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BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare, non-treatable and fatal neurological complication of measles, still present due to the return of the epidemic linked to the loosening of vaccination policies. Its mechanism remains unexplained. OBJECTIVE: The main objective was to investigate explanatory variables relating to the risk of developing SSPE and its pathophysiology. METHODS: Literature analysis was focused on different varieties of SSPE: perinatal forms, short-incubation forms similar to acute measles inclusion body encephalitis (MIBE), rapidly evolving forms, forms occurring in the immunosuppressed, adult forms, and family forms. In addition, several studies on the parameters of innate immunity and interferon responses of patients were analyzed. RESULTS: Two main data were highlighted: a relationship between the so-called fulminant forms and the prescription of corticosteroids was established. In familial SSPE, two groups were individualized according to the duration of the latency period, prompting an analysis of patient exomes. CONCLUSION: Treatment with corticosteroids should be banned. Knowledge of the genes involved and epigenetics should be useful for understanding the pathophysiology of SSPE and other late-onset neurological infections with RNA viruses.
Assuntos
Doenças Transmissíveis , Epidemias , Sarampo , Panencefalite Esclerosante Subaguda , Adulto , Feminino , Humanos , Sarampo/complicações , Sarampo/epidemiologia , Gravidez , Panencefalite Esclerosante Subaguda/diagnóstico , Panencefalite Esclerosante Subaguda/epidemiologia , VacinaçãoRESUMO
STUDY QUESTION: Are body size across the life course and adult height associated with endometriosis? SUMMARY ANSWER: Endometriosis is associated with lean body size during childhood, adolescence and adulthood; tall total adult height; and tall sitting height. WHAT IS KNOWN ALREADY: The literature suggests that both adult body size and height are associated with endometriosis risk, but few studies have investigated the role of body size across the life course. Additionally, no study has investigated the relationships between components of height and endometriosis. STUDY DESIGN, SIZE, DURATION: We used a nested case-control design within E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale), a prospective cohort of French women. Data were updated every 2-3 years through self-administered questionnaires. Odds ratios (ORs) and 95% CIs were computed using logistic regression models adjusted for a priori confounding factors. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 2416 endometriosis cases were reported as surgically ascertained among the 61 208 included women. MAIN RESULTS AND THE ROLE OF CHANCE: The odds of endometriosis were lower among women who reported having a large versus lean body size at 8 years (P for trend = 0.003), at menarche (P for trend < 0.0001) and at ages 20-25 years (P for trend < 0.0001). Women in the highest quartiles of height had statistically significantly increased odds of endometriosis compared to those in the lowest (<158 cm) (162-164 cm: OR = 1.28, 95% CI = 1.12-1.46; ≥165 cm: OR = 1.33, 95% CI = 1.18-1.49, P for trend < 0.0001). Statistically significantly increased odds were also observed among women with a taller sitting height (OR = 1.24, 95% CI = 1.05-1.47, P for trend = 0.01). Leg length was not statistically significantly associated with endometriosis. LIMITATIONS REASONS FOR CAUTION: Endometriosis cases may be prone to misclassification; however, we restricted our case definition to surgically-confirmed cases, which showed a high validation rate. Body size is based on retrospective self-report, which may be subject to recall bias. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study suggest that endometriosis is positively associated with lean body size across the life course and total adult height. They also suggest that components of height are associated with endometriosis, which should be investigated further. STUDY FUNDING/COMPETING INTEREST(S): The Mutuelle Générale de l'Education Nationale (MGEN); the European Community; the French League against Cancer (LNCC); Gustave Roussy; the French Institute of Health and Medical Research (Inserm). L.V.F. was supported by a T32 grant (#HD060454) in reproductive, perinatal and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute (3R25CA057711) National Institutes of Health. M.K. was supported by a Marie Curie Fellowship within the seventh European Community Framework Programme (#PIOF-GA-2011-302078). The authors have no conflicts of interest to declare.
Assuntos
Estatura/fisiologia , Peso Corporal/fisiologia , Endometriose/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Endometriose/diagnóstico , Feminino , Humanos , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: To describe and assess the presence of a new indirect sign of partial agenesis of the corpus callosum (pACC): an abnormally shaped cavum septi pellucidi (CSP). METHODS: We analyzed retrospectively images from all 71 cases of pACC seen at two referral centers between September 2006 and April 2014. Abnormally shaped CSP was diagnosed when its lateral dimension was greater than its anteroposterior dimension in the axial transthalamic plane, and the incidence of this sign was assessed. We also examined the following variables: gestational age at referral, indication for referral, which (if any) of the four corpus callosal segments were abnormal, presence of other, previously established, indirect signs of callosal agenesis (ACC) and presence of additional cerebral or extracerebral anomalies. RESULTS: In 56 of the 71 (79%) cases, the CSP was measurable; it was abnormally shaped in 19 (34%) of these cases, 15 (79%) of which had no other indirect signs of pACC. Of 23 cases with isolated pACC and no other indirect signs, 12 (52%) had an abnormally shaped CSP. CONCLUSIONS: In a significant proportion of cases of pACC detected prenatally, the shape of the CSP is abnormal. This should be considered an additional indirect sign of pACC, and is frequently the only clue to the diagnosis. When observing this sign in a screening context, pACC should be considered, and an attempt to visualize the corpus callosum directly in the midsagittal plane is suggested.
Assuntos
Agenesia do Corpo Caloso/diagnóstico , Corpo Caloso/patologia , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal , Adulto , Agenesia do Corpo Caloso/embriologia , Agenesia do Corpo Caloso/epidemiologia , Corpo Caloso/embriologia , Feminino , França/epidemiologia , Idade Gestacional , Humanos , Israel/epidemiologia , Gravidez , Estudos Retrospectivos , Septo Pelúcido/anormalidades , Septo Pelúcido/embriologia , Septo Pelúcido/patologiaRESUMO
OBJECTIVES: To identify at prenatal ultrasound (US) the features of apparently isolated subependymal pseudocysts (SEPC) that may indicate underlying pathology and should lead to further investigations. METHODS: This was a retrospective study of cases with SEPC detected on prenatal US and/or magnetic resonance imaging (MRI). Those with apparently isolated SEPC at US were classified into two groups as follows: Group 1 (n = 29): normal prenatal US and MRI (except for SEPC) and normal outcome; Group 2 (n = 12): normal prenatal cerebral US (except for SEPC) and abnormal prenatal cerebral MRI with or without abnormal outcome. A third group (n = 9) included cases with abnormal prenatal US and MRI. The latter cases with obvious cerebral abnormalities at US were excluded from the statistical analysis as they do not represent a diagnostic dilemma for clinicians. Groups 1 and 2 were analyzed, comparing them with respect to their SEPC characteristics (size, number, location in relation to the caudothalamic notch and the ventricular horns and morphology) and extracerebral abnormalities. RESULTS: The mean ± SD SEPC great axis was longer in Group 2 (11.67 ± 5.82 mm) than it was in Group 1 (8.00 ± 5.64 mm) (P = 0.021), suggesting an optimal cut-off for size of SEPC of ≥ 9 mm (sensitivity = 75%, specificity = 62%) to maximize sensitivity for predicting pathological outcome. SEPC adjacent to the temporal horns and SEPC located posterior to the caudothalamic notch were observed more frequently in Group 2, indicating their association with poor outcome (P = 0.003 and P = 0.003, respectively). Atypical morphology and extracerebral abnormalities were observed more frequently in Group 2 (P = 0.013 and P = 0.044, respectively). There was no statistically significant difference between groups for either number or location of cysts along the inferior wall or adjacent to the lateral wall of the frontal horns (P = 0.591 and P = 0.156, respectively). CONCLUSION: When apparently isolated SEPC are observed at prenatal US, further investigations should be performed under the following circumstances: (1) SEPC great axis ≥ 9 mm; (2) SEPC adjacent to the occipital and temporal horns; (3) SEPC located posterior to the caudothalamic notch; (4) SEPC with atypical morphology.
Assuntos
Encefalopatias/embriologia , Cistos/embriologia , Doenças Fetais/diagnóstico , Imageamento por Ressonância Magnética/estatística & dados numéricos , Ultrassonografia Pré-Natal/estatística & dados numéricos , Adulto , Encefalopatias/diagnóstico por imagem , Cistos/diagnóstico por imagem , Feminino , Doenças Fetais/diagnóstico por imagem , Humanos , Recém-Nascido , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To describe the prenatal ultrasound and magnetic resonance imaging (MRI) findings suggestive of periventricular nodular heterotopia (PNH). METHODS: This retrospective case series included fetuses referred to our institution for brain MRI between 2007 and 2012, which were diagnosed with PNH and confirmed by postnatal MRI or autopsy. The type of PNH, associated ventriculomegaly and associated malformations are reported. RESULTS: We included 11 fetuses (nine female, two male) with a mean gestational age at diagnosis of 31 (range, 23-34) weeks. PNH lesions were small and diffuse (n = 7), large and multiple (n = 1) or single (n = 3). A targeted ultrasound examination performed before fetal MRI missed the diagnosis in four cases (one diffuse and three single); a further ultrasound examination performed after MRI diagnosed PNH in two of these four cases. Ventriculomegaly was present in six cases (four unilateral and two bilateral). PNH appeared in all cases as nodules of intermediate echogenicity protruding into the ventricular lumen. In all cases of diffuse PNH, the frontal horns and bodies of the lateral ventricles appeared square in shape on coronal view, with irregular borders on axial view. Associated cerebral malformations were observed in seven cases and included corpus callosal agenesis (n = 4, with additional malformations in two) and retrocerebellar cyst (n = 3). Extracerebral malformations were also present in two cases. Maternal MRI was performed in five of the six cases of isolated small and diffuse PNH in female fetuses, and demonstrated PNH in two of these. CONCLUSION: PNH is underdiagnosed at prenatal ultrasound, even on targeted scans. Irregular ventricular borders on axial view and irregular square-shaped lateral ventricles on coronal view are suggestive of PNH at prenatal ultrasound.
Assuntos
Heterotopia Nodular Periventricular/diagnóstico , Autopsia , Ventrículos Cerebrais/anormalidades , Diagnóstico Tardio , Feminino , Filaminas/genética , Idade Gestacional , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Mutação/genética , Heterotopia Nodular Periventricular/genética , Estudos Retrospectivos , Ultrassonografia Pré-Natal/métodosAssuntos
Veias Cerebrais/patologia , Plexo Corióideo/diagnóstico por imagem , Dura-Máter/irrigação sanguínea , Diagnóstico Pré-Natal/métodos , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem , Adulto , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Veias Cerebrais/anormalidades , Veias Cerebrais/diagnóstico por imagem , Plexo Corióideo/patologia , Dura-Máter/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Gravidez , Ultrassonografia Doppler Transcraniana/métodos , Trombose Venosa/diagnósticoAssuntos
Hemorragia Cerebral/genética , Colágeno Tipo IV/genética , Doenças Fetais/genética , Mutação/genética , Aborto Induzido , Adulto , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/embriologia , Feminino , Doenças Fetais/diagnóstico por imagem , Humanos , Gravidez , Ultrassonografia Pré-NatalRESUMO
We report a rare case of polymicrogyria diagnosed at 27 weeks' gestation on ultrasound examination and associated with cytomegalovirus (CMV) infection. The ultrasound finding suggesting this diagnosis was the direct visibility of the overfolded cortical ribbon. The cerebral surface was clearly visible because of a markedly enlarged pericerebral space associated with micrencephaly secondary to CMV infection. Bilateral opercular dysplasia was also present. Very few sonographic markers of infectious fetopathy were observed other than periventricular cysts located behind both ventricular horns. Magnetic resonance imaging (MRI) of the fetal brain confirmed the ultrasound findings and also showed the presence of marked micrencephaly, whereas cephalic measurements acquired on ultrasound examination (biparietal diameter and head circumference) were within the normal range. This case emphasizes the complementary roles of sonography and MRI in the prenatal diagnosis of cerebral abnormalities. Moreover, it illustrates the fact that polymicrogyria is easier to diagnose on ultrasound examination during the second trimester, before the development of secondary sulci.
Assuntos
Infecções por Citomegalovirus/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Ultrassonografia Pré-Natal , Aborto Induzido , Adulto , Encefalopatias/diagnóstico por imagem , Cistos/diagnóstico por imagem , Infecções por Citomegalovirus/patologia , Feminino , Humanos , Malformações do Desenvolvimento Cortical/virologia , Microcefalia/diagnóstico por imagem , Gravidez , Terceiro Trimestre da GravidezRESUMO
Visceral pain and intestinal dysbiosis are associated with Irritable Bowel Syndrome (IBS), a common functional gastrointestinal disorder without available efficient therapies. In this study, a decrease of Faecalibacterium prausnitzii presence has been observed in an IBS-like rodent model induced by a neonatal maternal separation (NMS) stress. Moreover, it was investigated whether F. prausnitzii may have an impact on colonic sensitivity. The A2-165 reference strain, but not its supernatant, significantly decreased colonic hypersensitivity induced by either NMS in mice or partial restraint stress in rats. This effect was associated with a reinforcement of intestinal epithelial barrier. Thus, F. prausnitzii exhibits anti-nociceptive properties, indicating its potential to treat abdominal pain in IBS patients.
Assuntos
Faecalibacterium prausnitzii/fisiologia , Mucosa Intestinal , Síndrome do Intestino Irritável/etiologia , Animais , Colo/imunologia , Colo/metabolismo , Colo/microbiologia , Modelos Animais de Doenças , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/microbiologia , Masculino , Privação Materna , Camundongos , Permeabilidade , Estresse FisiológicoRESUMO
BACKGROUND: Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav 3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. METHODS: This bench-to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav 3.2-KO mice. Colonic sensitivity and Cav 3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav 3.2 expression. KEY RESULTS: Wild-type, but not Cav 3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav 3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav 3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. CONCLUSIONS & INFERENCES: This translational study supports the involvement of the calcium channels Cav 3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels.
Assuntos
Canais de Cálcio Tipo T/biossíntese , Colo/metabolismo , Modelos Animais de Doenças , Síndrome do Intestino Irritável/metabolismo , Dor Visceral/metabolismo , Animais , Canais de Cálcio Tipo T/genética , Colo/patologia , Feminino , Expressão Gênica , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Dor Visceral/genética , Dor Visceral/patologiaRESUMO
INTRODUCTION: Parry-Romberg's syndrome or progressive facial hemiatrophy is a rare disorder of unknown etiology which may be accompanied by neurological complications, frequently epilepsy, usually focal refractory epilepsy. The associated brain lesions are located on the same side as the half face atrophy and may progress. OBSERVATION: We report the cases of two patients with Parry-Romberg's syndrome and epilepsy. Neurosurgery was performed in one patient, enabling a histological study. CONCLUSION: The link between Parry-Romberg's syndrome and epilepsy is discussed and the neurodevelopmental theory with vascular dysgenesis is suggested.
Assuntos
Epilepsia/complicações , Hemiatrofia Facial/complicações , Anticonvulsivantes/uso terapêutico , Encéfalo/patologia , Pré-Escolar , Eletroencefalografia , Epilepsia/patologia , Epilepsia/cirurgia , Hemiatrofia Facial/patologia , Hemiatrofia Facial/cirurgia , Feminino , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Tomografia Computadorizada por Raios XRESUMO
We previously gave an account of an increased ion transport activity in choroid plexus from spontaneously hypertensive rats. We have since examined this organ in scanning and transmission electronic microscopy. In the choroid plexus from young spontaneously hypertensive rats, the epithelial cells showed the following: a partial loss of the brush border and infoldings of basolateral membranes, an increased number of Golgi apparatus, vesicles, and mitochondria, and an activated nucleus. In adult hypertensive rats, the mitochondria had increased in number and tended to fill the cytoplasma while the nuclei had returned to a resting level. These ultrastructural changes furthermore suggest an increased secretory activity in the choroid plexus in spontaneously hypertensive rats.
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Plexo Corióideo/ultraestrutura , Ratos Endogâmicos SHR/anatomia & histologia , Envelhecimento , Animais , Masculino , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Microvilosidades/ultraestrutura , Mitocôndrias/ultraestrutura , Ratos , Ratos Endogâmicos WKY , Coloração e RotulagemRESUMO
The stroke-prone spontaneously hypertensive rat (SHR-SP) is one of the most suitable models for stroke study. The present trial work was undertaken so as to obtain further information concerning the action of a new furopyridine, cicletanine. Forty-six males--SHR-SP/Iffa Credo rats--aged 7 weeks, were divided into three groups. Group 1 was a control group, groups 2 and 3 were orally treated with cicletanine at 30 and 100 mg/kg. Their drinking water contained 1% NaCl. Systolic blood pressure, body weight, and survival were recorded. After 6 weeks, all the rats were sacrificed. Samples of heart, brain, and kidney were fixed for light and ultrastructural examination. We found that cicletanine treatment (30 and 100 mg/kg) had significantly inhibited the incidence of hypertensive cerebral damages as characterized by cerebral infarction and vascular alterations with fibrinoid necrosis. Compared with the control group, the rats treated with the cicletanine had a significantly increased survival rate (P less than .001); the cicletanine also had an important protective effect on tissue. Cicletanine administration prevented the development of hypertensive cerebral vascular damage, probably through direct action on the vascular walls.
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Antiarrítmicos/uso terapêutico , Transtornos Cerebrovasculares/prevenção & controle , Diuréticos/uso terapêutico , Hipertensão/tratamento farmacológico , Piridinas , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/patologia , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/patologia , Hipertensão/complicações , Hipertensão/patologia , Masculino , Meninges/patologia , Ratos , Ratos EndogâmicosRESUMO
Brain spectrin is a cytoskeletal protein involved in neuronal polarization and differentiation. We have studied the intraneuronal expression of non-erythroid (NE) alpha-spectrin mRNA in the rat brain during the development of the CA3 pyramidal cells, and compared it with alpha-tubulin mRNA expression. In contrast to alpha-tubulin expression, which remains located in the neuronal somata, NE alpha-spectrin mRNA was present in the dendritic compartment during the first 2 weeks of life. NE alpha-Brain spectrin mRNA transport into the dendrites coincides with critical development events, including dendritic arborization, growth and synaptogenesis, and could be dependent on the appearance of synaptic activity at the mossy fibre/CA3 synapse.
Assuntos
Química Encefálica/fisiologia , Dendritos/metabolismo , RNA Mensageiro/biossíntese , Espectrina/biossíntese , Animais , Autorradiografia , Transporte Biológico/fisiologia , Hibridização In Situ , Masculino , Sondas de Oligonucleotídeos , Células Piramidais/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Sinapses/metabolismo , Sinapses/fisiologia , Tubulina (Proteína)/biossínteseRESUMO
The effects on intestinal myoelectric activity of (1DME)Y8Fa (D-Tyr-D-Leu[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2), a synthetic analog of the neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) were examined in rats after central (i.c.v.) administration performed before acute morphine and after chronic morphine treatment. The acute administration of morphine sulphate (5 mg/kg s.c.) inhibited the occurrence of intestinal migrating myoelectric complexes (MMC) for 46.0 +/- 15.2 min and increased the number of contractions on the proximal colon (13.5 +/- 2.9 vs 8.1 +/- 0.6/10 min). The duration of the MMC disruption was significantly (P < 0.05) reduced (19.0 +/- 5.6 min) by central administration of naloxone (100 micrograms/kg) but not of (1DME)Y8Fa. In rats rendered tolerant to morphine by injections of a slow-release emulsion containing morphine (75 mg/rat over 48 h), intestinal MMC were disrupted and replaced by a continuous irregular activity. Central administration of naloxone (100 micrograms/kg) restored MMC after having induced for 38.3 +/- 7.3 min a motor pattern typical of the diarrhoeal state, termed minute rhythm. No change in colonic motility was observed despite the occurrence of dirrahoea. The effects of naloxone were reproduced by (1DME)Y8Fa (100 micrograms/kg) that induced a pattern of minute rhythm for 48.9 +/- 15.7 min. These features indicate that neuropeptide FF has no action on the acute effects of morphine on intestinal motility but exerts anti-opioid activities in digestive motor alterations associated to morphine withdrawal.
Assuntos
Motilidade Gastrointestinal/efeitos dos fármacos , Dependência de Morfina , Morfina/farmacologia , Antagonistas de Entorpecentes/farmacologia , Oligopeptídeos/farmacologia , Sequência de Aminoácidos , Animais , Eletromiografia , Masculino , Dados de Sequência Molecular , Morfina/administração & dosagem , Naloxona/farmacologia , Neuropeptídeos/farmacologia , Ratos , Ratos WistarRESUMO
The modulatory effects of 1DMe (d-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2), an agonist of Neuropeptide FF (NPFF) receptors, on opioid antinociceptive activity have been compared in naive and tolerant mice in the tail-flick and the hot-plate tests. In naive mice, 1DMe alone had no effect on pain threshold but decreased dose-dependently (3-22 nmol) the analgesic activity of morphine in both tests. In tolerant mice, injections of 60-fold lower doses of 1DMe (0.05-0.5 nmol) reverse morphine-induced analgesia in the tail-flick test but this anti-opioid effect was no longer observed with the highest doses of 1DMe tested (3-22 nmol). In the hot-plate test, the anti-opioid action of 1DMe was not detected, whatever doses tested. Neither the NPFF-like immunoreactivity content of spinal cord and of olfactory bulbs, nor the density of NPFF receptors in olfactory bulbs, were altered. These results indicate that a chronic morphine treatment modifies the pharmacological properties of NPFF but the type of pain test is crucial in determining NPFF effects.
Assuntos
Dependência de Morfina/tratamento farmacológico , Morfina/farmacologia , Antagonistas de Entorpecentes/análise , Entorpecentes/farmacologia , Oligopeptídeos/análise , Animais , Anticorpos , Tolerância a Medicamentos , Temperatura Alta , Masculino , Camundongos , Antagonistas de Entorpecentes/imunologia , Neuropeptídeos/farmacologia , Nociceptores/efeitos dos fármacos , Bulbo Olfatório/química , Bulbo Olfatório/fisiologia , Oligopeptídeos/agonistas , Oligopeptídeos/imunologia , Oligopeptídeos/farmacologia , Dor/tratamento farmacológico , Dor/fisiopatologia , Medição da Dor , Receptores de Neuropeptídeos/análise , Receptores de Neuropeptídeos/imunologia , Reflexo/efeitos dos fármacos , Medula Espinal/química , Medula Espinal/fisiologiaRESUMO
Neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) is able to modulate opioid analgesia. Intracerebroventricular treatment for 5 days with antisense-oligodeoxynucleotides complementary to the sequence of human SQA-neuropeptide FF (Ser-Gln-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) precursor gene or by mismatch-oligodeoxynucleotides did not change the antinociceptive activity of morphine in the mouse tail flick test. In contrast, antisense- but not mismatch-oligodeoxynucleotides attenuated significantly the tolerance to the analgesic activity of morphine and the withdrawal syndrome precipitated by naloxone in morphine-treated mice. These treatments with oligodeoxynucleotides did not modify neuropeptide FF-immunoreactivity content in whole brain but repeated injections of an agonist of neuropeptide FF receptors increased the intensity of morphine tolerance. These results demonstrate the important role of neuropeptide FF in opioid pharmacodependence.
Assuntos
Tolerância a Medicamentos , Dependência de Morfina/prevenção & controle , Morfina/farmacologia , Antagonistas de Entorpecentes/farmacologia , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Oligopeptídeos/farmacologia , Sequência de Aminoácidos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/metabolismo , Humanos , Injeções Intraventriculares , Masculino , Camundongos , Dependência de Morfina/tratamento farmacológico , Antagonistas de Entorpecentes/metabolismo , Antagonistas de Entorpecentes/uso terapêutico , Entorpecentes/farmacologia , Oligodesoxirribonucleotídeos Antissenso/uso terapêutico , Oligopeptídeos/metabolismo , Oligopeptídeos/uso terapêutico , Síndrome de Abstinência a Substâncias/prevenção & controleRESUMO
We report on the biochemical, cellular and pharmacological activities of SQA-neuropeptide FF (Ser-Gln-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2), a peptide sequence contained in the human neuropeptide FF (neuropeptide FF, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) precursor. Quantitative autoradiography revealed that, in the superficial layers of the rat spinal cord, SQA-neuropeptide FF displayed the same high affinity for [125I]1DMe ([125I]D-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2) binding sites (Ki = 0.33 nM) as did neuropeptide FF (Ki = 0.38 nM). In acutely dissociated mouse dorsal root ganglion neurones, SQA-neuropeptide FF reduced by 40% the depolarisation-induced rise in intracellular Ca2+ as measured with the Ca2+ indicator, Fluo-3. In mice, 1DMe and SQA-neuropeptide FF dose-dependently inhibited the antinociceptive effect of intracerebroventricular (i.c.v.) injections of morphine, but SQA-neuropeptide FF was less potent than 1DMe. Furthermore, SQA-neuropeptide FF, as well as 1DMe, produced marked hypothermia following third ventricle injections in mice. These data demonstrate that the human peptide, SQA-neuropeptide FF, exhibits biochemical and pharmacological properties similar to those of neuropeptide FF or neuropeptide FF analogues, and belongs to the neuropeptide FF family.