Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 116
Filter
1.
Neuroscience ; 210: 33-7, 2012 May 17.
Article in English | MEDLINE | ID: mdl-22433298

ABSTRACT

The organization of the minimal neuronal substrate capable of generating locomotor rhythmicity in vertebrates is investigated in several species, with an emphasis on identifying evolutionary-conserved features. In lamprey, an eel-like lower vertebrate that swims by undulatory movements of the body, the network has been identified as a recurrent network of excitatory interneurons localized in each spinal hemisegment. This conclusion rested upon the observation that each side of the spinal cord is able to express rhythmic locomotor-related bursting after being surgically separated along the midline, even in the absence of inhibition. An important caveat, however, is that this rhythmicity must be an intrinsic capability of the hemisegmental networks and not a newly acquired property as a result of a plastic remodeling of the network occurring after the lesion. Here we examine this issue by recording the motor output expressed by the electrically activated hemicord in the first minutes after hemisection. We observed clear rhythmic bursting in the frequency range previously linked to the operation of the central pattern generator for swimming. Moreover, we recorded the output of the unilateral networks in the intact spinal cord (i.e. no midline section performed) by activating them with asymmetrical stimulation. We thus conclude that the lamprey hemicord does possess the intrinsic capability of generating the basic rhythmic drive of locomotion. The wider significance of these data stems from the lamprey being a model of axial locomotion, and from the many lesion studies previously performed in other animals.


Subject(s)
Functional Laterality/physiology , Motor Activity/physiology , Nerve Net/physiology , Spinal Cord/physiology , Animals , Electrophysiology , Lampreys , Locomotion/physiology , Organ Culture Techniques , Periodicity
2.
Man Ther ; 8(3): 141-50, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12909434

ABSTRACT

The objective of this study was to conduct a systematic analysis of the literature to assess the efficacy of stretching for prevention of exercise-related injury. Randomized clinical trials (RCTs) and controlled clinical trials (CCTs) investigating stretching as an injury prevention measure were selected. A computer-aided search of the literature was conducted for relevant articles, followed by assessment of the methods of the studies. The main outcome measures were scores for methodological quality based on four main categories (study population, interventions, measurement of effect, and data presentation and analysis) and main conclusions of authors with regard to stretching. One RCT (25%) and three CCTs (100%) concluded that stretching reduced the incidence of exercise-related injury. Three RCTs (75%) concluded that stretching did not reduce the incidence of exercise-related injury. Only two studies scored more than 50 points (maximum score=100 points) indicating that most of the studies selected were of poor quality. Neither of the two highest scoring RCTs showed positive effects for stretching. Due to the paucity, heterogeneity and poor quality of the available studies no definitive conclusions can be drawn as to the value of stretching for reducing the risk of exercise-related injury.


Subject(s)
Athletic Injuries/complications , Exercise , Pain/etiology , Pain/prevention & control , Range of Motion, Articular , Athletic Injuries/physiopathology , Controlled Clinical Trials as Topic , Humans , Isotonic Contraction , Pain/physiopathology , Randomized Controlled Trials as Topic , Research Design/standards , Treatment Outcome
3.
ILAR J ; 44(1): 20-7, 2003.
Article in English | MEDLINE | ID: mdl-12473828

ABSTRACT

In recent years, the emergence or re-emergence of critical issues in infectious disease and public health has presented new challenges and opportunities for laboratory animal care professionals. The re-emergence of bioterrorism as a threat activity of individuals or small groups has caused a heightened awareness of biosecurity and improved biosafety. The need for animal work involving high-risk or high-consequence pathogens and for arthropod-borne diseases has stimulated renewed interest in animal biosafety matters, particularly for work in containment. Application of these principles to animals retained in outdoor environments has been a consequence of disease eradication programs. The anticipated global eradication of wild poliovirus has prompted the promulgation of new biosafety guidelines for future laboratory and animal work. Increased concern regarding the use of biologically derived toxins and hazardous chemicals has stimulated a new categorization of facility containment based on risk assessment. Recognition that prion disease agents and other high-consequence pathogens require safe handling and thorough destruction during terminal decontamination treatment has led to the development of new biosafety guidelines and technologies. The implementation of these guidelines and technologies will promote state-of-the-art research while minimizing risk to laboratory animals, researchers, and the environment.


Subject(s)
Bioterrorism , Medical Waste Disposal , Occupational Health , Safety , Security Measures , Animals , Animals, Laboratory , Animals, Wild , Humans , Laboratories , Medical Laboratory Personnel , Organizational Policy , Poliovirus/pathogenicity , Prions , Risk Assessment , Toxins, Biological/adverse effects
4.
Neurobiol Dis ; 11(1): 20-7, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12460543

ABSTRACT

Disturbances in biological rhythms pose a major disease problem, not the least in the aging population. Experimental sleeping sickness, caused by Trypanosoma brucei brucei, in rats constitutes a unique and robust chronic model for studying mechanisms of such disturbances. The spontaneous postsynaptic activity was recorded in slice preparations of the suprachiasmatic nuclei (SCN), which contain the master pacemaker for circadian rhythms in mammals, from trypanosome-infected rats. The excitatory synaptic events, which in normal rats show a daily variation, were reduced in frequency, while the inhibitory synaptic events did not significantly differ. This indicates selective disturbances in glutamate receptor-mediated neurotransmission in the SCN. Treatment with interferon-gamma in combination with lipopolysaccharide, which has synergistic actions with cytokines, and tumor necrosis factor-alpha similarly caused a reduction in excitatory synaptic SCN activity. We suggest that changes in the synaptic machinery of SCN neurons play an important pathogenetic role in sleeping sickness, and that proinflammatory cytokines can mimic these changes.


Subject(s)
Circadian Rhythm/physiology , Suprachiasmatic Nucleus/parasitology , Synaptic Transmission/physiology , Trypanosoma brucei brucei , Trypanosomiasis, African/physiopathology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Antineoplastic Agents/pharmacology , Glutamic Acid/physiology , Interferon-gamma/pharmacology , Lipopolysaccharides/pharmacology , Male , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Suprachiasmatic Nucleus/physiology , Trypanosomiasis, African/immunology , Tumor Necrosis Factor-alpha/pharmacology
5.
J Neurosci ; 21(19): RC169, 2001 Oct 01.
Article in English | MEDLINE | ID: mdl-11567080

ABSTRACT

One of the main characteristics of central sensitization associated with postinjury pain and chronic pain is increased excitability of the dorsal horn neurons in the spinal cord. Two electrophysiological features associated with the origin and modulation of central sensitization are wind-up of action potential frequency and long-term potentiation (LTP), which have been demonstrated previously in the intact dorsal horn. Here we present evidence for electrically evoked sensitization of dorsal horn neurons in a two-compartment cell culture system of rat dorsal root ganglia (DRGs) and dorsal horn neurons. Whole-cell recordings of dorsal horn neurons showed that repetitive low-frequency stimulation of DRG axons induced a frequency-dependent cumulative depolarization of the membrane potential with a concomitant increase in action potential frequency in a subset of neurons (41%). The characteristics presented here for dissociated cells are in accordance with those ascribed to classical wind-up in the intact dorsal horn. In addition, tetanic stimulation of DRG axons resulted in a significant increase in the number of action potentials in response to test stimuli in 42% of the cells tested. This prolonged potentiation of neuronal excitability in the dorsal horn lasted throughout the recording period (>1 hr) and tended to be voltage dependent in an LTP-like manner. To our knowledge, this is the first time that wind-up and LTP-like responses are reported for dorsal horn neurons in cell culture.


Subject(s)
Ganglia, Spinal/physiology , Models, Neurological , Posterior Horn Cells/physiology , Synaptic Transmission/physiology , Action Potentials/physiology , Cells, Cultured , Diffusion Chambers, Culture/methods , Electric Stimulation , Excitatory Postsynaptic Potentials/physiology , Ganglia, Spinal/cytology , Long-Term Potentiation/physiology , Patch-Clamp Techniques , Posterior Horn Cells/cytology , Sensory Thresholds/physiology
6.
Brain Res Bull ; 55(3): 421-9, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11489350

ABSTRACT

In order to study mechanisms by which a neurotropic strain of influenza A virus (A/WSN/33) may affect neuronal function or cause nerve cell death, hippocampal cultures from embryonic rats were infected with this virus. Approximately 70% of the neurons in the infected cultures became immunopositive for viral antigens and showed reduced voltage-dependent Ca(2+) currents in whole-cell patch clamp recordings, but no changes in other membrane properties or in cytosolic Ca(2+) concentration were seen. These immunopositive neurons underwent apoptosis 3-4 days after infection. Ca(2+) channel inhibitors had no significant effect on neuronal survival. The immunonegative population of neurons survived, but displayed increased frequency of miniature inhibitory postsynaptic currents of gamma-amino-butyric acid origin compared with controls. The frequency of alpha-amino-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) receptor-mediated miniature excitatory postsynaptic currents was not altered. Viral nucleoproteins, overexpressed using the Semliki Forest virus system, were localized to the dendritic spines as shown by double immunolabeling with actinin, but did not by themselves cause neuronal death or changes in synaptic transmission as measured by AMPA-mediated excitatory postsynaptic currents. Our results show that an influenza A virus infection can cause selective neurophysiological changes in hippocampal neurons and that these can persist even after the viral antigens have been cleared.


Subject(s)
Calcium/physiology , Hippocampus/physiopathology , Influenza A virus , Neurons/physiology , Orthomyxoviridae Infections/physiopathology , gamma-Aminobutyric Acid/physiology , Animals , Cell Survival , Cells, Cultured , Electric Conductivity , Excitatory Postsynaptic Potentials/physiology , Hippocampus/cytology , Influenza A virus/metabolism , Intracellular Membranes/metabolism , Nucleoproteins/metabolism , Orthomyxoviridae Infections/pathology , Osmolar Concentration , Rats , Rats, Sprague-Dawley , Viral Proteins/metabolism
7.
Life Sci ; 68(16): 1817-26, 2001 Mar 09.
Article in English | MEDLINE | ID: mdl-11292060

ABSTRACT

NMDA receptors are glutamate-regulated ion channels of critical importance for many neurophysiological and neuropathological processes. Mg2+ blocks the NMDA receptor by binding to the channel pore with an apparent affinity that depends on the membrane potential. We have investigated the effect of NMDA and the required co-agonist glycine on the affinity of the Mg2+ block site in NR1-1a/NR2A NMDA receptors expressed in Xenopus oocytes. We found that NMDA and glycine increase the IC50 value of the Mg2+-block site at pH 7.4 and in the presence of physiological concentration of Ca2+. The increase the IC50 value may correspond to a decrease in Mg2+-block affinity. This effect may result in an increased influx of Ca2+, and this influx may constitute up to a third of the total Ca2+ influx induced by NMDA. At high pH, or at low concentrations of Ca2+, NMDA and glycine have an opposite effect and instead decreased the IC50 value of the Mg2+-block. These results indicate that glutamate and glycine can regulate the affinity of the Mg2+-block site. This effect may have implications for the understanding the role of NMDA receptors both under physiological and pathophysiological conditions.


Subject(s)
Glycine/pharmacology , Magnesium/metabolism , N-Methylaspartate/pharmacology , Oocytes/drug effects , Receptors, N-Methyl-D-Aspartate/metabolism , Animals , Calcium/pharmacology , Hydrogen-Ion Concentration , Ion Channels/antagonists & inhibitors , Ion Channels/physiology , Membrane Potentials/physiology , Oocytes/metabolism , Patch-Clamp Techniques , RNA, Messenger/biosynthesis , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/genetics , Xenopus laevis
8.
Brain Res ; 896(1-2): 18-29, 2001 Mar 30.
Article in English | MEDLINE | ID: mdl-11277968

ABSTRACT

Extended release of interferon-gamma (IFN-gamma) in the nervous system during immunological and infectious conditions may trigger demyelinating disorders and cause disturbances in brain function. The aim of this study was to examine the effects of IFN-gamma on neuronal function in rat hippocampal cell cultures by using whole cell patch clamp analysis together with quantitative immunocytochemistry. Acute application of IFN-gamma to differentiated neurons in culture caused no immediate neurophysiological responses, but recordings after 48 h of incubation displayed an increase in frequency of AMPA receptor (AMPAR)-mediated spontaneous excitatory postsynaptic currents (EPSCs). Quantitative immunocytochemistry for the AMPAR subunit GluR1 showed no alteration in receptor clustering at this time point. However, prolonged treatment with IFN-gamma for 2 weeks resulted in a significant reduction in AMPAR clustering on dendrites but no marked differences in EPSC frequency between treated neurons and controls could be observed. On the other hand, treatment of hippocampal neurons for 4 weeks, instituted at an immature stage (1 day in culture), caused a significant reduction in spontaneous EPSC frequency. These neurons developed with no overt alterations in dendritic arborization or in the appearance of dendritic spines as visualized by alpha-actinin immunocytochemistry. Nonetheless, there was a marked reduction in AMPAR clustering on dendrites. These observations show that a key immunomodulatory molecule, IFN-gamma, can cause long-term modifications of synaptic activity and perturb glutamate receptor clustering.


Subject(s)
Antiviral Agents/pharmacology , Interferon-gamma/pharmacology , Neurons/physiology , Receptors, AMPA/metabolism , Synaptic Transmission/drug effects , Animals , Calcium/metabolism , Cells, Cultured , Dendrites/drug effects , Dendrites/metabolism , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Fetus/cytology , Gene Expression/drug effects , Hippocampus/cytology , Neurons/ultrastructure , Neurons/virology , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Receptors, AMPA/genetics , Time Factors , Virus Diseases/drug therapy , Virus Diseases/metabolism
9.
J Neurosci Methods ; 105(2): 175-84, 2001 Feb 15.
Article in English | MEDLINE | ID: mdl-11275274

ABSTRACT

Here we present a two-compartment in vitro model in which embryonic rat dorsal root ganglia (DRG) neurons are cultured separately from their target dorsal horn neurons. Although separated, synaptic contact can be established between the peripheral and central neurons since the system allows the DRG axons to project into the other compartment, which contains a network of dorsal horn neurons. The efficacy of the model was evaluated by immunocytochemical, calcium imaging and electrophysiological experiments. The results showed that a subpopulation of the DRG neurons had nociceptor characteristics and that these made synaptic contact with the dorsal horn network. Application of current pulses, according to the stimulus paradigm used, evoked action potentials in DRG axons selectively. This in turn gave rise to increased postsynaptic activity in the network of dorsal horn neurons. The model offers a high degree of efficiency since large numbers of DRG axons can be stimulated simultaneously, thus permitting recording of strong output responses from the dorsal horn neurons. This in vitro model provides a means for studying the mechanisms by which modulatory factors, such as immunoregulatory molecules, applied at either the PNS or the CNS level, can affect synaptic activity and nociceptive transmission in single neurons or network of neurons in the dorsal horn.


Subject(s)
Cell Compartmentation/drug effects , Cell Culture Techniques/methods , Nociceptors/physiology , Pain/physiopathology , Synaptic Transmission/physiology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Calcitonin Gene-Related Peptide/metabolism , Calcium/metabolism , Calcium Signaling/drug effects , Calcium Signaling/physiology , Cell Compartmentation/physiology , Female , Fetus , Ganglia, Spinal/cytology , Ganglia, Spinal/embryology , Ganglia, Spinal/physiology , Immunohistochemistry , Models, Neurological , Neural Pathways/cytology , Neural Pathways/embryology , Neural Pathways/physiology , Neurons, Afferent/cytology , Neurons, Afferent/drug effects , Neurons, Afferent/physiology , Nociceptors/cytology , Nociceptors/drug effects , Posterior Horn Cells/cytology , Posterior Horn Cells/drug effects , Posterior Horn Cells/physiology , Rats , Rats, Sprague-Dawley , Synaptic Transmission/drug effects , Tubulin/metabolism
10.
Photochem Photobiol ; 71(6): 743-6, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10857371

ABSTRACT

The objective of this study was to determine whether exposure of early suckling young of the opossum Monodelphis domestica to ultraviolet A (UVA) radiation (320-400 nm) can lead to the development of melanocytic lesions similar to those induced after exposure to ultraviolet B (UVB) radiation (280-320 nm) to total doses as low as 380 J/m2. A total of 576 sucklings received nine exposures of 0.6, 2.6 or 15.5 kJ/m2 per dose (total doses approximately 6, 23 and 140 kJ/m2, respectively) from a Blak Ray lamp source with a narrow range emission at 365 nm. A further 280 sucklings were exposed in the same way to doses of 2.6 kJ/m2 per dose (total approximately 23 kJ/m2) broad-band UVA with visible wavelengths from a Dermalight lamp. Frequency of litter loss following all of the UVA-exposure protocols was similar to that within the same stocks in the colony at large. Only one of the 856 UVA-exposed individuals possessed a melanocytic lesion at the 5 month assessment point. No radiation-induced lesions of any type were evident on the skin of the other animals exposed as sucklings. The affected male was from a group of 70 individuals exposed to the highest total dose (140 kJ/m2) from the Blak Ray light source. The melanocytic hyperplasia was provisionally identified as a potential melanoma but it slowly regressed as the animal aged. We conclude that in the opossum suckling exposure system, the potency of UVA for melanoma induction is extremely low compared with that of UVB. Possible explanations, amenable to further investigations, are given for the low UVA sensitivity of the suckling model compared to the adult exposure model of Ley (Ley, R. D. [1997] Cancer Res. 57, 3682-3684).


Subject(s)
Animals, Suckling , Melanoma, Experimental/pathology , Neoplasms, Radiation-Induced/pathology , Radiation Dosage , Skin Neoplasms/pathology , Animals , Disease Models, Animal , Male , Opossums , Ultraviolet Rays
11.
Thyroid ; 10(2): 177-83, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10718556

ABSTRACT

Two patients with widely metastatic papillary thyroid cancer demonstrated progressive growth of diffuse pulmonary lesions. One patient had no apparent response to high doses of 131I and the other hand no 131I uptake. 111In-pentetreotide scans revealed that many of the metastatic lesions expressed somatostatin receptors. The baseline metabolic activity and three-dimensional volume of the lesions were determined by 18F-fluoro-de-oxyglucose positron emission tomography (FDG-PET). After 3 or 4 months of octreotide (Sandostatin LAR Depot; Novartis Pharmaceutical, East Hanover, NJ) therapy, repeat FDG-PET scans revealed reductions in tumor volume and decreases in the standard uptake values of FDG. We conclude that octreotide therapy can change the biological activity of metastatic thyroid cancer lesions that exhibit somatostatin receptors.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Carcinoma, Papillary/metabolism , Octreotide/therapeutic use , Thyroid Neoplasms/metabolism , Antineoplastic Agents, Hormonal/administration & dosage , Carcinoma, Papillary/diagnostic imaging , Carcinoma, Papillary/drug therapy , Delayed-Action Preparations , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Octreotide/administration & dosage , Radiopharmaceuticals , Receptors, Somatostatin/metabolism , Somatostatin/analogs & derivatives , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/drug therapy , Tomography, Emission-Computed , Tomography, Emission-Computed, Single-Photon
12.
Environ Res ; 82(1): 1-6, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10677141

ABSTRACT

Employees at a health center in Georgia were concerned that symptoms experienced by some employees were related to pesticide exposure at the center. Malathion and DDT, used for mosquito control from 1969 to 1981, had been stored and handled at the center's first floor. We surveyed 117 (91%) of 129 employees to determine whether reported symptoms were associated with pesticide exposure. We performed environmental sampling for pesticides. We analyzed serum samples for 17 chlorinated pesticides, and urine samples for malathion. We found that 37% of the participants had reported a diagnosis of sinusitis and 24% of bronchitis since working at the health center. Frequently reported symptoms were eye irritation (44%) and headache (68%). DDT and malathion were found at levels of 2.4 and 11%, respectively, in bulk samples from the loading dock of the building. Multivariate analysis of responses to the questionnaire showed that the perception of odors, inadequate air flow, and length of employment were significantly associated with the employees' health complaints. Pesticide concentrations in employees' serum and urine samples were not associated with any health complaint. The health complaints reported by the employees at the health center were precipitated by both environmental and psychological factors. The epidemiology and laboratory components of this study highlight the importance of obtaining biological measurements in episodes of perceived environmental exposure.


Subject(s)
Air Pollution, Indoor , Community Health Centers , DDT , Insecticides , Malathion , Occupational Exposure , Adult , Aged , Educational Status , Female , Georgia , Health Personnel , Humans , Male , Middle Aged , Mosquito Control , Surveys and Questionnaires , Workforce
13.
Toxicol Ind Health ; 15(1-2): 168-79, 1999.
Article in English | MEDLINE | ID: mdl-10188199

ABSTRACT

Pesticides are used on a massive scale in the United States. The widespread use of these pesticides has made it virtually impossible for the average person to avoid exposure at some level. Generally, it is believed that low-level exposure to these pesticides does not produce acute toxic effects; however, various cancers and other noncancer health endpoints have been associated with chronic exposure to several groups of pesticides. Therefore, it is imperative that well-designed studies investigate the potential relationship between contemporary pesticide exposure and health effects. For these studies to be accurate, reliable methods for determining individual exposure must be used. Biological monitoring is a useful tool for assessing exposure to some contemporary pesticides. As with any analytical method, biological monitoring entails many difficulties, but, in many instances, they can be overcome by the logical use of available information and information acquired in carefully designed studies. At the Centers for Disease Control and Prevention (CDC), we have acquired extensive experience in the development and application of specific techniques for biological monitoring of a variety of toxicants, including many of the contemporary-use pesticides. We have used these methods to measure the internal dose of pesticides received by people in acute and chronic incidents resulting from both environmental and industrial exposure. Additionally, we have established normative values, or reference ranges, of several pesticides based on measurements of their metabolites in the urine of randomly selected adults in the US population. These data have been successfully used to distinguish overt exposures from 'background' exposure. In this paper, we present several examples of the usefulness of biological monitoring in urine and blood and describe the difficulties involved with developing methods in these matrices. We also present a general strategy, considerations, and recommendations for developing biological monitoring techniques for measuring the internal dose of contemporary-use pesticides.


Subject(s)
Environmental Exposure/analysis , Environmental Monitoring/methods , Pesticides/adverse effects , Adult , Humans , Occupational Exposure , Pesticides/analysis , Pesticides/pharmacology , Reference Values , Risk Assessment
14.
Epidemiology ; 10(2): 130-4, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10069247

ABSTRACT

Toxic oil syndrome appeared in epidemic form in Spain in 1981. Epidemiologic studies have demonstrated that illness was caused by consumption of rapeseed oil that had been denatured with aniline. Chemical analyses of oil specimens conducted in conjunction with epidemiologic studies have established that consumption of specific oils containing fatty acid anilide contaminants was associated with increased risk for disease. New chemical analytic methods identified a family of compounds, the di-fatty acid esters of phenylamino propane-diol, and one of these compounds, the 1,2-di-oleyl ester of 3-(N-phenylamino)-1,2-propanediol (DPAP), has been found to be more strongly associated with disease status than the fatty acid anilides. We found the odds ratio for exposure to DPAP (OR = 26.4, 95% CI = 6.4-76.3) is much higher than the odds ratio for exposure to oleyl anilide (OR = 4.1, 95% CI = 2.2-7.8), implying that exposure to DPAP was a more relevant risk factor for development of toxic oil syndrome than exposure to oleyl anilide. In this paper, we review and present analyses of data from multiple studies of the possible etiologic role of DPAP in toxic oil syndrome. The presence of DPAP in oil collected from affected and unaffected households was a more specific correlate of case relatedness than was the presence of fatty acid anilides, and it was equally sensitive. Moreover, DPAP was found in oil from the only refinery whose oil was clearly associated with illness.


Subject(s)
Brassica , Disease Outbreaks , Environmental Exposure , Plant Oils/poisoning , Propylene Glycols/analysis , Anilides/analysis , Fatty Acids, Monounsaturated , Humans , Odds Ratio , Rapeseed Oil , Spain/epidemiology , Syndrome
15.
Environ Health Perspect ; 106(5): 279-89, 1998 May.
Article in English | MEDLINE | ID: mdl-9560354

ABSTRACT

To determine the contaminants that should be studied further in the subsequent population-based study, a profile of Great Lakes (GL) sport fish contaminant residues were studied in human blood and urine specimens from 32 sport fish consumers from three Great Lakes: Lake Michigan (n = 10), Lake Huron (n = 11), and Lake Erie (n = 11). Serum was analyzed for 8 polychlorinated dioxin congeners, 10 polychlorinated furan congeners, 4 coplanar and 32 other polychlorinated biphenyl (PCB) congeners, and 11 persistent chlorinated pesticides. Whole blood was analyzed for mercury and lead. Urine samples were analyzed for 10 nonpersistent pesticides (or their metabolites) and 5 metals. One individual was excluded from statistical analysis because of an unusual exposure to selected analytes. Overall, the sample (n = 31) consumed, on average, 49 GL sport fish meals per year for a mean of 33 years. On average, the general population in the GL basin consume 6 meals of GL sport fish per year. The mean tissue levels of most persistent, bioaccumulative compounds also found in GL sport fish ranged from less than a twofold increase to that of PCB 126, which was eight times the selected background levels found in the general population. The overall mean total toxic equivalent for dioxins, furans, and coplanar PCBs were greater than selected background levels in the general population (dioxins, 1.8 times; furans, 2.4 times; and coplanar PCBs, 9.6 times). The nonpersistent pesticides and most metals were not identified in unusual concentrations. A contaminant pattern among lake subgroups was evident. Lake Erie sport fish consumers had consistently lower contaminant concentrations than consumers of sport fish from Lake Michigan and Huron. These interlake differences are consistent with contaminant patterns seen in sport fish tissue from the respective lakes; GL sport fish consumption was the most likely explanation for observed contaminant levels among this sample. Frequent consumers of sport fish proved to be effective sentinels for identifying sport fish contaminants of concern. In the larger study to follow, serum samples will be tested for PCBs (congener specific and coplanar), DDE, dioxin, and furans.


Subject(s)
Metals/blood , Metals/urine , Pesticides/blood , Pesticides/urine , Sentinel Surveillance , Water Pollution , Animals , Benzofurans/blood , Dibenzofurans, Polychlorinated , Diet , Fishes , Great Lakes Region , Humans , Polybrominated Biphenyls/blood , Polychlorinated Biphenyls/blood
16.
Eur J Neurosci ; 9(8): 1773-7, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9283832

ABSTRACT

Clostridial neurotoxins proteolyse specific proteins implicated in synaptic vesicle exocytosis, but their actions on the release machinery in functional synapses is not well understood. Here we examine the effects of botulinum toxin A (BoNT/A) and tetanus toxin (TeTx) on autaptic transmission in cultured rat hippocampal neurons using whole-cell voltage clamp recordings. The proportion of cells responding to stimulation with an excitatory postsynaptic current (EPSC) and the magnitude of the remaining responses decreased gradually with increasing concentration of either toxin. However, the activity-dependent modulation (5 Hz repetitive stimulation) of EPSCs remaining after toxin inhibition differed markedly between the two toxins. The TeTx inhibition was associated with a persistent activity-dependent depression similar to that in control cells. In contrast, the BoNT/A inhibition was accompanied by a reversal of the modulation into facilitation, resembling that induced by lowering of the calcium concentration. These results demonstrate a difference between BoNT/A and TeTx in their mode of inhibition of synaptic vesicle exocytosis, which suggests that they exert their preferential actions at distinct steps of the release process.


Subject(s)
Botulinum Toxins/pharmacology , Hippocampus/drug effects , Neurons/drug effects , Tetanus Toxin/pharmacology , Animals , Cells, Cultured , Evoked Potentials/drug effects , Hippocampus/cytology , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley
20.
J Neurovirol ; 3(5): 369-79, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9372458

ABSTRACT

The effects of a mumps virus infection on functional properties of embryonic hippocampal neurons in culture were analysed with special emphasis on voltage-dependent Ca2+ channels. Cultures with higher or lower density of glial cells (not treated or treated with mitotic inhibitor, respectively) were infected with the relatively non-cytolytic RW strain of mumps virus and currents were recorded from neurons using whole cell voltage clamp. More than 65% of neurons and glial cells contained viral antigens 1-2 days post infection (p.i.). Glial cells remained infected 6-7 days p.i., while the ratio of infected versus uninfected neurons, especially in cultures with higher glial cell density, was reduced. In both infected and uninfected cultures the somal voltage-dependent Ca2+ currents were stronger in cultures with a higher glial cell density, which indicates that these currents are influenced by glial cells. Introduction of the virus into cultures caused a selective decrease in inward Ca2+ currents, which was most marked at days 6-7 p.i., and which included both infected and unifected neurons. Spontaneous synaptic currents and other ion channel conductances appeared normal in the infected cultures. Dantrolene, which inhibits release of Ca2+ from intracellular stores, decreased the neurons that died during the infection. Taken together the results show that a mumps viral infection can selectively alter the number of function of somal voltage dependent Ca2+ channels in immature hippocampal neurons and that this may reflect a disturbed glia-nerve cell interaction.


Subject(s)
Calcium Channels/metabolism , Hippocampus/embryology , Mumps virus , Mumps/metabolism , Neuroglia/metabolism , Neurons/metabolism , Action Potentials/drug effects , Animals , Calcium Channel Blockers/pharmacology , Cells, Cultured , Dantrolene/pharmacology , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/virology , Neuroglia/drug effects , Neuroglia/virology , Neurons/drug effects , Neurons/virology , Nifedipine/pharmacology , Rats
SELECTION OF CITATIONS
SEARCH DETAIL
...