Indometacina como tratamiento de granuloma eosinófilo multifocal / Indomethacin as a treatment for multifocal Eosinophilic granuloma

Granuloma eosinófilo es la variante más frecuente de histiocitosis de células de Langerhans. La mayoría de las lesiones ocurren en cráneo, costillas, columna vertebral o huesos largos, y pueden ser únicas o múltiples. El tratamiento depende del lugar de la afectación y del número de lesiones. Las opciones terapéuticas incluyen un agente único con prednisona, la combinación de vinblastina y prednisona, curetaje de las lesiones óseas o instilación intralesional de esteroides. Indometacina parece ser efectiva como tratamiento de lesiones de histiocitosis de células de Langerhans del hueso en niños y es bien tolerada. Presentamos el caso de un paciente varón de 4 años de edad con afectación de 2 huesos del cuerpo, cráneo y vértebra, tratado con curetaje de la lesión craneal e indometacina oral durante 19 meses, con completa curación de las lesiones y sin recurrencia 4 meses después de suspenderla. Concluimos que indometacina parece ser efectiva en el tratamiento de lesiones óseas de histiocitosis de células de Langerhans en niños, evitando otras terapias más agresivas. (AU)

Eosinophilic granuloma of the bone is the most common variant of Langerhans cell histiocytosis. Most of the lesions occur in the skull, ribs, spine or long bones and may be single or multiple. Therapy is generally chosen based on the site involved and the number of lesions. Treatment options include single agent with prednisone, the combination of vinblastine and prednisone, curettage of bone lesions or intralesional steroids injection. Indomethacin seems to be effective in treating isolated Langerhans cell histiocytosis of the bone in children and is generally well-tolerated. We present the case of a 4-year-old boy with involvement of 2 bones, skull and vertebra, treated with curettage of the skull and indomethacin for 19 months. There was complete healing of the lesions at the end of the treatment and no evidence of recurrence 4 months post-treatment. We conclude that indomethacin seems to be effective in the treatment of Langerhans cell histiocytosis of the bone in children, avoiding more aggressive therapies. (AU)

Langerhans cell histiocytosis in the mandibular condyle and ramus. Endoscopic diagnosis. Case report / Histiocitosis de células de Langerhans en cóndilo y rama mandibular. Diagnóstico por vía endoscópica. Reporte de un caso

Langerhans cell histiocytosis (LCH) is a rare disease caused by uncontrolled proliferation and accumulation of immature bone marrow-derived myeloid dendritic cells. It is common in the pediatric population under 15 years of age and usually affects bones such as the skull, femur and mandibular body. This study presents the case of a 6-year-old female patient, with a bone lesion in the right mandibular ramus and condyle at an unusual location. A sample of the pathological tissue was taken by intraoral endoscopy to avoid comorbidities and esthetic sequelae. After a joint medical evaluation, the lesion was diagnosed as a monofocal LCH with special site involvement, establishing a single systemic treatment with indomethacin, as opposed to the chemotherapy regimen recommended by the International Histiocyte Society, in order to reduce the adverse effects of the latter. Two months after the beginning of the pharmacological treatment, reosification of the affected area was observed, with no recurrences after the end of the treatment. (AU)

La histiocitosis de células de Langerhans (LCH) es una afección rara originada por proliferación y acumulación descontrolada de células dendríticas mieloides inmaduras derivadas de la médula ósea. Su presentación es común en población pediátrica menor a 15 años, y suele afectar a huesos como el cráneo, fémur y cuerpo mandibular.En esta publicación se presenta el caso de un paciente de género femenino de 6 años, con lesión ósea en rama y cóndilo mandibular derecho de localización poco frecuente. Destaca la toma de muestra del tejido patológico mediante vía endoscópica intraoral con el fin de evitar comorbilidades y secuelas estéticas. Después de una evaluación médica conjunta, se diagnosticó como LCH monofocal con compromiso de sitio especial, estableciendo un tratamiento único de forma sistémica con indometacina, diferente a la quimioterapia recomendada por la Sociedad Internacional de Histiocitosis, de tal forma que disminuya los efectos adversos de esta. Se observó a los 2 meses de iniciado el tratamiento farmacológico reosificación de la zona afectada y sin recidivas posterior al término de este. (AU)

Uso de indometacina y antibioterapia para el manejo de cérvix corto asintomático / Use of indomethacin and antibiotherapy for the management of asymptomatic short cervix

El cérvix corto es un factor de riesgo para el parto pretérmino con etiopatogenia variada y tratamiento aún por dilucidar. Se piensa que la indometacina y la antibioterapia podrían ser útiles en su manejo, lo que ayudaría a disminuir la morbimortalidad asociada al parto pretérmino. Dada la controversia existente se ha realizado una búsqueda bibliografía en las principales bases de datos sobre su uso y beneficio. El uso de indometacina podría evitar los casos de parto pretérmino en edades gestacionales extremas según los últimos estudios, con una tasa de efectos secundarios baja. Mientras tanto, la antibioterapia sería beneficiosa al intervenir en la resolución de la infección o inflamación estéril intraamniótica y del sludge. Sin embargo, el tratamiento de cérvix corto persiste en revisión y discusión, al igual que el uso o no de la amniocentesis para el estudio del líquido amniótico en estos casos. El consenso en cuanto a su manejo está dificultado por la gran variedad de actuaciones que se realizan en la práctica basadas en la experiencia clínica. Esto impide el establecimiento de una serie de pautas concretas de asistencia.(AU)

Short cervix is a risk factor for preterm delivery with varied aetiopathogenesis and its treatment is still to be specified. It is thought that indomethacin and antibiotherapy could be useful in its management, which would help reduce the morbidity and mortality associated with preterm delivery. Given the existing controversy, a literature search about its use and benefit was conducted in the main databases. The use of indomethacin could prevent cases of preterm birth at extreme gestational ages according to recent studies, with a low rate of side effects. Meanwhile antibiotherapy would be beneficial in intervening in the resolution of infection or sterile intraamniotic inflammation and sludge. However, the treatment of short cervix remains under review and discussion, as does the use or otherwise of amniocentesis to study the amniotic fluid in these cases. Consensus on its management is hampered by the great variety of actions that are carried out in practice based on clinical experience. This prevents the establishment of a series of specific care guidelines.(AU)

Paroxysmal Hemicrania-Trigeminal Neuralgia (PH-Tic) syndrome with no structural lesion in a Brazilian woman: the first case-report / Síndrome de Neuralgia Paroxística Hemicrânia-Trigêmea (PH-Tic) sem lesão estrutural em mulher brasileira: primeiro relato de caso

Introduction: In Brazil there is only one case report of a patient diagnosed with Paroxysmal Hemicrania-Trigeminal (PH-Tic) syndrome reported, however it was observed in a patient with Chiari I malformation. Objective: Here, we describe the first case of primary PH-Tic syndrome in the country. Method: Case report. CARE guideline was used to guide the structuring of this article. This case report was approved by the ethics committee and has been registered under the protocol number 70705623.7.0000.5440 on "Plataforma Brasil". Results:A 72-year-old woman with a five-month history of headaches was admitted at our headache outpatient clinic. The pain was sharp, intense, localized in the periorbital and left temporal regions. Blood counts, liver, renal and thyroid function were normal, as well as brain magnetic resonance imaging. Despite using carbamazepine, the patient had pain in only the left side of the face. Indomethacin was added until the dose of 100 mg a day and resulted in improvement of headache frequency. Conclusion: PH-Tic should be hypothesized in patients with short-lasting headaches associated with facial pain that partially improve with carbamazepine or indomethacin.

Introdução: No Brasil há apenas um relato de caso de paciente com diagnóstico de síndrome Paroxística Hemicrania-Trigeminal (PH-Tic), porém foi observado em um paciente com malformação de Chiari I. Objetivo: Descrevemos aqui o primeiro caso de síndrome PH-Tic primária no país. Método: Relato de caso. A diretriz CARE foi utilizada para orientar a estruturação deste artigo. Este relato de caso foi aprovado pelo comitê de ética e registrado sob o número de protocolo 70705623.7.0000.5440 na "Plataforma Brasil". Resultados: Uma mulher de 72 anos com história de cefaleias há cinco meses foi internada em nosso ambulatório de cefaleias. A dor era aguda, intensa, localizada nas regiões periorbital e temporal esquerda. Os hemogramas, as funções hepática, renal e tireoidiana estavam normais, assim como a ressonância magnética cerebral. Apesar do uso de carbamazepina, o paciente apresentava dor apenas no lado esquerdo da face. A indometacina foi adicionada até a dose de 100 mg ao dia e resultou em melhora da frequência da cefaleia. Conclusão: O PH-Tic deve ser hipotetizado em pacientes com cefaleias de curta duração associadas a dores faciais que melhoram parcialmente com carbamazepina ou indometacina.

Cisteína oral N-Acetyl versus indometacina retal para prevenção de pancreatite pós-CPRE: um ensaio controlado randomizado multinacional multicêntrico / Oral n-acetyl cysteine versus rectal indomethacin for prevention of post ercp pancreatitis: a multicenter multinational randomized controlled trial

ABSTRACT Background This multicenter multinational RCT designed to compare the efficacy of suppository indomethacin and NAC for prevention of PEP. Methods: During a 6-month period, all of the ERCP cases in seven referral centers were randomly assigned to receive either 1200 mg oral NAC, indomethacin suppository 100 mg, 1200 mg oral NAC plus indomethacin suppository 100 mg or placebo 2 hours before ERCP. The primary outcomes were the rate and severity of any PEP. Results: A total of 432 patients included (41.4% male). They were originally citizens of 6 countries (60.87% Caucasian). They were randomly allocated to receive either NAC (group A, 84 cases), rectal indomethacin (group B, 138 cases), NAC + rectal indomethacin (group C, 115 cases) or placebo (group D, 95 cases). The rate of PEP in groups A, B and C in comparison with placebo were 10.7%, 17.4%, 7.8% vs 20% (P=0.08, 0.614 & 0.01 respectively). The NNT for NAC, indomethacin and NAC + indomethacin was 11, 38 and 8 respectively. Conclusion: Oral NAC is more effective than rectal indomethacin when compared to placebo for prevention of PEP and the combination of NAC and Indomethacin had the lowest incidence of PEP and may have synergistic effect in preventing of PEP (IRCT20201222049798N1; 29/12/2020).

RESUMO Contexto: Este estudo randomizado, controlado multicêntrico e multinacional foi projetado para comparar a eficácia da indometacina supositório e N-acetil cisteína (NAC) para prevenção de pancreatite pós colangiografia endoscópica. Métodos: Durante um período de 6 meses, todos os pacientes submetidos à CPRE em sete centros de referência foram aleatoriamente atribuídos para receber 1200 mg de NAC oral, supositório de indometacina 100 mg, 1200 mg de NAC oral mais supositório de indometacina 100 mg ou placebo 2 horas antes do procedimento. Os resultados primários foram a taxa e a gravidade de qualquer pancreatite pós procedimento (PPP). Resultados: Um total de 432 pacientes foram incluídos (41,4% do sexo masculino). Eram originalmente cidadãos de seis países (60,87% caucasianos). Foram alocados aleatoriamente para receber NAC (grupo A, 84 casos), indometacina retal (grupo B, 138 casos), NAC + indometacina retal (grupo C, 115 casos) ou placebo (grupo D, 95 casos). A taxa de PPP nos grupos A, B e C em comparação com o placebo foi de 10,7%, 17,4%, 7,8% vs 20% (P=0,08, 0,614 e 0,01, respectivamente). Conclusão A NAC oral é mais eficaz do que a indometacina retal quando comparado ao placebo para prevenção de PPP e a combinação de NAC e indometacina teve a menor incidência de PPP e pode ter efeito sinérgico na sua prevenção de PPP. (IRCT20201222049798N1; 29/12/2020).

Caracterización fisicoquímica y evaluación in vitro de sistemas autoemulsionables de liberación de indometacina

Objetivo: incorporar la indometacina en sistemas autoemulsionables de liberación con la finalidad de aumentar su solubilidad en medio acuoso, la velocidad de disolución y permeación in vitro. Metodología: se llevaron a cabo ensayos de solubilidad al equilibrio para preparar formulaciones con los excipientes, en los cuales la indome-tacina presentó mayor incremento de solubilidad; los sistemas fueron caracterizados por medio del tiempo de autoemulsificación, estabilidad física, tamaño de partícula, potencial zeta, perfiles de disolución y permeación a través de membrana sintética. Resultados: el diseño experimental de los sistemas autoemulsionables de liberación permitió crear formulaciones que aumentaron la solubilidad de la indometacina en un orden de 105 veces con respecto a la solubilidad acuosa. Las formulaciones que resultaron viables presentaron tiempos de autoemulsificación menores que 60 segundos, además, las distribuciones de tamaño de partícula de las dispersiones fueron inferiores a los 300 nm, presentó índices de polidispersión inferiores a 0,3 y valores de potencial zeta menores de -25 mV. Los perfiles de disolución mostraron que las formulaciones cumplen con un valor de factor de similitud mayor que 50, además, la permeabilidad a través de membrana sintética es mayor para las formulaciones autoemulsionables que el producto de referencia. Conclusiones: la formulación de indometacina en sistemas autoemulsionables de liberación incrementa la solubilidad en medio acuoso, aumenta la disolución y liberación. Estos resultados sugieren que la administración oral de indometacina incorporada en sistemas autoe-mulsionables puede acelerar el inicio del efecto farmacológico.

SUMMARY Aim: To load indomethacin into self-emulsifying delivery systems in order to increase, water-solubility, rate dissolution and in vitro permeation. Methodology: Equilibrium solubility tests were carried out to prepare formulations with the excipients, in which indomethacin presented a greater increase in solubility; the systems were characterized by self-emulsification time, physical stability, particle size, zeta potential, dissolution profiles and permeation through synthetic membrane. Results: The experimental design of self-emulsifying delivery systems allowed to create formulations that increase the solubility of indomethacin in an order of 105 times with respect to the aqueous solubility. The feasible formulations presented autoemulsification times less than 60 seconds, in addition, the particle size distributions of the dispersions were less than 300 nm, with polydispersity index smaller than 0.3, and zeta potential values lower than -25 mV. The dissolution profiles showed that the formulations comply with a similarity factor value greater than 50, in addition, the permeability through a synthetic membrane is higher for the self-emulsifying formulations than the reference product. Conclusion: The formulation of indomethacin into self-emulsifying delivery systems enhances the solubility in aqueous medium, increases dissolution and accelerate release. These results suggest that the oral administration of indomethacin incorporated into self-emulsifying delivery systems can accelerate the onset of the pharmacological effect.

Objetivo: incorporar a indometacina em sistemas de liberação autoemulsificantes a fim de aumentar sua solubilidade em meio aquoso, a taxa de dissolução e permeação in vitro. Metodologia: foram realizados testes de solubilidade de equilíbrio para preparar formulações com os excipientes, nas quais a indometacina apresentou maior aumento na solubilidade; os sistemas foram caracterizados quanto ao tempo de autoemulsificação, estabilidade física, tamanho de partícula, potencial zeta, perfis de dissolução e permeação através de membrana sintética. Resultados: o desenho experimental dos sistemas de liberação autoemulsificantes permitiu a criação de formulações que aumentaram a solubilidade da indometacina na ordem de 105 vezes em relação à solubilidade aquosa. As formulações que se mostraram viáveis apresentaram tempos de autoemulsificação inferiores a 60 segundos, além disso, as distribuições granulométricas das dispersões foram inferiores a 300 nm, apresentaram índices de polidispersidade inferiores a 0,3 e valores de potencial zeta inferiores a -25 mV. Os perfis de dissolução mostraram que as formulações atendem a um valor de fator de similaridade maior que 50, além disso, a permeabilidade através da membrana sintética é maior para as formulações autoemulsionantes do que para o produto de referência. Conclusões: a formulação de indometacina em sistemas de liberação autoemulsificantes aumenta a solubilidade em meio aquoso, aumenta a dissolução e a liberação. Esses resultados sugerem que a administração oral de indometacina incorporada em sistemas autoemulsificantes pode acelerar o início do efeito farmacológico.

Efectividad de la indometacina vs analgésico habitual en el tratamiento del dolor posthisterectomía / Effectiveness of using indomethacin vs usual analgesic in the management of postoperative pain in hysterectomy

Resumen: OBJETIVO: Determinar la efectividad de la indometacina, por vía rectal, en el tratamiento del dolor posthisterectomía versus paracetamol o metamizol administrados por vía intravenosa. MATERIALES Y MÉTODOS: Estudio experimental, comparativo y prospectivo llevado a cabo en el Hospital Central del Estado de Chihuahua entre noviembre y diciembre de 2019. Criterios de inclusión: pacientes histerectomizadas, con expediente clínico completo y de cualquier edad. Criterios de exclusión: pacientes con alteraciones en el umbral del dolor, inconsistencias en el expediente, histerectomía total no ginecológica. Criterios de eliminación: pacientes con limitantes en la información que no permitieron relacionar la variable dependiente con la independiente. El seguimiento del dolor referido se efectuó con la escala análoga del dolor y valoraciones a las 12 y 24 horas posteriores a la cirugía. RESULTADOS: Se reunieron 141 pacientes, que se dividieron en tres grupos. Grupo 1: metamizol intravenoso e indometacina por vía rectal (n = 24). Grupo 2: paracetamol intravenoso e indometacina por vía rectal (n = 19). Grupo 3: paracetamol y metamizol intravenosos (n = 98). La mayoría de las pacientes de los grupos 1 y 2 reportaron, a las 24 h, una escala visual análoga menor de 3 vs las del grupo 3. Diez de 98 pacientes requirieron tratamiento en el servicio de Anestesiología. CONCLUSIÓN: La administración de indometacina por vía rectal a pacientes histerectomizadas demostró menor dolor que con metamizol y paracetamol, y evolución clínica y alta hospitalaria más temprana.

Abstract: OBJECTIVE: To determine the effectiveness of indomethacin in the treatment of post-hysterectomy pain versus paracetamol or metamizole administered intravenously. MATERIALS AND METHODS: Experimental, comparative and prospective study at the Central Hospital of the State of Chihuahua, period November to December 2019, patients undergoing hysterectomy with complete clinical record, any age. Patients with alterations in the pain threshold, inconsistencies in the file, total non-gynecological hysterectomy were excluded, patients with information limitations were eliminated, which did not allow to relate the dependent variable, with the independent one. RESULTS: 141 patients were collected, which were divided into three groups. Group 1: intravenous metamizole and indomethacin rectally (n = 24). Group 2: intravenous paracetamol and indomethacin rectally (n = 19). Group 3: intravenous paracetamol and metamizole (n = 98). Most of the patients in groups 1 and 2 reported, at 24 hours, a visual analog scale of less than 3 vs those of group 3. Ten of 98 patients required treatment in the Anesthesiology service. CONCLUSION: The administration of indomethacin rectally in postoperative patients of hysterectomy has been shown to reduce pain more effectively than conventional analgesics such as metamizole and paracetamol, relating to clinical evolution and early hospital discharge.

Tratamiento farmacológico del conducto arterioso permeable en recién nacidos prematuros / Pharmacological treatment of patent ductus arteriosus in premature infants

Resumen Introducción. Por lo general, el manejo farmacológico del conducto arterioso permeable (CAP) comprende inhibidores no selectivos de la enzima ciclooxigenasa, en especial indometacina e ibuprofeno. En años recientes también se ha sugerido al acetaminofén como alternativa terapéutica. Objetivo. Realizar una revisión narrativa de la literatura acerca del manejo farmacológico del CAP. Materiales y métodos. Se realizó una búsqueda estructurada de la literatura en las bases de datos ProQuest, EBSCO, ScienceDirect, PubMed, LILACS, Embase, Trip Database, SciELO y Cochrane Library con los términos "Ductus Arteriosus, patentAND therapeutics"; "Ductus Arteriosus, patent AND indometacin"; "Ductus Arteriosus, PatentAND ibuprofen", y "Ductus Arteriosus, patent AND acetaminophen". La búsqueda se hizo en inglés con sus equivalentes en español. Resultados. Se encontraron 69 artículos con información relevante para llevar a cabo la presente revisión. Conclusiones. En neonatos prematuros, la base del tratamiento farmacológico del CAP continúa siendo los inhibidores no selectivos de la ciclooxigenasa, indometacina e ibuprofeno, ambos con perfiles similares de seguridad y eficacia. La evidencia disponible sugiere que el acetaminofén podría constituir una alternativa útil para el manejo, pero resulta insuficiente para realizar recomendaciones definitivas respecto a la eficacia y seguridad de este medicamento.

Abstract Introduction: Pharmacological management ofpatent ductus arteriosus (PDA) usually includes non-selective inhibitors of the enzyme cyclooxygenase, especially indomethacin and ibuprofen. Recently, acetaminophen has also been suggested as a therapeutic alternative. Objective: To conduct a narrative review of the literature on pharmacological management of PDA. Materials and methods: Structured literature search conducted on the ProQuest, EBSCO, ScienceDirect, PubMed, LILACS, Embase, Trip Database, SciELO and Cochrane Library databases, with the terms "Ductus Arteriosus, patentAND therapeutics"; "Ductus Arteriosus, patent AND indometacin"; "Ductus Arteriosus, Patent AND ibuprofen", and "Ductus Arteriosus, patent AND acetaminophen", and their equivalents in Spanish. Results: 69 articles had relevant information to carry out the present review. Conclusions: In premature infants, the mainstay of pharmacological treatment for PDA continues to be non-selective cyclooxygenase inhibitors, indomethacin and ibuprofen, all with similar safety and efficacy profiles. The available evidence suggests that acetaminophen may be a useful alternative for management, but it is insufficient to make definitive recommendations regarding the efficacy and safety of this drug.

Atosiban efficacy and safety in pregnant women with threatened preterm delivery: systematic review of the literature with network meta-analysis / Eficacia y seguridad de atosiban en mujeres gestantes con diagnóstico de amenaza de parto pretérmino: revisión sistemática de la literatura con metaanálisis en red

ABSTRACT Objective: To assess the efficacy and safety of atosiban in pregnant women with risk of preterm delivery as compared to nifedipine, indomethacin, terbutaline, fenoterol and placebo. Materials and methods: A systematic literature review was carried out in eight electronic databases, including Medline, Central, and Embase, using free and standardized search terms. Outcomes assessment included time delay until delivery, neonatal mortality, ratio of adverse maternal events, and ratio of neonatal complications. The quality of the evidence was evaluated per study and for the body of evidence and, whenever feasible, the information was synthesized into a meta-analysis. Alternatively, a narrative summary was presented. Results: Eleven studies were included. Atosiban did not show any statistically significant differences in terms of delaying delivery versus other uterine contraction inhibitors. The neonatal mortality was lower compared to indomethacin (RR = 0.21; 95% CI: 0.05 to 0.92), and the percentage of total maternal adverse events was lower compared to fenoterol (RR = 0.16; 95% CI: 0.08 to 0.31), nifedipine (RR = 0.48; 95% CI: 0.3 to 0.78), and terbutaline (RR = 0.44; 95% CI: 0.28 to 0.71). Conclusions: Atosiban has similar efficacy for delivery delay in patients with risk of preterm delivery as compared to other agents (moderate certainty), showing some advantages regarding neonatal mortality (low certainty) versus indomethacin, and compared to fenoterol, nifedipine and terbutaline in terms of maternal adverse events (moderate certainty).

RESUMEN Objetivo: evaluar la eficacia y seguridad de atosiban en gestantes con amenaza de parto pretérmino comparado con nifedipino, indometacina, terbutalina, fenoterol y placebo. Materiales y métodos: se realizó una revisión sistemática de la literatura en ocho bases de datos electrónicas (Medline, Central, Embase, entre otras), mediante términos de búsqueda libres y estandarizados. Los desenlaces evaluados incluyeron tiempo de retardo del parto, mortalidad neonatal, proporción de eventos adversos maternos y proporción de complicaciones neonatales. Se evaluó la calidad de la evidencia por estudio y para el cuerpo de evidencia, y se sintetizó la información mediante metaanálisis, cuando fue posible; de lo contrario, se resumió de forma narrativa. Resultados: se incluyeron once estudios. Atosiban no mostró diferencias estadísticamente significativas en retardo del parto contra otros uteroinhibidores. Mostró menor mortalidad neonatal que la indometacina (RR = 0,21; IC 95 %: 0,05 a 0,92), y menor proporción de eventos adversos maternos totales que el fenoterol (RR = 0,16; IC 95 %: 0,08 a 0,31), el nifedipino (RR = 0,48; IC 95 %: 0,3 a 0,78) y la terbutalina (RR = 0,44; IC 95 %: 0,28 a 0,71). Conclusiones: atosiban tiene una eficacia similar para retardar el parto ante la amenaza de un parto pretérmino con otros comparadores (certeza moderada), con ventajas frente a indometacina en mortalidad neonatal (certeza baja) y frente a fenoterol, nifedipino y terbutalina en eventos adversos maternos (certeza moderada).

Acetylcholine produces contractions mediated by the cyclooxygenase pathway in arterial vessels in the Chilean frog (Calyptocephalella gayi) / Acetilcolina produz contrações mediadas pela via da ciclooxigenase em vasos arteriais da rã chileno (Calyptocephalella gayi)

Abstract Previous studies performed in marine fish (I. conceptionis and G. laevifrons) showed that indomethacin blocked arterial contraction mediated by acetylcholine (ACh). The objective of this study was to determine if contraction induced by acetylcholine is mediated by the cyclooxygenase pathway in several arterial vessels in the Chilean frog Calyptocephalella gayi. Arteries from the pulmonary (PA), dorsal (DA), mesenteric (MA) and iliac (IA) regions were dissected from 6 adult specimens, and isometric tension studies were done using dose response curves (DRC) for ACh (10-13 to 10-3 M) in presence of a muscarinic antagonist (Atropine 10-5 M) and an unspecific inhibitor of cyclooxygenases (Indomethacin, 10-5M). All the studied arteries exhibited vasoconstriction mediated by ACh. This vasoconstriction was abolished in the presence of atropine in DA, MA and IA and attenuated in PA. Indomethacin abolished the vasoconstriction in MA and attenuated the response in PA, DA and IA. Similar to marine fish, C. gayi have an ACh-mediated vasoconstrictor pattern regulated by muscarinic receptors that activate a cyclooxygenase contraction pathway. These results suggest that the maintenance in vasoconstrictor mechanisms mediated by ACh→COX →vasoconstriction is conserved from fish to frogs.

Resumo Estudos feitos em peixes marinhos (I. conceptionis e G. laevifrons) têm demostrado que a indometacina bloqueia a contração arterial mediada por acetilcolina (ACh). O objetivo do presente estudo foi avaliar o efeito da via da ciclooxigenase na contração induzida por ACh em vasos arteriais da rã chilena Calyptocephalella gayi. Foram dissecadas regiões das artérias pulmonares (PA), dorsal (DA), mesentérica (MA) e ilíaca (IA) de seis espécimes adultos e realizados estudos de tensão isométrica utilizando curvas dose-resposta (CDR) de ACh (10-13 a 10-3 M) na presença de um antagonista muscarínico (atropina, 10-5 M) e um inibidor das ciclooxigenases (indometacina, 10-5 M). Todas as artérias evidenciaram uma resposta vasoconstritora mediada por ACh. Esta resposta vasoconstrictora foi suprimida na presença de atropina nas artérias DA, MA, IA e atenuada na PA. A indometacina suprimiu a vasoconstrição na artéria MA e atenuou a resposta nas artérias PA, DA e IA. Tal como os peixes marinhos, a C. gayi tem um padrão de vasoconstrição mediado por Ach que é regulado pelos receptores muscarínicos e pela ciclooxigenase. Estes resultados sugerem a conservação dos mecanismos vasoconstrictores mediados por ACh→COX em peixes e rãs.

Screening of wild fruit trees with gastroprotective activity in different experimental models / Triagem de plantas frutíferas silvestres com ação gastroprotetora em modelos in vivo

ABSTRACT BACKGROUND Given the increase of people with gastrointestinal disorders, the search for alternative treatments with fewer side effects is vital, as well as the demand for food or plants that can help protect the stomach. OBJECTIVE The aim of this study was to evaluate the gastroprotective action of the extracts of wild fruit trees of Myrcianthes pungens (guabiju); Inga vera Willd. (ingá-banana) and Marlierea tomentosa Cambess. (guarapuruna) in in vivo pharmacological models. METHODS The different parts of the fruits were separately subjected to a process of extraction by methanol. Two experimental pharmacological models were conducted in mice; the gastric ulcer model induced by non-steroidal anti-inflammatory (indomethacin), and the gastric ulcer model induced by ethanol/HCl, which allowed us to evaluate the gastroprotective activity of the extracts at a dose of 250 mg/kg. Subsequently, the total lesion area (mm2) and relative lesion area (%) were determined. RESULTS The results showed significant gastroprotective activity against the aggressive agents used - ethanol and indomethacin - for all the extracts tested. CONCLUSION It is assumed that the fruits have bioactive compounds such as antioxidant substances that act on the prostaglandin levels, protecting them from the damage caused by ethanol and indomethacin. These results prompt further studies to isolate and identify the active properties.

RESUMO CONTEXTO Devido ao aumento de pessoas com distúrbios gastrointestinais, a busca de tratamentos alternativos com menos efeitos cola­terais é fundamental, assim como a demanda por alimentos ou plantas que possam ajudar a proteger o estômago. OBJETIVO O presente estudo teve como objetivo avaliar a ação gastroprotetora dos extratos plantas frutíferas silvestres Myrcianthes pungens (guabiju); Inga vera Willd. (ingá-banana) e Marlierea tomentosa Cambess. (guarapuruna) em modelos farmacológicos in vivo. MÉTODOS As diferentes partes do fruto foram submetidas se­paradamente a um processo de maceração em solução metanólica a frio. Foram realizados dois modelos experimentais em camundongos, modelo de úlcera gástrica induzida por anti-inflamatório não-esteroidal (indometacina) e modelo de úlcera gástrica induzida por etanol/HCl, que permitiram avaliar a atividade gastroprotetora dos extratos na dose de 250 mg/kg. Posteriormente, foram determinadas a área total de lesão (mm2) e a área relativa lesada (%). RESULTADOS Os resultados apresentaram atividade gastroprotetora significativa para todos os extratos estudados frente aos agentes agressores utilizados, etanol e indometacina. CONCLUSÃO Supõe-se que os frutos apresentam compostos bioativos, como as substancias antioxidantes, que atuam sobre os níveis de prostaglandinas, protegendo dos danos causados pelo etanol e indometacina. Os resultados encorajam futuros estudos para isolamento e identificação dos princípios ativos dos frutos.

Complicaciones digestivas y renales por indometacina e ibuprofeno en prematuros extremos con ductus arterioso permeable / Digestive and Kidney Complications by indomethacin and ibuprofen in extreme preterm infants with patent ductus arteriosus

El ductus arterioso permeable sintomático (DAPs) es frecuente en prematuros extremos (PE), siendo importante su cierre para disminuir la repercusión hemodinámica. Para ello se usa indometacina o ibuprofeno con los riesgos subyacentes. OBJETIVO: Caracterizar las complicaciones digestivas y renales en PE tratados por DAPs. PACIENTES Y MÉTODO: Estudio retrospectivo en PE nacidos entre enero de 2004 y diciembre de 2013. Según diagnóstico se distribuyeron en 3 grupos: sin DAPs, con DAPs tratados con indometacina y con ibuprofeno. Se excluyeron PE con otras complicaciones graves. Se evaluaron complicaciones digestivas y renales graves. Se usó significación estadistica con p ≤ 0,05. RESULTADOS: Se enrolaron 599 PE; 33,1% recibió tratamiento por DAPs, 66,9% no lo requirió. Hubo asociación estadística entre DAPs y menor edad gestacional, depresión neonatal y distrés respiratorio. Del grupo no tratado, el 5% presentó enterocolitis y el 0,25% falla renal; entre los tratados el 2,5% presentó enterocolitis y el 1,0% falla renal. No hubo diferencias estadísticas significativas considerando ambas complicaciones (p = 0,17), sólo enterocolitis (p = 0,11) o sólo falla renal (p = 0,33) entre tratados y no tratados; tampoco las hubo al comparar complicaciones entre tratados con indometacina o ibuprofeno. CONCLUSIONES: Los resultados en nuestra población demuestran que el tratamiento médico del DAPs, en ausencia de otras complicaciones clínicas, no representa un mayor riesgo de complicaciones graves digestivas o renales. No se demostraron ventajas entre la indometacina e ibuprofeno.

The symptomatic patent ductus arteriosus (sPDA) is common in extremely premature infants (EPI). In order to decrease the hemodynamic repercussion and avoid complications it is necessary to close it. Indomethacin or ibuprofen are used for this purpose with its associated risks. OBJECTIVE: Characterize digestive and renal complications in EPI who received indomethacin or ibuprofen as sPDA treatment. PATIENTS AND METHOD: Retrospective study on EPI between January-2004 and December-2013. Three groups were compared: treated with indomethacin or ibuprofen and a non-treated group. EPI with other serious complications were excluded. The primary outcomes on each group were digestive and/or renal complications. Statistical significance was p < 0.05. RESULTS: 599 EPI were included, 33.1% with PDA received treatment and 66.9% did not need it. A statistical association was found between sPDA and lower gestational ages, neonatal depression and respiratory distress. In the non-treated group, 5% presented enterocolitis and 0.25% renal failure; on the treated group, 2.5% presented enterocolitis and 1.0% renal failure. No significant differences were found between the treated and non-treated groups in relation to complications considering enterocolitis (p = 0.11) or renal failure (p = 0.33) alone, or combined (p = 0.17). No difference were detected either between those treated with indomethacin or ibuprofen. CONCLUSIONS: The results show that in absence of other clinical complication, medical treatment of sPDA with indomethacin or ibuprofen, do not increase the risk of serious digestive or renal disorders. There were no advantages of using indomethacin or ibuprofen over the other.

Ibuprofen and indomethacin for the closure of the patent ductus arteriosus / Ibuprofen, indometacina e fechamento do canal arterial

The ductus arteriosus connects the pulmonary artery with the aorta and allows right ventricular blood to bypass the unexpanded lungs. In mature infants, the ductus arteriosus closes after birth. Patent ductus arteriosus occurs in 70% of preterm infants with a birth weight < 1,000 grams. Failure of the ductus arteriosus to close has been associated with intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leukomalacia, renal failure, and persistent pulmonary hypertension. The drugs used to treat the patent ductus arteriosus are ibuprofen and indomethacin which are potent non-selective inhibitors of cyclo-oxygenase (COX) and therefore inhibit prostaglandin E2 synthesis. Prostaglandin E2 relaxes smooth muscle and tends to inhibit the closure of the patent ductus arteriosus. Intravenous ibuprofen and indomethacin inhibit prostaglandin E2 synthesis and thereby close the patent ductus arteriosus with similar efficacy. Indomethacin reduces the blood flow velocity in kidneys, intestine and brain. Ibuprofen has less effect on blood flow velocity in these organs. There is a significant increase in serum creatinine after indomethacin administration but not after ibuprofen and infants treated with ibuprofen have higher creatinine clearance. Oliguria (urine output < 1 ml/kg/h) occurs more frequently with indomethacin than with ibuprofen. Indomethacin requires furosemide for urine output more often than ibuprofen. Ibuprofen reduces the risk of necrotizing enterocolitis and transient renal insufficiency and it is the drug of choice for closing the patent ductus arteriosus. Ibuprofen and indomethacin may be administered orally. In conclusion, intravenous ibuprofen and indomethacin close the patent ductus arteriosus at the same rate, but indomethacin is more toxic than ibuprofen.

O canal arterial conecta a artéria pulmonar com a aorta e permite que o sangue oriundo do ventrículo direito evite passar pelos pulmões fetais não expandidos. Em recém-nascidos maduros, o canal arterial se fecha após o nascimento. A persistência do canal arterial ocorre em 70% dos recém-nascidos prematuros com peso de nascimento < 1.000 gramas. O não fechamento do canal arterial associa-se a hemorragia intraventricular, enterocolite necrosante, displasia bronco-pulmonar, leucomalacia periventricular, insuficiência renal e hipertensão pulmonar persistente. Os medicamentos utilizados para tratar a persistência do canal arterial são o ibuprofeno e a indometacina. Ambos são potentes inibidores não seletivos da ciclo-oxigenase e inibem a síntese de prostaglandina E2. Esta relaxa a musculature vascular lisa e tende a inibir o fechamento do canal arterial. O ibuprofeno e a indometacina inibem a síntese de prostaglandina E2 e favorecem o fechamento do canal arterial. A indometacina reduz a velocidade do fluxo sanguíneo renal, intestinal e cerebral. O Ibuprofeno tem efeito menor sobre a velocidade do fluxo de sangue nesses órgãos. Há um aumento significativo da creatinina sérica após a administração de indometacina, mas não após o ibuprofeno; por isso, recém-nascidos tratados com ibuprofeno têm maior depuração da creatinina. A oligúria ocorre mais frequentemente com a indometacina vs. ibuprofeno. A indometacina requer furosemida para a produção de urina mais frequentemente do que o ibuprofeno. O ibuprofeno reduz o risco de enterocolite necrotizante e de insuficiência renal transitória e é a droga de escolha para o fechamento do canal arterial patente. O ibuprofeno e a indometacina podem ser ministrados por via oral. Em conclusão, o ibuprofeno e a indometacina fecham o canal arterial patente com a mesma velocidade, mas a indometacina é mais tóxica.

Efecto antiulceroso del extracto hidroalcohólico de Plantago lanceolata (llantén menor) sobre la úlcera gástrica inducida en ratas / Anti-ulcer effect of hydroalcoholic extract of Plantago lanceolata (plantain minor) on gastric ulcer induced in rats

Objetivo: Determinar el efecto antiulceroso del extracto hidroalcohólico de Plantago lanceolata L. (llantén menor) en animales de experimentación. Metodología: Es un estudio de tipo experimental, en donde se indujo las úlceras gástricas con indometacina a dosis única de 80 mg/kg vía subcutanea. Se realizó el análisis fitoquímico cualitativo para la determinación de metabolitos secundarios. Para la determinación del efecto antiulceroso se formaron 06 grupos: grupo control solución salina fisiológica a 4 mL/kg, grupo indometacina (I), y cuatro grupos experimentales indometacina más extracto a 200 y 400 mg/kg, omeprazol a 20 mg/kg y ranitidina a 100 mg/kg respectivamente. Se administraron los extractos y medicamentos estándar a las 24, 12 y una hora antes de la inducción de la úlcera gástrica. Se realizó el examen macroscópico y microscópico de las mucosas gástricas de todas las ratas determinándose el porcentaje de inhibición antiulceroso. Resultados: El extracto hidroalcohólico a la dosis de 200 y 400 mg/kg presentó efecto antiulceroso en los indicadores evaluados de hiperemia, edema, úlcera y hemorragias siendo estadísticamente significativos y un porcentaje de inhibición de 83,1 % y 98,9 % respectivamente en comparación al omeprazol (67,4 %) y Ranitidina (44,9 %). A nivel microscópico no se evidenciaron alteraciones histológicas significativas. Conclusiones: El extracto hidroalcohólico de Plantago lanceolata L. (llantén menor) presenta flavonoides, compuestos fenólicos, alcaloides, triterpenos y/o esteroides y presentó efecto antiulceroso a las dosis evaluadas en el modelo empleado sin signos de toxicidad aguda.

Acetylcholine produces contraction mediated by cyclooxigenase pathway in arterial vessels in the marine fish (Isacia conceptionis) / Função vascular nas artérias do peixe marinos Isacia conceptionis

Preliminary studies showed that dorsal artery contraction mediated by acetylcholine (ACh) is blocked with indomethacin in intertidal fish (G. laevifrons). Our objective was to characterize the cholinergic pathway in several artery vessels of the I. conceptionis. Afferent and efferent branchial, dorsal and mesenteric arteries were dissected of 6 juvenile specimens, isometric tension studies were done using doses response curves (DRC) for Ach (10–13 to 10–3 M), and cholinergic pathways were obtained by blocking with atropine or indomethacin. CRC to ACh showed a pattern of high sensitivity only in efferente branchial artery and low sensibility in all vessels. Furthermore, these contractions were blocked in the presence of atropine and indomethacin in all vessels. Our results corroborate previous results observed in intertidal species that contraction induced by acetylcholine is mediated by receptors that activate a cyclooxygenase contraction pathway.

Estudos preliminares mostraram que a contração da artéria dorsal mediada por acetilcolina (ACh) é bloqueada com indometacina em peixes marinhos (G. laevifrons). Nosso objetivo foi caracterizar a via colinérgica em várias artérias de I. conceptionis. Artérias aferentes e eferentes branquiais, dorsais e mesentéricas foram dissecadas de 6 espécimes juvenis. Os estudos de tensão isométrica foram feitos utilizando-se a curva dose - resposta (CDR) para Ach (10–13 a 10–3M), e identificaram-se as vias colinérgicas, bloqueando com atropina e indometacina. CRC para ACh mostrou um padrão de alta sensibilidade na artéria eferentes branquiais e baixa sensibilidade em todos os vasos sanguineos. Essas contrações foram bloqueadas na presença de atropina e indometacina em todas as artérias avaliadas. Nossos resultados confirmam que a contração induzida por acetilcolina é mediada por receptores muscarínicos que ativam ciclo-oxigenase.

Comparação de ibuprofeno via oral e indometacina intravenosa no tratamento da persistência do canal arterial em neonatos com extremo baixo peso ao nascer / Comparison of oral ibuprofen and intravenous indomethacin for the treatment of patent ductus arteriosus in extremely low birth weight infants

OBJETIVO: Existem poucos relatórios publicados com relação à eficácia do ibuprofeno via oral no tratamento da persistência do canal arterial (PCA) em neonatos com extremo baixo peso ao nascer (EBPN). Comparamos o ibuprofeno via oral à indometacina intravenosa no que diz respeito à eficácia e segurança no tratamento de PCA em neonatos com peso inferior a 1.000 g ao nascer. MÉTODO: Este foi um estudo retrospectivo em um único centro. Coletamos dados de neonatos com EBPN que tiveram PCA ecocardiograficamente confirmada. Os neonatos foram tratados tanto com indometacina intravenosa quanto com ibuprofeno via oral. A taxa de fechamento do canal, a necessidade de tratamentos adicionais, os efeitos colaterais ou as complicações relacionadas ao medicamento e a mortalidade foram comparados entre os dois grupos de tratamento. RESULTADO: Examinamos 26 neonatos que receberam indometacina e 22 que receberam ibuprofeno. A taxa geral de fechamento do canal foi semelhante nos dois tratamentos: o fechamento do canal ocorreu em 23 dos 26 neonatos (88,5%) no grupo indometacina, e em 18 dos 22 neonatos (81,8%) no grupo ibuprofeno (p = 0,40). A taxa de ligadura cirúrgica (11,5% em comparação a 18,2%; p = 0,40) não diferiu de forma significativa entre os dois grupos de tratamento. Após o tratamento, não foi encontrada nenhuma diferença significativa nas concentrações de creatinina sérica entre os dois grupos. Não houve diferenças significativas com relação a efeitos colaterais ou complicações adicionais. CONCLUSÃO: Em neonatos com EBPN, o ibuprofeno via oral é tão eficaz quanto a indometacina intravenosa no tratamento da PCA. Não há diferenças entre os medicamentos no que diz respeito à segurança. O ibuprofeno via oral poderia ser usado como um agente alternativo no tratamento da PCA em neonatos com EBPN.

OBJECTIVE: There are few published reports concerning the efficacy of oral ibuprofen for the treatment of patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Oral ibuprofen was compared to intravenous indomethacin regarding efficacy and safety in the treatment of PDA in infants weighting less than 1,000 g at birth. METHOD: This was a retrospective study in a single center. Data on ELBW infants who had an echocardiographically confirmed PDA were collected. The infants were treated with either intravenous indomethacin or oral ibuprofen. Rate of ductal closure, need for additional treatment, drug-related side effects or complications, and mortality were compared between the two treatment groups. RESULT: 26 infants who received indomethacin and 22 infants who received ibuprofen were studied. The overall rate of ductal closure was similar between the two treatments: it occurred in 23 of 26 infants (88.5%) treated with indomethacin, and in 18 of 22 infants (81.8%) treated with ibuprofen (p = 0.40). The rate of surgical ligation (11.5% versus 18.2%; p = 0.40) did not differ significantly between the two treatment groups. No significant difference was found in post-treatment serum creatinine concentrations between the two groups. There were no significant differences regarding additional side effects or complications. CONCLUSION: In ELBW infants, oral ibuprofen is as efficacious as intravenous indomethacin for the treatment of PDA. There were no differences between the two drugs with respect to safety. Oral ibuprofen could be used as an alternative agent for the treatment of PDA in ELBW infants.

Avaliação da atividade protetora gástrica do extrato hidroalcoólico da semente de girassol em ratas / Evaluation of the gastroprotective activity of hydroalcoholic extract of sunflower seed in rats

JUSTIFICATIVA E OBJETIVOS: Avaliar a proteção gástrica do extrato hidroalcoólico da semente de girassol (EHSG) em relaçãoao estresse, ao uso de indometacina e etanol. MÉTODO: Foi realizado um estudo experimental envolvendo 90 ratas (Rattus norvegicus albinus), da linhagem Wistar, fêmeas, com peso corporal médio de 150-230 g, divididos em 18 grupos distintos os quais receberam os seguintes tratamentos: EHSG:250 mg/kg, 500 mg/kg, 1000 mg/kg e 2000 mg/kg; etanol 0,5mL; cimetidina 60 mg/kg; indometacina 20 mg/kg; água 1 mL. Os dados foram analisados utilizando o programa Grand PadPrism 5 com aplicação de testes estatísticos considerando o nível de significância de 5%. RESULTADOS: O EHSG apresenta proteção contra as lesões gástricas em ratas, nas doses de 250 e 1000 mg, tanto no modelo pelo estresse, quanto na indução por etanol e indometacina. CONCLUSÃO: Os dados obtidos no presente estudo mostram que o EHSG apresenta proteção gástrica em determinadas doses.

BACKGROUND AND OBJECTIVES: To evaluate the gastric protection hidroalcoólico extract the sunflower seed (EHSG) in relation to stress, the use of indomethacin and ethanol. METHOD: We conducted an experimental study involving 90 rats (Rattus norvegicus albinos), Wistar, females, mean body weight of 150-230 g were divided into 18 distinct groups which received the following treatments: EHSG: 250mg/kg , 500 mg/kg, 1000 mg/kg and 2000 mg/kg; 0.5 mL ethanol, cimetidine 60 mg/kg, 20 mg/kg indomethacin; 1 mL water. Data were analyzed using the GrandPad Prism 5 with application of statistical tests, the significance level of 5%. RESULTS: The EHSG has protective against gastric injury in rats at doses 250 mg and 1000, both in the model by stress, as in the induction by ethanol and indomethacin. CONCLUSION: The data obtained in this study show that has EHSG gastric protection in certain doses.

Efecto secuestrador del D-002 sobre radicales hidroxilo en mucosa gástrica / Scavenger effect of D-002 on hydroxyl radicals in the gastric mucosa

Introducción: el agente causal de la ulceración gástrica está asociado al desequilibrio entre factores agresivos y defensivos que actúan sobre la mucosa gástrica. El D-002, mezcla de seis alcoholes alifáticos primarios superiores purificada de la cera de abejas, produce efectos gastroprotectores mediados por múltiples mecanismos y reducción de la peroxidación lipídica en la mucosa gástrica. Objetivo: determinar si el D-002 es capaz de capturar el radical hidroxilo añadido in vitro o generado in vivo en ratas con úlcera gástrica inducida por indometacina. Métodos: En la experiencia in vitro el D-002 se añadió a concentraciones entre 0,9 y 1 000 mg/mL. En la experiencia in vivo las ratas se distribuyeron en seis grupos: un control negativo y cinco que recibieron indometacina: un control positivo tratado con el vehículo, tres con D-002 (5, 25, y 100 mg/kg, respectivamente, p.o.) y otro con omeprazol (20 mg/kg i.p.). Los tratamientos se administraron una hora (vehículo y D-002) o 30 min (omeprazol), respectivamente, antes de inducir las úlceras. En ambas experiencias se tomaron alícuotas de mucosa gástrica, y se determinó el daño a la 2-desoxirribosa por el radical hidroxilo. Resultados: la administración oral del D-002, no in vitro, protegió a la 2-desoxirribosa del daño oxidativo de modo marcado, significativo y dependiente de la dosis con respecto al control positivo. Conclusiones: los resultados indican que la capacidad del D-002 (25 y 100 mg/kg) administrado por vía oral para secuestrar el radical hidroxilo, generado en la mucosa gástrica por la indometacina, pudiera contribuir a sus efectos antioxidantes y gastroprotectores sobre el daño que los antiinflamatorios no esteroideos producen sobre la mucosa gástrica.

Introduction: the etiology of the gastric ulceration is associated to the imbalance between aggressive and defensive factors acting upon the gastric mucosa. D-002, a mixture of 6 higher primary alcohols purified from the beeswax, cause some multiple mechanism-mediated gastroprotective effects and decrease of lipid peroxidation in the gastric mucosa. Objective: to determine whether D-002 can scavenge the in vivo added or in vivo generated hydroxyl radical in rats with indometacin-induced gastric ulcer or not. Methods: For the in vitro experiment, D-002 was added at concentrations 0.9 and 1 000 mg/mL For the in vivo experiment, the rats were randomized into 6 groups: one negative control, and five indometacin-treated groups as follows a positive excipient-treated control, three under D-002 treatment (5, 25 or 100 mg/kg, respectively, p.o.), and another group treated with Omeprazole (20 mg/kg i.p.). These lines of treatment were given 1 hour (excipient and D-002) or 30 min (Omeprazole) prior to inducing the ulcers. In both experiments, aliquots from the gastric mucosa were taken and the damage infringed to 2-deoxiribose by the hydroxyl radical was determined. Results: oral administration of D-002, rather than in vitro addition, significantly protected 2-desoxiribose from the oxidative damage depending on the dosage as compared to the positive control. Conclusions: these results indicate that the ability of the orally administered D-002 (25 and 100 mg/kg) to scavenge the hydroxyl radical endogenously generated on the gastric mucosa by indometacin could contribute to its antioxidant and gastroprotective effects against the damage that the non-steroidal anti-inflammatory drugs carry to the gastric mucosa.

Efecto secuestrador del D-002 sobre radicales hidroxilo en mucosa gástrica / Scavenger effect of D-002 on hydroxyl radicals in the gastric mucosa

Introducción: el agente causal de la ulceración gástrica está asociado al desequilibrio entre factores agresivos y defensivos que actúan sobre la mucosa gástrica. El D-002, mezcla de seis alcoholes alifáticos primarios superiores purificada de la cera de abejas, produce efectos gastroprotectores mediados por múltiples mecanismos y reducción de la peroxidación lipídica en la mucosa gástrica. Objetivo: determinar si el D-002 es capaz de capturar el radical hidroxilo añadido in vitro o generado in vivo en ratas con úlcera gástrica inducida por indometacina. Métodos: En la experiencia in vitro el D-002 se añadió a concentraciones entre 0,9 y 1 000 mg/mL. En la experiencia in vivo las ratas se distribuyeron en seis grupos: un control negativo y cinco que recibieron indometacina: un control positivo tratado con el vehículo, tres con D-002 (5, 25, y 100 mg/kg, respectivamente, p.o.) y otro con omeprazol (20 mg/kg i.p.). Los tratamientos se administraron una hora (vehículo y D-002) o 30 min (omeprazol), respectivamente, antes de inducir las úlceras. En ambas experiencias se tomaron alícuotas de mucosa gástrica, y se determinó el daño a la 2-desoxirribosa por el radical hidroxilo. Resultados: la administración oral del D-002, no in vitro, protegió a la 2-desoxirribosa del daño oxidativo de modo marcado, significativo y dependiente de la dosis con respecto al control positivo. Conclusiones: los resultados indican que la capacidad del D-002 (25 y 100 mg/kg) administrado por vía oral para secuestrar el radical hidroxilo, generado en la mucosa gástrica por la indometacina, pudiera contribuir a sus efectos antioxidantes y gastroprotectores sobre el daño que los antiinflamatorios no esteroideos producen sobre la mucosa gástrica.(AU)

Introduction: the etiology of the gastric ulceration is associated to the imbalance between aggressive and defensive factors acting upon the gastric mucosa. D-002, a mixture of 6 higher primary alcohols purified from the beeswax, cause some multiple mechanism-mediated gastroprotective effects and decrease of lipid peroxidation in the gastric mucosa. Objective: to determine whether D-002 can scavenge the in vivo added or in vivo generated hydroxyl radical in rats with indometacin-induced gastric ulcer or not. Methods: For the in vitro experiment, D-002 was added at concentrations 0.9 and 1 000 mg/mL For the in vivo experiment, the rats were randomized into 6 groups: one negative control, and five indometacin-treated groups as follows a positive excipient-treated control, three under D-002 treatment (5, 25 or 100 mg/kg, respectively, p.o.), and another group treated with Omeprazole (20 mg/kg i.p.). These lines of treatment were given 1 hour (excipient and D-002) or 30 min (Omeprazole) prior to inducing the ulcers. In both experiments, aliquots from the gastric mucosa were taken and the damage infringed to 2-deoxiribose by the hydroxyl radical was determined. Results: oral administration of D-002, rather than in vitro addition, significantly protected 2-desoxiribose from the oxidative damage depending on the dosage as compared to the positive control. Conclusions: these results indicate that the ability of the orally administered D-002 (25 and 100 mg/kg) to scavenge the hydroxyl radical endogenously generated on the gastric mucosa by indometacin could contribute to its antioxidant and gastroprotective effects against the damage that the non-steroidal anti-inflammatory drugs carry to the gastric mucosa.(AU)