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1.
Pediatr Clin North Am ; 56(6): 1519-37, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19962034

ABSTRACT

Throughout the world, injuries and violence are a leading cause of mortality and suffering among Indigenous communities. Among American Indian and Alaska Native children aged 1 to 19 years, 71% of deaths are from injuries. Motor-vehicle accidents, attempted suicide, and interpersonal violence are the most common causes of injuries in highly industrialized countries. For Indigenous populations in middle- and low-income countries, trauma caused by motor-vehicle accidents, agricultural injuries, interpersonal violence, child labor, and the ravages of war are priorities for intervention. To be effective, injury-prevention efforts should be based on scientific evidence, be developmentally and culturally appropriate, and draw on the inherent strengths of Indigenous communities.


Subject(s)
Developing Countries/statistics & numerical data , Population Groups/statistics & numerical data , Primary Prevention/methods , Wounds and Injuries/epidemiology , Wounds and Injuries/prevention & control , Accidental Falls/statistics & numerical data , Accidents, Traffic/prevention & control , Accidents, Traffic/statistics & numerical data , Adolescent , Age Distribution , Alcohol Drinking/adverse effects , Australia/epidemiology , Burns/epidemiology , Canada/epidemiology , Child , Child Abuse/prevention & control , Child Abuse/statistics & numerical data , Cultural Characteristics , Drowning/epidemiology , Homicide/statistics & numerical data , Humans , Indians, North American/statistics & numerical data , New Zealand/epidemiology , Program Development , Program Evaluation , Suicide, Attempted/prevention & control , Suicide, Attempted/statistics & numerical data , United States/epidemiology , Young Adult
2.
J Safety Res ; 37(2): 213-7, 2006.
Article in English | MEDLINE | ID: mdl-16697414

ABSTRACT

UNLABELLED: The Journal of Safety Research has partnered with the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, USA, to briefly report on some of the latest findings in the research community. This report is the fourth edition in a series of CDC articles. BACKGROUND: An active injury and illness surveillance system was established by the Centers for Disease Control and Prevention (CDC) along with the Louisiana Department of Health and Hospitals (LDHH) in the aftermath of Hurricane Katrina in functioning hospitals and medical clinics. RESULTS: The surveillance system recorded 7,543 nonfatal injuries among residents and relief workers between September 8-October 14, 2005. The leading mechanisms of injury identified in both groups were fall and cut/stab/pierce, with a greater proportion of residents compared to relief workers injured during the repopulation period. Clean-up was the most common activity at the time of injury for both groups. CONCLUSION: Injuries documented through this system underscore the need for surveillance of exposed populations to determine the injury burden and initiate injury prevention activities and health communication campaigns.


Subject(s)
Disasters/statistics & numerical data , Population Surveillance , Relief Work , Wounds and Injuries/epidemiology , Adolescent , Adult , Aged , Ambulatory Care Facilities/statistics & numerical data , Centers for Disease Control and Prevention, U.S. , Child , Child, Preschool , Female , Hospitals/statistics & numerical data , Humans , Infant , Infant, Newborn , Louisiana/epidemiology , Male , Middle Aged , Public Health Administration , Time Factors , United States , Wounds and Injuries/classification , Wounds and Injuries/prevention & control
3.
Acta Diabetol ; 42(3): 147-52, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16258738

ABSTRACT

Urinary bladder dysfunction is a major complication in diabetes mellitus and its mechanism has been attributed to altered neurological function (autonomic and/or peripheral neuropathy). Previous studies have demonstrated impaired nerve deficiencies, including either loss of nerve function and/or anatomical loss of neuromuscular nerve terminals. While the phenomenon of diabetes-related neurological injury is well recognised, its pathogenesis is not well understood. Using a well established rat model of diabetes (streptozotocin model), we investigated the prevalence of sympathetic and parasympathetic nerves and relative prevalence of connexin isoforms (gap junction proteins) during diabetes-related bladder dysfunction. Immunohistochemistry and digital image analysis was used to detect the prevalence of postsynaptic neuronal markers, NOS1 and connexin isoform expressions. Immunohistochemistry showed significant increases in tyrosine hydroxylase (marker of sympathetic innervation) and decreased vesicular acetylcholine transporter (marker of parasympathetic innervation), predominantly in the smooth muscle layer, 3 days after diabetes induction, when compared to age-matched controls. Time-dependent and cell-specific decreases in the connexin 43 isoform, but transient increases in connexin 32 and 26, were also observed in diabetic rats vs. controls (p<0.05). These data suggest that selective and time-dependent expression of gap junction proteins and altered prevalence of sympathetic/parasympathetic innervation are early events during diabetes-related bladder dysfunction and remodelling.


Subject(s)
Connexins/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetic Neuropathies/metabolism , Urinary Bladder/metabolism , Animals , Biomarkers/metabolism , Diabetes Mellitus, Experimental/physiopathology , Disease Models, Animal , Immunohistochemistry , Male , Nitric Oxide Synthase Type I/metabolism , Protein Isoforms/metabolism , Rats , Rats, Sprague-Dawley , Tyrosine 3-Monooxygenase/metabolism , Urinary Bladder/innervation , Vesicular Acetylcholine Transport Proteins/metabolism
4.
Biochem Soc Trans ; 33(Pt 5): 977-80, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16246025

ABSTRACT

The human malaria parasite Plasmodium falciparum possesses a single mitochondrion and a plastid-like organelle called the apicoplast. Both organelles contain members of the KADH (alpha-keto acid dehydrogenase) complexes--multienzyme complexes that are involved in intermediate metabolism. In the asexual blood stage forms of the parasites, the alpha-ketoglutarate dehydrogenase and branched chain KADH complexes are both located in the mitochondrion, whereas the pyruvate dehydrogenase is exclusively found in the apicoplast. In agreement with this distribution, Plasmodium parasites have two separate and organelle-specific pathways that guarantee lipoylation of the KADH complexes in both organelles. A biosynthetic pathway comprised of lipoic acid synthase and lipoyl (octanoyl)-ACP:protein Nepsilon-lipoyltransferase B is present in the apicoplast, whereas the mitochondrion is supplied with exogenous lipoic acid, and ligation of the metabolite to the KADH complexes is accomplished by a lipoate protein ligase A similar to that of bacteria and plants. Both pathways are excellent potential targets for the design of new antimalarial drugs.


Subject(s)
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)/metabolism , Mitochondria/enzymology , Plasmodium falciparum/enzymology , Thioctic Acid/metabolism , Animals , Humans , Organelles/enzymology
5.
J Head Trauma Rehabil ; 20(3): 205-14, 2005.
Article in English | MEDLINE | ID: mdl-15908821

ABSTRACT

OBJECTIVES: To compare the incidence of nonfatal traumatic brain injury (TBI) hospitalization among American Indians/Alaska Natives (AI/AN) with that of other race groups and to assess alcohol and protective equipment (PE) use among those who sustained TBI related to a motor vehicle (MV) incident. METHODS: Data were obtained from 13 states funded by the Centers for Disease Control and Prevention to conduct TBI surveillance from 1997 to 1999. Rates by race and by cause were calculated for the 13 states combined. Blood alcohol concentration (BAC) levels and PE use were compared between AI/AN and "other" races in a subgroup of these states. RESULTS: Although not significantly different, AI/AN had the highest overall age-adjusted TBI hospitalization rate (71.5 per 100,000). Rates were significantly higher among AI/AN than among whites for ages 20 to 44 years (78.5 per 100,000 vs 54.7 per 100,000, P < .0001). MV incidents were the leading cause of TBI (40.1% of cases) among AI/AN, and AI/AN injured in MV incidents had higher BAC levels (65.7% > or = 0.08 g/dL vs 31.6% > or = 0.08 g/dL, P < .0001) and lower PE use (22.0% vs 40.4%, P < .0001) than the "other" race group. CONCLUSION: AI/AN have high rates of TBI hospitalization compared with other races. High BAC levels and low use of PE in MV incidents appear to be associated with the higher rates in this population.


Subject(s)
Brain Injuries/epidemiology , Hospitalization/statistics & numerical data , Indians, North American/statistics & numerical data , Accidental Falls/statistics & numerical data , Accidents, Traffic/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Alcohol Drinking/blood , Central Nervous System Depressants/blood , Child , Child, Preschool , Ethanol/blood , Humans , Infant , Infant, Newborn , Middle Aged , Protective Devices/statistics & numerical data , United States/epidemiology , Violence/statistics & numerical data
6.
Vet Comp Orthop Traumatol ; 18(1): 37-42, 2005.
Article in English | MEDLINE | ID: mdl-16594215

ABSTRACT

OBJECTIVE: The purpose of this study is to evaluate the changes in structural anatomy of cadaver pelves, with specific emphasis on axial rotation, resulting from the application of TPO plates differing by type, angle and orientation. SAMPLE POPULATION: Nine cadaver pelves procedure: The degree of axial rotation was determined for three different pelvic osteotomy plate types, four different plate angles and two different orientations of the same plate. RESULTS: The observed degree of axial rotation was significantly different than the degree of axial rotation predicted by the plate angle for each group except the Rooks pelvic osteotomy plate. CONCLUSIONS/CLINICAL RELEVANCE: In the triple pelvic osteotomy the final degree of axial rotation may be significantly different than the predetermined plate angle.


Subject(s)
Bone Plates/veterinary , Dogs/injuries , Fracture Fixation, Intramedullary/veterinary , Fractures, Bone/veterinary , Osteotomy/veterinary , Pelvic Bones/injuries , Acetabulum/injuries , Acetabulum/physiology , Acetabulum/surgery , Animals , Cadaver , Dogs/surgery , Fracture Fixation, Intramedullary/methods , Fractures, Bone/surgery , Osteotomy/methods , Pelvic Bones/physiology , Pelvic Bones/surgery , Range of Motion, Articular
7.
Nucleosides Nucleotides Nucleic Acids ; 23(8-9): 1441-4, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15571273

ABSTRACT

Purine antimetabolites have been very successful therapeutic agents against a host of infectious diseases and malignancies. Success of the treatment relies as much on the efficient accumulation by the target cell or organism as it does on selective action on a vital biochemical pathway of the target cell. Here we compare the ability of a new class of tricyclic purine antimetabolites to interact with transporters from human erythrocytes or Trypanosoma brucei. We show that these compounds display a remarkable selectivity for the parasite's transporters. The adenine analogue showed greater trypanocidal activity than the hypoxanthine or guanine analogues in vitro.


Subject(s)
Antimetabolites/metabolism , Purines/metabolism , Allopurinol/pharmacology , Animals , Antimetabolites/chemical synthesis , Biological Transport , Dose-Response Relationship, Drug , Erythrocytes/metabolism , Humans , Kinetics , Models, Chemical , Nucleobase Transport Proteins/chemistry , Oxazines/pharmacology , Purines/chemistry , Rats , Trypanosoma brucei brucei , Xanthenes/pharmacology
8.
Med J Malaysia ; 59 Suppl B: 125-6, 2004 May.
Article in English | MEDLINE | ID: mdl-15468850

ABSTRACT

Avian demineralized bone matrix (ADBM) powder prepared from chicken, pigeon, and turkey sources induced bone formation via endochondral and intramembranous processes, as in mammalian studies. There were no significant differences in percentage of new bone, percentage of cartilage, surface-forming osteoblast area, or osteoclast count between gaps treated with chicken, pigeon, and turkey DBM. However, there was a significantly (p<0.05) higher percentage of inflammatory area in gaps treated with chicken DBM than in gaps treated with pigeon DBM.


Subject(s)
Bone Matrix , Bone Substitutes , External Fixators , Osseointegration/physiology , Ulna/surgery , Animals , Bone Demineralization Technique , Chickens , Columbidae , Powders , Turkeys , Ulna/pathology
9.
Inj Prev ; 8(3): 216-20, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12226119

ABSTRACT

BACKGROUND: Navajo motor vehicle mortality is the highest among the 12 Indian Health Service (IHS) administrative areas. In July 1988, the Navajo Nation enacted a primary enforcement safety belt use and a child restraint law. OBJECTIVE: Assess the impact of the laws on the rate and severity of pediatric (0-19 years) motor vehicle injury resulting in hospitalizations in the Navajo Nation. METHODS: Hospitalizations associated with motor vehicle related injury discharges were identified by International Classification of Diseases, 9th revision, CM E codes, 810-825 (.0,.1) from the Navajo IHS hospital discharge database. Age specific rates for the period before the law, 1983-88, were compared with those after enactment and enforcement, 1991-95. Severity of injury, measured by the abbreviated injury scale (AIS) score and new injury severity score (NISS), was determined with ICDMAP-90 software. Wilcoxon rank sum and chi(2) tests were used for analysis. RESULTS: Discharge rates (SE) for motor vehicle injury (per 100 000) decreased significantly in all age groups: 0-4 years (62 (7) to 28 (4)), 5-11 years (55.3 (6) to 26 (4)), and 15-19 years (139 (14) to 68 (7)); p=0.0001. In children 0-4 years, the median AIS score decreased from 1.5 (1,3) (25th, 75th centile) to 1 (1,2), p=0.06, and the median NISS decreased from 3.5 (1,9) to 2 (1,5), p=0.07. The proportion of children with NISS scores >4 decreased significantly for the 0-4 year age group (p=0.03). CONCLUSIONS: Concurrent with enactment of the Navajo Nation occupant and child restraint laws there was a reduction in the rate of motor vehicle related hospital discharges for children. Severity of injury declined in very young Navajo children. The effect of enactment and enforcement of this Native American child occupant restraint law may serve as an example of an effective injury control effort directed at Native American children.


Subject(s)
Accidents, Traffic/statistics & numerical data , Indians, North American/statistics & numerical data , Seat Belts/statistics & numerical data , Wounds and Injuries/prevention & control , Abbreviated Injury Scale , Accidents, Traffic/legislation & jurisprudence , Accidents, Traffic/prevention & control , Adolescent , Adult , Chi-Square Distribution , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Seat Belts/classification , Seat Belts/legislation & jurisprudence
10.
Acta Diabetol ; 39(1): 23-7, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12043935

ABSTRACT

Urinary bladder dysfunction and remodeling are well-recognized phenomena in diabetes but detailed assessments of tissue morphological changes have not been conducted. We studied time-dependent morphological changes in bladders from diabetic rats (streptozotocin model) and evaluated the usefulness of automated digital imaging technology as an unbiased, reproducible, and convenient method for the bladder morphometric analysis. Urinary bladders were isolated from diabetic (3 days, 2 weeks or 5 weeks after single injection of streptozotocin, 65 mg/kg) or control rats (0 or 5 weeks) and were processed for histochemical evaluations (hematoxylin/eosin and Mason's trichrome staining). Digital image analysis was used to quantify equatorial cross-sectional areas of bladder tissue and lumen, as well as relative prevalence of the three primary tissue components viz. smooth muscle, urothelium, and extracellular matrix. Digital imaging and color segmentation provided reliable and unbiased evaluations of the bladder tissue sections. Progressive increases in total bladder tissue and lumen area were observed in the diabetic animals relative to controls (p<0.05), demonstrating classic hypertrophy and dilation. Prevalence of smooth muscle and urothelium (% of total tissue) both increased significantly, but collagen content decreased. Average bladder wall thickness and urothelium thickness were unchanged. Bladder remodeling during experimental diabetes is associated with time-dependent chamber dilation and increased tissue mass. Changes in bladder wall composition also occurred in a time-dependent manner, most notably increased smooth muscle and urothelium and decreased collagen prevalence. Furthermore, automated digital imaging technologies provide an unbiased, reproducible, and convenient method for detailed morphometric analysis of bladder tissues.


Subject(s)
Diabetes Mellitus, Experimental/pathology , Urinary Bladder/pathology , Animals , Collagen/analysis , Male , Muscle, Smooth/pathology , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Time Factors , Urothelium/pathology
11.
Vet Surg ; 30(4): 341-50, 2001.
Article in English | MEDLINE | ID: mdl-11443595

ABSTRACT

OBJECTIVE: To compare external fixator clamps from Kirschner-Ehmer (K-E), Synthes, and Meynard with respect to 6 mechanical parameters. Study Design-A bench test of mechanical properties. METHODS: Specially designed fixtures were used to mechanically test 6 clamps of each type at 2.5, 5.0, and 7.5 Newton-Meters of clamp bolt-tightening torque. RESULTS: Components slipped axially and torsionally in the K-E clamp at higher forces for all parameters except for clamp bolt axis pivot. No bolt axis pivot occurred with the Synthes clamp. Instead, the clamp plastically deformed at the fixator-pin interface. This failure occurred at a higher applied torque than the pivot torque for other clamps. The Meynard clamp withstood significantly greater force than the K-E clamp when torsion was applied to the clamp bolt axis in the clockwise direction. Pivot forces for the K-E clamp were significantly higher than the Meynard clamp in the counterclockwise direction. CONCLUSIONS: Overall, the K-E clamp was able to resist higher axial and torsional forces before slipping than the Meynard clamp or the Synthes clamp. The Synthes clamp was best able to resist torsion around the clamp bolt axis. Torsional resistance at the clamp-fixator pin and clamp-connecting bar interface was the weakest parameter of clamp mechanics. CLINICAL RELEVANCE: The ability to resist motion within a clamp is related to fracture-reduction stability. Knowledge of the mechanical properties of fixator clamps will improve a clinician's ability to apply rigid fixation.


Subject(s)
External Fixators/veterinary , Fracture Fixation/veterinary , Fractures, Bone/veterinary , Animals , Equipment Design/veterinary , Equipment Failure/veterinary , Fracture Fixation/instrumentation , Fractures, Bone/surgery , Stress, Mechanical
12.
J Am Anim Hosp Assoc ; 37(4): 374-83, 2001.
Article in English | MEDLINE | ID: mdl-11450839

ABSTRACT

In large- and giant-breed dogs, fibrocartilaginous embolic myelopathy (FCEM) is a well-recognized syndrome of acute spinal cord infarction caused by embolization of fibrocartilage. The miniature schnauzer is reportedly the most frequently affected small breed, although clinical data from only six miniature schnauzers with FCEM is available in the literature. The purposes of this study were to determine the relative frequency of FCEM compared to other causes of myelopathy in miniature schnauzers, to characterize the clinicopathological features of FCEM in 38 miniature schnauzers, and to directly compare FCEM and intervertebral disk herniation in miniature schnauzers with respect to age at diagnosis; gender; neuroanatomical localization; and progression, asymmetry, and severity of neurological deficits. Fibrocartilaginous embolic myelopathy was the most common cause of myelopathy in miniature schnauzers. Age at diagnosis, asymmetry and severity of neurological deficits, and lack of progression of clinical signs after 24 hours assisted in distinguishing FCEM from intervertebral disk herniation. Fibrocartilaginous embolic myelopathy-related mortality in miniature schnauzers was significantly lower than mortality rates reported for affected large and giant breeds. Only 22% of miniature schnauzers were euthanized because of their disease, although the vast majority of survivors failed to achieve complete neurological recovery.


Subject(s)
Dog Diseases/epidemiology , Embolism/veterinary , Spinal Cord Diseases/veterinary , Animals , Breeding , Cartilage , Dog Diseases/etiology , Dogs , Embolism/complications , Embolism/epidemiology , Female , Indiana/epidemiology , Intervertebral Disc Displacement/epidemiology , Intervertebral Disc Displacement/veterinary , Male , Minnesota/epidemiology , Ohio/epidemiology , Records/veterinary , Retrospective Studies , Spinal Cord Diseases/epidemiology , Spinal Cord Diseases/etiology
13.
J Neurosci ; 21(11): RC149, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11344255

ABSTRACT

Peroxynitrite formation has been demonstrated in several neurodegenerative disorders; thus far, protein nitration and consequent alterations in protein function are implicated as mechanistic events. Free 3-nitrotyrosine (free-3NT) is also elevated in these settings; a neurotoxic role for this modified amino acid has not been investigated. We tested the hypothesis that free-3NT is neurotoxic in vivo, using a mouse model of striatal degeneration. The neurodegenerative effects of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) (unilateral intrastriatal injection, 64 nmol) were compared with free-3NT (32 nmol) or free-tyrosine (free-TYR) (32 nmol). 6-OHDA-treated mice exhibited significant ipsilateral turning behavior after d-amphetamine challenge, indicative of unilateral striatal injury (ipsilateral-contralateral turning differential, 21.1 +/- 6.8). Significant turning behavior was also observed in free-3NT-treated mice but not in free-tyrosine-treated mice (free-3NT, 16.0 +/- 3.9; free-TYR, 1 +/- 2.7; p < 0.01). Immunohistochemistry was used to evaluate striatal tyrosine hydroxylase (TH) content. 6-OHDA or free-3NT treatment caused severe reductions in TH immunoreactivity in injected striata compared with the contralateral hemisphere (injected/contralateral immunoreactivity ratio: 6-OHDA, 0.23 +/- 0.07; free-3NT, 0.49 +/- 0.02). Free-tyrosine treatment had no effect (1.03 +/- 0.09). Turning behavior was correlated with striatal TH ratio (p < 0.01). Furthermore, we observed a striking unilateral reduction in TH-positive cell body counts in the substantia nigra pars compacta of 6-OHDA- and free-3NT-treated mice (injected/contralateral cell count ratio: 6-OHDA, 0.40 +/- 0.04; free-3NT, 0.59 +/- 0.02). Free-tyrosine treatment had no effect (1.05 +/- 0.04). No evidence for increased striatal protein incorporation of 3NT was observed in any treatment group. These data represent the first evidence that free-3NT can elicit neurodegenerative effects in vivo; free-3NT may have a causal role in neurodegenerative conditions.


Subject(s)
Corpus Striatum/drug effects , Neurodegenerative Diseases/chemically induced , Tyrosine/analogs & derivatives , Tyrosine/toxicity , Animals , Cell Count , Corpus Striatum/enzymology , Corpus Striatum/pathology , Dextroamphetamine/pharmacology , Disease Models, Animal , Immunohistochemistry , Mice , Motor Activity/drug effects , Neurodegenerative Diseases/enzymology , Neurodegenerative Diseases/pathology , Neurons/drug effects , Neurons/enzymology , Neurons/pathology , Oxidopamine/administration & dosage , Oxidopamine/toxicity , Substantia Nigra/drug effects , Substantia Nigra/enzymology , Substantia Nigra/pathology , Tyrosine/administration & dosage , Tyrosine 3-Monooxygenase/analysis , Tyrosine 3-Monooxygenase/metabolism
14.
Pharmacol Biochem Behav ; 67(2): 241-6, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11124387

ABSTRACT

We have been studying sensitization of psychostimulant-induced stereotyped behavior in mice using both single and multiple pretreatment paradigms. In the present study, we tested whether NMDA receptor antagonists and an inhibitor of nitric oxide synthesis inhibit expression of sensitization in either of these models. Male CF-1 mice were pretreated with a single dose or with three daily doses of amphetamine (14 mg/kg) or apomorphine (40 mg/kg). Two days following these pretreatments, mice were injected with ((+/-)3-(2-carboxypiperazine-4yl)-propyl-1-phosphonic acid (CPP, 20 mg/kg), dizocilpine maleate (MK-801, 0.1 mg/kg), 7-nitroindazole (25 mg/kg), or vehicle 30 min before receiving amphetamine (7 mg/kg) or apomorphine (3 mg/kg). The stereotyped behavioral response was enhanced in mice pretreated with amphetamine or apomorphine, indicating that sensitization had developed. CPP, MK-801, and 7-nitroindazole prevented the expression of the sensitized stereotyped response induced by either amphetamine or apomorphine in both paradigms. These drugs did not attenuate the stereotypy elicited by amphetamine and apomorphine in drug-naïve mice. The effect of 7-nitroindazole was reversed by pretreatment with 500 mg/kg of L-arginine but not by D-arginine. These results suggest that glutamatergic transmission and subsequent NMDA receptor activation and the production of nitric oxide play a critical role in the expression of the sensitized stereotyped behavioral response elicited by amphetamine or apomorphine.


Subject(s)
Amphetamine/pharmacology , Apomorphine/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Stereotyped Behavior/drug effects , Animals , Arginine/pharmacology , Behavior, Animal/drug effects , Dizocilpine Maleate/pharmacology , Enzyme Inhibitors/pharmacology , Indazoles/pharmacology , Male , Mice , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Piperazines/pharmacology , Receptors, N-Methyl-D-Aspartate/drug effects , Receptors, N-Methyl-D-Aspartate/metabolism
15.
Behav Brain Res ; 114(1-2): 167-74, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10996057

ABSTRACT

We have been studying sensitization of psychostimulant-induced stereotyped behavior in mice using both a context-dependent and a context-independent paradigm. In the present study, we tested whether N-methyl-D-aspartate (NMDA) receptor antagonists prevent development of sensitization in either of these models. Male CF-1 mice were pretreated with 20 mg/kg (+)3-(2-carboxypiperazine-4yl)-propyl-1-phosphonic acid (CPP), 0.1 mg/kg (+)5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohopten-5, 10-imine maleate (MK-801, dizocilpine maleate), or 25 mg/kg 7-nitroindazole 30 min before a single dose (context-dependent paradigm) or each of three daily doses (context-independent paradigm) of 14 mg/kg amphetamine or 40 mg/kg apomorphine. Two days following this pretreatment, mice were injected with 7 mg/kg amphetamine or 3 mg/kg apomorphine. The stereotyped behavioral response was enhanced in mice pretreated with amphetamine or apomorphine alone, indicating that sensitization had developed. Both CPP and MK-801 prevented the development of sensitization in the context-dependent model but not in the context-independent paradigm. 7-Nitroindazole did not attenuate development of sensitization in either model. The results suggest that activation of glutamatergic receptors is important in some sensitization paradigms but not others, indicating that glutamate can be important but is not always required for the development of sensitization.


Subject(s)
Amphetamine/pharmacology , Apomorphine/pharmacology , Central Nervous System Stimulants/pharmacology , Receptors, N-Methyl-D-Aspartate/drug effects , Stereotyped Behavior/drug effects , Animals , Dizocilpine Maleate/pharmacology , Dopamine/physiology , Environment , Enzyme Inhibitors/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Indazoles/pharmacology , Male , Mice , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Piperazines/pharmacology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
16.
Pharmacol Biochem Behav ; 66(4): 671-7, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10973502

ABSTRACT

The present study was designed to determine whether single and repeated pretreatment regimens with amphetamine or apomorphine differ in the context dependency of sensitization of stereotyped behavior. Male CF-1 mice that were pretreated with a single high dose of amphetamine (14 mg/kg, IP) or apomorphine (40 mg/kg, SC) only became sensitized to a lower test dose of amphetamine (7 mg/kg, IP) or apomorphine (3 mg/kg, SC) when placed in an environment that was the same as the pretreatment environment. However, animals pretreated with three high doses (24 h apart) of amphetamine (14 mg/kg, IP) or apomorphine (40 mg/kg, SC) did demonstrate sensitization to a lower test dose of amphetamine (7 mg/kg, IP) or apomorphine (3 mg/kg, SC) when placed in an environment that was different from the pretreatment environment. Context-dependent sensitization, but not context-independent sensitization, was extinguished by pairing the test environment with saline injections instead of drug injections. In addition, it was determined that neither sensitization model could be related to pharmacokinetic factors. Therefore, the results indicate that repeated exposure to amphetamine or apomorphine overcomes the context-dependent component of sensitization of amphetamine- or apomorphine-induced stereotyped behavior.


Subject(s)
Amphetamine/pharmacology , Apomorphine/pharmacology , Dopamine Agonists/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Environment , Stereotyped Behavior/drug effects , Amphetamine/administration & dosage , Amphetamine/pharmacokinetics , Animals , Apomorphine/administration & dosage , Apomorphine/pharmacokinetics , Brain/metabolism , Dopamine Agonists/administration & dosage , Dopamine Agonists/pharmacokinetics , Dopamine Uptake Inhibitors/administration & dosage , Dopamine Uptake Inhibitors/pharmacokinetics , Dose-Response Relationship, Drug , Excitatory Postsynaptic Potentials/drug effects , Male , Mice , Receptors, Presynaptic/drug effects
17.
Pharmacol Biochem Behav ; 66(2): 435-41, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10880702

ABSTRACT

The present study was designed to determine whether single and repeated pretreatment regimens with amphetamine or apomorphine differ in the context-dependency of sensitization of stereotyped behavior. Male CF-1 mice that were pretreated with a single high dose of amphetamine (14 mg/kg intraperitoneally [IP]) or apomorphine (40 mg/kg subcutaneously [SC]) only became sensitized to a lower test dose of amphetamine (7 mg/kg IP) or apomorphine (3 mg/kg SC) when placed in an environment that was the same as the pretreatment environment. However, animals pretreated with 3 high doses (24-h apart) of amphetamine (14 mg/kg IP) or apomorphine (40 mg/kg SC) did demonstrate sensitization to a lower test dose of amphetamine (7 mg/kg IP) or apomorphine (3 mg/kg SC) when placed in an environment that was different from the pretreatment environment. Context-dependent sensitization, but not context-independent sensitization, was extinguished by pairing the test environment with saline injections instead of drug injections. In addition, it was determined that neither sensitization model could be related to pharmacokinetic factors. Therefore, the results indicate that repeated exposure to amphetamine or apomorphine overcomes the context-dependent component of sensitization of amphetamine- or apomorphine-induced stereotyped behavior.


Subject(s)
Apomorphine/administration & dosage , Dextroamphetamine/administration & dosage , Stereotyped Behavior/drug effects , Animals , Apomorphine/pharmacokinetics , Brain/metabolism , Dose-Response Relationship, Drug , Environment , Male , Mice , Models, Neurological
18.
Psychopharmacology (Berl) ; 146(1): 42-8, 1999 Sep 01.
Article in English | MEDLINE | ID: mdl-10485963

ABSTRACT

RATIONALE: The role of the environment in the sensitization of the stereotyped behavioral effects of apomorphine is unclear, since sensitization of this drug effect has either been difficult to demonstrate or has been shown to occur with a low but not a higher dose of apomorphine. OBJECTIVES: The present study was designed to determine whether sensitization of the stereotyped behavioral effects induced by a single dose of apomorphine is dependent on environmental context. METHODS: CF-1 mice were pretreated with apomorphine or vehicle under different environmental conditions and tested for stereotyped behavior after apomorphine challenge. Animals were scored positively for stereotyped behavior if they remained stationary and exhibited repetitive head and/or fore-limb movements, and data are reported as the percentage of mice rated as positive for stereotyped behavior. RESULTS: When mice were pretreated with 40 mg/kg apomorphine and later tested in the same environment, the dose-response curve for stereotyped behavior elicited by apomorphine was shifted threefold to the left 48 h after pretreatment, and this sensitization persisted for at least 28 days after pretreatment. Mice pretreated with apomorphine did not have higher brain levels of apomorphine after administration of the test dose of apomorphine. When the pretreatment environment was different from the test environment, mice did not exhibit sensitization to apomorphine. CONCLUSIONS: These results show that pre-exposure to a single high dose of apomorphine induces a long-lasting sensitization of apomorphine-induced stereotyped behavior that is context dependent. Since apomorphine directly activates dopamine receptors, these observations suggest that a mechanism located postsynaptic to dopamine neurons may be responsible for sensitization of stereotyped behavior.


Subject(s)
Apomorphine/pharmacology , Stereotyped Behavior/drug effects , Animals , Dose-Response Relationship, Drug , Male , Mice , Receptors, Dopamine/drug effects
19.
Pharmacol Biochem Behav ; 63(2): 263-9, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10371655

ABSTRACT

The present study was designed to determine whether the environmental context in which amphetamine is administered plays a role in the development of sensitization to the stereotyped behavioral effects of amphetamine in mice. In male CF-1 mice, the dose-response curve for stereotyped behavior elicited by amphetamine was shifted 1.9-fold to the left 48 h after pretreatment with 14 mg/kg amphetamine. Behavioral sensitization only developed in mice that were pretreated in the same or a similar environment as that of the test environment. In addition, when mice were placed in an environment that attenuated the acute expression of stereotyped behavior elicited by the pretreatment dose of amphetamine, sensitization never developed. A further experiment showed that 96% of the mice that expressed stereotypy after the ED50 pretreatment dose of 10 mg/kg amphetamine showed a stereotyped behavioral response to the lesser dose of 7 mg/kg 48 h later, indicating sensitization. In contrast, mice that did not express stereotypy after the ED50 dose of amphetamine failed to show a significant stereotyped behavioral response to amphetamine challenge compared to vehicle-pretreated controls. Therefore, the results indicate that preexposure to a single high dose of amphetamine produces context- and response-dependent sensitization to amphetamine-induced stereotyped behavior.


Subject(s)
Central Nervous System Stimulants/pharmacology , Dextroamphetamine/pharmacology , Stereotyped Behavior/drug effects , Animals , Central Nervous System Stimulants/administration & dosage , Dextroamphetamine/administration & dosage , Dose-Response Relationship, Drug , Drug Resistance , Male , Mice , Time Factors
20.
J Am Anim Hosp Assoc ; 35(2): 135-46, 1999.
Article in English | MEDLINE | ID: mdl-10102182

ABSTRACT

The clinicopathological features of cervical fractures in 56 dogs were reviewed. "Hit by car" (HBC) was the most common inciting cause, and the axis and atlas were the vertebrae most frequently affected. Surgical treatment was associated with high (36%) perioperative mortality. However, all dogs that survived the perioperative period achieved functional recovery. Functional recovery was achieved in 25 (89%) of 28 nonsurgically treated dogs with adequate follow-up. Overall, severity of neurological deficits (nonambulatory status) and prolonged interval (five days or longer) from trauma to referral were associated with poorer outcome. Nonsurgical treatment is a viable therapeutic approach for many dogs with cervical fractures. Early neck immobilization and prompt referral are recommended, because delay in referral decreases the likelihood of functional recovery.


Subject(s)
Cervical Vertebrae/injuries , Dogs/injuries , Dogs/surgery , Spinal Fractures/veterinary , Accidents, Traffic , Animals , Radiography , Records/veterinary , Recovery of Function , Retrospective Studies , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Treatment Outcome
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