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1.
J Pediatr Hematol Oncol ; 35(4): 260-6, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23612376

RESUMEN

Infants affected by neuroblastoma with symptomatic epidural compression require early diagnosis and appropriate treatment to avoid severe late complications. However, no established guidelines are available regarding the optimal treatment of these patients. We describe 5 such infants. The interval between the onset of symptoms and tumor diagnosis was 3 to 8 days in 4/5 cases. None developed paraplegia before or after treatment. Treatment for epidural compression included first-line laminoplasty followed by chemotherapy in 3 patients, and chemotherapy first in the remaining 2. To date, all are alive and none have developed severe complications after a follow-up of 9 to 39 months (median, 20).


Asunto(s)
Neuroblastoma/tratamiento farmacológico , Neuroblastoma/cirugía , Compresión de la Médula Espinal/tratamiento farmacológico , Compresión de la Médula Espinal/cirugía , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Laminectomía , Masculino , Neuroblastoma/diagnóstico , Compresión de la Médula Espinal/diagnóstico
2.
EClinicalMedicine ; 43: 101251, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35024594

RESUMEN

BACKGROUND: Children with high-risk medulloblastoma are treated with chemotherapeutic protocols which may affect heart function. We aimed to assesscardiovascular events (CVE) in children with medulloblastoma/primitive neuroectodermal tumors (PNET). METHODS: We retrospectively collected data from a case series of 22 children with high-risk medulloblastoma/PNET admitted to the Santobono-Pausilipon Hospital, Naples, Italy from 2008 to 2016. All patients received the Milan HART protocol for high-risk brain malignancies as first line treatment (induction phase), followed by a consolidation phase with Thiotepa and hematopoietic stem cells transplantation, except for 1 patient who received the Milan HART as second line therapy. Four patients also received second line treatment, while 4 patients also received maintenance therapy. Patients underwent cardiac examination, including ECG, echocardiography and serum biomarkers, before antineoplastic treatment initiation and then when clinically needed. Six patients developed CVE (CVE group); 16 patients had no CVE (NO-CVE group). FINDINGS: In the CVE group, 3 patients presented acute CVE during chemotherapy (2 patients with left ventricular (LV) dysfunction, 1 patient with arterial hypertension), while 3 patients presented chronic CVE after chemotherapy completion (2 patients with LV dysfunction, 1 patient with ectopic atrial tachycardia). After a 51 months median follow-up, 9 patients died: 4 from the CVE group (in 2 cases heart failure-related deaths) and 5 from the NO-CVE group (progression of disease). INTERPRETATION: A relevant percentage of children treated for medulloblastoma/PNET develops CVE. Heart failure potentially due to chemotherapy may represent a cause of death. Hence, in these patients, strict cardiac surveillance is essential. FUNDING: No funding was associated with this study.

3.
J Pediatr ; 158(2): 288-92.e1, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20828714

RESUMEN

OBJECTIVE: To evaluate the efficacy of a hypotonic oral rehydration solution (ORS) containing zinc and prebiotics for treatment of acute diarrhea in children. STUDY DESIGN: We conducted a single-blind, prospective, controlled trial including children (age range, 3-36 months) with acute diarrhea randomly assigned to standard hypotonic ORS (group 1) or to new hypotonic ORS containing zinc and prebiotics (group 2). The main outcome was the rate of resolution of diarrhea at 72 hours. RESULTS: A total of 60 children in group 1 (34 male; mean age, 18.58 months; 95% CI, 15.5-21.6) and 59 in group 2 (36 male; mean age, 19.26 months; 95% CI, 15.9-22.6) completed the study protocol. The rate of diarrhea resolution at 72 hours was higher in group 2 (50% versus 72.9%, P = .010). Total ORS intake in the first 24 hours was higher in group 2 (50 mL/kg; 95% CI, 41-59 versus 22 mL/kg; 95% CI, 17-29; P < .001). The mean number of missed working days by the parents of children in group 2 was lower (0.39; 95% CI, 0.08-0.70 versus 1.45; 95% CI 1.02-1.88; P < .001). Fewer patients in group 2 needed adjunctive drugs for the treatment of diarrhea 6/59 versus 19/60, P = .004. No adverse events were observed in either of the two groups. CONCLUSION: The addition of zinc and prebiotics to ORS limits diarrhea duration in children.


Asunto(s)
Diarrea/terapia , Fluidoterapia/métodos , Prebióticos , Soluciones para Rehidratación/uso terapéutico , Zinc/uso terapéutico , Enfermedad Aguda , Preescolar , Intervalos de Confianza , Diarrea/diagnóstico , Diarrea/mortalidad , Diarrea Infantil/diagnóstico , Diarrea Infantil/mortalidad , Diarrea Infantil/terapia , Femenino , Estudios de Seguimiento , Humanos , Soluciones Hipotónicas/uso terapéutico , Lactante , Italia , Estimación de Kaplan-Meier , Masculino , Oportunidad Relativa , Estudios Prospectivos , Valores de Referencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Método Simple Ciego , Tasa de Supervivencia , Resultado del Tratamiento
4.
Pediatr Res ; 70(6): 549-54, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21857380

RESUMEN

Several studies analyzing the immune responses in patients with cow's milk allergy (CMA) have used T-cell lines or T-cell clones that require prolonged in vitro cell culturing and may result in a switched cell phenotype and function. We investigated immune responses to beta-lactoglobulin (b-LG) in peripheral blood mononuclear cells after a short in vitro antigen stimulation in children with acute CMA (both IgE-mediated and non-IgE-mediated forms) and in those who outgrew an IgE-mediated CMA. Healthy controls were also investigated. Peripheral blood mononuclear cells were assayed for IL-13, IFN-γ, IL-4, and IL-10. Although b-LG induced a cytokine production and/or cell proliferation almost in all children, included healthy controls, differences were observed among the four groups. Children with IgE-mediated CMA had a marked Th2-response, with high IL-13 production and proliferation, but low IFN-γ; by contrast, children with non-IgE-mediated CMA produced no, or very low, IL-13 and cell proliferation. Children, who outgrew CMA, showed a shift to a Th1-response, with reduced IL-13 and increased IFN-γ. IL-10-responses were high in all groups, with the highest level in healthy children; by contrast, IL-4 was undetectable in all children. This study highlights the use of shortly stimulated peripheral blood cells to investigate the food-induced immune responses.


Asunto(s)
Hipersensibilidad Inmediata/inmunología , Lactoglobulinas/farmacología , Leucocitos Mononucleares/inmunología , Hipersensibilidad a la Leche/inmunología , Leche/efectos adversos , Factores de Edad , Animales , Estudios de Casos y Controles , Proliferación Celular/efectos de los fármacos , Niño , Preescolar , Femenino , Humanos , Hipersensibilidad Inmediata/inducido químicamente , Lactante , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Lactoglobulinas/inmunología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Masculino , Estadísticas no Paramétricas , Células Th2/inmunología , Células Th2/metabolismo
5.
Pediatr Allergy Immunol ; 21(5): 889-91, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20663077

RESUMEN

The prevalence and severity of atopic manifestations in children are increasing in western countries in the last decades. Specific nutritional intervention may prevent or delay the onset of atopic diseases in infants at high risk of developing allergy. These nutritional interventions should be applied early in the perinatal period to have a chance of success. Thus, we assessed adherence to the dietary management recommendations of the Committee on Nutrition and Section on Allergy and Immunology of the American Academy of Pediatrics (AAP) for the prevention of atopic diseases in neonatal age through an audit study. Questionnaire was administered to the chiefs of 30 maternity units (MU) with more than 1500 live births/yr to report the policy applied in their MU. Twenty-two MU returned the questionnaire. Identification of high-risk newborns was routinely performed only in 7/22 MU (31.8%). High-risk newborns were identified by the presence of at least two or one first-degree relative (parent or sibling) with documented allergic disease by 18.2% and 45.5% of MU, respectively. Specific maternal dietary restrictions during lactation were adopted in 7/22 MU (31.8%). Extensively or partially hydrolyzed formula was prescribed for bottle-fed high-risk infants in 22.7% of MU. Only 2/22 MU have a policy in complete agreement with the nutritional intervention proposed by the AAP. Our study suggest a poor adherence to dietary recommendations for primary prevention of atopic disease in neonatology clinical practice. Further efforts should be planned to improve the knowledge and the application of these preventive strategies.


Asunto(s)
Hipersensibilidad Inmediata/epidemiología , Hipersensibilidad Inmediata/prevención & control , Cooperación del Paciente , Guías de Práctica Clínica como Asunto , Alimentación con Biberón , Encuestas de Atención de la Salud , Humanos , Hipersensibilidad Inmediata/dietoterapia , Incidencia , Lactante , Alimentos Infantiles , Recién Nacido , Prevalencia , Índice de Severidad de la Enfermedad
6.
Ital J Pediatr ; 45(1): 80, 2019 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-31300063

RESUMEN

BACKGROUND: Malignant spinal cord compression (MSCC) is associated withpoor prognosis and may lead to permanent paralysis, sensory loss, and sphincter dysfunction. Very limited data are available on incidence and etiology of MSCC in pediatric population. We aimed to examine etiology, clinical presentation and treatment of pediatric patient with MSCC admitted to the Santobono-Pausilipon Children's Hospital, Naples, Italy. METHODS: Forty-four children under 18 yearsadmitedsince 2007 and assessed for MSCC clinical presentations, evaluation, and treatment.were retrospectively collected from our institutional pediatric oncology and neurosurgery database. RESULTS: The median age at time of MSCC diagnosis was 52 months, with a peak in young (≤3 years) patients. The leading cause of MSCC was extramedullary tumors (63.6%), in particular neuroblastoma (27.2%) followed by Ewing sarcomas (15.9%). Cord compression was the presenting feature of a new malignancy in 33 (75%) patients, and a consequence of metastatic disease progression or relapse in the remaining 11 (25%) patients. Motor deficit was the initial symptoms of spinal compression in all patients, while pain was present in about 60% of patients, followed by sphincteric deficit (43.2%). The primary tumor site was located in the neck in 3 (6.8%) patients, thorax in 16 (36.4%), cervico-thoracic region in 3 (6.8%), thoraco-lumbar region in 8 (18.2%), abdomen in 5 (11.4%), lumbar-sacral region in 7 (15.9%) and thoracic-lumbar-sacral region in 1 (2.3%). The median length of the interval between symptom onset and tumor diagnosis varied widely from 0 to 360 days in the entire population, however this interval was significantly shorter in patients with known neoplasia in comparisonto patients with new diagnosis (at relapse 7 days [interquartile range 3-10] vs at diagnosis 23 days [7-60]). Pre and post-operative spine magnetic resonance imagingwas performed in all cases, and most(95%) patients underwent neurosurgical treatment as first treatment. Severe motor deficit was associated with younger age and severe motor deficit at diagnosis was associated withworst motor outcomes at discharge from neurosurgery. Patients with progression or relapsed disease showed a worst prognosis, while the majority of patients (70.5%) were alive at 5 years after diagnosis. CONCLUSIONS: The natural history of MSCC in children is associated to permanent paralysis, sensory loss, and sphincter dysfunction, thus prompt diagnosis and correct management are needed to minimize morbidity. Treatment strategies differed widely among cancer types and study groups in the absence of optimal evidence-based treatment guidelines. When the diagnosis is uncertain, surgery provides an opportunity to biopsy the lesion in addition to treating the mass.


Asunto(s)
Neoplasias/complicaciones , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/patología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Italia , Masculino , Pronóstico , Estudios Retrospectivos
7.
Curr Opin Pediatr ; 20(5): 584-9, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18781123

RESUMEN

PURPOSE OF REVIEW: To give an update about the optimal diagnostic work-up for children with suspected food allergy. RECENT FINDINGS: Food allergy has become a very severe health problem not only for many children and parents, but also for the entire medical and paramedical community. The financial and social costs related to these conditions are increasing, but, contemporarily, basic and clinical research are deeply involved in the search of possible solutions to facilitate the management of these patients. SUMMARY: Food allergy is defined as an abnormal immunological reaction to food proteins, which causes an adverse clinical reaction. Over 90% of food allergies in childhood are caused by eight foods: cow's milk, hen's egg, soy, peanuts, tree nuts, wheat, fish and shellfish. The evaluation of a child with suspected food allergy includes detailed medical history, physical examination, screening tests and response to elimination diet and to oral food challenge. None of the screening tests, alone or in combination, can definitely diagnose or exclude it. The main principle of food allergy management is avoidance of the offending antigen. An incorrect diagnosis is likely to result in unnecessary dietary restrictions, which, if prolonged, may adversely affect the child's nutritional status and growth.


Asunto(s)
Alérgenos , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/metabolismo , Pruebas del Parche , Adolescente , Distribución por Edad , Niño , Preescolar , Femenino , Estudios de Seguimiento , Hipersensibilidad a los Alimentos/epidemiología , Humanos , Inmunoglobulina E/análisis , Incidencia , Masculino , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Distribución por Sexo , Pruebas Cutáneas
8.
J Med Case Rep ; 12(1): 243, 2018 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-30172261

RESUMEN

BACKGROUND: Diagnosis and treatment of primary lung adenocarcinoma in children remains challenging given its rarity. Here we highlight the clinical history, pathological evaluation, genomic findings, and management of a very young patient with metastatic lung adenocarcinoma. CASE PRESENTATION: A 10-year-old white girl presented with brain metastases due to primary pulmonary adenocarcinoma. Next generation sequencing analysis with "Comprehensive Cancer Panel" highlighted the presence of multiple non-targetable mutations in the FLT4, UBR5, ATM, TAF1, and GUCY1A2 genes. She was treated aggressively with chemotherapy, surgery, and radiation therapy for local and distant recurrence. Eventually, therapy with nivolumab was started compassionately, and she died 23 months after diagnosis. CONCLUSIONS: Extremely rare cancers in children such as lung adenocarcinoma need accurate and specific diagnosis in order to develop an optimal plan of treatment. It is also necessary to underline that "children are not little adults," thus implying that an adult-type cancer in the pediatric population might have a different etiopathogenesis. Diagnostic confirmation and primary treatment of such rare conditions should be centralized in reference centers, collaborative networks, or both, with multidisciplinary approaches and very specific expertise.


Asunto(s)
Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/terapia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/secundario , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Niño , Resultado Fatal , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología
9.
AIDS ; 21(1): 108-10, 2007 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-17148977

RESUMEN

Diarrhoea-related morbidity is reduced by zinc supplementation in HIV-1-infected children. The mechanisms of this effect are largely undefined. We provide evidence for role for Tat (transactivating peptide produced by HIV-1) in the pathogenesis of diarrhoea in AIDS patients. In this study we showed that zinc, preventing Tat-induced fluid secretion, directly limits a specific mechanism of HIV-1-related diarrhoea. Our data support a 'zinc approach' in adjunct to specific antiretroviral therapy in HIV-1-infected children.


Asunto(s)
Diarrea/tratamiento farmacológico , Diarrea/etiología , Infecciones por VIH/complicaciones , VIH-1 , Micronutrientes/uso terapéutico , Zinc/uso terapéutico , Niño , Diarrea/fisiopatología , Productos del Gen tat/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/fisiopatología , Humanos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/virología , Iones , Productos del Gen tat del Virus de la Inmunodeficiencia Humana
10.
AIDS ; 20(1): 5-10, 2006 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-16327313

RESUMEN

OBJECTIVE: The pathophysiology of HIV-1-related intestinal dysfunction is largely unknown. We previously found that the transactivator factor peptide (Tat) produced by HIV-1 induces ion secretion and inhibits cell proliferation in human enterocytes. Because sugar malabsorption is a frequent feature in AIDS patients, we evaluated whether Tat inhibits intestinal glucose absorption. DESIGN AND METHODS: We measured Na-D-glucose symporter (SGLT-1) activity and determined its phenotypic expression in Caco-2 cells, in the presence and absence of Tat, in uptake experiments using a non-metabolized radiolabelled glucose analogue, and by western blot analysis, respectively. alpha-Tubulin staining was used to study the effects exerted by Tat on cell structure. RESULTS: Tat dose dependently inhibited glucose uptake by human enterocytes. This effect was prevented by anti-Tat polyclonal antibodies and by L-type Ca channels agonist Bay K8644. Western blot analysis of cellular lysates and brush-border membrane preparations showed that Tat induced SGLT-1 missorting. Tat also caused a dramatic decrease in alpha-tubulin staining, which indicates dysruption of the cytoskeleton organization. CONCLUSIONS: Tat acutely impairs intestinal glucose absorption through SGLT-1 missorting. This result indicates that Tat is directly involved in AIDS-associated intestinal dysfunction.


Asunto(s)
Productos del Gen tat/farmacología , VIH-1/química , Absorción Intestinal/efectos de los fármacos , Transportador 1 de Sodio-Glucosa/metabolismo , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Biomarcadores/análisis , Western Blotting/métodos , Células CACO-2 , Agonistas de los Canales de Calcio/farmacología , Canales de Calcio/metabolismo , Medios de Cultivo , Citoesqueleto/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Técnica del Anticuerpo Fluorescente/métodos , Glucosa/farmacocinética , Humanos , Transportador 1 de Sodio-Glucosa/análisis , Tubulina (Proteína)/análisis , Productos del Gen tat del Virus de la Inmunodeficiencia Humana
11.
World J Gastroenterol ; 12(29): 4710-5, 2006 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-16937444

RESUMEN

AIM: Growth hormone (GH) directly interacts with the enterocyte stimulating ion absorption and reducing ion secretion induced by agonists of cAMP. Since nitric oxide (NO) is involved in the regulation of transepithelial ion transport and acts as a second messenger for GH hemodynamic effects, we tested the hypothesis that NO may be involved in the resulting effects of GH on intestinal ion transport. METHODS: Electrical parameters reflecting trans-epithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers and exposed to GH and cholera toxin (CT) alone or in combination, in the presence or absence of the NO synthase (NOS) inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME). Similar experiments were conducted to determine cAMP and nitrite/nitrate concentrations. NOS expression was assayed by Western blot analysis. RESULTS: L-NAME causes total abrogation of absorptive and anti-secretory effects by GH on intestinal ion transport. In addition, L-NAME was able to inhibit the GH-effects on intracellular cAMP concentration under basal conditions and in response to CT. GH induced a Ca(2+)-dependent increase of nitrites/nitrates production, indicating the involvement of the constitutive rather than the inducible NOS isoform, which was directly confirmed by Western blot analysis. CONCLUSION: These results suggest that the GH effects on intestinal ion transport, either under basal conditions or in the presence of cAMP-stimulated ion secretion, are mediated at an intracellular level by the activity of cNOS.


Asunto(s)
AMP Cíclico/metabolismo , Hormona del Crecimiento/fisiología , Mucosa Intestinal/metabolismo , Transporte Iónico/efectos de los fármacos , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico/metabolismo , Células CACO-2 , Línea Celular , Toxina del Cólera/farmacología , Inhibidores Enzimáticos/farmacología , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/efectos de los fármacos , Intestinos/citología , Intestinos/efectos de los fármacos , Transporte Iónico/fisiología , NG-Nitroarginina Metil Éster/farmacología , Transducción de Señal/fisiología
12.
J Acad Nutr Diet ; 114(9): 1432-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24933388

RESUMEN

Although dietary counseling is generally recommended in children with food allergy (FA), its effect on the nutritional status of these patients has not yet been evaluated. Our nonrandomized multicenter prospective intervention study was undertaken to investigate the effects of dietary counseling on children with FA. Anthropometric data, dietary intakes, and laboratory biomarkers of nutritional status were evaluated in children with FA (aged 6 to 36 months) before and after dietary counseling, by multidisciplinary teams composed of pediatricians, dietitians, and nurses. Ninety-one children with FA (49 boys and 42 girls; mean age 18.9 months, 95% CI 16.5 to 21.3) were evaluated; 66 children without FA (41 boys and 25 girls; mean age 20.3 months, 95% CI 17.7 to 22.8) served as controls providing baseline values only. At enrollment, energy and protein intakes were lower in children with FA (91 kcal/kg/day, interquartile range [IQR]=15.1, minimum=55.2, maximum=130.6; and 2.2 g/kg/day, IQR=0.5, minimum=1.5, maximum=2.7, respectively) than in children without FA (96 kcal/kg/day, IQR=6.1, minimum=83.6, maximum=118.0; and 4.6 g/kg/day, IQR=1.2, minimum=2.0, maximum=6.1, respectively; P<0.001). A weight to length ratio <2 standard deviations was more frequent in children with FA than in children without FA (21% vs 3%; P<0.001). At 6 months following dietary counseling, the total energy intake of children with FA was similar to the baseline values of control children. Dietary counseling also resulted in a significant improvement of their anthropometric and laboratory biomarkers of nutritional status. The results of our study support the crucial role of dietary counseling in the clinical management of children with FA.


Asunto(s)
Consejo , Dietética/métodos , Hipersensibilidad a los Alimentos/dietoterapia , Peso Corporal , Preescolar , Ingestión de Energía , Femenino , Humanos , Lactante , Masculino , Evaluación Nutricional , Estado Nutricional , Estudios Prospectivos
13.
Eur J Pharmacol ; 626(2-3): 266-70, 2010 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-19819236

RESUMEN

Zn(2+) is effective in the treatment of acute diarrhea, but its mechanisms are not completely understood. We previously demonstrated that Zn(2+) inhibits the secretory effect of cyclic adenosine monophosphate but not of cyclic guanosine monophosphate in human enterocytes. The aim of the present study was to investigate whether Zn(2+) inhibits intestinal ion secretion mediated by the Ca(2+) or nitric oxide pathways. To investigate ion transport we evaluated the effect of Zn(2+) (35 microM) on electrical parameters of human intestinal epithelial cell monolayers (Caco2 cells) mounted in Ussing chambers and exposed to ligands that selectively increased intracellular Ca(2+) (carbachol 10(-6)M) or nitric oxide (interferon-gamma 300 UI/ml) concentrations. We also measured intracellular Ca(2+) and nitric oxide concentrations. Zn(2+) significantly reduced ion secretion elicited by carbachol (-87%) or by interferon-gamma (-100%), and inhibited the increase of intracellular Ca(2+) and nitric oxide concentrations. These data indicate that Zn(2+) inhibits ion secretion elicited by Ca(2+) and nitric oxide by directly interacting with the enterocyte. They also suggest that Zn(2+) interferes with three of the four main intracellular pathways of intestinal ion secretion that are involved in acute diarrhea.


Asunto(s)
Calcio/metabolismo , Enterocitos/efectos de los fármacos , Enterocitos/metabolismo , Iones/metabolismo , Óxido Nítrico/metabolismo , Zinc/farmacología , Células CACO-2 , Enterocitos/citología , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Transporte Iónico/efectos de los fármacos , Reproducibilidad de los Resultados , Transducción de Señal/efectos de los fármacos
14.
J Infect Dis ; 191(7): 1072-7, 2005 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-15747242

RESUMEN

BACKGROUND: Because zinc deficiency in malnourished children is associated with severe diarrhea, use of zinc supplementation has been proposed as an adjunct to oral rehydration. However, the effects of zinc on enterocyte ion transport are largely unknown. The objective of the present study was to investigate the effects of zinc on transepithelial ion transport under basal conditions and under conditions of enterotoxin-induced ion secretion. METHODS: Ion transport was investigated by monitoring electrical parameters in human intestinal Caco-2 cells that were mounted in Ussing chambers and exposed to increasing concentrations of zinc, both in the absence and presence of either cholera toxin (CT) or Escherichia coli heat-stable enterotoxin (ST). Intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations were also determined. RESULTS: The addition of zinc to the luminal or basolateral side of enterocytes induced a chloride-dependent, dose-related decrease in short-circuit current, indicating ion absorption. It also resulted in a substantial reduction in CT-induced ion secretion and in cAMP concentration. E. coli ST-induced ion secretion and cGMP concentration were not affected. Ion absorption peaked at 35 mu mol/L zinc, whereas excess zinc load induced active ion secretion. CONCLUSIONS: By causing a decrease in cAMP concentration, zinc directly promotes ion absorption and substantially reduces CT-induced, but not E. coli ST-induced, ion secretion.


Asunto(s)
Toxinas Bacterianas/antagonistas & inhibidores , Toxina del Cólera/antagonistas & inhibidores , Enterocitos/metabolismo , Enterotoxinas/antagonistas & inhibidores , Transporte Iónico/efectos de los fármacos , Zinc/farmacología , Toxinas Bacterianas/toxicidad , Células CACO-2 , Toxina del Cólera/toxicidad , AMP Cíclico/análisis , GMP Cíclico/análisis , Enterocitos/efectos de los fármacos , Enterocitos/enzimología , Enterotoxinas/toxicidad , Inhibidores Enzimáticos/farmacología , Escherichia coli , Proteínas de Escherichia coli , Humanos
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