Human Health Disorders Research Articles

Preventive Efficacy of Bulk and Nanocurcumin Against Lead-Induced Oxidative Stress in Mice

Chronic lead exposure is associated with several health disorders in humans and animals. Lead exposure leads to the generation of reactive oxygen species and depletes body antioxidant enzymes causing damage to various macromolecules and ultimately cell death. Curcumin has been widely recognized to protect against metal toxicity but has major limitations of reduced bioavailability. Nanoencapsulation of curcumin could be an effective strategy to combat lead induced toxic manifestations. The present study investigates the protective efficacy of bulk and nanocurcumin against lead-induced toxicity. Swiss albino mice were daily exposed to lead acetate (25 mg/kg, i.p.) alone and after 1 h treated either with curcumin (15 mg/kg, orally) or nanocurcumin (15 mg/kg, orally) for two consecutive weeks. The preventive efficacy of nanocurcumin was evaluated against various altered biochemical variables suggestive of oxidative stress and lead accumulation in blood and soft tissues. Coadministration of nanocurcumin with lead restored the altered δ-aminolevulinic acid dehydratase activity, glutathione (reduced and oxidized) levels, and also decreased reactive oxygen species, and thiobarbituric acid reactive substances levels. Nanocurcumin due to its possible chelating property and enhanced bioavailability efficiently removed lead from blood and soft tissues compared to bulk curcumin. Results demonstrate the enhanced preventive efficacy of nanocurcumin and suggest an interesting and novel approach for better treatment of lead toxicity.

The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage.

BackgroundWe describe the genome of the western painted turtle, Chrysemys picta bellii, one of the most widespread, abundant, and well-studied turtles. We place the genome into a comparative evolutionary context, and focus on genomic features associated with tooth loss, immune function, longevity, sex differentiation and determination, and the species' physiological capacities to withstand extreme anoxia and tissue freezing.ResultsOur phylogenetic analyses confirm that turtles are the sister group to living archosaurs, and demonstrate an extraordinarily slow rate of sequence evolution in the painted turtle. The ability of the painted turtle to withstand complete anoxia and partial freezing appears to be associated with common vertebrate gene networks, and we identify candidate genes for future functional analyses. Tooth loss shares a common pattern of pseudogenization and degradation of tooth-specific genes with birds, although the rate of accumulation of mutations is much slower in the painted turtle. Genes associated with sex differentiation generally reflect phylogeny rather than convergence in sex determination functionality. Among gene families that demonstrate exceptional expansions or show signatures of strong natural selection, immune function and musculoskeletal patterning genes are consistently over-represented.ConclusionsOur comparative genomic analyses indicate that common vertebrate regulatory networks, some of which have analogs in human diseases, are often involved in the western painted turtle's extraordinary physiological capacities. As these regulatory pathways are analyzed at the functional level, the painted turtle may offer important insights into the management of a number of human health disorders.

Prevention of Chronic Lead Toxicity on Adult Worker with Calcium Supplement

Lead can cause health disorders in humans, albeit at a lower level than the permitted maximum blood lead level. Therefore, a treatment should be sought that will reduce lead in the blood, especially in adults. Communities who have a high risk for chronic lead poisoning from the ambient air are employees who work on the road. This study aims to analyze the effects of calcium supplementation on blood lead levels in adult workers. This research uses quasi-experimental design with a community trial design for as many as 150 people, the group consisted of 75 control and 75 treated groups which were given calcium supplements at a dose of 500 mg 3 times daily for three months. Measurements of blood lead levels were taken before consuming calcium and three months afterwards by using Spectrofotometer at Clinical Laboratory. Subjects who completed the study on a regular basis totaled 87 people, divided into a control group of 46 people and the treated group of 41 people. The results showed that: (1) the initial blood lead levels in the control group 6.11 μg/dL and 4.16 μg/dL after treatment. Initial blood lead levels in the treated group 10.35 μg/dL and 3.2 8 μg/dL after treatment; (2) calcium treatment with a dose of 3 x 500 mg a day orally for 3 months can reduce blood lead levels significantly. This study found that calcium tablets can be used to reduce blood lead levels in adult workers.

Commentary: Epidemiology, iodine deficiency and the power of multidisciplinary sufficiency

It is pleasing to see this article being accorded ‘classic’ status. I am also glad to be able to offer comment on it since, by coincidence, I was ‘on the sidelines’ during the development of several stages of what became a multidisciplinary research-and-intervention odyssey, spanning the 1960s to the 1980s. Around 1970, Basil Hetzel, Foundation Professor of Social and Preventive Medicine at Monash University, Melbourne, Australia—and supervisor of my (unrelated) PhD—saw clearly the need and opportunity to pursue a programme of research for which this classic article is the prime foundation. The programme sought, via epidemiological research and then animal experimental studies, a fuller understanding of the developmental and health consequences of lifelong iodine deficiency. Whereas goitre (sometimes associated with cretinism) had been known to medicine in Europe and China for many centuries, its usual causation by micronutrient deficiency was not understood and neither was its linkage with a wider range of disabilities. Hence the importance of research to achieve, first, the elaboration of the full spectrum of iodine deficiency disorders (IDDs), and, second, the mobilization of international agency support for large-scale population interventions and evaluations. Basil Hetzel was Professor of Medicine during my undergraduate clinical years (1964–66) at the University of Adelaide. I knew nothing, then, of his nascent interest in the problem of iodine deficiency and goitre in the Papua New Guinea (PNG) highlands. In describing the source of his interest, he has noted in his autobiographical book, Chance and Commitment: Memoirs of a Medical Scientist (2005), the role of serendipity in one’s research life—in this case, his being asked to review a journal paper, in 1963, on an exploratory study of goitre prevention in PNG. During my first 2 years in the Department of Social and Preventive Medicine at Monash University, there were occasional frissons of excitement relating to the ongoing randomized controlled trial of cretinism prevention in newborns in a sample of villages in the PNG highlands. The intervention, in 1966, entailed intramuscular injection of reproductive-aged, alternate, women with iodized oil or saline. Follow-up of pregnancy outcome occurred over the next 3 years, via copious boot-leather epidemiology in the mountainous PNG highlands. This classically experimental study was a relatively novel epidemiological research design in the late 1960s—and especially so for non-communicable disease outcomes. (Further, of course, it was carried out at a time when the process of research ethical review was a much lesser source of delay and frustration than is now the case.) Interestingly, at that time, the concepts and terminology of epidemiological research, especially for non-communicable diseases, were in a rather intuitive and unsystematized state. The leading epidemiology textbook of the day, by McMahon and Pugh, did not mention the actual word ‘confounding’. (When I arrived in 1972 at the highly regarded Department of Epidemiology, University of North Carolina, the senior academics there referred to case– control studies as ‘association studies’). Hetzel was fortunate to have able and energetic field-working colleagues, well-attuned to tramping around the PNG highlands—Drs Ian Buttfield and, especially, Peter Pharoah. The support from the PNG Department of Public Health was also invaluable. Meanwhile, back in Australia, the other side of the ‘iodine coin’ was causing public health concern. Tasmania, with its long-standing problem of iodine deficiency and adult goitre, had introduced iodine-supplemented bread in 1966. At that same time, coincidentally, iodine-based sterilizers (iodophors) were introduced into the dairy industry to ensure a safe milk supply. This became a second, unintended, source of iodine supplementation in the diet. A subsequent rise in thyrotoxicosis occurred due to over-exposure to supplementary iodine and, hence, overactive thyroid glands. Hetzel was called in as an advisor. Here was further confirmation of a central role for dietary iodine imbalance as a source of various human health disorders. Published by Oxford University Press on behalf of the International Epidemiological Association

Abuse of Pharmaceutical Drugs-antibiotics in Dairy Cattle in Kosovo and Detection of their Residues in Milk

Introduction: Pharmaceutical drugs-antibiotics are given to livestock by veterinarians for the prevention and treatment of disease, but also as a stimulant for animal growth and conversion. Regardless of the way the drugs are inserted into the body of the animal, there will always be residual risk in milk which exceed the maximum level allowed. Thus, it can lead to health disorders in humans and in some cases even death. Aim of study: The main aim of this study is to discover the use of pharmaceutical drugs – antibiotics in dairy cows and to detect betalactam and sulfonamide residues in milk. Methods and materials used: During the period January to August 2011, were collected 127 milk samples from cows treated with pharmaceutical drugs – antibiotics. Samples were analysed in the Veterinary Institute in Skopje using “Elissa” screening method and “HPLC” confirmatory method. Results: The study shows that of 127 samples of milk analysed, over 70% of them (64 were contaminated with betalactam residues and 24 with sulphonamide residues) contains residues of drugs, while over 20% of them (15 being beta-lactams and 4 sulphonamides) have passed the maximum residue limit allowed. Conclusion: 70% of the drugs given to dairy cattle in Kosovo are pharmaceutical – antibiotics and their residues are present in milk. We conclude that pharmaceutical drugs – antibiotics that are used in humans should not be used in animals too and their provision should be limited to a reasonable and lawful level.

Kluyveromyces lactis: a suitable yeast model to study cellular defense mechanisms against hypoxia-induced oxidative stress.

Studies about hypoxia-induced oxidative stress in human health disorders take advantage from the use of unicellular eukaryote models. A widely extended model is the fermentative yeast Saccharomyces cerevisiae. In this paper, we describe an overview of the molecular mechanisms induced by a decrease in oxygen availability and their interrelationship with the oxidative stress response in yeast. We focus on the differential characteristics between S. cerevisiae and the respiratory yeast Kluyveromyces lactis, a complementary emerging model, in reference to multicellular eukaryotes.

The Journal of Physiologyat SfN 2011

In this, our second dedicated neuroscience issue, we are pleased to announce that The Journal of Physiology will once again be at SfN. The Journal has sponsored satellite symposia at SfN Annual meetings since 1999 on topics ranging from the Physiology of brain–computer interfaces to Mechanisms of neocortical development. This year we are sponsoring a satellite symposium on Cortical inhibitory neuron ‘basket cells’: from circuit function to disruption at the Washington Convention Centre on Friday 12 November 2011 from 3 to 6 pm. The role for local circuit inhibitory interneurons in shaping the timing and excitability of cortical circuits is well established. Given the central role for interneurons in CNS function it comes as no surprise that loss or dysregulation of this important cell type has been implicated in numerous human mental health disorders, including the epilepsies, stroke, Alzheimer's disease, schizophrenia and cognitive defects. Within this anatomically and functionally diverse cell population two distinct basket cell types exist, the so-called parvalbumin-containing ‘fast-spiking’ and the cholecystokinin-containing ‘non-fast-spiking’ cell types. Studies over the last 2–3 years have placed these two cell types front and centre as regulators of cortical timing and neuromodulation during development, maturation and ageing. Despite possessing anatomical similarities, new evidence suggests that these two cell types have their embryonic origins in distinct areas of the ventral telencephalon. Their distinct origins subject them to differing neuromodulatory signals and maturation processes as they migrate and populate the emerging cortex and hippocampus. Perturbations of these developmental cues and the consequent anomalous interneuron function are rapidly being implicated in a number of CNS disorders. Speakers will highlight recent research on the embryogenesis and maturation of basket cells and their respective circuits, the function and modulation of the distinct basket cells in physiological cortical operation and the malfunction of cortical circuits, and the roles implicated for basket cells in determining a number of mental health disorders. The symposium, which does not require pre-registration and is free to anyone wishing to attend, is organised by former Senior Editor of The Journal of Physiology Chris McBain (NIH, Washington, DC, USA). We are expecting excellent attendance to hear the internationally renowned speakers, who include: Kenneth Pelkey (NIH, Washington, DC, USA) on Embryogenesis, development and maturation of a hippocampal basket cell circuit Tibor Harkany (University of Aberdeen, Scotland, UK) on Cannabinoid receptors and the development of CCK basket cell networks Marlene Bartos (University of Freiburg, Freiburg, Germany) on Differential roles for parvalbumin and CCK basket cells in cortical function Ivan Soltesz (University of California, Irvine, CA, USA) on Modulation of pre- and postsynaptic receptors of basket cell synapses Edward M. Callaway (Salk Institute for Biological Studies, La Jolla, CA, USA) on Rabies-based tools for elucidating neural circuits and linking connectivity to function David A. Lewis (University of Pittsburgh, Pittsburgh, PA, USA) on Cortical excitatory/inhibitory balance and cognitive dysfunction in schizophrenia As for all our previous symposia, we will publish a set of reviews based on the talks. These will appear in one of our future dedicated neuroscience issues early in 2012. The Journal of Physiology will also be raising awareness of our dedicated neuroscience issues – JPn for short – throughout the SfN meeting. We hope these issues, focusing on neuroscience and containing our usual mix of reviews, research articles and commentaries, will come to be recognised by the neuroscience community as a source of authoritative information on diverse aspects of the physiology of the brain and nervous system and as first choice for the best work of neuroscientists whose research encompasses physiological mechanisms. The Journal's scope and statistics can be found online in our Author Guideline web pages (http://jp.physoc.org/site/misc/author.xhtml#scope). Readers attending at SfN 2011 can learn more about The Journal of Physiology at The Physiological Society stand (no. 3134). We hope all readers enjoy this JPn issue. If you do not already read The Journal of Physiology regularly why not sign up for e-alerts for our neuroscience content at http://jp.physoc.org/cgi/alerts/collalert. Our next dedicated issue will be published on 1 December 2011.

Folk medicine in the northern coast of Colombia: an overview

BackgroundTraditional remedies are an integral part of Colombian culture. Here we present the results of a three-year study of ethnopharmacology and folk-medicine use among the population of the Atlantic Coast of Colombia, specifically in department of Bolívar. We collected information related to different herbal medicinal uses of the local flora in the treatment of the most common human diseases and health disorders in the area, and determined the relative importance of the species surveyed.MethodsData on the use of medicinal plants were collected using structured interviews and through observations and conversations with local communities. A total of 1225 participants were interviewed.ResultsApproximately 30 uses were reported for plants in traditional medicine. The plant species with the highest fidelity level (Fl) were Crescentia cujete L. (flu), Eucalyptus globulus Labill. (flu and cough), Euphorbia tithymaloides L. (inflammation), Gliricidia_sepium_(Jacq.) Kunth (pruritic ailments), Heliotropium indicum L. (intestinal parasites) Malachra alceifolia Jacq. (inflammation), Matricaria chamomilla L. (colic) Mentha sativa L. (nervousness), Momordica charantia L. (intestinal parasites), Origanum vulgare L. (earache), Plantago major L. (inflammation) and Terminalia catappa L. (inflammation). The most frequent ailments reported were skin affections, inflammation of the respiratory tract, and gastro-intestinal disorders. The majority of the remedies were prepared from freshly collected plant material from the wild and from a single species only. The preparation of remedies included boiling infusions, extraction of fresh or dry whole plants, leaves, flowers, roots, fruits, and seeds. The parts of the plants most frequently used were the leaves. In this study were identified 39 plant species, which belong to 26 families. There was a high degree of consensus from informants on the medical indications of the different species.ConclusionsThis study presents new research efforts and perspectives on the search for new drugs based on local uses of medicinal plants. It also sheds light on the dependence of rural communities in Colombia on medicinal plants.

Effects of Pinus massoniana bark extract on the adhesion and migration capabilities of HeLa cells

Pinus massoniana Lamb is a Chinese red pine species used in traditional medicine for the treatment of a variety of human health disorders. Recent studies have shown that P. massoniana bark extract (PMBE) has an anti-proliferation effect on cancer cells. However, it is not clear if PMBE affects cancer cell migration and/or invasion. We tested the effect of PMBE, which has B-type procyanidin as its main constituent, on the adhesion and migration capabilities of HeLa cells, a human cervical cancer cell line, cultured in vitro. Our results showed that PMBE has no significant effect on the adhesion capability of HeLa cells, but strongly inhibits their migration. This finding suggests that PMBE could be a potential therapeutic agent for metastatic cancer.

HIPPOCRATES IS CARE: HISTORY AND SOME BIOLOGICAL PATHWAYS ON CAREGIVER

Abstract Hippocrates is the mainstay of care. Plato and Aristotle state humoralism as the way that Hippocrates understands human health disorders. He closely observed patients to restore humoral equilibrium, relying on healing power of nature to recover health, rejecting drugs or any kind of procedure that could harm the individual. The development of a common ground of understanding is desirable as a process of negotiating treatment goals and methods which may create an atmosphere of support and solidarity. The concept of supportive care was formalized in Belgium in 1992 with attention to multicultural aspect of our population. The biological basis on care are backed on cortical circuitries, association of pathways, existence of several neurotransmitters, which mediates integrative process promoting behavior, emotion and cognitive. Care may influence favorably all these biological systems and help to improve quality of live or even cure the patient. Descriptors: Hippocrates is Care, Biological Basis on Care, Pathways of Care.

Dissemination in Pigtailed Macaques after Primary Infection of Dengue-3 Virus

Nonhuman primates (NHPs) play as indispensable animal model in biomedical research for studying a variety of human health issues, diseases and disorders, therapies, and preventive strategies. Since the immunological and physiological responses of NHPs, at some extent, to experimental viral infections are similar to humans, it is possible that studies of dengue infection in NHPs may aid understanding of dengue infection in humans. In this study,we used pigtailed macaques ( Macaca nemestrina ) as the experimental animal to study dengue-3 (DEN-3) virus infection.We evaluated DEN-3 viral distribution and replication sites after a primary infection in all collected tissues. Sequential localization in tissue of DEN-3 virus was studied in pigtailed macaques euthanized three days post viral inoculation (10 pfu mL ). Pigtailed macaque that was inoculated subcutaneously or intravenously; showed the highest viremia (62.94 pfu mL and 58.62 pfu mL ) detected by one step reverse transcription real time PCR. The virus inoculated in pigtailed macaques by subcutaneous injection was rapidly disseminated from the inoculation site to the lymph nodes, adrenal glands, kidneys, heart, thyroid, liver, prostate gland, and seminal vesicles. Meanwhile, dissemination of dengue virus in pigtailed macaques inoculated intravenously was detected in lymph nodes, thymus, salivary glands, liver, and prostate gland. This study suggested that the above mentioned-tissue specimens are involved or affected by DEN-3 virus replication and the route of infection seemed to have influenced the virus dissemination.

Dietary hyperglycemia, glycemic index and metabolic retinal diseases

The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during the early postprandial stage (0-2h) and a compensatory hyperlipidemia associated with counter-regulatory hormone responses during late postprandial stage (4-6h). Over the past three decades, several human health disorders have been related to GI. The strongest relationship suggests that consuming low-GI foods prevents diabetic complications. Diabetic retinopathy (DR) is a complication of diabetes. In this aspect, GI appears to be useful as a practical guideline to help diabetic people choose foods. Abundant epidemiological evidence also indicates positive associations between GI and risk for type 2 diabetes, cardiovascular disease, and more recently, age-related macular degeneration (AMD) in people without diabetes. Although data from randomized controlled intervention trials are scanty, these observations are strongly supported by evolving molecular mechanisms which explain the pathogenesis of hyperglycemia. This wide range of evidence implies that dietary hyperglycemia is etiologically related to human aging and diseases, including DR and AMD. In this context, these diseases can be considered as metabolic retinal diseases. Molecular theories that explain hyperglycemic pathogenesis involve a mitochondria-associated pathway and four glycolysis-associated pathways, including advanced glycation end products formation, protein kinase C activation, polyol pathway, and hexosamine pathway. While the four glycolysis-associated pathways appear to be universal for both normoxic and hypoxic conditions, the mitochondria-associated mechanism appears to be most relevant to the hyperglycemic, normoxic pathogenesis. For diseases that affect tissues with highly active metabolism and that frequently face challenge from low oxygen tension, such as retina in which metabolism is determined by both glucose and oxygen homeostases, these theories appear to be insufficient. Several lines of evidence indicate that the retina is particularly vulnerable when hypoxia coincides with hyperglycemia. We propose a novel hyperglycemic, hypoxia-inducible factor (HIF) pathway, to complement the current theories regarding hyperglycemic pathogenesis. HIF is a transcription complex that responds to decrease oxygen in the cellular environment. In addition to playing a significant role in the regulation of glucose metabolism, under hyperglycemia HIF has been shown to increase the expression of HIF-inducible genes, such as vascular endothelial growth factor (VEGF) leading to angiogenesis. To this extent, we suggest that HIF can also be described as a hyperglycemia-inducible factor. In summary, while management of dietary GI appears to be an effective intervention for the prevention of metabolic diseases, specifically AMD and DR, more interventional data is needed to evaluate the efficacy of GI management. There is an urgent need to develop reliable biomarkers of exposure, surrogate endpoints, as well as susceptibility for GI. These insights would also be helpful in deciphering the detailed hyperglycemia-related biochemical mechanisms for the development of new therapeutic agents.

Peroxisome proliferator-activated receptor gamma in osteoarthritis

Osteoarthritis (OA) is among the most prevalent chronic human health disorders and the most common form of arthritis. It is a leading cause of disability in developed countries. This disease is characterized by cartilage deterioration, synovitis, and remodeling of the subchondral bone. There is not yet a satisfactory treatment to stop or arrest this disease process. Although several candidates for therapeutic approaches have been put forward, recent studies suggest that activation of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is an interesting target for this disease. PPARγ is a ligand-activated transcription factor and member of the nuclear receptor superfamily. Agonists of PPARγ inhibit inflammation and reduce synthesis of cartilage degradation products both invitro and invivo, and reduce the development/progression of cartilage lesions in OA animal models. This review will highlight the recent experimental studies on the presence of PPARγ in articular tissues and its effect on inflammatory and catabolic responses in chondrocytes and synovial fibroblasts, as well as the protective effects of PPARγ ligands in arthritis experimental models. Finally, the role of PPARγ polymorphism in the pathogenesis of OA and related musculoskeletal diseases will also be discussed.

In the Shadow of Academic Medical Centers: A Systematic Review of Urban Health Research in Baltimore City

The city of Baltimore is a typical, large, urban center in the United States with several major academic medical institutions surrounded by disadvantaged neighborhoods with multiple poor health indices. In order to understand the extent to which academic research agendas reflect the health concerns of Baltimore's local population, a systematic review was conducted to identify research about four key, health-related topic areas. We classified papers on: disease prevalence and health status, utilization of health services, population-based interventions, and the unmet health needs of Baltimore City residents. Approximately 4,150 citations were identified in the search and two levels of screening yielded a total of 288 papers. The majority of articles (n = 189) examined prevalence of health conditions such as Human Immunodeficiency Virus (HIV), mental health and mental disorders, and sexually transmitted diseases. Papers about specific target populations focused primarily on adults, African Americans, and females. Despite a significant body of research concerning several health conditions and priority populations, significant gaps in knowledge about health services utilization, community interventions, unmet health needs, and the prevalence of specific health issues remain. This review provides valuable insight into the extent of health research conducted about the city of Baltimore and whether community health priorities have been investigated. It provides a basis for examining the potential directions of academic research centers to effectively identify and address collective, urban health priorities of the communities in which they reside.

Laser-Ionization TOF Mass Spectrometer Characterization of Benzene Destruction in Atmospheric Pressure Pulsed Discharge

Benzene is a major industrial air pollutant and can cause serious human health disorders. In this paper an investigation on benzene destruction, in an atmospheric-pressure fast-flow pulsed DC-discharge by means of laser ionization combined with time-of-flight (TOF) mass spectrometry, is reported. Most by-products including transient reactive species from the benzene discharge were characterized by molecular beam sampling combined with TOF mass spectrometry. It is showed that, with a gas mixture of 0.5% C6H6 in Ar, benzene can be effectively destroyed by discharge plasma. The intermediate species consisted of small fragments of CnHm (n = 3∼5, m = 1∼11), cycle-chain species of CnHm (n = 6∼9, m = 7∼10) and polycyclic species CnHm (n ≥9, m = 8∼12). The alternation of mass peaks (intensity) with even/odd electrons was observed in the measured mass spectra. The results indicated that the alternation is mainly due to the different ionization potentials of the open shell and close shell species. Based on the examination of the features of the species' composition, the primary reaction pathways are proposed and discussed.

Engineering in Genomics [variable number tandem repeats as agents of functional regulation in the genome

The explosion of genetic data availability in the last decade has opened up many new avenues for the application of genetics to the improvement of human health, particularly, the common and complex disorders, which previously largely defied researchers seeking to understand their etiology. However, the utilization of this data in healthcare and by the pharmaceutical industry is still in its infancy, with the current focus being almost solely on two forms of genetic variation single nucleotide polymorphisms (SNPs), involving the substitution of one base in DNA for another and copy number variations, involving the deletion and multiplication of regions > 1,000 base pairs (bp). However, there is currently a relative paucity of funding and general interest in a third form of variation called microsatellites and mini- satellites.

Les glycosyltransférases chondrocytaires : nouvelles cibles pharmacologiquespour les atteintes dégénératives du cartilage articulaire ?

Arthritis, osteoarthritis and other degenerative diseases characterized by cartilage deterioration are the most prevalent chronic human health disorders. Despite their major socioeconomic impact there is still no satisfactory treatment. Their frequency is increasing with the lengthening of life expectancy, creating a major public health challenge for coming years. It is important to diagnose such diseases at an early stage and to develop new effective therapies. We are attempting to develop new therapeutic approaches in this context, keeping in mind that cartilage is one of the few human tissues which is unable to regenerate. We intend to identify and characterize key proteins involved in the biosynthesis of cartilage matrix components. One innovative strategy consists of gene transfer, triggering overexpression of native or recombinant factors that can stimulate chondrocyte anabolic activity in order to promote cartilage repair The loss of matrix components, and especially glycosaminoglycans (GAG), is the earliest event in cartilage degeneration. We therefore looked at glycosyltransferases, and especially galactose beta1,3-glucuronosyltransferase-I (GlcAT-1), which catalyses one of the first steps in GAG biosynthesis. We found that any variation in GlcAT-I activity in chondrocytes or cartilage explants (overexpression, or repression with antisense RNA) affected the GAG content of cartilage. Interestingly, overexpression of this enzyme completely counteracted the GAG depletion produced by the proinflammatory cytokine interleukin 1-beta. The neosynthesized GAG was qualitatively identical to that present in the original cartilage matrix. These results are encouraging for therapeutic approaches based on gene transfer We also investigated the structure-function relationship of human recombinant GlcAT-I upon expression in the methyltrophic yeast Pichia pastoris. This allowed us to determine the molecular basis of the recognition of the donor and acceptor substrates of the enzyme. This multidisciplinary research, based on genetic and protein engineering, molecular modelling and glycochemistry will lay the groundwork for designing original glycomimetics able to stimulate GAG synthesis.

Findings of interest from immunology and psychoneuroimmunology

The biopsychosocial paradigm is now the main model when dealing with most human health disorders. One of the strengths of this model is that it encourages broader thinking when assessing and managing patients. It also encourages broader reading into areas not traditionally associated with manual therapy. Immunology and neuroscience are amongst the fastest growing medical sciences. These fields come together in the relatively new area of psychoneuroimmunolgy. This article examines some findings from these fields that are not widely discussed in the physical therapy professions. These findings are of relevance to many of the disciplines within the physical therapies. It is the authors aim to stimulate further interest in the relevant, yet often under explored areas of immunology and psychoneuroimmunology.

Dietary exposure to lead, cadmium, mercury and radionuclides of an adult urban population in Lebanon: A total diet study approach

Human exposure to toxic chemicals is suspected of being responsible for a wide range of human health disorders. This study is the first in Lebanon to evaluate the dietary exposure of an adult urban population to three heavy metals (lead, cadmium and mercury) and to radionuclides. Exposure assessment was performed by means of the total diet study approach as recommended by the Word Health Organization. Five ‘total diets’ were collected during 2003–04. Average and maximal consumer exposure estimates to heavy metals were calculated and compared with appropriate reference values and with intakes reported from other countries. The average dietary intakes of lead, cadmium and mercury represented 7, 17 and 5.6%, respectively, of the appropriate provisional tolerable weekly intakes (PTWI). The mean dietary intake of methylmercury represented 17.5% of the appropriate PTWI. Cs-134 and I-131 were not detected in any of the food samples. Traces of Cs-137 were only found in five food samples. The exposure assessment conducted places Lebanon among countries least exposed to heavy metals through the diet and it highlights the safety of the food supply from radioactive contamination.

Economy-wide estimates of the implications of climate change: Human health

We study the economic impacts of climate-change-induced change in human health, viz. cardiovascular and respiratory disorders, diarrhoea, malaria, dengue fever and schistosomiasis. Changes in morbidity and mortality are interpreted as changes in labour productivity and demand for health care, and used to shock the GTAP-E computable general equilibrium model, calibrated for the year 2050. GDP, welfare and investment fall (rise) in regions with net negative (positive) health impacts. Prices, production, and terms of trade show a mixed pattern. Direct cost estimates, common in climate change impact studies, underestimate the true welfare losses.