RESUMO
Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.
Assuntos
Algoritmos , Lista de Checagem , Traumatismos Craniocerebrais/diagnóstico , Serviços Médicos de Emergência/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Adulto JovemRESUMO
Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.
Assuntos
Concussão Encefálica/diagnóstico , Concussão Encefálica/terapia , Serviço Hospitalar de Emergência , Adulto , Encéfalo/efeitos da radiação , Certificação , Lista de Checagem , Criança , Maus-Tratos Infantis/diagnóstico , Maus-Tratos Infantis/terapia , Pré-Escolar , Técnicas de Apoio para a Decisão , Educação Médica Continuada , Escala de Coma de Glasgow , Humanos , Lactente , Recém-Nascido , Doses de Radiação , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
Studies in mice have identified the ob gene product, leptin, as a signaling factor regulating body weight homeostasis and energy balance. Defective production of the encoded protein may be one of the causes for the development of obesity. Using a high affinity antibody, that in immunohistochemical studies specifically stained human adipocytes, a radioimmunoassay was established and leptin immunoreactivity was quantified in plasma of lean and obese human subjects. Chromatographic analysis suggested that the immunoreactive material in plasma is identical to that found in extracts from human fat and represent a protein with a molecular size of approximately 16 kD. Fasting levels were measured in plasma of 75 lean and obese human subjects (body mass index (BMI) 17.7 - 87.3). The mean concentration of leptin in plasma of lean subjects (BMI < or = 28) was 69.3 +/- 36.9 fmol/ml plasma (mean +/- SD, n=27). The highest concentration measured in obese was 533.3 fmol/ml plasma. The levels showed a strong positive correlation with BMI (r=0.77, p<0.001). A subgroup of diabetic patients did not significantly differ in their leptin plasma levels from non-diabetic subjects with similar BMI.
Assuntos
Diabetes Mellitus/sangue , Obesidade/sangue , Proteínas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Índice de Massa Corporal , Diabetes Mellitus/patologia , Feminino , Humanos , Imuno-Histoquímica , Leptina , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Obesidade/patologia , RadioimunoensaioRESUMO
OBJECTIVE: To characterize ouabain-like immunoreactivity in human urine. METHODS: Sensitive radioimmunoassay for ouabain characterized by high-performance liquid chromatography. RESULTS: Serial dilution of urinary immunoreactive ouabain paralleled the standard curve, but not so plasma immunoreactive ouabain. Intravenous administration of 86 nmol (62.5 micrograms) ouabain caused a rapid rise in ouabain immunoreactivity in plasma of healthy volunteers with a maximum of 1.7 nmol/l 8 min after injection and returned to basal levels after 6 h. Ouabain immunoreactivity rose to 36 nmol/l in urine, suggesting that exogenously administered ouabain can be measured reliably in plasma and urine. Analytical reversed-phase high-performance liquid chromatography (isopropanol-propanol biphasic gradient; linear acetonitrile gradient) of sample extracts before assay demonstrated measurable amounts of ouabain-related material only in native urine, but not in plasma. When plasma and urine were spiked with ouabain standard or normal volunteers were injected with ouabain, the assay reliably measured ouabain. CONCLUSION: A substance closely related to ouabain can be detected in urine, but circulates, if at all, in small amounts in human plasma.
Assuntos
Ouabaína/urina , Adulto , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Ouabaína/imunologia , CoelhosRESUMO
The opioid-like heptadecapeptide nociceptin (NC) has the following effects in the airways (investigated in isolated tracheae and bronchi from guinea pig or rat): the electric field stimulation (EFS)-induces release of acetylcholine (ACh), the tachykinin substance P (SP) and calcitonin gene-related peptide (CGRP) is reduced after pretreatment with NC, and EFS-induced tachykinergic nonadrenergic-noncholinergic (NANC) bronchoconstriction is inhibited by NC. Both the NC-mediated inhibition of neurotransmission and of smooth muscle contraction occurred in a concentration-dependent manner. Because these effects were naloxone-insensitive, were blocked by the NC receptor antagonist [F/G]NC(1-13)NH(2), and could be mimicked by the NC analogs, NCNH(2) and NC(1-13)NH(2), it is thought that they are distinct from the classic opioid receptors. That these pharmacological actions of NC are of relevance for airway physiology is highly probable given the presence of NC-immunoreactivity in the nerve fibers of the airways and of opioid-like receptor (ORL-1) transcripts in the jugular ganglia, from where the tachykinin-containing afferents arise.
Assuntos
Brônquios/metabolismo , Peptídeos Opioides/metabolismo , Traqueia/metabolismo , Acetilcolina/metabolismo , Animais , Brônquios/efeitos dos fármacos , Broncoconstrição/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Relação Dose-Resposta a Droga , Terapia por Estimulação Elétrica , Eletrofisiologia , Cobaias , Humanos , Contração Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Neurotransmissores/metabolismo , Peptídeos Opioides/farmacologia , Ratos , Substância P/metabolismo , Traqueia/efeitos dos fármacos , Vasodilatadores/farmacologia , NociceptinaRESUMO
The hormone leptin is expressed and secreted by the adipose tissue and impacts on the central nervous system. Leptin is involved in the regulation of energy balance, satiety, and body composition. The lack of active leptin results in obesity, high food intake, hyperglycemia, and hyperinsulinemia. We present data supporting effects of leptin on the endocrine pancreas. We found the leptin receptor to be expressed in insulin- and glucagon-secretin cells derived from mouse, hamster, and rat pancreas. In the isolated perfused rat pancreas leptin is a potent inhibitor of basal and glucose-induced insulin secretion, especially during the first phase of the insulin response. At isolated mouse islets and insulin-secreting INS-1 cells leptin reduced promptly and persistently the intracellular Ca2+ levels. Cytoplasmic Ca2+ oscillation amplitude was decreased and the oscillation frequency increased. These findings suggest functional active receptors for leptin on insulin-secreting B-cells. Therefore, leptin is a metabolic hormone and not only a signal to the brain indicating filled fat stores. Our data suggest that leptin is also a signal back to the endocrine pancreas that no more insulin is required to replenish fat stores. Thus, an "adipo-insular axis" operating with two arms exists: insulin and glucagon are signals to the adipocyte. This releases leptin, which could be the mediator of the respective feedback to the pancreas. A defective leptin suppression of insulin secretion could contribute to hyperinsulinemia and disturbances of glucose metabolism.
Assuntos
Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Proteínas/fisiologia , Receptores de Superfície Celular , Animais , Cálcio/metabolismo , Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Células Cultivadas , Cricetinae , Glucagon/metabolismo , Antagonistas da Insulina/farmacologia , Secreção de Insulina , Leptina , Masculino , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos DBA , Proteínas/farmacologia , RNA/biossíntese , Ratos , Ratos Wistar , Receptores para Leptina , Proteínas Recombinantes/farmacologia , Células Tumorais CultivadasRESUMO
Leptin is an adipocyte derived hormone with profound behavioural and metabolic effects exerted by both central and peripheral sites of action. One of its targets in the central nervous system appears to be the epithelial cells of the choroid plexus where leptin receptor (OB-R) expression is particularly high. The most abundant receptor subtype at this site is OB-Ra which is truncated at its intracellular part and has been suggested to serve functions such as leptin transport or clearance. The choroid plexus may thus be a site where receptor mediated exchange of leptin between cerebrospinal fluid and blood takes place. The study here shows that porcine plexus epithelia preserve their ability of OB-R expression when grown in culture. In addition, our experiments suggest that leptin is rapidly internalized upon binding to these cells supporting the view of an OB-R mediated transport of leptin across the choroid plexus.
Assuntos
Plexo Corióideo/metabolismo , Leptina/metabolismo , Receptores de Superfície Celular , Animais , Transporte Biológico , Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Células Cultivadas , Plexo Corióideo/citologia , Células Epiteliais/metabolismo , Radioisótopos do Iodo , Ligação Proteica , Ensaio Radioligante , Receptores para Leptina , SuínosRESUMO
Several lines of evidence suggest that obese individuals have a higher set point for body weight regulation relative to lean subjects. Since obese rodents and humans have high serum levels of leptin, it has been hypothesized that this may be the result of an insensitivity to this weight reducing hormone. In this experiment we assessed whether feeding of a high-fat diet to rats affects leptin receptor (OB-R) transcript levels or induces up-regulation of the suppressors of leptin/cytokine induced signaling, SOCS-3 and PIAS-3. We found that despite a significant weight gain associated with markedly increased circulating leptin levels neither OB-R gene expression nor SOCS-3 or PIAS-3 mRNA levels were significantly altered in the high-fat fed rats. This was in contrast to control experiments where administration of exogenous leptin induced a several-fold increase in SOCS-3. It is concluded that high-caloric food intake per se is not sufficient to provoke suppression of leptin signaling via these factors in animals without genetic predisposition to obesity.
Assuntos
Proteínas de Transporte/metabolismo , Gorduras na Dieta/administração & dosagem , Proteínas/metabolismo , Receptores de Superfície Celular , Proteínas Repressoras , Transdução de Sinais , Fatores de Transcrição , Tecido Adiposo Marrom/metabolismo , Animais , Peso Corporal , Proteínas de Transporte/genética , Primers do DNA/química , Epididimo/metabolismo , Epididimo/patologia , Hipotálamo/metabolismo , Leptina/sangue , Leptina/farmacologia , Masculino , Proteínas/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores para Leptina , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de CitocinaRESUMO
M3E3/C3 is a clonal fetal hamster lung epithelial cell line which is used for studies of epithelial differentiation as well as for in vitro toxicologic tests. In this study growth kinetics, xenobiotic metabolism, chromosomal stability and transformation were investigated at increasing culture passage numbers up to 150. Cells of higher passages grew faster and reached higher cell densities than the cells of lower ones. As an indicator of xenobiotic metabolism we measured the activity of 7-ethoxycoumarin-deethylase (ECD), an enzyme belonging to the mixed function oxidase system. Up to passage number 100 the ECD activity strongly increased, followed by a slight decrease in additional passages. The chromosomal stability was assessed by the induction of micronuclei by benzo[a]pyrene (BaP) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). More micronuclei were always detected in cells of higher passages than of lower passages. The capability of cells to be transformed to anchorage independent growth by chemical carcinogens was examined using a soft agar test. After carcinogen exposure with BaP and MNNG, cells of higher passages showed higher transformation frequencies than cells of lower passages. Many cells at passage 150 exhibited an especially high soft agar growth even without carcinogen treatment and were therefore characterized as spontaneously transformed. These results show that metabolic and genetic characteristics of permanently growing cells differ remarkably depending on the culture passage. This has always to be considered when permanently growing cells are used for toxicological studies.
Assuntos
Divisão Celular/fisiologia , Linhagem Celular/fisiologia , Transformação Celular Neoplásica , Técnicas Citológicas , O-Dealquilase 7-Alcoxicumarina/metabolismo , Análise de Variância , Animais , Benzo(a)pireno , Contagem de Células , Linhagem Celular/metabolismo , Senescência Celular , Cricetinae , Células Epiteliais , Estudos de Viabilidade , Feto/citologia , Mesocricetus , Metilnitronitrosoguanidina , Testes para Micronúcleos , Análise de Regressão , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Relatively few studies have examined the relation of different hymenoptera sting reactions. OBJECTIVE: To investigate the relation of anaphylactic reactions against stings of different hymenoptera subspecies in the Mediterranean population of Albania. MATERIALS AND METHODS: A retrospective study was conducted using the clinic files of 111 patients who were diagnosed for hymenoptera sting reactions from 1987 to 1996. Antigens used consisted of purified hymenoptera venom (bee, wasp, and paperwasp). The patients were diagnosed by intracutaneous tests in concentrations of 0.001 microgram/ml, 0.01 microgram/ml, 0.1 microgram/ml, and 1 microgram/ml. RESULTS: The median age of the patients was 27 years. 57% of stings occurred between 20 to 40 years of age. The majority of anaphylactic reactions were recorded during the months of June to October, 81% of the patients were admitted to the hospital due to Mueller grade II to III reactions. In 26% of all cases, crossreactions (bee-wasp 16%, bee-wasp-paperwasp 7%, wasp-paperwasp 2%, bee-paperwasp 1%) were found. Of all anaphylactic reactions, 64% were attributed to bees, 24% to wasps, 8% to both bees and wasps, and 2% to paperwasps. CONCLUSIONS: In contrast to industrialized countries such as the United States or Western Europe where urban populations predominate, reactions to bee venom were more prevalent in the present study population.
Assuntos
Anafilaxia , Himenópteros , Mordeduras e Picadas de Insetos , Adolescente , Adulto , Albânia/epidemiologia , Anafilaxia/epidemiologia , Animais , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Estações do AnoRESUMO
BACKGROUND: Histamine receptors play an important role in the pathogenesis of nasal allergy. Activation of histamine receptor 1 (H1R) and 2 (H2R) can cause allergic symptoms which can be blocked effectively by antihistamines. H1R and H2R transcript levels have been found to be up-regulated in perennial - but not in seasonal - allergic rhinitis (AR). The present study aimed to explore H1R and H2R expression in complex tissues of the nasal mucosa of perennial allergic rhinitis (PAR). METHODS: Ten patients with PAR and 13 non-AR subjects were recruited for the study by medical history, physical examination and laboratory screening tests. In this study, we have analysed single cells dissected from the nasal mucosa biopsies by laser-assisted microdissection. H1R mRNA expression was analysed in different cell types such as epithelial, endothelial, mucus and inflammatory cells isolated from the nasal mucosa of PAR in comparison with non-AR subjects. RESULTS: H1R mRNA gene expression level was significantly increased in the nasal mucosa of PAR in comparison with non-AR (P<0.0001). H1R mRNA was significantly elevated in epithelial (P<0.001) and mucus cells (P<0.05) of PAR in comparison with non-AR whereas H1R gene expression levels in endothelial cells between both groups were not changed (P=0.23). Interestingly, inflammatory cells in the nasal mucosa of PAR patients were also strongly expressed H1R mRNA (P<0.001). CONCLUSION: The present study indicates that PAR alters the expression of H1R mRNA in epithelial, mucus and inflammatory cells of the nasal mucosa and but not in endothelial cells. Therefore, epithelial, mucus and inflammatory cells may play an important role in histamine-mediated allergic airway inflammation in PAR.
Assuntos
Mucosa Nasal/patologia , Receptores Histamínicos H1/genética , Rinite Alérgica Perene/genética , Adolescente , Adulto , Idoso , Células Endoteliais/química , Células Epiteliais/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Muco/química , Mucosa Nasal/química , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/genética , Rinite Alérgica Perene/patologia , Transcrição Gênica/genéticaRESUMO
C-Jun and c-Fos belong to the family of immediate early genes. Apart from their role as transcription factors, a basal expression was shown for them in central nervous system tissues. The expression of c-Jun and c-Fos in sensory ganglia of guinea pig, rat and murine sensory ganglia was examined under normal, unstimulated conditions by quantitative double-immunohistochemistry. 4.6 +/- 2.8% of neuron-specific protein gene-product 9.5 -positive cells in nodose ganglia, 51.6 +/- 2.1% in jugular ganglia, 46.4 +/- 3.0% in trigeminal ganglia and 42.5 +/- 1.3% of cervical dorsal root ganglia neurons were positive for c-Jun in the guinea pig (less than 1% for c-Fos). In rat and mouse, less than 1% of the sensory neurons exhibited c-Jun and c-Fos-immunoreactivity. The high basal expression of c-Jun in guinea pig sensory neurons suggests that in this species the presence of c-Jun does not only depend on specific stimulation and is not exclusively associated with neuronal plasticity of gene expression and functional changes.
Assuntos
Gânglios Sensitivos/metabolismo , Regulação da Expressão Gênica , Genes Precoces , Proteínas Imediatamente Precoces/genética , Animais , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Genes jun , Cobaias , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Gânglio Nodoso/citologia , Gânglio Nodoso/metabolismo , Proteínas Proto-Oncogênicas c-jun/genética , Ratos , Ratos Sprague-Dawley , Gânglio Trigeminal/citologia , Gânglio Trigeminal/metabolismoRESUMO
Airway hyperresponsiveness, a keystone of allergic asthma, is mediated by the extrinsic airway innervation. As pathophysiological stimuli can induce the expression JUN proteins, which belong to the immediate early gene (IEG) family of transcription factors, the expression of c-Jun was examined under basal conditions and allergen challenge in guinea pig paravertebral and prevertebral sympathetic ganglia by quantitative double-labeling immunohistochemistry. C-Jun immunoreactivity was seen in 78.4 +/- 3.5% under normal and 82.6 +/- 4.6% under allergen-challenged conditions of protein-gene product (PGP) 9.5-positive sympathetic neurons of guinea pig superior cervical ganglia and 73.1 +/- 2.8% (normal) and 76.1 +/- 3.5% (allergen) of stellate ganglion neurons. In the coeliac-superior mesenteric ganglion, 59.5 +/- 5.0% (normal) and 57.5 +/- 4.4% (allergen) of the PGP 9.5-positive sympathetic neurons were labeled for c-Jun. The high basal levels of c-Jun expression indicate that the presence of c-Jun is not exclusively related to noxious stimulation such as allergic airway inflammation in the guinea pig.
Assuntos
Gânglios da Base/imunologia , Gânglios da Base/metabolismo , Testes de Provocação Brônquica , Gânglios Simpáticos/imunologia , Gânglios Simpáticos/metabolismo , Proteínas Proto-Oncogênicas c-jun/biossíntese , Proteínas Proto-Oncogênicas c-jun/imunologia , Animais , Modelos Animais de Doenças , Cobaias , Imuno-Histoquímica , Masculino , Neurônios/citologia , Neurônios/imunologia , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-jun/efeitos dos fármacos , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/metabolismo , Tioléster Hidrolases/imunologia , Tioléster Hidrolases/farmacologia , Ubiquitina TiolesteraseRESUMO
Heme oxygenases (HOs) are responsible for heme degradation. Besides their enzymatic activities, HOs are involved in tissue protection. Failing upregulation of HOs has been linked to increased necrosis in inflammatory tissues. Interestingly, previously published data indicated that mice exposed to sonic stress during early gestation show an augmented production of decidual inflammatory T-helper 1 (Th1) cytokines, thus resulting in increased abortion rate. No data linked the Th1-inducer interleukin (IL)-12 with the event of abortion. As little is known about the role of HO in pregnancy maintenance, we evaluated the expression of decidual and placental HO-1 and HO-2 in the abortion-prone murine mating combination CBA/J x DBA/2 J with (1) CBA/J female control mice, (2) CBA/J mice exposed to stress during early gestation and (3) CBA/J females injected with recombinant IL-12. Decidual and placental HOs protein expression was analysed by immunohistochemistry and mRNA levels by real time polymerase chain reaction (PCR). As expected, an increased abortion rate was present in mice exposed to stress compared with the control. IL-12 injections also boosted the abortion rate compared with control mice, mimicking the effect of stress. HOs' proteins could be detected in placenta and decidua. Real time PCR revealed lower levels of HO-1 and HO-2 mRNA in stress-triggered and IL-12-injected mice. We conclude that increased Th1-cytokine levels during murine pregnancy may result in low expression of HO-1 and HO-2, thus leading to placental necrosis and foetal rejection.
Assuntos
Aborto Espontâneo/imunologia , Heme Oxigenase (Desciclizante)/biossíntese , Interleucina-12/imunologia , Estresse Fisiológico/imunologia , Animais , Decídua/enzimologia , Decídua/imunologia , Regulação para Baixo , Feminino , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1 , Imuno-Histoquímica , Interleucina-12/administração & dosagem , Masculino , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Placenta/enzimologia , Placenta/imunologia , Gravidez , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Distribuição Aleatória , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Som/efeitos adversosRESUMO
The transport mechanism mediating brain uptake of tumor necrosis factor (TNF)-alpha has been studied. When (125)I-labeled rat TNF-alpha was used in internal carotid artery perfusions in rats, the cytokine showed transcytosis through the blood-brain barrier in intact form (permeability-surface area product 0.34 +/- 0.13 microl. min(-1). g(-1)). Uptake was inhibited by low nanomolar concentrations of unlabeled rat TNF-alpha. Human TNF-alpha, which does not interact with the p80 TNF receptor in rodents, showed no brain uptake. mRNA expression of both p60 and p80 receptors could be demonstrated in native brain microvessel preparations. These transcripts increased to 149% (p60) and 127% (p80) of control 4 h after a systemic immune stimulation (2 mg/kg bacterial endotoxin ip). Lipopolysaccharide treatment did not alter the rate of brain uptake of TNF-alpha measured between 4 and 24 h later. In conclusion, a receptor-mediated mechanism is responsible for the transcytosis of TNF-alpha. Saturable transport, requiring the p80 receptor, occurs at concentrations encountered under pathophysiological conditions and therefore constitutes a relevant mechanism of communication between the immune system and the brain.
Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Receptores do Fator de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa/farmacocinética , Animais , Barreira Hematoencefálica/fisiologia , Northern Blotting , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Humanos , Radioisótopos do Iodo , Masculino , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Necrose Tumoral/metabolismoRESUMO
BACKGROUND: Nerve growth factor (NGF) is elevated in allergic diseases such as bronchial asthma and can lead to an induction of substance P (SP) and related neuropeptides in guinea-pigs large-diameter, neurofilament-positive airway neurons. OBJECTIVE: In the present study, the effect of NGF on tyrosine kinase receptor trkA and the capsaicin receptor TRPV1 expression in airway-specific vagal sensory neurons located in the jugular-nodose ganglia complex (JNC) of mice was investigated. METHODS: Using retrograde neuronal tracing in combination with double-labelling immunohistochemistry, SP, trkA- and TRPV1-receptor expression was examined in airway-specific sensory neurons of BALB/c mice before and after NGF treatment. RESULTS: NGF injected into the lower airway was able to induce SP (13.0+/-2.03% vs. 5.9+/-0.33%) and trkA expression (78+/-2.66% vs. 60+/-2.11%) in larger diameter (>25 microm), capsaicin-insensitive and trkA-positive vagal sensory neurons that were retrograde-labelled with Fast Blue dye from the main stem bronchi. CONCLUSION: Based on the extent of SP and trkA co-expression in airway-specific neurons by NGF treatment, the present study suggests that, following a peripheral activation of trkA receptor on SP afferent by NGF which is elevated in allergic inflammation, there may be trkA-mediated SP induction to mediate neurogenic airway inflammation.
Assuntos
Capsaicina/imunologia , Fator de Crescimento Neural/imunologia , Neurônios Aferentes/imunologia , Gânglio Nodoso/imunologia , Sistema Respiratório/imunologia , Substância P/imunologia , Animais , Feminino , Imuno-Histoquímica/métodos , Canais Iônicos , Camundongos , Camundongos Endogâmicos BALB C , Receptor trkA/análise , Receptor trkA/imunologia , Sistema Respiratório/inervação , Canais de Cátion TRPVRESUMO
Aspirin-sensitive rhinitis is the manifestation of aspirin intolerance in the upper respiratory tract. The disease represents a pseudoallergy against aspirin or related nonsteroidal anti-inflammatory drugs. As a major immunomodulatory role for airway innervation has been proposed in airway inflammatory diseases, the present study assessed changes in human nasal mucosa innervation in patients with aspirin-sensitive rhinitis in comparison to a control group. Immunohistochemistry for protein gene product 9.5, tachykinins, calcitonin gene-related peptide, vasoactive intestinal peptide (VIP) and neuropeptide tyrosine was performed on cryostats sections of nasal mucosa and neuropeptide containing nerves were examined independently using a score grading. In comparison to the control, the aspirin-sensitive rhinitis group had a significant increase of VIP-like immunoreactivity in mucosal nerve fibres. In contrast to constant numbers of mast cells, highly significant increases in the numbers of eosinophils were found in the group of aspirin-sensitive rhinitis patients. In summary, the present quantification of neuropeptide-immunoreactivity of mucosal nerves demonstrated differences in the human nasal mucosa innervation between nonrhinitic and aspirin-sensitive rhinitic individuals. These differences may reflect a pathophysiological role of upper airway innervation in pseudoallergic reactions.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Mucosa Nasal/inervação , Mucosa Nasal/fisiopatologia , Rinite/imunologia , Rinite/fisiopatologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Neurônios/fisiologia , Neuropeptídeos/metabolismo , Rinite/induzido quimicamenteRESUMO
BACKGROUND: Allergic rhinitis (AR) is the most common allergic disease affecting the respiratory tract. Next to inflammatory changes, the airway innervation plays an important modulatory role in the pathogenesis of the disease. OBJECTIVE: To examine the participation of different neuropeptides in the human nasal mucosa of intermittent (seasonal) AR tissues in the allergic season. METHODS: Immunohistochemistry for substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide tyrosine (NPY) was related to the characterization of inflammatory cells in tissues of patients with seasonal AR (n=18). RESULTS: While there was a significant increase in the number of eosinophils present if compared with a control group, no changes occurred in mast cell numbers. Immunostaining was abundantly found in different nerve fibre populations of both groups. SP expression was significantly increased in mucosal nerve fibres of patients with intermittent (seasonal) AR. Also, significantly increased numbers of VIP- and NPY-immunoreactive nerve fibres were found in biopsies of rhinitis patients in comparison with sections of normal human nasal mucosa. In contrast, CGRP expression did not change significantly. CONCLUSION: The increase of neuropeptide expression in mucosal nerve fibres indicates a major role of the autonomous mucosal innervation in the pathophysiology of intermittent (seasonal) AR.