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Hyperthermia
Kinds of Hyperthermia Terms modified by Hyperthermia Selected AbstractsHyperthermia in utero due to maternal influenza is an environmental risk factor for schizophreniaCONGENITAL ANOMALIES, Issue 3 2007Marshall J. Edwards ABSTRACT A hypothesis is presented that the association between maternal influenza and other causes of fever during the second trimester of pregnancy and the subsequent development of schizophrenia in the child is due to the damage caused by hyperthermia to the developing amygdalohippocampal complex and associated structures in the fetal brain. Hyperthermia is a known cause of congenital defects of the central nervous system and other organs after sufficiently severe exposures during early organogenesis. The pathogenic mechanisms include death of actively dividing neuroblasts, disruption of cell migration and arborization and vascular damage. In experimental studies, hyperthermia during later stages of central nervous system development also caused damage to the developing brainstem that was associated with functional defects. This damage usually results in hypoplasia of the parts undergoing active development at the time of exposure. Recent studies have shown no evidence of direct invasion of the fetus by the influenza virus. Factors that might interact with hyperthermia include familial liability to schizophrenia, season of birth, maternal nutrition, severe stress and medications used to alleviate the symptoms of fevers. The time of the development of the fetal amygdalohippocampal complex and the changes found in its structure and associated areas of the brain are compatible with the known effects of hyperthermia. [source] Exposure to a hot environment can activate rostral ventrolateral medulla-projecting neurones in the hypothalamic paraventricular nucleus in conscious ratsEXPERIMENTAL PHYSIOLOGY, Issue 1 2008Joo Lee Cham A major integrative site within the brain for autonomic function is the hypothalamic paraventricular nucleus (PVN). Several studies have suggested that the PVN may be involved in the responses regulating body temperature. Hyperthermia elicits redirection of blood flow from the viscera to the periphery and involves changes in sympathetic nerve activity mediated by the central nervous system. The hypothalamic PVN includes neurones that project to the rostral ventrolateral medulla (RVLM), an important autonomic region involved in the tonic regulation of sympathetic nerve activity. This pathway could contribute to the cardiovascular changes induced by hyperthermia. The PVN has a high concentration of nitrergic neurones and it is known that nitric oxide within the brain mediates heat dissipation. Thus the aims of this study were to determine whether RVLM-projecting neurones in the PVN are activated by heat and whether those neurones are also nitrergic. The results show that, compared with control conditions, exposure of conscious rats to a hot environment of 39°C significantly increased the number of neurones containing a Fos-positive nucleus (a marker of activation) and significantly increased the number of activated RVLM-projecting neurones in the PVN. Also, although heating significantly increased the number of activated nitrergic PVN neurones, triple-labelled neurones (i.e. activated, nitrergic and RVLM projecting) in the PVN were rarely observed. The results suggest that RVLM-projecting neurones in the PVN may play a role in responses to heat exposure but these are not nitrergic. [source] Effects of induced hyperthermia on pharmacokinetics of ropivacaine in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2010Romain Guilhaumou Abstract Ropivacaine is a local anaesthetic used for epidural anaesthesia and postoperative pain relief. Hyperthermia is a very common sign of infection associated with variations in physiological parameters, which may influence drugs pharmacokinetics. The aim of this study was to determine the effects of induced hyperthermia on ropivacaine pharmacokinetics in rats. Two groups of six rats were given a single subcutaneous ropivacaine injection. Hyperthermia-induced animals were placed in a water bath to obtain a stable mean core temperature of 39.7 °C. After blood samples collection, ropivacaine serum concentrations and pharmacokinetic parameters were determined. Two other groups of six rats were sacrificed 30 min after ropivacaine injection to determine serum and tissues (brain and heart) concentrations. Our results (median ± inter quartile range) reveal a significant increase of the total apparent clearance (0.0151 ± 0.000800 L/min vs. 0.0134 ± 0.00134 L/min), apparent volume of distribution (Vd) (2.19 ± 0.27 L vs. 1.57 ± 0.73 L) and a significant decrease in exposure (488 ± 50.6 mg.min/L vs. 572 ± 110 mg.min/L) in induced-hyperthermia group. We observed a significant increase in brain ropivacaine concentration in hyperthermic rats (8.39 ± 8.42 ,g/g vs. 3.48 ± 3.26 ,g/g) and no significant difference between cardiac concentrations in the two groups (5.38 ± 4.83 ,g/g vs. 3.73 ± 2.44 ,g/g). Results suggest a higher tissular distribution of ropivacaine and an increase in blood,brain barrier permeability during hyperthermia. The hyperthermia-induced increase in Vd could be responsible for an increase in cerebral ropivacaine toxicity. These experimental data provide a basis for future clinical investigations in relation to local anaesthetic use in hyperthermic patients. [source] Fluorescent Polystyrene,Fe3O4 Composite Nanospheres for In Vivo Imaging and HyperthermiaADVANCED MATERIALS, Issue 21 2009Donglu Shi Quantum dots (QDs) are immobilized on the surfaces of magnetic Fe3O4 -composite nanospheres (MNSs, see figure). The QDs exhibit intense visible-light emission in fluorescence spectroscopy and successfully facilitate, for the first time, in vivo soft-tissue imaging in live mice. The Fe3O4 nanoparticles respond to an external magnetic field by increasing the temperature of the surrounding environment (i.e., hyperthermia), which can be used therapeutically. [source] Intracellular redistribution and modification of proteins of the Mre11/Rad50/Nbs1 DNA repair complex following irradiation and heat-shockJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004Joshua D. Seno Mre11, Rad50, and Nbs1form a tight complex which is homogeneously distributed throughout the nuclei of mammalian cells. However, after irradiation, the Mre11/Rad50/Nbs1 (M/R/N) complex rapidly migrates to sites of double strand breaks (DSBs), forming foci which remain until DSB repair is complete. Mre11 and Rad50 play direct roles in DSB repair, while Nbs1 appears to be involved in damage signaling. Hyperthermia sensitizes mammalian cells to ionizing radiation. Radiosensitization by heat shock is believed to be mediated by an inhibition of DSB repair. While the mechanism of inhibition of repair by heat shock remains to be elucidated, recent reports suggest that the M/R/N complex may be a target for inhibition of DSB repair and radiosensitization by heat. We now demonstrate that when human U-1 melanoma cells are heated at 42.5 or 45.5°C, Mre11, Rad50, and Nbs1 are rapidly translocated from the nucleus to the cytoplasm. Interestingly, when cells were exposed to ionizing radiation (12 Gy of X-rays) prior to heat treatment, the extent and kinetics of translocation were increased when nuclear and cytoplasmic fractions of protein were analyzed immediately after treatment. The kinetics of the translocation and subsequent relocalization back into the nucleus when cells were incubated at 37°C from 30 min to 7 h following treatment were different for each protein, which suggests that the proteins redistribute independently. However, a significant fraction of the translocated proteins exist as a triple complex in the cytoplasm. Treatment with leptomycin B (LMB) inhibits the translocation of Mre11, Rad50, and Nbs1 to the cytoplasm, leading us to speculate that the relocalization of the proteins to the cytoplasm occurs via CRM1-mediated nuclear export. In addition, while Nbs1 is rapidly phosphorylated in the nuclei of irradiated cells and is critical for a normal DNA damage response, we have found that Nbs1 is rapidly phosphorylated in the cytoplasm, but not in the nucleus, of heated irradiated cells. The phosphorylation of cytoplasmic Nbs1, which cannot be inhibited by wortmannin, appears to be a unique post-translational modification in heated, irradiated cells, and coupled with our novel observations that Mre11, Rad50, and Nbs1 translocate to the cytoplasm, lend further support for a role of the M/R/N complex in thermal radiosensitization and inhibition of DSB repair. J. Cell. Physiol. 199: 157,170, 2004© 2004 Wiley-Liss, Inc. [source] A Profound Effect of Hyperthermia on Survival of Litopenaeus vannamei Juveniles Infected with White Spot Syndrome VirusJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 4 2001Oscar M. Vidal This study was conducted to examine the effect of increasing seawater temperature on White Spot Syndrome Virus (WSSV) infection in juvenile Pacific White shrimp (Litopenaeus vannamei). Infection by WSSV was achieved using two methods, intramuscular injection and per os (oral) administration. Forty injected and 20 per os infected animals were kept in heated tanks at 32.3 ± 0.8 C, and the same number of WSSV infected animals were maintained in tanks at ambient temperature (25.8 ± 0.7 C). Despite the route of exposure, there were no survivors among the animals kept at ambient temperature; whereas, in heated tanks the survival of the WSSV infected juvenile shrimp was always above 80%, suggesting the existence of a beneficial effect from hyperthermia that mitigated the progression of WSSV disease. Moreover, this beneficial effect was not attributable to viral inactivation. Infected animals kept at 32 C had histologically detectable lymphoid organ spheroids suggestive of a chronic viral infection but were PCR negative (hemolymph) for WSSV. These findings might be related to low viral replication in WSSV-infected shrimp held at the higher environmental temperature. When the WSSV-infected shrimp were transferred from 32 C to ambient temperature, the mortality from WSSV ensued and was always 100%. Although the mechanism related to the beneficial effect of heating was not determined, our results indicate that increasing the water temperature modifies dramatically the natural history of the WSSV disease and the survival curves of WSSV-infected juvenile Pacific White shrimp. [source] The anaesthetic management of patients with congenital insensitivity to pain with anhidrosisPEDIATRIC ANESTHESIA, Issue 4 2004V. Rozentsveig MD Summary Background :,Congenital insensitivity to pain with anhidrosis (CIPA, or hereditary sensory and autonomic neuropathy type IV) is a rare, autosomal recessive disease, related to a mutation in the TrkA gene, characterized by inability to sweat, insensitivity to pain and recurrent episodes of hyperpyrexia. There are two Bedouin tribes in Israel with different mutations of the TrkA gene: one in the southern region and the other in the northern region. The Soroka University Medical Center is the referral centre for the entire southern region of Israel. One in 4500 anaesthesia cases involves a patient with CIPA. Methods :,We reviewed 40 anaesthesia records of 20 patients with CIPA for anaesthetic technique and incidence of side-effects. Results :,Sixteen patients developed complications in the immediate perioperative period: mild hypothermia in one patient and cardiovascular events in 15 others with one case of cardiac arrest. These complications were unrelated to the anaesthetic drug administered. There were no events of hyperthermia or postoperative nausea. Conclusions :,Cardiovascular complications following anaesthesia are common in patients with the southern Israel variant of CIPA. Hyperthermia, previously recognized as a major concern in patients with congenital insensitivity to pain with anhydrous, was not seen in our patients. We conclude that cardiovascular involvement is frequently encountered in CIPA patients following anaesthesia and is the major concern in their anaesthetic management. [source] Cross-calibration of X-ray µCT and MRX for tissue analysisPROCEEDINGS IN APPLIED MATHEMATICS & MECHANICS, Issue 1 2009H. Rahn Ferrofluids are being considered as an aid for local cancer treatments, such as Magnetic Drug Targeting (MDT) and Magnetic Hyperthermia (MHT). Both methods make use of the strong influence of a magnetic field on the nanoparticles, with the aim of treating the cancer locally while reducing, or even eliminating, the side effects that usually occur during conventional cancer treatments. Microcomputed tomography analysis has been performed on tumour tissue after MDT and MHT in order to examine the distribution of the magnetic nanoparticles within the tissue. The majority of the measurements has been performed in a laboratory based on a polychromatic X-ray source. The strong energy dependence of the attenuation coefficient and the occurrence of the so called beam hardening artefacts make the quantitative evaluation of data acquired with polychromatic tomography equipment very difficult. In this paper we present a cross-calibration method for magnetorelaxometry and polychromatic X-ray tomography for biological tissue samples enriched with magnetic nanoparticles. (© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] High temperature does not alter fatigability in intact mouse skeletal muscle fibresTHE JOURNAL OF PHYSIOLOGY, Issue 19 2009Nicolas Place Intense activation of skeletal muscle results in fatigue development, which involves impaired function of the muscle cells resulting in weaker and slower contractions. Intense muscle activity also results in increased heat production and muscle temperature may rise by up to ,6°C. Hyperthermia is associated with impaired exercise performance in vivo and recent studies have shown contractile dysfunction and premature fatigue development in easily fatigued muscle fibres stimulated at high temperatures and these defects were attributed to oxidative stress. Here we studied whether fatigue-resistant soleus fibres stimulated at increased temperature show premature fatigue development and whether increasing the level of oxidative stress accelerates fatigue development. Intact single fibres or small bundles of soleus fibres were fatigued by 600 ms tetani given at 2 s intervals at 37°C and 43°C, which is the highest temperature the muscle would experience in vivo. Tetanic force in the unfatigued state was not significantly different at the two temperatures. With 100 fatiguing tetani, force decreased by ,15% at both temperatures; the free cytosolic [Ca2+] (assessed with indo-1) showed a similar ,10% decrease at both temperatures. The oxidative stress during fatigue at 43°C was increased by application of 10 ,m hydrogen peroxide or tert-butyl hydroperoxide and this did not cause premature fatigue development. In summary, fatigue-resistant muscle fibres do not display impaired contractility and fatigue resistance at the highest temperature that mammals, including humans, would experience in vivo. Thus, intrinsic defects in fatigue-resistant muscle fibres cannot explain the decreased physical performance at high temperatures. [source] Analysis of RYR1 Haplotype Profile in Patients with Malignant HyperthermiaANNALS OF HUMAN GENETICS, Issue 1 2009D. Carpenter Summary This study represents a new approach to characterising patients at risk of malignant hyperthermia (MH) through the use of a recently published method for identifying high-risk haplotypes in candidate genes. We present analysis based upon the largest standardised and genotyped database of MH patients worldwide. We used unphased RYR1 SNP data directly to (1) assess RYR1 haplotype frequency differences between susceptible cases and control groups and (2) analyse population-based association via clustering of RYR1 haplotypes based on disease risk. Our results show a significant difference in RYR1 haplotype frequency between susceptible cases and UK Caucasian population controls. Furthermore we identify a high-risk cluster of haplotypes that is associated with the commonest UK MH mutation p.G2434R/c.7300G>A. These results demonstrate the applicability of this new and practical method for population based association analysis. [source] The effect of fever, febrile illnesses, and heat exposures on the risk of neural tube defects in a Texas-Mexico border populationBIRTH DEFECTS RESEARCH, Issue 10 2004Lucina Suarez Abstract BACKGROUND Hyperthermia produces neural tube defects (NTDs) in a variety of animal species. Elevated maternal body temperatures may also place the developing human embryo at risk. We examined the relation between maternal hyperthermia and the development of NTDs in a high-risk Mexican-American population. METHODS Case-women were Mexican-American women with NTD-affected pregnancies who resided and delivered in any of the 14 Texas counties bordering Mexico, during 1995,2000. Control-women were randomly selected from study area residents delivering normal live births, frequency-matched to cases by hospital and year. Information on maternal fevers, febrile illnesses, exposures to heat generated from external sources, and hyperthermia-inducing activities was gathered through in-person interviews, conducted about six weeks postpartum. RESULTS The risk effect (OR) associated with maternal fever in the first trimester, compared to no fever, was 2.9 (95% CI, 1.5,5.7). Women taking fever-reducing medications showed a lower risk effect (OR, 2.4; 95% CI, 1.0,5.6) than those who did not (OR, 3.8; 95% CI, 1.4,10.9). First-trimester maternal exposures to heat devices such as hot tubs, saunas, or electric blankets were associated with an OR of 3.6 (95% CI, 1.1,15.9). Small insignificant effects were observed for activities such as cooking in a hot kitchen (OR, 1.6; 95% CI, 1.0,2.6) and working or exercising in the sun (OR, 1.4; 95% CI, 0.9,2.2). CONCLUSIONS Maternal hyperthermia increases the risk for NTD-affected offspring. Women intending to become pregnant should avoid intense heat exposures, carefully monitor and manage their febrile illnesses, and routinely consume folic acid supplements. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source] Predictors of Mortality in Patients with Delirium TremensACADEMIC EMERGENCY MEDICINE, Issue 8 2008Ayesha Khan MD Abstract Objectives:, The objectives were to identify factors that may help predict mortality for patients with delirium tremens (DT). Methods:, The authors conducted a 1:1 gender- and age-matched case,control study of patients hospitalized for DT. Using McNemar chi-square tests and conditional logistic regression (CLR), risk factors for death, including demographics, location of diagnosis, vital sign derangements, treatment methods, and comorbid conditions, were evaluated. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) are reported. Results:, Thirty-five patients with DT died between January 2000 and June 2006. The majority (31; 88.6%) were male with a mean (±standard deviation [SD]) age of 51.7 (±7.6) years. Hyperthermia in the first 24 hours of DT diagnosis (OR = 10.0, 95% CI = 2.3 to 42.7), persistent tachycardia (OR = 24.0, 95% CI = 3.3 to 177.4), and use of restraints (OR = 7.50, 95% CI = 1.7 to 32.8) were associated with increased mortality by univariate analysis, while an emergency department (ED) diagnosis of DT (OR = 0.18, 95% CI = 0.05 to 0.6) and use of clonidine (OR = 0.10, 95% CI = 0.01 to 0.78) were associated with decreased mortality. In the CLR model, restraint use and hyperthermia were the only variables that remained significant (OR = 5.8, 95% CI = 1.0 to 32.2; and OR = 6.1, 95% CI = 1.2 to 30.4, respectively). Conclusions:, The use of restraints and hyperthermia is associated with increased odds of death for patients with DT. This study highlights the need for further research into modifiable factors influencing mortality from DT. [source] Self-regulating hyperthermia induced using thermosensitive ferromagnetic material with a low Curie temperatureCANCER SCIENCE, Issue 4 2008Hajime Saito Hyperthermia has been used for many years to treat a variety of malignant tumors. The Curie temperature (Tc) is a transition point at which magnetic materials lose their magnetic properties, causing a cessation of current and thus heat production. The Tc enables automatic temperature control throughout a tumor as a result of the self-regulating nature of the thermosensitive material. We have developed a method of magnetically-induced hyperthermia using thermosensitive ferromagnetic particles (FMPs) with low Tc (43°C), enough to mediate automatic temperature control. B16 melanoma cells were subcutaneously injected into the backs of C57BL/6 mice, after which tumors were allowed to grow to 5 mm in diameter. FMPs were then injected into the tumors, and the mice were divided into three groups: group I (no hyperthermia, control); group II (one hyperthermia treatment); and group III (hyperthermia twice a week for 4 weeks). When exposed to a magnetic field, the FMPs showed a sharp rise in heat production, reaching the Tc in tissue within 7 min, after which the tissue temperature stabilized at approximately the Tc. In groups I and II, all mice died within 30,45 days. In group III, however, 6 of 10 mice remained alive 120 days after beginning treatment. Our findings suggest that repeated treatment with magnetically-induced self-regulating hyperthermia, mediated by FMPs with a low Tc, is an effective means of suppressing melanoma growth. A key advantage of this hyperthermia system is that it is minimally invasive, requiring only a single injection for repeated treatments with automatic temperature control. (Cancer Sci 2008; 99: 805,809) [source] Exercise-induced hyperthermia in childhood: a case report and pilot studyACTA PAEDIATRICA, Issue 7 2009T Kallinich Abstract Hyperthermia is characterized by an increase of body core temperature due to exogenous heat exposure and/or endogenous heat production. Contrary to fever the hypothalamic-controlled temperature set point remains unchanged. Aim: To demonstrate that exercise-induced hyperthermia is a common phenomenon in childhood. Case: We describe a 5-year-old boy, who attended our outpatient clinic with a 6-month observation period of exercise-induced hyperthermia with rectal temperatures up to 39.0°C. Characteristically temperature dropped to normal values after cessation of exercise. Method: In eight children aged 5,8, tympanic and rectal temperatures were measured before and after exercise. Results: The rectal temperature increases frequently after exercise (p < 0.001), whereas tympanic temperature did not (p = 0.2). Conclusion:, Benign hyperthermia should be considered in children with increased body temperature of unknown sources. The site of temperature measurement might be critical in the identification of this condition. [source] Proposing magnetic nanoparticle hyperthermia in low-field MRICONCEPTS IN MAGNETIC RESONANCE, Issue 1 2010Pádraig Cantillon-Murphy Abstract This work examines feasibility, practical advantages, and disadvantages of a combined MRI/magnetic particle hyperthermia (MPH) system for cancerous tumor treatment in low perfusion tissue. Although combined MRI/hyperthermia systems have been proposed and constructed, the current proposal differs because the hyperthermia system would be specifically designed to interact with the magnetic nanoparticles injected at the tumor site. The proposal exploits the physical similarities between the magnetic nanoparticles currently employed for MPH and those used as superparamagnetic iron oxide (SPIO) contrast agents in MR imaging. The proposal involves the addition of a rotating magnetic field RF hyperthermia source perpendicular to the MRI B0 field which operates in a similar manner to the MRI RF excitation field, B1, but at significantly higher frequency and field strength such that the magnetic nanoparticles are forced to rotate in its presence. This rotation is the source of increases in temperature which are of therapeutic benefit in cancer therapy. For rotating magnetic fields with amplitudes much smaller than B0, the nanoparticles' suspension magnetization rapidly saturates with increasing B0. Therefore, the proposal is best suited to low-field MRI systems when magnetic saturation is incomplete. In addition, careful design of the RF hyperthermia source is required to ensure no physical or RF interference with the B1 field used for MRI excitation. Notwithstanding these caveats, the authors have shown that localized steady-state temperature rises in small spherical tumors of up to 10°C are conceivable with careful selection of the nanoparticle radius and concentration, RF hyperthermia field amplitude and frequency. © 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part A 36A: 36,47, 2010. [source] Hyperthermia in utero due to maternal influenza is an environmental risk factor for schizophreniaCONGENITAL ANOMALIES, Issue 3 2007Marshall J. Edwards ABSTRACT A hypothesis is presented that the association between maternal influenza and other causes of fever during the second trimester of pregnancy and the subsequent development of schizophrenia in the child is due to the damage caused by hyperthermia to the developing amygdalohippocampal complex and associated structures in the fetal brain. Hyperthermia is a known cause of congenital defects of the central nervous system and other organs after sufficiently severe exposures during early organogenesis. The pathogenic mechanisms include death of actively dividing neuroblasts, disruption of cell migration and arborization and vascular damage. In experimental studies, hyperthermia during later stages of central nervous system development also caused damage to the developing brainstem that was associated with functional defects. This damage usually results in hypoplasia of the parts undergoing active development at the time of exposure. Recent studies have shown no evidence of direct invasion of the fetus by the influenza virus. Factors that might interact with hyperthermia include familial liability to schizophrenia, season of birth, maternal nutrition, severe stress and medications used to alleviate the symptoms of fevers. The time of the development of the fetal amygdalohippocampal complex and the changes found in its structure and associated areas of the brain are compatible with the known effects of hyperthermia. [source] Etiology, pathogenesis and prevention of neural tube defectsCONGENITAL ANOMALIES, Issue 2 2006Rengasamy Padmanabhan ABSTRACT Spina bifida, anencephaly, and encephalocele are commonly grouped together and termed neural tube defects (NTD). Failure of closure of the neural tube during development results in anencephaly or spina bifida aperta but encephaloceles are possibly post-closure defects. NTD are associated with a number of other central nervous system (CNS) and non-neural malformations. Racial, geographic and seasonal variations seem to affect their incidence. Etiology of NTD is unknown. Most of the non-syndromic NTD are of multifactorial origin. Recent in vitro and in vivo studies have highlighted the molecular mechanisms of neurulation in vertebrates but the morphologic development of human neural tube is poorly understood. A multisite closure theory, extrapolated directly from mouse experiments highlighted the clinical relevance of closure mechanisms to human NTD. Animal models, such as circle tail, curly tail, loop tail, shrm and numerous knockouts provide some insight into the mechanisms of NTD. Also available in the literature are a plethora of chemically induced preclosure and a few post-closure models of NTD, which highlight the fact that CNS malformations are of hetergeneitic nature. No Mendelian pattern of inheritance has been reported. Association with single gene defects, enhanced recurrence risk among siblings, and a higher frequency in twins than in singletons indicate the presence of a strong genetic contribution to the etiology of NTD. Non-availability of families with a significant number of NTD cases makes research into genetic causation of NTD difficult. Case reports and epidemiologic studies have implicated a number of chemicals, widely differing therapeutic drugs, environmental contaminants, pollutants, infectious agents, and solvents. Maternal hyperthermia, use of valproate by epileptic women during pregnancy, deficiency and excess of certain nutrients and chronic maternal diseases (e.g. diabetes mellitus) are reported to cause a manifold increase in the incidence of NTD. A host of suspected teratogens are also available in the literature. The UK and Hungarian studies showed that periconceptional supplementation of women with folate (FA) reduces significantly both the first occurrence and recurrence of NTD in the offspring. This led to mandatory periconceptional FA supplementation in a number of countries. Encouraged by the results of clinical studies, numerous laboratory investigations focused on the genes involved in the FA, vitamin B12 and homocysteine metabolism during neural tube development. As of today no clinical or experimental study has provided unequivocal evidence for a definitive role for any of these genes in the causation of NTD suggesting that a multitude of genes, growth factors and receptors interact in controlling neural tube development by yet unknown mechanisms. Future studies must address issues of gene-gene, gene-nutrient and gene,environment interactions in the pathogenesis of NTD. [source] Cardiovascular function in the heat-stressed humanACTA PHYSIOLOGICA, Issue 4 2010C. G. Crandall Abstract Heat stress, whether passive (i.e. exposure to elevated environmental temperatures) or via exercise, results in pronounced cardiovascular adjustments that are necessary for adequate temperature regulation as well as perfusion of the exercising muscle, heart and brain. The available data suggest that generally during passive heat stress baroreflex control of heart rate and sympathetic nerve activity are unchanged, while baroreflex control of systemic vascular resistance may be impaired perhaps due to attenuated vasoconstrictor responsiveness of the cutaneous circulation. Heat stress improves left ventricular systolic function, evidenced by increased cardiac contractility, thereby maintaining stroke volume despite large reductions in ventricular filling pressures. Heat stress-induced reductions in cerebral perfusion likely contribute to the recognized effect of this thermal condition in reducing orthostatic tolerance, although the mechanism(s) by which this occurs is not completely understood. The combination of intense whole-body exercise and environmental heat stress or dehydration-induced hyperthermia results in significant cardiovascular strain prior to exhaustion, which is characterized by reductions in cardiac output, stroke volume, arterial pressure and blood flow to the brain, skin and exercising muscle. These alterations in cardiovascular function and regulation late in heat stress/dehydration exercise might involve the interplay of both local and central reflexes, the contribution of which is presently unresolved. [source] Cerebral oxygenation is reduced during hyperthermic exercise in humansACTA PHYSIOLOGICA, Issue 1 2010P. Rasmussen Abstract Aim:, Cerebral mitochondrial oxygen tension (PmitoO2) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO2) combined with hyperventilation-induced attenuation of cerebral blood flow (CBF). Heat stress challenges exercise capacity as expressed by increased rating of perceived exertion (RPE). Methods:, This study evaluated the effect of heat stress during exercise on PmitoO2 calculated based on a Kety-Schmidt-determined CBF and the arterial-to-jugular venous oxygen differences in eight males [27 ± 6 years (mean ± SD) and maximal oxygen uptake (VO2max) 63 ± 6 mL kg,1 min,1]. Results:, The CBF, CMRO2 and PmitoO2 remained stable during 1 h of moderate cycling (170 ± 11 W, ,50% of VO2max, RPE 9,12) in normothermia (core temperature of 37.8 ± 0.4 °C). In contrast, when hyperthermia was provoked by dressing the subjects in watertight clothing during exercise (core temperature 39.5 ± 0.2 °C), PmitoO2 declined by 4.8 ± 3.8 mmHg (P < 0.05 compared to normothermia) because CMRO2 increased by 8 ± 7% at the same time as CBF was reduced by 15 ± 13% (P < 0.05). During exercise with heat stress, RPE increased to 19 (19,20; P < 0.05); the RPE correlated inversely with PmitoO2 (r2 = 0.42, P < 0.05). Conclusion:, These data indicate that strenuous exercise in the heat lowers cerebral PmitoO2, and that exercise capacity in this condition may be dependent on maintained cerebral oxygenation. [source] Brainstem mechanisms underlying the sudden infant death syndrome: Evidence from human pathologic studiesDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2009Hannah C. Kinney Abstract The brainstem hypothesis is one of the leading hypotheses concerning the sudden infant death syndrome (SIDS). It states that SIDS, or an important subset of SIDS, is due to abnormal brainstem mechanisms in the control of respiration, chemosensitivity, autonomic regulation, and/or arousal which impairs the infant's response to life-threatening, but often occurring, stressors during sleep (e.g., hypoxia, hypercarbia, asphyxia, hyperthermia) and leads to sudden death in a vulnerable developmental period. In this review, we summarize neuropathologic evidence from SIDS cases that support this hypothesis, beginning with the seminal report of subtle brainstem gliosis three decades ago. We focus upon recent neurochemical studies in our laboratory concerning the neurotransmitter serotonin (5-HT) and its key role in mediating protective responses to homeostatic stressors via medullary circuits. The possible fetal origin of brainstem defects in SIDS is reviewed, including evidence for adverse effects of prenatal exposure to maternal cigarette smoking and alcohol upon the postnatal development of human brainstem 5-HT pathways. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 223,233, 2009 [source] The Effects of Ecstasy (MDMA) on Rat Liver BioenergeticsACADEMIC EMERGENCY MEDICINE, Issue 7 2004Daniel E. Rusyniak MD Abstract Objectives: Use of the drug ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) can result in life-threatening hyperthermia. Agents that uncouple mitochondrial oxidative phosphorylation are known to cause severe hyperthermia. In the present study, the authors tested the hypothesis that MDMA directly uncouples oxidative phosphorylation in rat liver mitochondria. Methods: Effects on mitochondrial bioenergetics were assessed both in vitro and ex vivo. In vitro studies consisted of measuring the effects of MDMA (0.1,5.0 mmol/L) on states of respiration in isolated rat liver mitochondria and on mitochondrial membrane potential in a rat liver cell line. In ex vivo studies, mitochondrial rates of respiration were measured in the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously). Results: With the in vitro mitochondrial preparations, only concentrations of 5 mmol/L MDMA showed evidence of uncoupling with a slight increase in state 4 respiration and a corresponding decrease in the respiratory control index. MDMA (0.1,5.0 mmol/L) failed to decrease the mitochondrial membrane potential in 3,3-dihexyloxacarbocyanide iodide,stained WB-344 cells after either one or 24 hours of incubation. Ex vivo rates of respiration obtained from the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously) showed no evidence of mitochondrial uncoupling. Conclusions: These data suggest that while high concentrations of MDMA have some mild uncoupling effects in isolated mitochondria, these effects do not translate to cell culture or ex vivo studies in treated animals. These data do not support the view that the hyperthermia induced by MDMA is from a direct effect on mitochondrial oxidative phosphorylation. [source] Application of DNA diffusion assay in earthworm coelomocytesENVIRONMENTAL TOXICOLOGY, Issue 2 2008A. A. Apte Abstract We have applied the DNA diffusion assay proposed by Singh (2000) Exp Cell Res 256:328,337, for quantitative estimation of apoptosis in earthworm coelomocytes, exposed to Chromium (VI) and cypermethrin as model toxicants in vitro. The DNA diffusion assay was originally described for mammalian cells. H2O2, Sodium ascorbate, and hyperthermia were used as positive controls in present study. Apoptosis such as DNA diffusion occurred in dose-dependent manner for Chromium (VI) and cypermethrin at very low concentration (1, 3, and 10 ppm for Chromium (VI) and 4, 8, and 16 ppm for cypermethrin). Three distinct patterns (apoptosis like DNA diffusion, necrosis, and normal) were observed in exposed and nonexposed cells. Present study is probably the first report of application of the DNA diffusion technique in earthworm coelomocytes. Findings of this study indicate that this assay has potential for use in invertebrate cells to differentiate between apoptosis and necrosis. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source] Status Epilepticus,Induced Neuronal Loss in Humans Without Systemic Complications or EpilepsyEPILEPSIA, Issue 8 2000Denson G. Fujikawa Summary: Purpose: To determine the regional distribution of neuronal damage caused strictly by status epilepticus (SE) without systemic complications, underlying brain pathology, or a history of preexisting epilepsy. Methods: The medical records and electroencephalograms (EEGs) of three deceased patients who developed SE in the hospital were reviewed. Their brains were formalin-fixed, and 17 brain regions were selected, embedded in paraffin, and sectioned. Alternate sections were stained with either hematoxylin and eosin and cresyl violet to determine the extent of neuronal loss and gliosis or glial fibrillary astrocytic protein to confirm the extent of astrocytic proliferation. Results: The three patients died 11 to 27 days after the onset of focal motor SE; none had hypotension, hypoxemia, hypoglycemia, or significant hyperthermia. Two patients had no prior seizures and no underlying brain pathology. The third patient, who had leptomeningeal carcinomatosis, had one seizure 2 months before the onset of SE. The duration of SE was 8.8 hours to 3 days. EEGs showed unilateral temporal lobe sharp-wave discharges in one patient and independent temporal lobe sharp-wave discharges bilaterally in the other two patients. In addition to widespread neuronal loss and reactive gliosis in the hippocampus, amygdala, dorsomedial thalamic nucleus, and Purkinje cell layer of the cerebellum, we report for the first time periamygdaloid (piriform) and entorhinal cortical damage occurring acutely after SE in humans. Conclusions: In the absence of systemic complications or preexisting epilepsy, SE produces neuronal loss in a distribution similar to that from domoic acid-induced SE in humans and from kainic acid- and pilocarpine-induced SE in rats. [source] PRECLINICAL STUDY: Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type AADDICTION BIOLOGY, Issue 2 2009Ema Alves ABSTRACT The administration of a neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ,ecstasy') to the rat results in mitochondrial oxidative damage in the central nervous system, namely lipid and protein oxidation and mitochondrial DNA deletions with subsequent impairment of the correspondent protein expression. Although these toxic effects were shown to be prevented by monoamine oxidase B inhibition, the role of monoamine oxidase A (MAO-A) in MDMA-mediated mitochondrial damage remains to be evaluated. Thus, the aim of the present study was to clarify the potential interference of a specific inhibition of MAO-A by clorgyline, on the deleterious effects produced by a binge administration of a neurotoxic dose of MDMA (10 mg MDMA/kg of body weight, intraperitoneally, every 2 hours in a total of four administrations) to an adolescent rat model. The parameters evaluated were mitochondrial lipid peroxidation, protein carbonylation and expression of the respiratory chain protein subunits II of reduced nicotinamide adenine dinucleotide dehydrogenase (NDII) and I of cytochrome oxidase (COXI). Considering that hyperthermia has been shown to contribute to the neurotoxic effects of MDMA, another objective of the present study was to evaluate the body temperature changes mediated by MDMA with a MAO-A selective inhibition by clorgyline. The obtained results demonstrated that the administration of a neurotoxic binge dose of MDMA to an adolescent rat model previously treated with the specific MAO-A inhibitor, clorgyline, resulted in synergistic effects on serotonin- (5-HT) mediated behaviour and body temperature, provoking high mortality. Inhibition of MAO-A by clorgyline administration had no protective effect on MDMA-induced alterations on brain mitochondria (increased lipid peroxidation, protein carbonylation and decrease in the expression of the respiratory chain subunits NDII and COXI), although it aggravated MDMA-induced decrease in the expression of COXI. These results reinforce the notion that the concomitant use of MAO-A inhibitors and MDMA is counter indicated because of the resulting severe synergic toxicity. [source] Surface Activation of a Ferrimagnetic Glass,Ceramic for Antineoplastic Drugs GraftingADVANCED ENGINEERING MATERIALS, Issue 7 2010Enrica Vernè A ferrimagnetic glass,ceramic, belonging to the system SiO2,Na2O,CaO,P2O5,FeO,Fe2O3, has been studied as potential carrier for antineoplastic agents, in order to exploit the combination of hyperthermia and chemotherapy. Different material pre-treatments, such as ultrasonic washing, water, or simulated body fluid dipping, were evaluated to promote the surface activation of the glass,ceramic, i.e., the hydroxyl groups formation on it. X-ray photoelectron spectroscopy, scanning electron microscopy, energy dispersion spectrometry, and wettability measurements were performed to observe the samples surface modification. The best results in terms of free hydroxyl groups exposition were obtained by dipping the samples in distilled water for 7 days at 37,°C. Two different anticancer drugs were selected in order to test the reactivity of the activated surface: cisplatinum and doxorubicin. The uptake and release of doxorubicin and cisplatinum were evaluated on glass,ceramic powders, by using UV,Visible spectrometry and graphite furnace atomic absorption spectroscopy, respectively. After 1 day of uptake at 37,°C, the quantity of doxorubicin incorporated into the glass,ceramic is 77,±,7 wt%, while only 42,±,9.6 wt% of cisplatinum is grafted onto the material surface. For both antitumoral agents, the maximum drug release after soaking in aqueous solutions at 37,°C was obtained in few hours, with a randomly distributed kinetics trend. [source] Cytotoxicity and Cell Cycle Effects of Bare and Poly(vinyl alcohol)-Coated Iron Oxide Nanoparticles in Mouse FibroblastsADVANCED ENGINEERING MATERIALS, Issue 12 2009Morteza Mahmoudi Super-paramagnetic iron oxide nanoparticles (SPIONs) are recognized as powerful biocompatible materials for use in various biomedical applications, such as drug delivery, magnetic-resonance imaging, cell/protein separation, hyperthermia and transfection. This study investigates the impact of high concentrations of SPIONs on cytotoxicity and cell-cycle effects. The interactions of surface-saturated (via interactions with cell medium) bare SPIONs and those coated with poly(vinyl alcohol) (PVA) with adhesive mouse fibroblast cells (L929) are investigated using an MTT assay. The two SPION formulations are synthesized using a co-precipitation method. The bare and coated magnetic nanoparticles with passivated surfaces both result in changes in cell morphology, possibly due to clustering through their magnetostatic effect. At concentrations ranging up to 80,×,10,3,M, cells exposed to the PVA-coated nanoparticles demonstrate high cell viability without necrosis and apoptosis. In contrast, significant apoptosis is observed in cells exposed to bare SPIONs at a concentration of 80,×,10,3,M. Nanoparticle exposure (20,80,×,10,3,M) leads to variations in both apoptosis and cell cycle, possibly due to irreversible DNA damage and repair of oxidative DNA lesions, respectively. Additionally, the formation of vacuoles within the cells and granular cells indicates autophagy cell death rather than either apoptosis or necrosis. [source] Exposure to a hot environment can activate rostral ventrolateral medulla-projecting neurones in the hypothalamic paraventricular nucleus in conscious ratsEXPERIMENTAL PHYSIOLOGY, Issue 1 2008Joo Lee Cham A major integrative site within the brain for autonomic function is the hypothalamic paraventricular nucleus (PVN). Several studies have suggested that the PVN may be involved in the responses regulating body temperature. Hyperthermia elicits redirection of blood flow from the viscera to the periphery and involves changes in sympathetic nerve activity mediated by the central nervous system. The hypothalamic PVN includes neurones that project to the rostral ventrolateral medulla (RVLM), an important autonomic region involved in the tonic regulation of sympathetic nerve activity. This pathway could contribute to the cardiovascular changes induced by hyperthermia. The PVN has a high concentration of nitrergic neurones and it is known that nitric oxide within the brain mediates heat dissipation. Thus the aims of this study were to determine whether RVLM-projecting neurones in the PVN are activated by heat and whether those neurones are also nitrergic. The results show that, compared with control conditions, exposure of conscious rats to a hot environment of 39°C significantly increased the number of neurones containing a Fos-positive nucleus (a marker of activation) and significantly increased the number of activated RVLM-projecting neurones in the PVN. Also, although heating significantly increased the number of activated nitrergic PVN neurones, triple-labelled neurones (i.e. activated, nitrergic and RVLM projecting) in the PVN were rarely observed. The results suggest that RVLM-projecting neurones in the PVN may play a role in responses to heat exposure but these are not nitrergic. [source] Exercise Heat Stress does not Reduce Central Activation to non-exercised Human Skeletal MuscleEXPERIMENTAL PHYSIOLOGY, Issue 6 2003Julian Saboisky In this study we measured the central activation ratio (CAR) of the leg extensors and the elbow flexor muscles before and after exhaustive exercise in the heat to determine whether exercise-induced hyperthermia affects the CNS drive to exercised (leg extensors) and/or non-exercised (forearm flexors) muscle groups. Thirteen subjects exercised at fixed intensities representative of a percentage of peak power output (PPO) for 10 min periods (50%, 40%, 60%, 50%) and then at 75% PPO until exhaustion in ambient conditions of 39.3 ± 0.8 °C and 60.0 ± 0.8% relative humidity. Before and immediately following exercise subjects performed a series of maximal voluntary contractions (MVCs) with the leg extensors (exercised muscles) and forearm flexors (non-exercised muscles). The degree of voluntary activation during the sustained MVCs was assessed by superimposing electrical stimulation to the femoral nerve and the biceps brachii. Exercise to exhaustion increased the rectal temperature from 37.2 ± 0.2 to 38.8 ± 0.2 °C (P < 0.0001). The mean heart rate at the end of exercise to exhaustion was 192 ± 3 beats min,1. Leg extensor voluntary force was significantly reduced from 595 ± 143 to 509 ± 105 N following exercise-induced hyperthermia but forearm flexor force was similar before and after exercise. The CAR of the leg extensors decreased from 94.2 ± 1.3% before exercise to 91.7 ± 1.5% (P < 0.02) following exercise-induced hyperthermia. However, the CAR for the forearm flexors remained at similar levels before and after exercise. The data suggest that the central nervous system selectively reduces central activation to specific skeletal muscles as a consequence of exercise-induced hyperthermia. [source] Integrated Multifunctional Nanosystems for Medical Diagnosis and TreatmentADVANCED FUNCTIONAL MATERIALS, Issue 21 2009*Article first published online: 9 OCT 200, Donglu Shi Abstract This article provides an overview on the development of integrated multifunctional nanosystems for medical diagnosis and treatment. In particular, a novel system is developed specifically for achieving simultaneous diagnosis and treatment of cancer. Critical issues are addressed on the architecture and assembly of nanocomponents based on medical requirements: targeted in vivo imaging, controlled drug release, localized hyperthermia, and toxicity. Nanotube-based carriers are summarized with surface functionalized properties. Other types of nanocarriers are also included such as super paramagnetic composite nanospheres and biodegradable hydroxylapatite nanoparticles. In addition, polymeric-based nanosystems are introduced with several novel features: they can be bio-dissolved due to environmental pH and temperature fluctuations. The nanocarriers are surface tailored with key functionalities: surface antibodies for cell targeting, anti-cancer drug loading, and magnetic nanoparticles for both hyperthermia and MRI. Future requirements, aims, and trends in the development of multifunctional nanosystems, particularly with intelligent functionalities for fundamental studies, are also provided. [source] Effects of induced hyperthermia on pharmacokinetics of ropivacaine in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2010Romain Guilhaumou Abstract Ropivacaine is a local anaesthetic used for epidural anaesthesia and postoperative pain relief. Hyperthermia is a very common sign of infection associated with variations in physiological parameters, which may influence drugs pharmacokinetics. The aim of this study was to determine the effects of induced hyperthermia on ropivacaine pharmacokinetics in rats. Two groups of six rats were given a single subcutaneous ropivacaine injection. Hyperthermia-induced animals were placed in a water bath to obtain a stable mean core temperature of 39.7 °C. After blood samples collection, ropivacaine serum concentrations and pharmacokinetic parameters were determined. Two other groups of six rats were sacrificed 30 min after ropivacaine injection to determine serum and tissues (brain and heart) concentrations. Our results (median ± inter quartile range) reveal a significant increase of the total apparent clearance (0.0151 ± 0.000800 L/min vs. 0.0134 ± 0.00134 L/min), apparent volume of distribution (Vd) (2.19 ± 0.27 L vs. 1.57 ± 0.73 L) and a significant decrease in exposure (488 ± 50.6 mg.min/L vs. 572 ± 110 mg.min/L) in induced-hyperthermia group. We observed a significant increase in brain ropivacaine concentration in hyperthermic rats (8.39 ± 8.42 ,g/g vs. 3.48 ± 3.26 ,g/g) and no significant difference between cardiac concentrations in the two groups (5.38 ± 4.83 ,g/g vs. 3.73 ± 2.44 ,g/g). Results suggest a higher tissular distribution of ropivacaine and an increase in blood,brain barrier permeability during hyperthermia. The hyperthermia-induced increase in Vd could be responsible for an increase in cerebral ropivacaine toxicity. These experimental data provide a basis for future clinical investigations in relation to local anaesthetic use in hyperthermic patients. [source] | ||||||||||||||||||||||||||||||||||||||||||||||