RESUMO
BACKGROUND: Historically, staging of civilian emergency medical services (EMS) during an active shooter incident was in the cold zone while these professionals awaited the scene to be completely secured by multiple waves of law enforcement. This delay in EMS response has led to the development of a more effective method: the Rescue Task Force (RTF). The RTF concept has the second wave of law enforcement escorting civilian EMS into the warm zone, thus decreasing EMS response time. To our knowledge, there are no data regarding the willingness of EMS professionals to enter a warm zone as part of an RTF. In this study, we assessed the willingness of EMS providers to respond to an active shooter incident as part of an RTF. METHODS: A survey was distributed at an annual, educational EMS conference in North Carolina. The surveys were distributed on the first day of the conference at the beginning of a general session that focused on EMS stress and wellness. Total attendance was measured using identification badges and scanners on exiting the session. Data were assessed using χ2 analysis, as were associations between demographics of interest and willingness to respond under certain conditions. A p value < .01 indicated statistical significance. RESULTS: The overall response rate was 76% (n = 391 of 515 session attendees). Most surveys were completed by paramedics (74%; n = 288 of 391). Most EMS professionals (75%; n = 293 of 391) stated they would respond to the given active shooter scenario as part of an RTF (escorted by the second wave of law enforcement) if they were given only ballistic gear. However, most EMS professionals (61%; n = 239 of 391) stated they would not respond if they were provided no ballistic gear and no firearm. Those with tactical or military training were more willing to respond with no ballistic gear and no firearm (49.6%; n = 68 of 137) versus those without such training (31%; n = 79 of 250; odds ratio, 2.2; 95% confidence interval, 1.4-3.3; p < .001). CONCLUSION: EMS professionals are willing to put themselves in harm's way by entering a warm zone if they are simply provided the proper training and ballistic equipment.
Assuntos
Atitude do Pessoal de Saúde , Auxiliares de Emergência/psicologia , Armas de Fogo , Trabalho de Resgate/organização & administração , Auxiliares de Emergência/educação , Equipamentos e Provisões/estatística & dados numéricos , Humanos , Aplicação da Lei , Inquéritos e QuestionáriosRESUMO
Mucolipidosis IIIC, or variant pseudo-Hurler polydystrophy, is an autosomal recessive disease of lysosomal hydrolase trafficking. Unlike the related diseases, mucolipidosis II and IIIA, the enzyme affected in mucolipidosis IIIC (N-Acetylglucosamine-1-phosphotransferase [GlcNAc-phosphotransferase]) retains full transferase activity on synthetic substrates but lacks activity on lysosomal hydrolases. Bovine GlcNAc-phosphotransferase has recently been isolated as a multisubunit enzyme with the subunit structure alpha(2)beta(2)gamma(2). We cloned the cDNA for the human gamma-subunit and localized its gene to chromosome 16p. We also showed, in a large multiplex Druze family that exhibits this disorder, that MLIIIC also maps to this chromosomal region. Sequence analysis of the gamma-subunit cDNA in patients from 3 families identified a frameshift mutation, in codon 167 of the gamma subunit, that segregated with the disease, indicating MLIIIC results from mutations in the phosphotransferase gamma-subunit gene. This is to our knowledge the first description of the molecular basis for a human mucolipidosis and suggests that the gamma subunit functions in lysosomal hydrolase recognition.
Assuntos
Lisossomos/metabolismo , Mucolipidoses/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Humanos Par 16 , Clonagem Molecular , Feminino , Fibroblastos , Mutação da Fase de Leitura , Ligação Genética , Humanos , Escore Lod , Lisossomos/enzimologia , Masculino , Dados de Sequência Molecular , Mucolipidoses/etiologia , Linhagem , RNA Mensageiro/metabolismo , Análise de Sequência , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismoRESUMO
Hybrid genetic elements, Mud-P and Mud-Q (collectively, Mud-P22s), have been constructed that carry two-thirds of the temperate Salmonella phage P22 genome sandwiched between the ends of transposon Mu. Insertions of these elements in the Salmonella chromosome generate locked-in P22 prophages that cannot excise. Upon induction (as a consequence of the inactivation of P22 c2 repressor), a locked-in prophage replicates its DNA in situ, resulting in the amplification of neighboring regions of the chromosome and the processive packaging of three contiguous headsful of adjacent DNA in one direction from the P22 packaging site, pac. Phage particles in an induced lysate of a Mud-P22 lysogen contain DNA molecules corresponding to several minutes of chromosomal DNA adjacent to the site of prophage insertion and transduce nearby genetic markers with high efficiencies. Mud-P22 prophages have been introduced into an F' episome by transposition; resident Mud insertions on the Salmonella chromosome may be converted to Mud-P22 insertions by homologous recombination in P22-mediated transductional crosses.
Assuntos
Cromossomos Bacterianos , Fagos de Salmonella/genética , Salmonella typhimurium/genética , Elementos de DNA Transponíveis , DNA Bacteriano/genética , Genes Virais , Marcadores Genéticos , Hibridização Genética , Plasmídeos , Ativação ViralRESUMO
OBJECTIVE: The purpose of this study was to define the correlation between HbA1c values and the percentage of home blood glucose (HBG) measurements within given ranges in a pie chart in three age-groups of subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: HbA1c values were compared with HBG measurements in subjects who did at least three blood glucose tests per day over 30 days in three age groups: 5-11, 12-16, and 17-35 years. The blood glucose values were arbitrarily divided into three groups, defined as the percentage of HBG measurements within, above, and below target range. Each range was then compared with the corresponding HbA1c value. Longitudinal data were also collected for 279 of the subjects after a mean of 139 days. RESULTS: A strong correlation (P = 0.001) was found between HbA1c values and the average blood glucose, and also with the percentage of HBG measurements within, above, and below target range in each of the three age-groups (P < 0.001). Analyses of longitudinal data showed a strong correlation of the changes in HbA1c values to the changes in blood glucose values. CONCLUSIONS: These data showed that a pie-shaped graph of the HBG data can be useful as a clinical parameter in helping patients and families attain desired HbA1c values.
Assuntos
Glicemia/metabolismo , Hemoglobinas Glicadas/metabolismo , Adolescente , Adulto , Automonitorização da Glicemia , Criança , Pré-Escolar , Interpretação Estatística de Dados , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , MasculinoRESUMO
OBJECTIVES: To evaluate the clinical utility of plasma beta 2-microglobulin (beta 2M) levels, acid-dissociated HIV-1 p24 antigen, and HIV-1 p24-antibody titers in predicting HIV-1 vertical transmission in 227 HIV-1-infected Ugandan pregnant women. DESIGN: Plasma beta 2M levels, acid-dissociated HIV-1 p24-antigen positivity, and HIV-1 p24-antibody titers were determined using commercial enzyme immunoassays (EIA) in a Ugandan cohort of 52 HIV-1-seropositive transmitting mothers, 175 HIV-1-seropositive non-transmitting mothers, and 52 seronegative mothers within 6 weeks prior to delivery. RESULTS: Transmitter mothers had significantly higher plasma concentrations of beta 2M (1.80 +/- 1.13 mg/l) than non-transmitter seropositive mothers (1.32 +/- 0.81 mg/l; P = 0.0013). Similarly, a significantly higher proportion of transmitter mothers had detectable p24 antigen than non-transmitter mothers [six out of 51 (11.8%) versus six out of 173 (3.5%); P = 0.03]. Compared with the vertical transmission rate of 23% in the seropositive group, the positive predictive values of a beta 2M level > 1.5 mg/l or detectable HIV-1 p24 antigen for vertical transmission were 34 and 50%, respectively. Five of six (83.3%) seropositive mothers with both a beta 2M level > 1.5 mg/l and detectable p24 antigenemia transmitted HIV-1 infection to their infants compared with 25 of 124 (20.2%) seropositive mothers with values below the cut-off values for both tests (P = 0.00249). However, beta 2M was not found to be a significant independent predictor of vertical transmission when analyzed in a multivariate model with p24 antigenemia. There was no significant difference in HIV-1 p24-antibody titers in transmitter mothers versus non-transmitter mothers (P = 0.299). CONCLUSION: beta 2M levels and acid-dissociated HIV-1 p24-antigen assays may be used to predict which HIV-1-infected pregnant women are at greatest risk for vertical transmission. However, only the p24-antigen test was independently predictive of vertical transmission and its clinical utility is limited.
Assuntos
Anticorpos Anti-HIV/sangue , Proteína do Núcleo p24 do HIV/análise , Infecções por HIV/transmissão , HIV-1 , Complicações Infecciosas na Gravidez , Microglobulina beta-2/análise , Adolescente , Adulto , Biomarcadores , Estudos de Coortes , Estudos de Avaliação como Assunto , Feminino , Proteína do Núcleo p24 do HIV/imunologia , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Concentração de Íons de Hidrogênio , Técnicas Imunoenzimáticas , Gravidez , Uganda/epidemiologiaRESUMO
GnRH antagonists suppress pituitary and gonadal function by competing with endogenous GnRH for binding to receptors on pituitary gonadotrophs. We studied the effects of GnRH antagonist administration to men in a protocol simulating a likely male contraceptive regimen combined with a low dose of testosterone. The GnRH antagonist Nal-Glu was given daily (10 mg, sc) for 20 weeks to eight normal men, and a low dose of testosterone enanthate (25 mg, sc) was given every week. Sperm counts started declining during week 4, and complete azoospermia was reached within 6-12 weeks in six of the eight subjects. Subjects 7 and 8, whose sperm counts and serum gonadotropin levels were not suppressed after 10 weeks, were given 20 mg Nal-Glu starting at week 10. One became azoospermic at week 16, while the other's total sperm counts continued declining and reached a nadir of 1.4 million by week 20. Sperm motility and viability in this subject were completely suppressed after week 14. Sperm counts returned to baseline levels 12-14 weeks after the end of Nal-Glu administration. The mean serum LH level of the first six subjects decreased from 3 +/- 03. U/L at baseline to less than 0.1 U/L until week 20, and then levels returned to baseline. FSH levels similarly decreased from a combined mean of 3.6 +/- 0.9 U/L at baseline to below 0.3 U/L after 4 weeks of Nal-Glu administration. Serum mean testosterone levels between weekly injections of testosterone enanthate ranged from 27.4 +/- 5.9 to 4.8 +/- 1.4 nmol/L, but remained in the hypogonadal range (less than 10 nmol/L) for 4 of the 7 days. None of the subjects, however, complained of decreased libido or potency, as assessed by a questionnaire. No systemic or significant local side-effects were observed, other than a minimal reaction at the injection site. These data suggest that complete sustained azoospermia can be achieved in man, without loss of libido, by chronic administration of a GnRH antagonist plus testosterone.
Assuntos
Anticoncepcionais Masculinos , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Libido/efeitos dos fármacos , Oligospermia/induzido quimicamente , Testosterona , Adulto , Sobrevivência Celular/efeitos dos fármacos , Anticoncepcionais Masculinos/efeitos adversos , Combinação de Medicamentos , Hormônios Esteroides Gonadais/sangue , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Testosterona/efeitos adversosRESUMO
Of 957 patients with type 1 diabetes without known Addison's disease 1.6% (n = 15) were positive for 21-hydroxylase autoantibodies. Among DQ8/DQ2 heterozygous patients, the percentage expressing 21-hydroxylase autoantibodies was 5% (10 of 208) vs. less than 0.5% of patients with neither DQ8 nor DQ2. Three of the diabetic patients found to have 21-hydroxylase autoantibodies on screening were subsequently diagnosed with Addison's disease. Overall, the genotype DQ8/DQ2, consisting of DRB1*0404/DQ8 with DRB1*0301/DQ2, was present in 14 of 21 patients with Addison's disease (8 of 12 with diabetes and 6 of 9 without diabetes or antiislet autoantibodies) vs. 0.7% of the general population (109 of 15,547; P < 10(-6)) and 11% of patients with DM without Addison's disease (62 of 578; P < 10(-6)). Among patients with diabetes with DQ8, Addison's disease was strongly associated with the specific DRB1 subtype, DRB1*0404 (8 of 9 patients from 8 families, in contrast to only 109 of 408 DQ8 DM patients with diabetes without Addison's disease having DRB1*0404; P < 0.001). Among 21-hydroxylase autoantibody-positive DQ8 patients, 80% with DRB1*0404 (12 of 15) had Addison's disease, in contrast to 1 of 10 autoantibody-positive patients with DRB1*0401 or DRB1*0402 (P < 0.001). We conclude that patients with DRB1*0404 and 21-hydroxylase autoantibodies are at high risk for Addison's disease. Patients with DRB1*0401 and DRB1*0402 have more limited progression to Addison's disease despite the presence of 21-hydroxylase autoantibodies.
Assuntos
Doença de Addison/etiologia , Alelos , Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/imunologia , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Esteroide 21-Hidroxilase/imunologia , Doença de Addison/genética , Adolescente , Adulto , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Cadeias HLA-DRB1 , Humanos , Lactente , Pessoa de Meia-Idade , RiscoRESUMO
Excitotoxic spinal cord injury (SCI) causes anatomic, physiologic and molecular changes within the spinal cord and brain. Intraspinal injection of quisqualic acid (QUIS) produces an excitotoxic injury that leads to the onset of behavioral syndromes, believed to be related to the clinical condition of chronic pain. The opioid system, classically involved in the suppression of pain transmission, has been associated with the onset of pain-related behaviors and changes in spinal opioid peptide expression have been demonstrated in various models of SCI and chronic pain. Recently, changes in opioid peptide expression have been demonstrated in both spinal and supraspinal areas following excitotoxic SCI. Therefore, the purpose of this study was to examine changes in opioid peptide gene expression as they relate to the onset of pain behaviors following excitotoxic SCI. Male, Long-Evans rats were given an intraspinal injection of 1.2 microl of 125 mM QUIS and allowed to survive for 10 days, a duration sufficient for the development of pain-related behaviors. Animals were assessed daily for the presence of excessive grooming behavior, i.e. self-directed biting and scratching resulting in damage to superficial and deeper layers of the skin. Animals were also tested for thermal hypersensitivity using a cold plate apparatus on days 5, 7, and 10 following QUIS injection. After sacrifice, quantitative in situ hybridization was performed on regions of the spinal cord surrounding the lesion site as well as whole brain sections through various levels of the thalamus and cortex. Spinal preproenkephalin (PPE) and preprodynorphin (PPD) expression was significantly increased in animals that developed excessive grooming behaviors vs. those that did not. For PPE, this difference was seen bilaterally, in areas of cord caudal to the site of injury. For PPD, this difference was seen only ipsilateral to the site of injection, rostral to the site of injury. In addition, PPE expression in the anterior cingulate cortex and PPD expression in the contralateral parietal cortex were significantly higher in grooming vs. non-grooming animals. These results support previous conclusions that both spinal and supraspinal regulation of endogenous opioid peptide expression plays a role in the response to or onset of post-SCI pain. These results also suggest that the opioid peptides are regulated independently and serve different functions in response to SCI.
Assuntos
Dinorfinas/metabolismo , Encefalinas/metabolismo , Expressão Gênica/fisiologia , Asseio Animal/fisiologia , Dor/metabolismo , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Medula Espinal/metabolismo , Animais , Encéfalo/metabolismo , Agonistas de Aminoácidos Excitatórios , Masculino , Peptídeos Opioides/metabolismo , Dor/psicologia , Ácido Quisquálico , Ratos , Ratos Long-Evans , Traumatismos da Medula Espinal/induzido quimicamente , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/psicologiaRESUMO
Interleukin-10 (IL-10) has been utilized as a neuroprotective agent in experimental models of spinal cord injury because of its potent anti-inflammatory properties. Previous studies have delivered a single dose (5 microg) of IL-10 following experimental spinal cord injury in the rat, and demonstrated various degrees of neuroprotection. However, the role of endogenous production of IL-10 has not been considered. Therefore, the purpose of the current study was to establish the role of endogenous IL-10 and demonstrate the true potential of exogenous IL-10 administration through the use of IL-10((-/-)) mice. Using the quisqualic acid model of spinal cord injury, we examined the extent of gray matter damage and onset of injury-induced pain behaviors at various time points following injury in wild-type vs. IL-10((-/-)) mice. Additionally, IL-10 was reconstituted in IL-10 deficient mice by the intraperitoneal administration of 50 ng recombinant murine (rm) IL-10 30 min following quisqualic acid injection. Animals were observed daily following injury for the onset of pain-behaviors. At days 1, 7, and 14 following injection, lesion analysis revealed a greater extent of damage at early time points (1 day, 7 days) following injury in the IL-10((-/-)) animals as compared with wild-type animals. However, by 14 days post-experimental spinal cord injury, the extent of damage between the two groups was not significant. IL-10((-/-)) animals that received the single (50 ng) rmIL-10 injection following injury displayed gray matter damage patterns similar to wild-type animals. The pronounced early damage noted in the IL-10((-/-)) animals was associated with an approximately two-fold increase in peripheral neutrophils, an index of an innate immune response to injury, compared with wild-type mice. In addition, wild type and IL-10((-/-)) animals receiving rmIL-10 demonstrated a delay in the onset of injury-induced pain behaviors. However, by 14 days post-experimental spinal cord injury the overall incidence of pain behaviors was similar between all treatment groups. Therefore, the absence of IL-10 expression accelerates the kinetics of lesion expansion, the onset of pain behaviors, and the peripheral immune response to spinal cord injury. Endogenous IL-10 and low doses of exogenous IL-10 are neuroprotective at 1 and 7 days following injury. Therefore, the results of the current study suggest that low dose IL-10 administration acutely following spinal cord injury has potential as a therapeutic agent for limiting tissue loss following injury.
Assuntos
Comportamento Animal/efeitos dos fármacos , Interleucina-10/metabolismo , Fármacos Neuroprotetores/metabolismo , Dor/psicologia , Substância Cinzenta Periaquedutal/patologia , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/psicologia , Animais , Contagem de Células Sanguíneas , Interleucina-10/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fármacos Neuroprotetores/farmacologia , Neurotoxinas , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/induzido quimicamenteRESUMO
Intraspinal injection of quisqualic acid, a mixed kainic acid/2-amino-3(3-hydroxy-5-methylisoxazol-4-yl)propionic acid and metabotropic glutamate receptor agonist, produces an excitotoxic injury that leads to the onset of both spontaneous and evoked pain behavior as well as changes in spinal and cortical expression of opioid peptide mRNA, preprodynorphin and preproenkephalin. What characteristics of the quisqualic acid-induced injury are attributable to activation of each receptor subtype is unknown. This study attempted to define the role of activation of the kainic acid/2-amino-3(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and metabotropic glutamate receptor subtypes in the regulation of opioid peptide expression and the onset of spontaneous and evoked pain-related behavior following excitotoxic spinal cord injury by comparing quisqualic acid-induced changes with those created by co-injection of quisqualic acid and the kainic acid/AMPA antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline, (NBQX) or the metabotropic antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA). Therefore, 42 male Long-Evans adult rats were divided into seven treatment groups and received intraspinal microinjections of saline (sham), 0.5% dimethylsulphoxide (sham), quisqualic acid (1.2 microl, 125 mM), NBQX (1.2 microl, 60 microM), AIDA (1.2 microl, 250 microM), quisqualic acid/NBQX (1.2 microl, 125 mM/60 microM), or quisqualic acid/AIDA (1.2 microl, 125 mM/250 microM) directed at spinal levels thoracic 12-lumbar 2. Behavioral observations of spontaneous and evoked pain responses were completed following surgery. After a 10-day survival period, animals were killed and brain and spinal cord tissues were removed and processed for histologic analysis and in situ hybridization. Both AIDA and NBQX affected the quisqualic acid-induced total lesion volume but only AIDA caused a decrease in the percent tissue damage at the lesion epicenter. Preprodynorphin and preproenkephalin expression is increased in both spinal and cortical areas in quisqualic acid-injected animals versus sham-, NBQX or AIDA-injected animals. NBQX did not affect quisqualic acid-induced spinal or cortical expression of preprodynorphin or preproenkephalin except for a significant decrease in preproenkephalin expression in the spinal cord. In contrast, AIDA significantly decreases quisqualic acid-induced preprodynorphin and preproenkephalin expression within the spinal cord and cortex. AIDA, but not NBQX, significantly reduced the frequency of, and delayed the onset of, quisqualic acid-induced spontaneous pain-related behavior. From these data we suggest that both the kainic acid/AMPA and metabotropic glutamate receptor subtypes are involved in the induction of the excitotoxic cascade responsible for quisqualic acid-induced neuronal damage and changes in opioid peptide mRNA expression, while metabotropic glutamate receptors may play a more significant role in the onset of post-injury pain-related behavior.
Assuntos
Comportamento Animal/efeitos dos fármacos , Neurotoxinas/farmacologia , Peptídeos Opioides/genética , Dor/metabolismo , RNA Mensageiro/metabolismo , Receptores de Glutamato/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Comportamento Animal/fisiologia , Dinorfinas/genética , Encefalinas/genética , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Asseio Animal/efeitos dos fármacos , Asseio Animal/fisiologia , Indanos/farmacologia , Masculino , Degeneração Neural/induzido quimicamente , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Peptídeos Opioides/biossíntese , Dor/induzido quimicamente , Dor/fisiopatologia , Medição da Dor/efeitos dos fármacos , Precursores de Proteínas/genética , Quinoxalinas/farmacologia , RNA Mensageiro/efeitos dos fármacos , Ratos , Ratos Long-Evans , Receptores de AMPA/efeitos dos fármacos , Receptores de AMPA/metabolismo , Receptores de Glutamato/efeitos dos fármacos , Receptores de Ácido Caínico/efeitos dos fármacos , Receptores de Ácido Caínico/metabolismo , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/induzido quimicamente , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Spinal cord injury in rats is known to cause anatomical, physiological and molecular changes within the spinal cord. These changes may account for behavioral syndromes that appear following spinal cord injury, syndromes believed to be related to the clinical condition of chronic pain. Intraspinal injection of quisqualic acid produces an excitotoxic injury with pathological characteristics similar to those associated with ischemic and traumatic spinal cord injury. In addition, recent studies have demonstrated changes in blood flow, neuronal excitability and gene expression in the brain following excitotoxic injury, indicating that behavioral changes may result from modification of neuronal substrates at supraspinal levels of the neuraxis. Because changes in spinal opioid peptide expression have been demonstrated in models of traumatic spinal cord injury and chronic pain, the present study investigated messenger RNA expression of the opioid peptides, preproenkephalin and preprodynorphin, at spinal and supraspinal levels following excitotoxic spinal cord injury. Male, Long-Evans rats were given three intraspinal injections of quisqualic acid (total 1.2 microl, 125mM). After one, three, five, seven or 10days, animals were killed and quantitative in situ hybridization performed on regions of the spinal cord surrounding the lesion site, as well as whole-brain sections through various levels of the thalamus. Preproenkephalin and preprodynorphin expression was increased in spinal cord areas adjacent to the site of quisqualic injection and in cortical regions associated with nociceptive function, preproenkephalin in the cingulate cortex and preprodynorphin in the parietal cortex, both ipsilaterally and contralaterally at various time-points following injury. These results further our knowledge of the secondary events that occur following spinal cord injury, specifically implicating supraspinal opioid systems in the CNS response to spinal cord injury.
Assuntos
Dinorfinas/metabolismo , Encefalinas/metabolismo , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Agonistas de Aminoácidos Excitatórios , Vértebras Lombares , Masculino , Peptídeos Opioides/metabolismo , Ácido Quisquálico , Ratos , Ratos Long-Evans , Traumatismos da Medula Espinal/induzido quimicamente , Vértebras TorácicasRESUMO
Mechanisms of acid-evoked CGRP release from gastric afferent nerves were investigated in rat antral mucosal/submucosal tissues. Low pH (pH 4.0, 5.0 and 6.0) stimulated antral CGRP release significantly and dose-dependently from rat antral fragments. Removal of extracellular calcium from the incubation medium resulted in significant inhibition (59%, P < 0.001) of acid (pH 4.0)-stimulated CGRP release. Conotoxin (1 x 10(-7) M), the selective blocker of N-type calcium channels, also significantly inhibited proton (pH 4.0)-induced CGRP release to values that were 74% below net stimulated levels. Neither nifedipine (1 x 10(-6) M), the L-type Ca(2+)-channel antagonist, nor indomethacin (1 x 10(-5) M), inhibitor of prostaglandin synthesis, altered acid-induced CGRP release. In contrast, ruthenium red (1 x 10(-5) M), capsaicin antagonist, almost completely prevented acid (pH 4.0)-stimulated CGRP release. Capsazepine (1 x 10(-4) M), a specific capsaicin receptor antagonist, also completely abolished acid-induced CGRP release. In conclusion, the results of these studies indicate that hydrogen ions are capable of evoking CGRP release from peripheral sensory neurons in rat antral mucosal/submucosal tissues. Proton-evoked CGRP release requires extracellular calcium and involves N-type calcium channels. Furthermore, acid appears to exert a capsaicin-like effect to evoke sensory neuropeptide release that is sensitive to capsazepine and ruthenium red. These data suggest that proton-induced antral CGRP release represents a direct action of hydrogen ions on mucosal/submucosal sensory dendritic nerve endings to effect local release of neuropeptide.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Concentração de Íons de Hidrogênio , Antro Pilórico/metabolismo , Animais , Toxina da Cólera/farmacologia , Indometacina/farmacologia , Masculino , Nifedipino/farmacologia , Antro Pilórico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Tetrodotoxina/farmacologia , Fatores de TempoRESUMO
The ability of exogenous calcitonin gene-related peptide (CGRP) to regulate gastric somatostatin and gastrin messenger RNA was studied in vitro in rat antral mucosal/submucosal tissues. Somatostatin and gastrin mRNA were quantified by Northern and dot blot hybridization and regulatory peptides were measured by radioimmunoassay. Incubation of antral tissues in the presence of CGRP [1 x 10(-7) M] for 60 min resulted in a reciprocal increase in somatostatin and a decrease in gastrin release: 214.7+/-28.5 vs. control of 81.7+/-5.9 pg somatostatin per gram of tissue and 2.2+/-0.3 vs. control of 5.5+/-0.7 ng gastrin per gram of tissue (P < 0.001). CGRP caused parallel changes in somatostatin and gastrin mRNA levels: somatostatin mRNA increased by 212% from 0.40+/-0.02 to 1.25+/-0.09 absorbance units (AU) (P < 0.001) and gastrin mRNA decreased by 73% from 0.55+/-0.08 to 0.15+/-0.02 AU (P < 0.001). Somatostatin monoclonal antibody prevented CGRP-mediated inhibition of both gastrin release and gastrin mRNA levels. In conclusion, CGRP is capable of modulating both the secretion and gene expression of regulatory peptides from antral G and D cells. Somatostatin immunoneutralization studies suggest that the actions of CGRP on gastrin release and gene expression are indirect and mediated through the paracrine influences of somatostatin.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Gastrinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Antro Pilórico/efeitos dos fármacos , Somatostatina/genética , Animais , Northern Blotting , Western Blotting , Cinética , Masculino , Antro Pilórico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Previous studies have shown that intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Significant changes in the functional properties of sensory neurons adjacent to the site of injury have also been observed in this model. Additionally, following QUIS injections, mechanical and cold allodynia, combined with excessive grooming behavior have been shown to be the behavioral correlates of these pathological and physiological changes. These behaviors are believed to be related to the clinical conditions of spontaneous and evoked pain following SCI. Given the therapeutic properties of adrenal chromaffin cell transplantation in conditions of neuropathic and cancer pain, it is proposed that the neuroactive substances released from chromaffin cells can alter or prevent the onset and progression of QUIS-induced behavioral changes. The effects of adrenal transplants were evaluated in 14 male Long-Evans rats that received intraspinal injections of QUIS. Pain behaviors, including the progression of excessive grooming behavior (n=8) and hypersensitivity to mechanical and thermal stimuli (n=6) were evaluated following transplantation. A 53% increase in mechanical thresholds was observed following adrenal transplants along with a 70% reduction in the area of skin targeted for excessive grooming. These behaviors were not affected in 11 animals receiving transplants of skeletal muscle. The effects of adrenal transplants on cold allodynia consisted of a stabilization of response latencies in contrast to the continued decrease in latencies, i.e., increased sensitivity, following transplants of skeletal muscle. The results are consistent with previous studies showing the therapeutic efficacy of adrenal chromaffin cell transplants in neuropathic pain, and support the use of this treatment strategy for the alleviation of chronic pain following spinal cord injury.
Assuntos
Medula Suprarrenal/transplante , Agonistas de Aminoácidos Excitatórios/farmacologia , Neurotoxinas/farmacologia , Dor/psicologia , Ácido Quisquálico/farmacologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiopatologia , Medula Suprarrenal/metabolismo , Animais , Comportamento Animal/fisiologia , Sobrevivência de Enxerto , Asseio Animal/fisiologia , Temperatura Alta , Masculino , Estimulação Física , Ratos , Ratos Endogâmicos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Previous studies have demonstrated that excitotoxic spinal cord injury (SCI) created by the intraspinal injection of quisqualic acid (QUIS) is capable of inducing opioid peptide gene expression within the spinal cord and cortex. The opioids are classically involved in the suppression of pain transmission but specifically, dynorphin, has been implicated in the secondary pathophysiologic response to SCI. Activation of the immediate early gene, c-fos, has been implicated in the induction of preprodynorphin (PPD) gene expression and therefore, may be an important intermediate step in the generation of the opioid response to SCI. The purpose of this study was to investigate whether intraspinal QUIS injection induces c-fos expression within the spinal cord. Male, Long-Evans, adult rats (n=5) received an intraspinal injection of 1.2 microl of 125 mM QUIS directed at spinal segments T12-L2. Four hours post-injection brain and spinal cord tissues were removed and processed for in situ hybridization. Integrated density of c-fos and PPD mRNA expression was increased in the spinal dorsal horn following QUIS injection as compared to sham-injected animals. This indicates that SCI rapidly induces c-fos and PPD expression and suggests that c-fos plays a role in the induction of PPD expression.
Assuntos
Dinorfinas/genética , Neurotoxinas/farmacologia , Dor/metabolismo , Células do Corno Posterior/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Dinorfinas/metabolismo , Agonistas de Aminoácidos Excitatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Masculino , Nociceptores/efeitos dos fármacos , Nociceptores/metabolismo , Dor/induzido quimicamente , Dor/fisiopatologia , Células do Corno Posterior/citologia , Células do Corno Posterior/efeitos dos fármacos , Precursores de Proteínas/metabolismo , Ácido Quisquálico/farmacologia , Ratos , Ratos Long-Evans , Traumatismos da Medula Espinal/induzido quimicamente , Traumatismos da Medula Espinal/fisiopatologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Hydroxyethyl methacrylate (HEMA) has been advocated as a polymerizing solution with which to prevent deflation of detachable balloons in interventional neuroradiology. It is pertinent to know if unpolymerized HEMA would have untoward effects if accidentally released into the carotid artery by balloon rupture or deflation. Seven mongrel dogs underwent transfemoral catheterization of the common carotid artery and subsequent injection of HEMA solution in volumes of 1 cc in five dogs, 2 cc in one, and 4 cc in one. Angiography performed at the time of injection revealed evidence of intravascular thrombosis as well as possible spasm. Three surviving animals were sacrificed at 48 hours; the brains were fixed and examined histopathologically. One brain was normal and one was autolyzed and could not be examined. Five of the seven animals had histopathologically documented cerebral infarctions of varying size. No foreign substance was seen within the blood vessels to suggest intravascular polymerization. The animals injected with 2 or 4 cc HEMA solution did not survive 48 hours. Literature review reveals little documentation of the toxicology of intravascular HEMA. With its increasing popularity as a compound for polymerization in detachable balloons introduced into the brain, further investigations are warranted to understand the physical properties of the compound and potential risks of its use.
Assuntos
Transtornos Cerebrovasculares/induzido quimicamente , Metacrilatos/efeitos adversos , Animais , Artérias Carótidas , Angiografia Cerebral , Cães , Embolização Terapêutica , Injeções Intra-ArteriaisRESUMO
OBJECTIVES: To determine the prevalence of herbal and/or dietary supplement use and identify patients at risk for herb-drug interactions. METHODS: A convenience sample of 944 patients were surveyed to determine the prevalence and types of supplements used. Patients with heart disease, diabetes, psychiatric disorders, and/or hypertension were assessed for potential interactions. RESULTS: One hundred thirty-five (14.3%) patients reported regular use. Of these, 79.3% were taking supplements concurrently with prescription medications, and 80.0% were administered medication(s) in the emergency department. Cardiac: 19.8% (n = 33) reported regular use, with four potential interactions. Hypertension: 20.3% (n = 54) reported regular use, with two potential interactions. Diabetes: 15.9% (n = 20) reported regular use, with no known interactions. Psychiatric: 15.9% (n = 10) reported regular use, with one potential interaction. CONCLUSIONS: Six patients were identified at risk for seven known herb-drug interactions. The prevalence of undisclosed herbal supplement use and lack of research on these supplements suggest that more patients may be at risk.
Assuntos
Interações Medicamentosas , Serviço Hospitalar de Emergência , Fitoterapia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Suplementos Nutricionais/estatística & dados numéricos , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
UNLABELLED: Previous studies have demonstrated that the public maintains unrealistic expectations of the potential for successful recovery following administration of cardiopulmonary resuscitation (CPR). Others have attributed this phenomenon to misrepresentation of CPR outcomes on television and other sources of public information. OBJECTIVES: To determine public expectations of CPR and correlate these expectations with various sources of information regarding CPR, including age, television, personal medical training, public programs, friends/family with medical training, and personal experience with CPR. METHODS: A written survey was randomly distributed to local church congregations and completed on a voluntary basis. RESULTS: Ninety-six percent of the respondents expected CPR to be unrealistically effective. Those factors found to increase predicted CPR survival rate were as follows: 1) being under 50 years of age, 2) use of television as a source of information regarding CPR, 3) personal medical training, and 4) use of public programs about CPR. Neither exposure to friends or family with medical training nor personal experience with CPR resulted in increased CPR survival predictions. CONCLUSIONS: Regardless of the source, the public is not accurately informed about the effectiveness of CPR. This creates a situation in which people may elect CPR for themselves or for family members when survival, not to mention recovery, is unlikely. Without dissemination of realistic statistics regarding survival and recovery following CPR, the public will maintain unrealistic expectations of CPR, and be unable to make well-informed decisions concerning its use.
Assuntos
Reanimação Cardiopulmonar/mortalidade , Opinião Pública , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Televisão , Resultado do TratamentoRESUMO
Ethanol withdrawal symptoms in clinical populations are observed to occur in unique clusters which differ in time of onset relative to the time of withdrawal and in their duration. Since periods of mild symptoms are sometimes observed between these clusters of more severe symptoms, the symptom clusters may reflect separate periods of hyperexcitability during which times different neuronal mechanisms are involved. To investigate this possibility in an animal model of ethanol withdrawal, rats were chronically exposed to ethanol in vapor inhalation chambers. Upon withdrawal from this exposure regimen, the time course of spontaneous seizure activity was observed for a period of 84 hr and compared to sensitivity to seizures elicited by audiogenic stimuli or by the convulsant drug picrotoxin. Spontaneous seizure events were observed to occur in clusters, and these clusters were differentially correlated with periods of increased sensitivity to induced seizure activity. These results further support the suggestion that seizure sensitivity during ethanol withdrawal may indicate the involvement of multiple, independent, neuronal mechanisms.
Assuntos
Etanol/efeitos adversos , Convulsões/induzido quimicamente , Síndrome de Abstinência a Substâncias , Estimulação Acústica , Animais , Suscetibilidade a Doenças , Masculino , Picrotoxina , Ratos , Ratos Endogâmicos , Convulsões/etiologia , Fatores de TempoRESUMO
A 60-year-old captive California desert tortoise (Gopherus agassizii) which died in August 1990 at the University of California, Davis, California (USA), during treatment for colonic impaction had marked caseous necrosis of the oral cavity, choana, trachea, and lungs. Numerous intranuclear inclusion bodies and a large number of syncytial giant cells were seen in the oral cavity and respiratory tract along with bacterial granulomas. Pasteurella testudinis, Streptococcus veridans, and coagulase-negative Staphilococcus spp. were cultured from the lesions. Using electron microscopy, herpesvirus particles were observed in intranuclear inclusions and cytoplasm. Viral stomatitis, tracheitis, and bronchopneumonia complicated by bacterial infection were diagnosed. Although respiratory disease is common in desert tortoises, this is believed to be the first report of association with a viral infection.