370 research outputs found
Bone Quality in Children with Severe Neurological Impairment and Intellectual Disability: Diagnostic methods and determinants of low bone quality
This thesis addresses bone quality in children with severe neurological impairment
and intellectual disability (ID). In clinical practice severe problems concerning bone
health are encountered in this group of severely disabled children
Exposição humana ao mercúrio e efeitos adversos à saúde na Amazônia: uma revisão
This paper examines issues of human mercury (Hg) exposure and adverse health effects throughout the Amazon region. An extensive review was conducted using bibliographic indexes as well as secondary sources. There are several sources of Hg (mining, deforestation, reservoirs), and exposure takes place through inhalation or from fish consumption. There is a wide range of exposure, with mean hair-Hg levels above 15µg/g in several Amazonian communities, placing them among the highest reported levels in the world today. Dietary Hg intake has been estimated in the vicinity of 1-2µg/kg/day, considerably higher than the USEPA RfD of 0.1µg/kg/day or the World Health Organization recommendation of 0.23µg/kg/day. Neurobehavioral deficits and, in some cases, clinical signs have been reported both for adults and children in relation to Hg exposure in several Amazonian countries. There is also some evidence of cytogenetic damage, immune alterations, and cardiovascular toxicity. Since fish provide a highly nutritious food source, there is an urgent need to find realistic and feasible solutions that will reduce exposure and toxic risk, while maintaining healthy traditional dietary habits and preserving this unique biodiversity.Este artigo examina questões sobre exposição humana ao mercúrio (Hg) e seus efeitos adversos à saúde na Amazônia, com base em extensa revisão da literatura. Diferentes bioindicadores revelam uma ampla faixa de exposição, com teores médios de Hg em cabelo acima de 15µg/g em diversas comunidades amazônicas, situando-as dentre as mais expostas no mundo atualmente. Taxas de ingestão diária de Hg foram estimadas em alguns estudos e situam-se entre 1-2µg/kg/dia, consideravelmente acima das doses de referência estabelecidas pela USEPA (0,1µg/kg/dia) ou pela OMS (0,23µg/kg/dia). Déficits neurocomportamentais e, em alguns casos, sinais clínicos relacionados à exposição mercurial têm sido relatados tanto em adultos quanto em crianças de diversos países amazônicos. Há também evidências de dano citogenético, mudanças imunológicas e toxicidade cardiovascular. Visto que peixe é altamente nutritivo e há diversas fontes de Hg nesta região, existe uma necessidade urgente de encontrar soluções realistas e viáveis capazes de reduzir os níveis de exposição e de risco tóxico, ao mesmo tempo mantendo os hábitos alimentares tradicionais, preservando a biodiversidade píscea e frutífera e melhorando a saúde das populações desfavorecidas e afetadas.International Development Research Center (IDRC) - CanadaCanadian Institutes of Health Research (CIHR)FAPES
Ocular transient receptor potential channel function in health and disease
Transient receptor potential (TRP) channels sense and transduce environmental
stimuli into Ca2+ transients that in turn induce responses essential for cell
function and adaptation. These non-selective channels with variable Ca2+
selectivity are grouped into seven different subfamilies containing 28
subtypes based on differences in amino acid sequence homology. Many of these
subtypes are expressed in the eye on both neuronal and non-neuronal cells
where they affect a host of stress-induced regulatory responses essential for
normal vision maintenance. This article reviews our current knowledge about
the expression, function and regulation of TRPs in different eye tissues. We
also describe how under certain conditions TRP activation can induce responses
that are maladaptive to ocular function. Furthermore, the possibility of an
association between TRP mutations and disease is considered. These findings
contribute to evidence suggesting that drug targeting TRP channels may be of
therapeutic benefit in a clinical setting. We point out issues that must be
more extensively addressed before it will be possible to decide with certainty
that this is a realistic endeavor. Another possible upshot of future studies
is that disease process progression can be better evaluated by profiling
changes in tissue specific functional TRP subtype activity as well as their
gene and protein expression
L-Carnitine Reduces in Human Conjunctival Epithelial Cells Hypertonic- Induced Shrinkage through Interacting with TRPV1 Channels
Background/Aims: Ocular surface health depends on conjunctival epithelial
(HCjE) layer integrity since it protects against pathogenic infiltration and
contributes to tissue hydration maintenance. As the same increases in tear
film hyperosmolarity described in dry eye disease can increase corneal
epithelial transient receptor potential vanilloid type-1 (TRPV1) channel
activity, we evaluated its involvement in mediating an osmoprotective effect
by L-carnitine against such stress. Methods: Using siRNA gene silencing,
Ca2+imaging, planar patch- clamping and relative cell volume measurements, we
determined if the protective effects of this osmolyte stem from its
interaction with TRPV1. Results: TRPV1 activation by capsaicin (CAP) and an
increase in osmolarity to≈450 mOsM both induced increases in Ca2+levels. In
contrast, blocking TRPV1 activation with capsazepine (CPZ) fully reversed this
response. Similarly, L-carnitine (1 mM) also reduced underlying whole-cell
currents. In calcein-AM loaded cells, hypertonic-induced relative cell volume
shrinkage was fully blocked during exposure to L-carnitine. On the other hand,
in TRPV1 gene-silenced cells, this protective effect by L-carnitine was
obviated. Conclusion: The described L-carnitine osmoprotective effect is
elicited through suppression of hypertonic-induced TRPV1 activation leading to
increases in L-carnitine uptake through a described Na+-dependent L-carnitine
transporter
Temperature-Sensitive Transient Receptor Potential Channels in Corneal Tissue Layers and Cells
We here provide a brief summary of the characteristics of transient receptor potential channels (TRPs) identified in corneal tissue layers and cells. In general, TRPs are nonselective cation channels which are Ca ²⁺ permeable. Most TRPs serve as thermosensitive molecular sensors (thermo-TRPs). Based on their functional importance, the possibilities are described for drug-targeting TRP activity in a clinical setting. TRPs are expressed in various tissues of the eye including both human corneal epithelial and endothelial layers as well as stromal fibroblasts and stromal nerve fibers. TRP vanilloid type 1 (TRPV1) heat receptor, also known as capsaicin receptor, along with TRP melastatin type 8 (TRPM8) cold receptor, which is also known as menthol receptor, are prototypes of the thermo-TRP family. The TRPV1 functional channel is the most investigated TRP channel in these tissues, owing to its contribution to maintaining tissue homeostasis as well as eliciting wound healing responses to injury. Other thermo-TRP family members identified in these tissues are TRPV2, 3 and 4. Finally, there is the TRP ankyrin type 1 (TRPA1) cold receptor. All of these thermo-TRPs can be activated within specific temperature ranges and transduce such inputs into chemical and electrical signals. Although several recent studies have begun to unravel complex roles for thermo-TRPs such as TRPV1 in corneal layers and resident cells, additional studies are needed to further elucidate their roles in health and disease
3-Iodothyronamine Activates a Set of Membrane Proteins in Murine Hypothalamic Cell Lines
3-Iodothyronamine (3-T1AM) is an endogenous thyroid hormone metabolite. The profound pharmacological effects of 3-T1AM on energy metabolism and thermal homeostasis have raised interest to elucidate its signaling properties in tissues that pertain to metabolic regulation and thermogenesis. Previous studies identified G protein-coupled receptors (GPCRs) and transient receptor potential channels (TRPs) as targets of 3-T1AM in different cell types. These two superfamilies of membrane proteins are largely expressed in tissue which influences energy balance and metabolism. As the first indication that 3-T1AM virtually modulates the function of the neurons in hypothalamus, we observed that intraperitoneal administration of 50 mg/kg bodyweight of 3-T1AM significantly increased the c-FOS activation in the paraventricular nucleus (PVN) of C57BL/6 mice. To elucidate the underlying mechanism behind this 3-T1AM-induced signalosome, we used three different murine hypothalamic cell lines, which are all known to express PVN markers, GT1-7, mHypoE-N39 (N39) and mHypoE-N41 (N41). Various aminergic GPCRs, which are the known targets of 3-T1AM, as well as numerous members of TRP channel superfamily, are expressed in these cell lines. Effects of 3-T1AM on activation of GPCRs were tested for the two major signaling pathways, the action of Gαs/adenylyl cyclase and Gi/o. Here, we demonstrated that this thyroid hormone metabolite has no significant effect on Gi/o signaling and only a minor effect on the Gαs/adenylyl cyclase pathway, despite the expression of known GPCR targets of 3-T1AM. Next, to test for other potential mechanisms involved in 3-T1AM-induced c-FOS activation in PVN, we evaluated the effect of 3-T1AM on the intracellular Ca2+ concentration and whole-cell currents. The fluorescence-optic measurements showed a significant increase of intracellular Ca2+ concentration in the three cell lines in the presence of 10 μM 3-T1AM. Furthermore, this thyroid hormone metabolite led to an increase of whole-cell currents in N41 cells. Interestingly, the TRPM8 selective inhibitor (10 μM AMTB) reduced the 3-T1AM stimulatory effects on cytosolic Ca2+ and whole-cell currents. Our results suggest that the profound pharmacological effects of 3-T1AM on selected brain nuclei of murine hypothalamus, which are known to be involved in energy metabolism and thermoregulation, might be partially attributable to TRP channel activation in hypothalamic cells
Bone mineral density and fractures in institutionalised children with epilepsy and intellectual disability
Background Long-term use of antiseizure drugs is associated with a low bone mineral density (BMD) and an increased fracture risk. The literature regarding institutionalised children on chronic antiseizure drugs is limited. Therefore, the aim of this cross-sectional study is to evaluate the prevalence of low BMD and the history of fractures in institutionalised children with epilepsy and intellectual disability (ID). Methods A dual-energy X-ray absorptiometry of lumbar spine (L1-L4) and hip was performed in 24 children, residing in a long-stay care facility in the Netherlands. Additionally, serum concentrations of albumin, calcium and 25-hydroxyvitamin D were determined. Data on fractures were retrospectively extracted from the medical files. Results Ages of the children (14 male and 10 female) ranged from 5 to 17 years with a mean age of 13.0 (+/- 3.2). The criteria of the International Society for Clinical Densitometry (ISCD) were used for classification of bone mineral disorders. Eight (33.3%) children had a normal BMD (Z-score > - 2.0). Of the 16 children with a low BMD (Z-score <= - 2.0), three were diagnosed as osteoporotic, based on their fracture history. Ten children (41.7%) were reported to have at least one fracture in their medical history. Serum concentrations of albumin-corrected calcium (2.28-2.50 mmol/L) and (supplemented) vitamin D (16-137 nmol/L) were within the normal range. Conclusions This study demonstrated that 67% of institutionalised children with epilepsy and ID had low BMD and 42% had a history of at least one fracture, despite supplementation of calcium and vitamin D in accordance with the Dutch guidelines
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