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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carmustina/farmacología , Carmustina/uso terapéutico , Citarabina/farmacología , Citarabina/uso terapéutico , Etopósido/farmacología , Etopósido/uso terapéutico , Femenino , Humanos , Masculino , Melfalán/farmacología , Melfalán/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenAsunto(s)
Crioterapia/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Melfalán/efectos adversos , Mieloma Múltiple/complicaciones , Estomatitis/etiología , Trasplante Autólogo/efectos adversos , Adulto , Anciano , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estomatitis/patología , Trasplante Autólogo/métodosRESUMEN
Cytosine arabinoside (Ara-C) is one of the key drugs for treating acute myeloid leukemia (AML). High intravenous doses may produce a number of central nervous system (CNS) toxicities and contribute to modifications in brain functional connectivity. sLORETA is a software used for localizing brain electrical activity and functional connectivity. The aim of this study was to apply sLORETA in the evaluation of possible effects of Ara-C on brain connectivity in patients with AML without CNS involvement. We studied eight patients with AML; four were administered standard doses of Ara-C while the other four received high doses. sLORETA was computed from computerized EEG data before treatment and after six months of treatment. Three regions of interest, corresponding to specific combinations of Brodmann areas, were defined. In the patients receiving high-dose Ara-C, a statistically significant reduction in functional connectivity was observed in the fronto-parietal network, which literature data suggest is involved in attentional processes. Our data highlight the possibility of using novel techniques to study potential CNS toxicity of cancer therapy.
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Mapeo Encefálico , Encéfalo/efectos de los fármacos , Citarabina/uso terapéutico , Inmunosupresores/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Vías Nerviosas/efectos de los fármacos , Adulto , Anciano , Encéfalo/fisiopatología , Electroencefalografía , Procesamiento Automatizado de Datos , Femenino , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiopatologíaRESUMEN
Wastewater treatment selection is a complex task usually addressed by applying separate tools for the correct assessment of multi-criteria evaluation. Novedar_EDSS integrates technical, environmental, economic and social assessment capabilities in one single platform. The aim of this work is to evaluate and demonstrate the capabilities of this environmental decision support system (EDSS). For that purpose, 4 case studies of real projects were selected to validate the results in the EDSS by comparing them with those from the study of alternatives performed by the decision makers. Moreover, 1 conceptual case study was applied to support the selection of the most properly strategy for plant retrofitting. Results have demonstrated that the EDSS provides key aspects when deciding the retrofitting process to apply and, when compared to real projects, it recommends analogue treatments as those applied in the projects, ranking them in the same order. Therefore, results in the validation process performed show that this tool provides a reliable basis to support decision makers to select properly treatment alternatives in wastewater treatment plant pre-design.
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Técnicas de Apoyo para la Decisión , Eliminación de Residuos Líquidos/métodos , Toma de Decisiones , Europa (Continente) , América del Sur , Aguas Residuales/análisisRESUMEN
This work investigated the pilot scale production of short chain fatty acids (SCFAs) from sewage sludge through alkaline fermentation and the subsequent membrane filtration. Furthermore, the impact of the fermentation liquid on nutrient bioremoval was examined. The addition of wollastonite in the fermenter to buffer the pH affected the composition of the carbon source produced during fermentation, resulting in higher COD/NH4-N and COD/PO4-P ratios in the liquid phase and higher content of propionic acid. The addition of wollastonite decreased the capillary suction time (CST) and the time to filter (TTF), resulting in favorable dewatering characteristics. The sludge dewatering characteristics and the separation process were adversely affected from the use of caustic soda. When wollastonite was added, the permeate flux increased by 32%, compared to the use of caustic soda. When fermentation liquid was added as carbon source for nutrient removal, higher removal rates were obtained compared to the use of acetic acid.
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Compuestos de Calcio/química , Ácidos Grasos Volátiles/biosíntesis , Aguas del Alcantarillado/química , Silicatos/química , Eliminación de Residuos Líquidos/métodos , Ácido Acético/química , Ácido Acético/metabolismo , Amoníaco/química , Amoníaco/metabolismo , Análisis de la Demanda Biológica de Oxígeno , Reactores Biológicos , Carbono/metabolismo , Ácidos Grasos Volátiles/aislamiento & purificación , Fermentación , Filtración/instrumentación , Filtración/métodos , Fósforo/química , Fósforo/metabolismo , Propionatos/química , Propionatos/metabolismo , Hidróxido de Sodio/química , Eliminación de Residuos Líquidos/instrumentación , Aguas Residuales/químicaRESUMEN
OBJECTIVES: The aim of the study was to investigate the occurence of anti-tissue transglutaminase antibodies (tTGA) in peripheral nerve disorders, and to correlate them with neurophysiologic findings and anti-glycolipid antibodies. MATERIALS AND METHODS: We examined tTGA immunoglobulin-A serum level from 220 patients with polyneuropathy (acute inflammatory: n=90; chronic inflammatory: n=56; non-inflammatory: n=74) and 110 with motor neuron disease (MND). RESULTS: Seven of the 330 neurologic patients (2.1%, six with polyneuropathy and one with MND) were positive for tTGA. Sixty-one of the 330 neurologic patients (18.4%) had slightly increased tTGA values compared with healthy controls. Increased tTGA values were associated with greater impairment of neurophysiologic findings, but not with the presence of anti-glycolipid antibodies. CONCLUSIONS: We found a high prevalence of tTGA reactivity in patients with peripheral nerve disorders or MND. However, we were unable to demonstrate an increased risk of celiac disease in these diseases.
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Autoanticuerpos/sangre , Inmunoglobulina A/sangre , Enfermedad de la Neurona Motora/sangre , Enfermedad de la Neurona Motora/inmunología , Enfermedades del Sistema Nervioso Periférico/sangre , Enfermedades del Sistema Nervioso Periférico/inmunología , Transglutaminasas/inmunología , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Proteínas de Unión al GTP , Glucolípidos/inmunología , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Enfermedad de la Neurona Motora/diagnóstico , Neuronas Motoras/inmunología , Neuronas Motoras/metabolismo , Nervios Periféricos/inmunología , Nervios Periféricos/metabolismo , Nervios Periféricos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Valor Predictivo de las Pruebas , Proteína Glutamina Gamma Glutamiltransferasa 2 , Estudios RetrospectivosRESUMEN
The study of the antiproliferative action of somatostatin (ss) is important not only to understand the regulation of neuroendocrine tumours that express receptors (sst), but also non-endocrine tumours which express these receptors. We previously demonstrated the presence of sst2 in a wide panel of cell lines from human neuroblastoma. Although hypotheses have been put forward that treatment with ss or its analogs may be beneficial in oncological patients, this does not appear to be the case in neuroblastoma; patients with high sst2 levels (who are therefore sensitive to ss treatment) have per se a relatively positive outcome. Therefore, adjuvant treatment with ss is not necessary. Viceversa, patients with a poor prognosis are essentially characterized by a low expression of sst2 (and therefore are insensitive to a therapy with ss). In these patients adjuvant treatment with ss might be indicated, but would have little chance of success. Although the majority of neuroendocrine tumours expresses sst2, pancreas and prostate cancer express sst1 but not sst2, and are therefore insensitive to octreotide treatment which binds preferentially to sst2. Tumours like colorectal carcinoma and breast cancer also express sst2 in their more favourable forms. However, the concentration of sst2 in colorectal cancer is similar, if not lower than that in the surrounding normal tissue. Therefore, the probability of successful adjuvant therapy with ss is relatively low. In breast cancer, it is possible that sensitivity to estrogens may have a positive influence on the expression of sst2. This might justify clinical trials with ss in breast cancer.
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Proteínas de Neoplasias/fisiología , Neoplasias/metabolismo , Receptores de Somatostatina/fisiología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Femenino , Humanos , Masculino , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neuroblastoma/genética , Neuroblastoma/metabolismo , Octreótido/uso terapéutico , Receptores de Somatostatina/biosíntesis , Receptores de Somatostatina/genética , Somatostatina/fisiología , Somatostatina/uso terapéuticoRESUMEN
BACKGROUND: The spinocerebellar ataxias (SCAs) are clinically heterogeneous disorders caused by triplet repeat expansions in the sequence of specific disease genes. Spinocerebellar ataxia type 8 (SCA8), originally described in a family characterized by pure cerebellar ataxia with slow disease progression, presents with expansion of combined CTA/CTG repeats. OBJECTIVE: To perform SCA8 repeat expansion analysis in a heterogeneous group of ataxic patients, to determine the prevalence of this mutation in our patients and establish the frequency of expanded CTA/CTG repeats in a large group of control subjects. PATIENTS: One hundred sixty-seven patients affected by sporadic, autosomal dominant and recessive hereditary ataxia were clinically examined and analyzed for SCA8 expansion. We further studied 161 control subjects and 125 patients with psychiatric disorders. RESULTS: We found abnormally expanded CTA/CTG repeats in 5 ataxic patients, 3 of them characterized by pure cerebellar ataxia. One patient had vitamin E deficiency and 1 patient with a sporadic case was affected by gluten ataxia. No evidence of expanded alleles was found in healthy control subjects and in patients with psychiatric disorders. CONCLUSIONS: Our data support the evidence that CTG expansions may be linked to SCA8, since the pathogenic expansions have been found only among patients with genetically unidentified forms of hereditary and sporadic ataxia. Patients carrying expanded alleles present peculiar phenotypic features, thus suggesting that unknown additional factors could probably predispose to the disease.
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Proteínas del Tejido Nervioso/genética , Ataxias Espinocerebelosas/genética , Expansión de Repetición de Trinucleótido , Adulto , Anciano , Femenino , Predisposición Genética a la Enfermedad , Humanos , Italia , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , ARN Largo no Codificante , ARN no Traducido , Ataxias Espinocerebelosas/fisiopatologíaRESUMEN
Neuroblastoma (NB) is the most common pediatric neuroendocrine tumor, and it is characterized by a quite variable clinical course. We previously found a great variability in the expression of somatostatin receptor type 2 (sst2) in several human NB cell lines and primary tumors. In this report we investigated whether expression of sst2 is somehow related to clinical outcome. We performed a retrospective study on 54 patients with a maximum follow-up of 100 months. The concentration of specific messenger ribonucleic acid (mRNA) for sst2 was measured by competitive RT-PCR and validated, in a small subset of samples, by quantitative imaging of gene (in situ hybridization) and protein (immunohistochemistry) expression. We found that sst2 mRNA was variably expressed in all NB tumors (range, 2.5 x 10(5) to 8 x 10(9) molecules/microg RNA) with a relevant reduction in the more advanced stage (P < 0.01). Analysis of Kaplan-Meier curves indicated that sst2 expression is positively related to the overall (P < 0.0001) and event-free (P < 0.0001) survival. Expression of sst2 was negatively related to tumor stage (P < 0.02) and MYCN amplification (P < 0.001), a poor prognostic factor. However, the prognostic information derived from sst2 is apparently independent from MYCN amplification, as assessed by stratifying sst2 values according to MYCN. In addition, the expression of sst2 was the only significant prognostic factor (P < 0.02) when it was included in a multivariate model containing other well known prognostic factors such as age, stage, and MYCN amplification. Hence, we propose that sst2 expression represents a new prognostic marker for NB. The main clinical value of a quantitative measure of sst2 lies in its ability to detect patients at low risk, independently from other prognostic factor, including MYCN amplification.
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Neoplasias Encefálicas/genética , Regulación Neoplásica de la Expresión Génica/genética , Neuroblastoma/genética , Receptores de Somatostatina/genética , Neoplasias Encefálicas/patología , Niño , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Hibridación in Situ , Neuroblastoma/patología , Valor Predictivo de las Pruebas , Pronóstico , ARN Mensajero/biosíntesis , ARN Mensajero/genética , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Increasing evidence suggests that tachykinins are involved in the control of pathophysiological states, such as inflammation. The precise localization of tachykinin receptors is of paramount importance in the search for their possible physiological and pathological role; in this study, therefore, we attempted to define cellular sites of substance P (NK-1R) and neurokinin A (NK-2R) receptor expression in the healthy and the inflamed human intestine by in situ hybridization and immunohistochemistry. In the normal ileum and colon, NK-1R and NK-2R were localized to smooth muscle cells of the muscularis mucosae and propria and a few inflammatory cells of the lamina propria; NK-1R expression was also found in the muscular wall of submucosal blood vessels, enteric neurons and, to a lesser degree, in surface epithelial cells. Patients with Crohn's disease and ulcerative colitis showed a dramatic increase in NK-1R density relative to controls, in both the inflamed and the uninvolved mucosa. Up-regulation of NK-1R was particularly evident on epithelial cells lining the mucosal surface and crypts, as well as on endothelial cells of capillaries and venules. Also, a marked increase in NK-2R expression was found in both groups of patients on inflammatory cells of the lamina propria, especially eosinophils. Our findings demonstrate that in the normal human intestine NK-1R and NK-2R are expressed in multiple cell types, which are endowed with different physiological functions; in addition, they demonstrate that both NK-1R and NK-2R are up-regulated in patients with Crohn's disease and ulcerative colitis. Taken together, these observations may have important physiological and pathophysiological implications, and provide the rationale for the use of NK-1R and NK-2R antagonists in the treatment of inflammatory bowel disease.
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Colitis Ulcerosa/genética , Colitis Ulcerosa/metabolismo , Enfermedad de Crohn/genética , Enfermedad de Crohn/metabolismo , Expresión Génica , Receptores de Neuroquinina-1/genética , Receptores de Neuroquinina-1/metabolismo , Receptores de Neuroquinina-2/genética , Receptores de Neuroquinina-2/metabolismo , Adolescente , Adulto , Anciano , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
OBJECTIVES: To perform a pilot study on bacterial contamination in some dental surgeries (n=51) in a local health unit in Brescia (Lombardy Region, Italy) and to evaluate the procedures to control cross infection used by the personnel to reduce the risk of infection in dental practice. METHODS: A survey was carried out by interviewing 133 dental personnel with a questionnaire on the procedures used to control infection. The autoclaves, chemical baths (chemiclaves), and ovens present in the surgeries were tested for sterilisation efficiency with a spore test, and already packed and sterilised instruments were randomly sampled and tested for sterility. Microbial contamination of air, surface, and dental unit water samples were also studied. RESULTS: The dental personnel did not generally follow the principal procedures for infection control: 30% of personnel were not vaccinated against hepatitis B virus, infected instruments were often not decontaminated, periodic checks of autoclave efficiency were lacking, and the knowledge of disinfection mechanisms and procedures was incomplete. High bacteriological contamination of water at dental surgeries was often found and total bacteriological counts in air samples were high. Surface studies showed widespread bacterial contamination. CONCLUSIONS: On the basis of these results, an educational programme for the prevention of infective hazards has been prepared and carried out. The results of this pilot study will be used for planning a national survey.
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Infección Hospitalaria/prevención & control , Consultorios Odontológicos , Contaminación de Equipos/prevención & control , Esterilización/normas , Bacterias/aislamiento & purificación , Competencia Clínica/normas , Equipo Dental , Educación Continua en Odontología , Exposición a Riesgos Ambientales/análisis , Conocimientos, Actitudes y Práctica en Salud , Humanos , Italia , Proyectos Piloto , Desarrollo de Programa , Encuestas y CuestionariosRESUMEN
BACKGROUND AND AIMS: Ulcerative colitis is a chronic inflammatory condition characterized by an altered intestinal immunoinflammatory response. Since increasing evidence indicates that neuropeptides play a key role in the regulation of gastrointestinal immune function, the aims of this study were: a) to determine tissue and plasma levels of Vasoactive Intestinal Polypeptide, Substance P, and Calcitonin Gene-Related Peptide in patients with ulcerative colitis, and b) to ascertain whether a relationship exists between tissue concentrations of neuropeptides and the histological grading of mucosal inflammation. METHODS: A total of 29 patients with active and 39 with inactive ulcerative colitis, and 16 control subjects took part in the study. Biopsy specimens of colonic mucosa and blood samples were obtained from each subject, and neuropeptide concentrations were measured by sensitive and specific radioimmunoassays. RESULTS: Both Vasoactive Intestinal Polypeptide and Substance P concentrations were found to be significantly reduced in endoscopic biopsy specimens of patients with ulcerative colitis compared to controls (p < 0.01 and p = 0.05, respectively), and the reduction appeared to be related to the degree of mucosal inflammation; in contrast, Calcitonin Gene-Related Peptide tissue levels were unchanged. In addition, there was no significant difference in the neuropeptide plasma levels between ulcerative colitis patients and control subjects. CONCLUSIONS: Taken together, our results suggest that the reduction of Vasoactive Intestinal Polypeptide and Substance P is probably a secondary phenomenon, correlated with the degree of mucosal inflammation; whatever the mechanism, the decreased availability of these neuropeptides in the local microenvironment may play an important role in the pathogenesis of ulcerative colitis, by affecting many components of the normal immune response. Moreover, based on our data, the measurement of neuropeptide plasma concentrations does not appear to be a useful tool to monitor disease activity.
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Péptido Relacionado con Gen de Calcitonina/metabolismo , Colitis Ulcerosa/metabolismo , Sustancia P/metabolismo , Péptido Intestinal Vasoactivo/metabolismo , Adulto , Anciano , Biomarcadores , Biopsia , Colitis Ulcerosa/patología , Colon , Colonoscopía , Femenino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Recto , Índice de Severidad de la EnfermedadRESUMEN
Substance P (SP) was analyzed in rat brain endothelium cultures after cytokine stimulation. SP secretion was found after stimulation with high doses of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). High doses of interferon-gamma (INF-gamma) had no effect on this secretion. Elevated SP release was found to be associated with mRNA expression of beta-preprotachykinin (beta-PPT), precursor of SP, in the cells. Under cytokine stimulation, part of SP was bound to brain endothelial cell surface, suggesting the existence of an autocrine network for this neuropeptide. These findings suggest that SP may have an immunomodulatory action at the blood-brain barrier during inflammatory and autoimmune processes in the central nervous system.
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Encéfalo/metabolismo , Citocinas/farmacología , Sustancia P/metabolismo , Animales , Autoinmunidad/inmunología , Células Cultivadas/efectos de los fármacos , Sistema Nervioso Central/inmunología , Endotelio/metabolismo , Femenino , Inflamación/inmunología , Interferón gamma/farmacología , Interleucina-1/farmacología , Masculino , Ratas , Sustancia P/biosíntesis , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
This study investigated the role of endogenous and exogenous calcitonin gene-related peptide (CGRP) in water immersion stress (WIS)-induced gastric ulcers in rats. WIS produced gastric ulcers which were inversely correlated to the decrease in CGRP-like immunoreactivity observed in the whole thickness of the corpus stomach but not in its mucosal layers. Systemic administration of CGRP (100 micrograms kg-1 s.c.) produced a significant decrease in lesion index of WIS-ulcers and this protection was inhibited by functional ablation of afferent neurons induced by capsaicin pretreatment (100 mg kg-1 s.c. in two days, a week before the experiments). These findings suggest that sensory endogenous CGRP plays a defensive role in WIS-ulcers.
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Antiulcerosos/uso terapéutico , Péptido Relacionado con Gen de Calcitonina/uso terapéutico , Úlcera Gástrica/prevención & control , Estrés Psicológico/complicaciones , Animales , Antiulcerosos/administración & dosificación , Péptido Relacionado con Gen de Calcitonina/administración & dosificación , Capsaicina/farmacología , Mucosa Gástrica/patología , Inmersión , Inyecciones Subcutáneas , Masculino , Ratas , Ratas Sprague-Dawley , Úlcera Gástrica/patologíaRESUMEN
Increasing evidence indicates that epidermal growth factor and transforming growth factor-alpha are involved in the maintenance of oesophageal mucosal integrity. However, their cellular origin and the exact localization of their receptor in the oesophagus are still unclear. Therefore, we examined the expression of the two growth factors and their shared receptor in the normal human oesophagus at both mRNA and protein level, by immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction. In addition to being expressed in the proliferative compartment of the oesophageal epithelium, the receptor was found in a variety of cells, including smooth muscle cells, submucosal gland cells and the epithelium lining their ducts. Immunohistochemically, the pattern of distribution of epidermal growth factor paralleled that of its receptor. In situ hybridization demonstrated epidermal growth factor mRNA expression in the oesophageal epithelium and submucosal glands. Additionally, amplified transcripts of predicted size were detected by reverse transcription-polymerase chain reaction, thus confirming that authentic transcripts of the growth factor exist in the normal human oesophagus. Transforming growth factor-alpha mRNA and protein expression, while similar to that of epidermal growth factor, predominated in the more differentiated cell layers of the stratified squamous epithelium. These results demonstrate that the normal oesophagus can synthesize both growth factors. Moreover, the peculiar distribution of these peptides and the concomitant expression of their receptor in multiple cell types suggest that the two growth factors may exert diverse physiological functions in the oesophagus and participate in defence and reparative events following mucosal injury.
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Factor de Crecimiento Epidérmico/biosíntesis , Receptores ErbB/biosíntesis , Esófago/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/biosíntesis , Factor de Crecimiento Transformador alfa/biosíntesis , Adulto , Anciano , Esófago/citología , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Accumulating evidence indicates that capsaicin-sensitive afferent fibers play a pivotal role in acute gastroprotection. However, whether they also influence healing of chronic gastric ulcers is still unknown. The effects of ablation of sensory neurons on acetic acid-induced chronic gastric ulcers in rats were investigated at morphologic and biochemical levels by computerized imaging analysis of the ulcerated area, histologic examination, and neuropeptide determination. Afferent nerve ablation, as a result of treating rats with a neurotoxic dose of capsaicin (50 + 50 mg/kg subcutaneously over 2 days), produced a significant increase in the ulcer area at 1 and 2 weeks after acetic acid injection. The delay in ulcer healing was associated with a marked and persistent decrease in tissue calcitonin gene-related peptide-like immunoreactivity, whereas gastric vasoactive intestinal polypeptide was unaffected by capsaicin pretreatment. Histologically, as compared with control rats, capsaicin-desensitized animals only differed in a slight increase in the inflammatory infiltrate during the early phase of ulcer formation. These findings suggest that capsaicin-sensitive afferent fibers may play a role in the healing of chronic experimental gastric ulcers in rats, but the underlying mechanisms remain to be elucidated and deserve further investigation.
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Capsaicina/farmacología , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/fisiología , Úlcera Gástrica/fisiopatología , Acetatos , Ácido Acético , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Enfermedad Crónica , Masculino , Ratas , Ratas Sprague-Dawley , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología , Péptido Intestinal Vasoactivo/metabolismo , Cicatrización de HeridasRESUMEN
Neurochemical and functional studies were performed to investigate and to compare the effects of resiniferatoxin and capsaicin in the rat stomach. Neonatal administration of resiniferatoxin (0.6-1.6 mumol/kg subcutaneously (s.c.)) produced a marked decrease in gastric calcitonin gene-related peptide-like immunoreactivity in both secretory and non-secretory region of the stomach. Almost complete depletion of the peptide was determined by neonatal administration of capsaicin (164 mumol/kg s.c.). Vasoactive intestinal polypeptide-like immunoreactivity was concomitantly unaffected by resiniferatoxin or capsaicin, thus showing the selectivity of action of the neurotoxins on gastric afferent fibers. Oral administration of an equimolar dose (0.3 nmol/kg) of resiniferatoxin or capsaicin together with 50% ethanol reduced at a similar extent gastric haemorrhagic lesions produced by the mucosal barrier-breaker agent. These findings provide evidence that resiniferatoxin and capsaicin may act on a common neuronal target in the rat stomach and that the acute exciting (protective) effect is of the same magnitude.
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Péptido Relacionado con Gen de Calcitonina/biosíntesis , Capsaicina/farmacología , Diterpenos/farmacología , Mucosa Gástrica/efectos de los fármacos , Administración Oral , Animales , Animales Recién Nacidos , Capsaicina/administración & dosificación , Capsaicina/toxicidad , Diterpenos/administración & dosificación , Relación Dosis-Respuesta a Droga , Etanol/toxicidad , Mucosa Gástrica/inervación , Mucosa Gástrica/metabolismo , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/fisiopatología , Hemorragia Gastrointestinal/prevención & control , Inyecciones Subcutáneas , Masculino , Neuronas Aferentes/química , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/metabolismo , Neurotoxinas/farmacología , Neurotoxinas/toxicidad , Ratas , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/fisiopatología , Úlcera Gástrica/prevención & control , Péptido Intestinal Vasoactivo/biosíntesisRESUMEN
Gastric calcitonin gene-related peptide-like immunoreactivity (CGRP-li) was decreased in the gastric corpus of rats treated with 75% or 96% ethanol but not with 50% ethanol. The extent of gastric lesions was related to the increasing concentrations of ethanol (50-96%). CGRP-li decrease was evident already at 5 min after the 96% ethanol challenge, whereas a peptide recovery resulted 10 days after, concomitant with the healing of gastric lesions. Ethanol (96%) produced a significant decrease of CGRP-li in the whole thickness of the gastric corpus but not in the mucosal layers of the same area, indicating that the muscular layer of the gastric corpus is the zone involved in this phenomenon. Pretreatment with the selective sensory neurotoxin capsaicin induced a gastric CGRP-li decrease in the corpus and forestomach. Ethanol (96%) did not further decrease gastric corpus CGRP-li in capsaicin-pretreated rats. These findings suggest that 96% ethanol induced a decrease of CGRP-li deriving from a capsaicin-sensitive pool and that CGRP may play a role in gastric ulcer pathogenesis of haemorrhagic lesions induced by concentrated ethanol.