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1.
Int J Paleopathol ; 3(4): 282-287, 2013 Dec.
Article in English | MEDLINE | ID: mdl-29539565

ABSTRACT

A proximal humeral articular surface from an ancient domestic dog deliberate burial was examined during survey of small mammal bones from a prehistoric early Late Woodland archeological site. An unusual lesion on the caudolateral articular surface prompted micro-computed tomography to define detailed structure. Results indicate cortical or immature woven bone arising subchondrally, replacing normal trabeculae, extending through a breach in the cortical surface, and having sharp transition with surrounding normal bone. Organized bone within the lesion indicates that the dog lived for months-to-years following insult. Differential diagnoses initially included: sharp penetrating trauma; intrinsic or extrinsic blunt fracturing force; osteochondrosis or complication of an osteochondral lesion; unusual osteoarthritis; and neoplasia. Computed tomography ruled out normal or unusual osteoarthritis, and neoplasia. The nature and small size of the lesion, relatively small size of the dog, and lack of evidence for complicating infection, suggest against sharp penetrating trauma as a sole cause. The most plausible differential diagnoses include: uncommon fracture-producing force in a companion animal, and blunt intrinsic or extrinsic force causing fracture at a weak point, such as an early osteochondral lesion, that was obliterated by healing. Combined gross examination, micro-computed tomography, and archeological-anthropological influences facilitated refinement of differential diagnosis.

2.
J Parasitol ; 88(1): 189-90, 2002 Feb.
Article in English | MEDLINE | ID: mdl-12053964

ABSTRACT

Baylisascaris procyonis is the common intestinal nematode of the raccoon and is well-recognized as a cause of visceral, ocular, and neural larva migrans in many species of wild and domestic birds and mammals, including humans. To develop data on the prevalence of B. procyonis in Orange County, California, 800 distinct raccoon latrine sites were sampled in 4 spatial zones from 15 January to 31 December 2000. Counts of fecal eggs per gram (EPG) were determined and evaluated with reference to spatial zone and season of collection. No significant differences in EPG were noted among the spatial zones. However, EPG exhibited a significant rise (37,730 +/- 1,865) in the fall and a significant decline (26,204 +/- 1,446) in the winter (ANOVA, P = 0.045). The overall egg prevalence was 100%, and the overall mean EPG was 30,265 +/- 867.


Subject(s)
Ascaridida Infections/veterinary , Ascaridoidea/isolation & purification , Feces/parasitology , Parasite Egg Count , Raccoons/parasitology , Animals , Ascaridida Infections/epidemiology , Ascaridida Infections/parasitology , California/epidemiology , Eliminative Behavior, Animal , Intestinal Diseases, Parasitic/epidemiology , Intestinal Diseases, Parasitic/parasitology , Intestinal Diseases, Parasitic/veterinary , Raccoons/physiology
3.
Exp Hematol ; 29(6): 766-74, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11378272

ABSTRACT

OBJECTIVE: The translocation from fetal liver hematopoiesis to secondary organs occurs during the second trimester of human gestation. It has been hypothesized that stem cells migrate and acquire lineage potential based on cues specific to the adopted microenvironment. We evaluated primitive hematopoietic cell populations in the fetal human to determine if lineage restriction precedes or follows translocation to sites of hematopoietic activity including thymus, spleen, bone marrow, and liver. METHODS: Sets of hematopoietic tissues from individual second-trimester human abortuses were used to compare and quantitate the lineage outcome of immunophenotypically primitive cells from each of the hematopoietic organs using ex vivo myeloid and lymphoid differentiation systems. RESULTS: Despite uniformity in immunophenotype, functional capabilities were highly restricted by the tissue of origin and alteration in the ex vivo differentiation context did not lead to a change in differentiation outcome. CONCLUSION: Translocation of primitive cells from fetal liver to tissues of mature hematopoietic activity is associated with tissue-specific, quantitative changes in differentiation potential that are unresponsive to alternative differentiation environments. These data suggest that multipotentiality is lost prior to or upon stem-cell migration in the developing human. It is not persistent with residence in a secondary hematopoietic organ.


Subject(s)
Antigens, CD/analysis , Hematopoiesis , Hematopoietic Stem Cells/cytology , Liver/embryology , Spleen/embryology , T-Lymphocytes/immunology , Thymus Gland/embryology , ADP-ribosyl Cyclase , ADP-ribosyl Cyclase 1 , Animals , Antigens, CD34/analysis , Antigens, Differentiation/analysis , Cell Culture Techniques/methods , Cell Separation , Cells, Cultured , Fetus , Hematopoietic Stem Cells/immunology , Humans , Immunophenotyping , Liver/cytology , Liver/immunology , Membrane Glycoproteins , Mice , Mice, Inbred C57BL , NAD+ Nucleosidase/analysis , Organ Specificity , Spleen/cytology , Spleen/immunology , T-Lymphocytes/cytology , Thymus Gland/cytology , Thymus Gland/immunology
4.
Waste Manag Res ; 19(6): 526-32, 2001 Dec.
Article in English | MEDLINE | ID: mdl-12201682

ABSTRACT

Plastics wastes from a municipal solid waste plant have a high energy content which make it an interesting option for co-processing with coal. The potential for adding plastic waste to a coal fired Texaco IGCC (Integrated Gasification Combined Cycle) power station is examined. The resulting efficiency increases due to the improved gasification qualities of plastic over coal. For the overall economics to be the same as the coal only case, the maximum amount that the power station can afford to spend on preparing the plastic waste for use is similar to the assumed coal cost, plus the avoided landfill cost, minus the transport cost. The location of the power station plays a key role, since this has an effect on the transport costs as well as on the landfill charges. The sensitivity of the economics of co-processing plastic waste with coal for a variety of power station operational parameters is presented.


Subject(s)
Coal , Conservation of Natural Resources , Plastics , Power Plants , Refuse Disposal/methods , Costs and Cost Analysis , Gases , Refuse Disposal/economics , Transportation/economics
5.
Vector Borne Zoonotic Dis ; 1(3): 239-42, 2001.
Article in English | MEDLINE | ID: mdl-12653152

ABSTRACT

Baylisascaris procyonis is one of the common nematodes of the raccoon (Procyon lotor), being well recognized as a cause of visceral, ocular, and neural larval migrans in many species of wild and domestic birds and mammals, including humana. Between January 15 and December 31, 2000 in Orange County, CA, 640 raccoons (P. lotor) were live-trapped in four spatial distributions zones, and B. procyonis egg shedding prevalence and fecal egg per gram (EPG) counts were determined in relation to spatial distribution zones, season of the year, age, and sex. Egg shedding prevalence rates were not statistically different between zones, but the EPG count in the primarily residential Zone D differed significantly from other zones. Egg shedding prevalence and EPG counts exhibited a significant rise in the fall and decline in the winter and were significantly higher in juvenile and male raccoons than in adult and female raccoons. The overall fecal egg shedding prevalence was 72.0 +/- 1.8% (461/640), and the overall EPG count was 27,982 +/- 1,006.


Subject(s)
Ascaridida Infections/veterinary , Ascaridoidea/isolation & purification , Feces/parasitology , Intestinal Diseases, Parasitic/veterinary , Raccoons/parasitology , Animals , Ascaridida Infections/epidemiology , California/epidemiology , Female , Intestinal Diseases, Parasitic/epidemiology , Intestinal Diseases, Parasitic/parasitology , Male , Parasite Egg Count/veterinary , Prevalence , Seasons
6.
Nat Biotechnol ; 18(8): 882-7, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10932160

ABSTRACT

Purging of tumor cells and selection of stem cells are key technologies for enabling stem cell transplantation and stem cell gene therapy. Here we report a strategy for cell selection based on physical properties of the cells. Exposing cells to an external pulsed electric field (PEF) increases the natural potential difference across the cell membrane until a critical threshold is reached and pore formation occurs, resulting in fatal perturbation of cell physiology. Attaining this threshold is a function of the applied field intensity and cell size, with larger cells porated at lower field intensities than smaller cells. Since hematopoietic stem cells are smaller than other hematopoietic cells and tumor cells, we found that exposure of peripheral blood mononuclear cells (PBMCs) to PEFs caused stepwise elimination of monocytes without affecting the function of smaller lymphocyte populations. Mobilized peripheral blood exposed to PEFs was enriched for CD34+/CD38- cells and stem cell function was preserved. Furthermore, PEF treatment was able to selectively purge blood preparations of tumor cells and eradicate transplantable tumor.


Subject(s)
Antigens, CD , Bone Marrow Purging , Cell Separation/methods , Hematopoietic Stem Cells/cytology , ADP-ribosyl Cyclase , ADP-ribosyl Cyclase 1 , Antigens, CD34/analysis , Antigens, Differentiation/analysis , Electricity , Hematopoietic Stem Cells/immunology , Humans , Membrane Glycoproteins , NAD+ Nucleosidase/analysis , Tumor Cells, Cultured
7.
Article in English | MEDLINE | ID: mdl-10942622

ABSTRACT

Multiple interacting factors contribute to the haematological manifestations of HIV disease. The effects of HIV-1 infection influence all haemopoietic cell lineages resulting in a spectrum of haematological abnormalities. Even in the absence of other pathological processes, bone marrow morphology is invariably abnormal, and anaemia, neutropenia and thrombocytopenia are all common during the course of disease. Intercurrent opportunistic infections may cause bone marrow suppression or induce specific cytopenias. Therapies used to treat HIV and its complications are frequently implicated as the cause of haematological dysfunction, and many have significant myelotoxic side-effects. Insights into the molecular basis for many of these abnormalities have permitted a clearer understanding of the pathophysiology of HIV-1 infection. Recombinant human growth factors that may be used to treat isolated cytopenias or to ameliorate the myelotoxic effects of other essential therapies. Lymph opoietic growth factors and the use of gene modified cells provide future therapeutic strategies that may alter the course of HIV disease.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Hematologic Diseases/virology , Acquired Immunodeficiency Syndrome/blood , Anemia/pathology , Anemia/virology , HIV-1 , Hematologic Diseases/pathology , Humans , Neutropenia/pathology , Neutropenia/virology , Thrombocytopenia/pathology , Thrombocytopenia/virology
8.
Nat Biotechnol ; 18(7): 729-34, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10888839

ABSTRACT

Biocompatible inorganic matrices have been used to enhance bone repair by integrating with endogenous bone architecture. Hypothesizing that a three-dimensional framework might support reconstruction of other tissues as well, we assessed the capacity of a tantalum-coated carbon matrix to support reconstitution of functioning thymic tissue. We engineered a thymic organoid by seeding matrices with murine thymic stroma. Co-culture of human bone marrow-derived hematopoietic progenitor cells within this xenogeneic environment generated mature functional T cells within 14 days. The proportionate T-cell yield from this system was highly reproducible, generating over 70% CD3+ T cells from either AC133+ or CD34+ progenitor cells. Cultured T cells expressed a high level of T-cell receptor excision circles (TREC), demonstrating de novo T lymphopoiesis, and function of fully mature T cells. This system not only facilitates analysis of the T-lymphopoietic potential of progenitor cell populations; it also permits ex vivo genesis of T cells for possible applications in treatment of immunodeficiency.


Subject(s)
Artificial Organs , Organoids/physiology , T-Lymphocytes/physiology , Thymus Gland/physiology , AC133 Antigen , Animals , Antigens, CD , Antigens, CD34/biosynthesis , Bone Marrow Cells/cytology , Carbon/metabolism , Coated Materials, Biocompatible , Coculture Techniques , Culture Techniques/methods , Flow Cytometry , Glycoproteins/metabolism , HIV-1/metabolism , Hematopoietic Stem Cells/cytology , Humans , Immunophenotyping , Mice , Mice, Inbred C57BL , Microscopy, Electron, Scanning , Organoids/ultrastructure , Peptides/metabolism , Polymerase Chain Reaction , T-Lymphocytes/cytology , Thymus Gland/cytology , Thymus Gland/ultrastructure , Time Factors
9.
J Clin Invest ; 105(9): 1299-305, 2000 May.
Article in English | MEDLINE | ID: mdl-10792005

ABSTRACT

Recruitment of macrophages to sites of cell death is critical for induction of an immunologic response. Calcium concentrations in extracellular fluids vary markedly, and are particularly high at sites of injury or infection. We hypothesized that extracellular calcium participates in modulating the immune response, perhaps acting via the seven-transmembrane calcium-sensing receptor (CaR) on mature monocytes/macrophages. We observed a dose-dependent increase in monocyte chemotaxis in response to extracellular calcium or the selective allosteric CaR activator NPS R-467. In contrast, monocytes derived from mice deficient in CaR lacked the normal chemotactic response to a calcium gradient. Notably, CaR activation of monocytes bearing the receptor synergistically augmented the transmigration response of monocytes to the chemokine MCP-1 in association with increased cell-surface expression of its cognate receptor, CCR2. Conversely, stimulation of monocytes with MCP-1 or SDF-1alpha reciprocally increased CaR expression, suggesting a dual-enhancing interaction of Ca(2+) with chemokines in recruiting inflammatory cells. Subcutaneous administration in mice of Ca(2+), MCP-1, or (more potently) the combination of Ca(2+) and MCP-1, elicited an inflammatory infiltrate consisting of monocytes/macrophages. Thus extracellular calcium functions as an ionic chemokinetic agent capable of modulating the innate immune response in vivo and in vitro by direct and indirect actions on monocytic cells. Calcium deposition may be both consequence and cause of chronic inflammatory changes at sites of injury, infection, and atherosclerosis.


Subject(s)
Calcium/pharmacology , Chemotaxis, Leukocyte , Monocytes/drug effects , Receptors, Cell Surface/metabolism , Animals , Calcium Signaling , Cytosol/metabolism , Dose-Response Relationship, Drug , Humans , Lipopolysaccharide Receptors , Mice , Receptors, CCR2 , Receptors, Calcium-Sensing , Receptors, Chemokine/biosynthesis , Signal Transduction , Skin/cytology
10.
Nat Med ; 6(5): 543-8, 2000 May.
Article in English | MEDLINE | ID: mdl-10802710

ABSTRACT

Movement towards or away from a given stimulus guides the directional migration of prokaryotes, simple eukaryotes and neurons. As bi-directional cues may influence entry and exit of immune effector cells from tissue sites, we evaluated the migratory responses of T-cell subsets to varying concentrations of the chemokine stromal cell derived factor-1 (SDF-1). There was selective repulsion of subpopulations of T cells at high concentrations of recombinant SDF-1 or naturally occurring bone marrow-derived SDF-1, which could be inhibited by pertussis toxin and antibody against the chemokine receptor CXCR4. Distinct sensitivity profiles to genistein, herbimycin and 8-Br-cAMP biochemically distinguished movement of cells towards or away from an SDF-1 gradient. In vivo, antigen-induced T-cell recruitment into the peritoneal cavity was reversed by high but not low concentrations of SDF-1. The phenomenon of movement away from a chemokine represents a previously unknown mechanism regulating the localization of mature T cells. It adds to the functional repertoire of chemokines that may participate in immune physiology and may be applied therapeutically to alter the immune response.


Subject(s)
Chemokines, CXC/pharmacology , Chemotaxis, Leukocyte/physiology , T-Lymphocyte Subsets/drug effects , Adult , Bone Marrow/physiology , Chemokine CXCL12 , Diffusion Chambers, Culture , Dose-Response Relationship, Drug , Humans , Inflammation , Pertussis Toxin , Signal Transduction , Virulence Factors, Bordetella/pharmacology
12.
J Infect ; 36(2): 236-9, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9570666

ABSTRACT

A 29-year-old Caucasian woman presented to hospital with a 2-day history of diarrhoea, anorexia and rigors. Investigations showed abnormal liver function tests, hyponatremia, hypoalbuminaemia and lymphopenia. The initial chest radiograph was normal. A bone marrow trephine biopsy showed non-caseating granulomata and she subsequently developed miliary shadowing on the chest radiograph. A transjugular liver biopsy confirmed the presence of acid-alcohol fast bacilli. Despite starting triple therapy for miliary tuberculosis she remained febrile and developed massive hepatosplenomegaly, jaundice and pancytopenia. Standard triple therapy was substituted with ethambutol, streptomycin and oral prednisolone and the patient made a dramatic recovery. The clinical symptoms of miliary tuberculosis are frequently non-specific and the onset of the illness is often insidious. The liver is involved in almost all patients with miliary tuberculosis, but massive hepatosplenomegaly and jaundice are rare. Standard triple-therapy should be discontinued when there is significant liver dysfunction, and corticosteroids should be considered for patients with miliary tuberculosis who fail to respond to conventional therapy.


Subject(s)
Hepatomegaly/etiology , Jaundice/etiology , Pancytopenia/etiology , Splenomegaly/etiology , Tuberculosis, Miliary/complications , Adrenal Cortex Hormones/therapeutic use , Adult , Antitubercular Agents/therapeutic use , Drug Therapy, Combination , Female , Humans , Liver/pathology , Tomography, X-Ray Computed , Tuberculosis, Miliary/drug therapy , Tuberculosis, Miliary/pathology
13.
Neuropharmacology ; 37(6): 745-50, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9707288

ABSTRACT

The present study aimed to compare the actions of the selective kappa opioid receptor agonist enadoline (CI-977) with morphine in order to see if there is a heterogeneity of opioid receptors between spinal reflex pathways. High (C- and A-fibre evoked activity) and low (A-fibres only) intensity electrical stimulation of dorsal roots in the neonatal rat hemisected spinal cord preparation in vitro was used to distinguish between synaptic activity measured in the corresponding ventral root. Enadoline selectively depressed the high intensity-evoked EPSP with an EC50 of 7.6 nM (n = 7), contrasting with our previous finding in this preparation that morphine is an equipotent depressant of A- and C-fibre-mediated synaptic responses. The depressant effects of enadoline and morphine were reversed by naloxone giving apparent Kd values of 14 +/- 3 nM (n = 4) for enadoline-induced and 4.2 +/- 1 nM (n = 4) for morphine-induced depression. These data suggest that activation of kappa opioid receptors has a selective depressant action on C-fibre-mediated synaptic activity. Such a functional difference mediated at a subclass of opioid receptors has not been previously observed in an in vitro spinal preparation.


Subject(s)
Benzofurans/pharmacology , Pyrrolidines/pharmacology , Receptors, Opioid, kappa/agonists , Spinal Cord/drug effects , Animals , Animals, Newborn , In Vitro Techniques , Morphine/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Opioid, kappa/physiology , Spinal Cord/physiology
14.
Br J Pharmacol ; 124(3): 507-12, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9647475

ABSTRACT

1. Alpha2-adrenoceptor agonists have a spinal site of analgesic action. In the current study the synaptic depressant actions of xylazine, detomidine, romifidine and dexmedetomidine have been compared on segmental reflexes containing NMDA receptor-mediated components in the neonatal rat hemisected spinal cord preparation in vitro. 2. Reflexes were evoked in the ventral root following either supramaximal electrical stimulation of the corresponding ipsilateral lumbar dorsal root to evoke the high intensity excitatory postsynaptic potential (e.p.s.p.) involving all primary afferent fibres, or low intensity stimulation to evoke the solely A fibre-mediated low intensity e.p.s.p. The high intensity e.p.s.p. contains a greater NMDA receptor-mediated component. 3. Xylazine, romifidine, detomidine and dexmedetomidine all depressed both the high intensity e.p.s.p. and the low intensity e.p.s.p. giving respective EC50 values of 0.91+/-0.2 microM (n=12), 23.4+/-3 nM (n=12), 37.7+/-7 nM (n=8) and 0.84+/-0.1 nM (n=4) for depression of the high intensity e.p.s.p. and 0.76+/-0.1 microM (n=12), 22.0+/-3 nM (n=12), 24.9+/-6 nM (n=4) and 2.7+/-0.6 nM (n=4) for depression of the low intensity e.p.s.p., respectively. Unlike the other three drugs, the two values for dexmedetomidine, showing a greater selectivity for the high intensity e.p.s.p., are significantly different. 4. Each of these depressant actions was reversed by the selective alpha2-adrenoceptor antagonist atipamezole (1 microM). 5. In contrast to previous reports of the actions of alpha2-adrenoceptor agonists on the in vitro spinal cord preparation, at concentrations ten fold higher than the above EC50 values xylazine, romifidine, detomidine and dexmedetomidine depressed the initial population spike of motoneurons (MSR). This depression was not reversed by atipamezole. 6. Comparison of the rank order of the present EC50 values for depression of the high intensity e.p.s.p. with potency ratios from in vivo analgesic tests in previous studies show a close correlation between the present in vitro tests and analgesic potency. There is no correlation between the present data and previously obtained affinities of the agonists at non-adrenergic imidazoline binding sites. 7. The current findings therefore suggest that xylazine, romifidine, detomidine and dexmedetomidine are exerting their central analgesic actions at the spinal level principally through alpha2-adrenoceptors. All four agonists showed the same profile of selective depression of the NMDA receptor-mediated component of reflexes similar to that reported previously for clonidine. However dexmedetomidine, unlike the other ligands, selectively depressed the high intensity e.p.s.p.


Subject(s)
Adrenergic alpha-2 Receptor Agonists , Adrenergic alpha-Agonists/pharmacology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Spinal Cord/drug effects , Synaptic Transmission/drug effects , Animals , Animals, Newborn , Electric Stimulation , Evoked Potentials/drug effects , In Vitro Techniques , Nerve Fibers/drug effects , Rats , Rats, Sprague-Dawley , Reflex/drug effects
15.
Eur J Pharmacol ; 342(2-3): 203-8, 1998 Jan 26.
Article in English | MEDLINE | ID: mdl-9548386

ABSTRACT

The novel tachykinin receptor antagonist CGP49823 ((2R,4S)-2-benzyl-1-(3,5-dimethylbenzoyl)-4-(quinolin-4-y lmethylamino)piperidine) has been compared with three other selective non-peptide tachykinin NK1 receptor antagonists. The drugs were tested as antagonists of the depolarization of spinal motoneurones induced by bath application of the selective tachykinin NK1 receptor agonist septide-(6-11) (300 nM) for 120 s at 15 min intervals. The antagonists were bath applied and the depolarizations were recorded from lumbar ventral roots of 7 to 12 day old rat and gerbil hemisected spinal cords in vitro. The gerbil preparation is considered to model the human species variant of the tachykinin NK1 receptor. With the exception of SR140333 ((S)-1-[2-[3-(3,4-dichlorophenyl)-1-[[3-(1-methylethoxy)phenyl]ace tyl]-3-piperidinyl]ethyl]-4-phenyl-1-azoniabicyclo[2.2.2]octane chloride), the antagonists were approximately thirty-fold more potent on gerbil preparations. The respective mean IC50 values from gerbil preparations produced by CP96345 ((2S-cis)-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-azabicy clo[2.2.2]octan-3-amine), CGP49823, SR140333 and CP99994 ((2S-cis)-N-[(2-methoxyphenyl)methyl]-2-phenyl-3-piperidinamine) were, in microM +/- S.E. (n) 0.10 +/- 0.02 (6), 0.22 +/- 0.03 (6), 0.30 +/- 0.10 (5) and 0.38 +/- 0.02 (5) and the corresponding values from the rat preparations were 3.7 +/- 0.4 (5), 7.8 + 1.3 (5), 1.06 +/- 0.16 (6) and 10.5 +/- 2.2 (7). Dominance of tachykinin NK1 receptor activity in the measured responses was confirmed by low potency of the tachykinin NK2-selective antagonist SR48968 ((S)-N-methyl-N[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl] benzamide) which yielded an IC50 value of 12.0 +/- 2.8 (5) on gerbil preparations and produced less than 50% depression of septide-induced depolarization of rat motoneurones at the highest concentration (100 microM) tested.


Subject(s)
Anti-Anxiety Agents/pharmacology , Motor Neurons/drug effects , Piperidines/pharmacology , Receptors, Tachykinin/antagonists & inhibitors , Animals , Gerbillinae , In Vitro Techniques , Neurokinin-1 Receptor Antagonists , Neuromuscular Depolarizing Agents/pharmacology , Peptide Fragments/pharmacology , Pyrrolidonecarboxylic Acid/analogs & derivatives , Quinolines/pharmacology , Rats , Rats, Inbred Strains , Receptors, Neurokinin-2/antagonists & inhibitors , Substance P/analogs & derivatives , Substance P/pharmacology
16.
Neuroscience ; 78(1): 243-50, 1997 May.
Article in English | MEDLINE | ID: mdl-9135104

ABSTRACT

Recordings of whole-cell synaptic current responses elicited by electrical stimulation of dorsal roots were made from motoneurons, identified by antidromic invasion, in isolated spinal cord preparations from five- to eight-day-old Wistar rats. Supramaximal electrical stimulation of the dorsal root evoked complex excitatory postsynaptic currents with mean latencies (+/- S.E.M.) of 6.1 +/- 0.26 ms, peak amplitude of -650 +/- 47 pA and duration of 4.30 +/- 0.46 s (n=34). All phases of excitatory postsynaptic currents were potentiated to approximately 20% above control levels in the presence of the metabotropic glutamate receptor antagonists S-2-amino-2-methyl-4-phosphonobutanoate (MAP4; 200 microM; n=15) and 2S, 1'S,2'S-2-methyl-2-(carboxycyclopropyl)glycine (MCCG; 200 microM; n=9). A similar level of potentiation was produced by the GABA(B) receptor antagonist 3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-P-benzyl-p hosphinic acid (CGP55845; 200 nM; n=5). MAP4 (200 microM) produced a six-fold rightward shift in the concentration-effect plot for the depressant action of the metabotropic glutamate receptor agonist S-2-amino-4-phosphonobutanoate (L-AP4), whereas CGP55845 produced no significant change in the potency of L-AP4. MAP4 did not antagonize the depressant actions of baclofen (n=8), 1S,3S-1-aminocyclopentane-1,3-dicarboxylate (n=4) or 2-S,1'S,2'S-2-(carboxycyclopropyl)glycine (n=4). The metabotropic glutamate receptor antagonists produced no change in the holding current of any of the neurons, indicating that they had no significant postsynaptic excitatory actions. These results are the first to indicate a possible physiological role for metabotropic glutamate receptors in the spinal cord. Like GABA(B) receptors, they control glutamatergic synaptic transmission in the segmental spinal pathway to motoneurons. This is likely to be a presynaptic control mechanism.


Subject(s)
GABA-B Receptor Antagonists , Ganglia, Spinal/physiology , Motor Neurons/physiology , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Spinal Cord/physiology , Synaptic Transmission/drug effects , Animals , Animals, Newborn/physiology , Electric Stimulation , Electrophysiology , Female , GABA-B Receptor Agonists , Ganglia, Spinal/cytology , Male , Membrane Potentials/physiology , Motor Neurons/drug effects , Patch-Clamp Techniques , Rats , Rats, Wistar , Receptors, Metabotropic Glutamate/agonists , Spinal Cord/cytology , Spinal Cord/drug effects
17.
Br J Pharmacol ; 120(7): 1390-6, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9105717

ABSTRACT

1. Population synaptic responses of motoneurones were recorded from a ventral root following electrical stimulation of the corresponding lumbar dorsal root in neonatal rat hemisected spinal cord preparations in vitro. Two levels of electrical stimulation were used to elicit dorsal root compound action potentials that contained either an A fibre component alone or both A and C fibre components. The effects of centrally acting analgesics and an N-methyl-D-aspartate (NMDA) receptor antagonist were tested on synaptic responses produced by these two levels of stimulation. 2. At stimulus intensities below four times threshold (T) there was no C fibre component in the dorsal root compound action potential. Responses to a single pulse at 3T (the low intensity excitatory postsynaptic potential (e.p.s.p.)), a train of five pulses at 2T (the train e.p.s.p.) and a single supramaximal pulse (the high intensity e.p.s.p.) were used to compare the depressant actions of morphine, clonidine and the competitive NMDA antagonist CGP40116 (D-(E)-2- amino-4-methyl-5-phosphono-pentenoic acid). The train e.p.s.p. (mean half-time to decay 5 +/- 0.6 s, n = 6) had a similar profile to the high intensity e.p.s.p. (mean half-time to decay 6.8 +/- 0.7, n = 8). 3. The monosynaptic compound action potential of motoneurones (MSR) was resistant to all three drugs irrespective of the intensity of dorsal root stimulation. The low intensity e.p.s.p., the train e.p.s.p. and the high intensity e.p.s.p. were depressed by all three drugs. The EC50 values for depression by morphine were 79 +/- 1 nM (n = 8) for the high intensity e.p.s.p. and 99 +/- 1 nM (n = 4) for the low intensity e.p.s.p. The corresponding values for clonidine were 25 +/- 1 nM (n = 8) and 9 +/- 1 nM (n = 4) and those for CGP40116 were 860 +/- 1.3 nM (n = 4) and 76 +/- 1.1 nM (n = 4). 4. The depressant profile of the NMDA antagonist, having the least depressant activity on the C fibre-mediated response, was different from that of the two analgesics. CGP40116 (3 microM) depressed the high intensity e.p.s.p. to 62 +/- 8%, the low intensity e.p.s.p. to 22 +/- 4% and the train e.p.s.p. to 16 +/- 2% of control values. 5. The depressant actions of morphine were fully reversed by naloxone (1 microM) and those of clonidine were fully reversed by atipamezole (1 microM). 6. These results show that, in contrast to previous findings, activation of primary afferent C fibres in dorsal roots is not required for generation of morphine- or clonidine-sensitive synaptic responses in ventral roots of this in vitro preparation.


Subject(s)
Action Potentials/drug effects , Analgesics, Opioid/pharmacology , Clonidine/pharmacology , Morphine/pharmacology , Spinal Cord/drug effects , 2-Amino-5-phosphonovalerate/analogs & derivatives , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Animals, Newborn , Excitatory Amino Acid Antagonists/pharmacology , Rats , Rats, Sprague-Dawley , Spinal Cord/physiology
18.
Neuropharmacology ; 36(3): 313-8, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9175609

ABSTRACT

The patch-clamp technique has been used to record synaptic responses, elicited by electrical stimulation of dorsal roots, in 28 single motoneurones of in vitro spinal cord preparations from neonate (P5 to P8) rats. The effects of (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) (200 microM), a potent antagonist at L-2-amino-4-phosphonobutanoate (AP4)-sensitive receptors, and (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (500 microM), which is a less selective antagonist of mGluRs, were tested on EPSCs alone and as antagonists of AP4-induced depression of EPSCs. The EC50 for depression of EPSCs by AP4 (1.16 +/- 0.12 microM, n = 8) was increased to 18.9 +/- 0.7 microM (n = 6) by MPPG. MCPG (500 microM) had no significant effect on the depressant potency of AP4. Under control conditions, EPSCs had mean peak amplitudes of 983 pA +/- 64 SEM and mean charge transferred of 306 +/- 37 pC (n = 28). These values were increased significantly (p < 0.05) to 1168 +/- 68 pA and 363 +/- 39 pC by MPPG (n = 6), and 1150 +/- 54 pA and 358 +/- 33 pC (n = 6) by MCPG. There was no significant difference between the enhancement of the initial peak of the EPSCs (mean latency from stimulus artifact 5.9 +/- 0.3 ms) and later components, suggesting mGluRs to be present on primary afferent terminals presynaptic to motoneurones as well as in pathways via interneurones. These results are consistent with the presence of at least two types of presynaptic mGluR that modulate release of glutamate in segmental pathways convergent onto motoneurones. These receptors appear to be activated by interstitial glutamate tonically present in the present preparations.


Subject(s)
Motor Neurons/drug effects , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Spinal Cord/drug effects , Synaptic Transmission/drug effects , Animals , Dose-Response Relationship, Drug , Glycine/pharmacology , In Vitro Techniques , Rats
19.
J Zoo Wildl Med ; 28(1): 97-100, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9226623

ABSTRACT

From May 1987 to September 1994, 19 eastern box turtles (Terrapene carolina carolina) originating from scattered locations on Long Island, New York (USA) were presented with one or more of the following signs: listlessness, ocular and nasal discharge, conjunctivitis, blepharitis, and otitis media. Numerous species of bacteria and yeast were isolated by aerobic culture. Histopathologic findings confirmed chronic active bacterial infections. Toxicologic analyses of livers revealed elevated concentrations of chlordane metabolites in two diseased turtles. A third turtle liver contained residues of endosulfan sulfate. Immunosuppressive effects of low-level exposure to organochlorines, including chlordane and endosulfan, could be involved in the pathogenesis of the observed infections.


Subject(s)
Animals, Wild , Hydrocarbons, Chlorinated , Insecticides/poisoning , Turtles , Animals , Environmental Exposure , Female , Insecticides/analysis , Liver/chemistry , Male , New York
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