine-3,5-dicarbaldehyde derivative of an amino group (MHHDC adduct). The other adduct is a 1:1 adduct of malondialdehyde and acetaldehyde and was identified as the 2-formyl-3-(alkylamino)butanal derivative of an amino group (FAAB adduct). In this study, information on the mechanism of MAA adduct formation was obtained, focusing on whether the FAAB adduct serves as a precursor for the MDHDC adduct. Upon the basis of chemical analysis and NMR spectroscopy, two initial reaction steps appear to be a prerequisite for MDHDC formation. One step involves the reaction of one molecule of malondialdehyde and one of acetaldehyde with an amino group of a protein to form the FAAB product, while the other step involves the generation of a malondialdehyde-enamine. It appears that generation of the MDHDC adduct requires the FAAB moiety to be transferred to the nitrogen of the MDA-enamine. For efficient reaction of FAAB with the enamine to take place, additional experiments indicated that these two intermediates likely must be in positions on the protein of close proximity to each other. Further studies showed that the incubation of liver proteins from ethanol-fed rats with MDA resulted in a marked generation of MDHDC adducts, indicating the presence of a pool of FAAB adducts in the liver of ethanol-fed animals. Overall, these findings show that MDHDC-protein adduct formation occurs via the reaction of the FAAB moiety with a malondialdehyde-enamine, and further suggest that a similar mechanism may be operative in vivo in the liver during prolonged ethanol consumption.

The toxins of Lyngbya majuscula and their human and ecological health effects

Lyngbya majuscula is a benthic filamentous marine cyanobacterium, which in recent years appears to have been increasing in frequency and size of blooms in Moreton Bay, Queensland. It has a worldwide distribution throughout the tropics and subtropics in water to 30m. It has been found to contain a variety of chemicals that exert a range of biological effects, including skin, eye and respiratory irritation. The toxins lyngbyatoxin A and debromoaplysiatoxin appear to give the most widely witnessed biological effects in relation to humans, and experiments involving these two toxins show the formation of acute dermal lesions. Studies into the epidemiology of the dermatitic, respiratory and eye effects of the toxins of this organism are reviewed and show that Lyngbya induced dermatitis has occurred in a number of locations. The effects of aerosolised Lyngbya in relation to health outcomes were also reported. Differential effects of bathing behaviour after Lyngbya exposure were examined in relation to the severity of health outcomes. The potential for Lyngbya to exhibit differential toxicologies due to the presence of varying proportions of a range of toxins is also examined. This paper reviews the present state of knowledge on the effects of Lyngbya majuscula on human health, ecosystems and human populations during a toxic cyanobacterial bloom. The potential exists for toxins from Lyngbya majuscula affecting ecological health and in particular marine reptiles. (C) 2001 Elsevier Science Ltd. All rights reserved.

First report of the cyanotoxins cylindrospermopsin and deoxycylindrospermopsin from Raphidiopsis curvata (Cyantobacteria)

A strain of Raphidiopsis (Cyanobacteria) isolated from a fish pond in Wuhan, P. R. China was examined for its taxonomy and production of the alkaloidal hepatotoxins cylindrospermopsin (CYN) and deoxy-cylindrospermopsin (deoxy-CYN). Strain HB1 was identified as R. curvata Fritsch et Rich based on morphological examination of the laboratory culture. HB1 produced mainly deoxy-CYN at a concentration of 1.3 mg(.)g(-1) (dry ut cells) by HPLC and HPLC-MS/MS. CYN was also detected in trace amounts (0.56 mug(.)g(-1)). A mouse bioassay did not show lethal toxicity when tested at doses up to 1500 mg dry weight cells(.)kg(-1) body weight within 96 h, demonstrating that production of primarily deoxy CYN does not lead to significant mouse toxicity by strain BB I. The presence of deoxy-CYN and CYN in R curvata suggests that Raphidiopsis belongs to the Nostocaceae, but this requires confirmation by molecular systematic studies. Production of these cyanotoxins by Raphidiopsis adds another genus, in addition to Cylindrospemopsis, Aphanizomenon, and Umezakia, now known to produce this group of hepatotoxic cyanotoxins. This is also the first report from China of a CYN and deoxy-CYN producing cyanobacterium.

Perceived constraints and social support for active leisure among mothers with young children

Evidence suggests that women who are mothers of young children have lower levels of physical activity than women of similar age who do not have children (Brown, Lee, Mishra, & Bauman, 2000). The purposes of this study were to explore the factors that constrain mothers of young children from being more physically active, and the relationship between physical activity and levels of social support available to the women. The empirical basis for this examination was provided through a study of activity levels and barriers to physical activity experienced by a sample of 543 mothers of young children from differing socioeconomic backgrounds. The data indicate that: (a) more than two-thirds of the mothers were inadequately active in their leisure time for health benefit; (b) while the vast majority of mothers expressed a desire to be more active, they were inhibited in their ability to act out their leisure preferences by a combination of structural (e.g., lack of time, money, energy) and ideological influences (e.g., sense of commitment to others); (c) access to social support (from partners, family, and friends) was seen to place some women in a better position than others to negotiate constraints that inhibit leisure participation; and (d) within groups of varying socioeconomic status (SES) there was wide variation in the amount of time spent each week in active leisure.

Historical PCDD Inputs and Their Source Implications from Dated Sediment Cores in Queensland (Australia)

Recent investigations have demonstrated the presence of an unidentified source of polychlorinated dibenzo-p-dioxins (PCDDs) in the coastal zone of Queensland (Australia). The present study provides new information on the possible PCDD sources and their temporal input to this environment. Two estuarine sediment cores were collected in northern Queensland for which radiochemical chronologies were established. Core sections from different depositional ages, up to three centuries, have been analyzed for 2,3,7,8-substituted PCDDs and polychlorinated dibenzofurans (PCDFs). Variations of PCDD concentrations in the sediment cores over several centuries of depositional history were relatively small, and elevated PCDD levels were still present in sediment slices from the early 17th century. PCDD/F isomer patterns and congener profiles in sediments deposited during the last 350 years were almost identical and correlated well to the characteristic profiles observed in surface sediments and soils from the entire Queensland coastline. Profiles were dominated by higher chlorinated PCDDs, in particular octachlorodibenzodioxin (OCDD), whereas PCDF concentrations were below or near the limit of detection. These results indicate the presence of a PCDD source prior to industrialization and production of commercial organochlorine products. Further, the present study demonstrates that PCDD input patterns have been similar along an extensive but localized area over at least several centuries, contributing relatively high concentrations of PCDDs to the coastal system of Queensland.

Evidence for the presence of a widespread PCDD source in coastal sediments and soils from Queensland, Australia

Recent studies have demonstrated the occurrence of elevated levels of higher chlorinated PCDDs in the coastal environment of Queensland, Australia. This study presents new data for OCDD contamination and full PCDD/F profile analysis in the environment of Queensland. Marine sediments, irrigation drain sediments and topsoil were collected from sites that were expected to be influenced by specific land-use types. High OCDD concentrations were associated mainly with sediments collected near the mouth of rivers which drain into large catchments in the tropical and subtropical regions. Further, analysis of sediments from irrigation drains could be clearly differentiated on the basis of OCDD contamination, with high concentrations in samples from sugarcane drains collected from coastal regions, and low concentrations in drain sediments from drier inland cotton growing areas. PCDD/F congener-specific analysis demonstrated almost identical congener profiles in all samples collected along the coastline. This indicates the source to be widespread. Profiles were dominated by higher chlorinated PCDDs, in particular OCDD whereas 2,3,7,8-substituted PCDFs were below the limit of quantification in the majority of samples. The full PCDD/F profile analysis of samples strongly resemble those reported for lake sediments from Mississippi and kaolinite samples from Germany, Strong similarities to these samples with respect to congener profiles and isomer patterns may indicate the presence of a similar source and/or formation process that is yet unidentified. (C) 2001 Elsevier Science Ltd. All rights reserved.

Pectenotoxins - an issue for public health - A review of their comparative toxicology and metabolism

Pectenotoxins (PTXs) are a group of toxins associated with diarrhetic shellfish poisoning (DSP) and isolated from DSP toxin-producing dinoflagellate algae. Consumption of shellfish contaminated with PTXs has been associated with incidences of severe diarrhetic illness resulting in hospitalisation. Concern has been raised for public health following the discovery that these toxins are not only hepatotoxic and can cause diarrhetic effects in mammals, but that they are potently cytotoxic to human cancer cell lines and have been found to be tumour promoters in animals. With advances in knowledge and technology, more PTXs are being identified, but little is known of their toxicology and the potential impact these toxins may have on public health in the long term. Without such information, adequate health-risk assessments for the consumption of shellfish contaminated with PTXs cannot be performed. This review gives a brief introduction to diarrhetic shellfish toxins, details the known toxicology and metabolism of PTXs in animals, and discusses known incidences of PTX poisoning in humans. (C) 2001 Elsevier Science Ltd. All rights reserved.

Human Fatalities from Cyanobacteria: Chemical and Biological Evidence for Cyanotoxins

An outbreak of acute liver failure occurred at a dialysis center in Caruaru, Brazil (8 degrees 17 'S, 35 degrees 58 'W), 134 km from Recife, the state capital of Pernambuco. At the clinic, 116 (89%) of 131 patients experienced visual disturbances, nausea, and vomiting after routine hemodialysis treatment on 13-20 February 1996. Subsequently, 100 patients developed acute liver failure, and of these 76 died. As of December 1996, 52 of the deaths could be attributed to a common syndrome now called Caruaru syndrome. Examination of phytoplankton from the dialysis clinic's water source, analyses of the clinic's water treatment system, plus serum and liver tissue of clinic patients led to the identification of two groups of cyanobacterial toxins, the hepatotoxic cyclic peptide microcystins and the hepatotoxic alkaloid cylindrospermopsin. Comparison of victims' symptoms and pathology using animal studies of these two cyanotoxins leads us to conclude that the major contributing factor to death of the dialyses patients was intravenous exposure to microcystins, specifically microcystin-YR, -LR, and -AR. From liver concentrations and exposure volumes, it was estimated that 19.5 mug/L microcystin was in the water used for dialysis treatments. This is 19.5 times the level set as a guideline for safe drinking water supplies by the World. Health Organization.

Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol

Aims Previous studies suggest that estimated creatinine clearance, the conventional measure of renal function, does not adequately reflect charges in renal drug handling in some patients, including the immunosuppressed. The aim of this study was to develop and validate a cocktail of markers. to be given in a single administration, capable of detecting alterations in the renal elimination pathways of glomerular filtration, tubular secretion and tubular reabsorption. Methods Healthy male subjects (n = 12) received intravenously infused 2500 mg sinistrin (glomerular filtration) and 440 mg p-aminohippuric acid (PAH; anion secretion), and orally administered 100 mg fluconazole (reabsorption) and 15 mg rac-pindolol (cation secretion). The potential interaction between these markers was investigated in a pharmacokinetic study where markers (M) or fluconazole (F) were administered alone or together (M + F). Validated analytical methods were used to measure plasma and urine concentrations in order to quantify the renal handling of each marker. Plasma protein binding of fluconazole was measured by ultrafiltration. All subjects had an estimated creatinine clearance within the normal range. The renal clearance of each marker (Mean +/- s.d.) was calculated as the ratio of the amount excreted in urine and thearea-under-the-concentration-time curve. Statistical comparisons were made using a paired t-test and 95% confidence intervals were reported. Results The renal clearances of sinistrin (M: 119 +/- 31 ml min(-1); M + F: 130 +/- 40 ml min(-1); P = 0.32), PAH (M: 469 +/- 145 ml min(-1); M + F: 467 +/- 146 ml min(-1); P = 0.95), R-pindolol (M: 204 +/- 41 ml min(-1); M + F: 190 +/- 41 ml min(-1); P = 0.39; n = 11), S-pindolol (M: 225 +/- 55 ml min(-1); M + F: 209 +/- 60 ml min(-1); P = 0.27; n = 11) and fluconazole (F: 14.9 +/-3.8 ml min(-1); M + F: 13.6 +/- 3.4 ml min(-1); P = 0.16) were similar when the markers or fluconazole were administered alone (M or F) or as a cocktail (M + F). Conclusions This study found no interaction between markers and fluconazole in healthy male subjects, suggesting that a single administration of this cocktail of markers of different renal processes call be used to simultaneously investigate pathways of renal drug elimination.

Long-term outcomes of genetic counseling in women at increased risk of developing hereditary breast cancer Information,

This multicenter study evaluated the impact of genetic counseling in 218 women at risk of developing hereditary breast cancer. Women were assessed prior to counseling and 12-month post-counseling using self-administered, mailed questionnaires. Compared to baseline, breast cancer genetics knowledge was increased significantly at follow-up. and greater increases in knowledge were associated with educational level. Breast cancer anxiety decreased significantly from baseline to follow-up, and these decreases were associated with improvements in perceived risk. A significant decrease in clinical breast examination was observed at the 12-month follow-up. Findings suggest that women with a family history of breast cancer benefit from attending familial cancer clinics as it leads to increases in breast cancer genetics knowledge and decreases in breast cancer anxiety. The lowered rates of clinical breast examination indicate that the content of genetic counseling may need to be reviewed to ensure that women receive and take away the right message. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Telemedicine and developing countries - successful implementation will require a shared approach

Telemedicine is often proposed as a solution to certain health-care problems in the developing world. There seems to be little published experience on which to make judgements. A literature search revealed 39 articles, of which only two related to any kind of direct clinical work; most of them were review articles or editorials. The majority of the work reported was educational in nature, and there has been little clinical experience. It seems probable that telemedicine can help with the education of health-care workers and patients; it seems likely that it could bring major benefits to the organization of health-care. Without proper trials, it will be impossible to determine the place of health-care in the developing world. Trials are the only way in which rational decisions can ultimately be reached regarding whether scarce resources should be devoted to telemedicine in developing countries, or whether they should be employed in more conventional health-care measures whose outcomes are known to be cost-effective.