Effects of ATP on Pacemaker Activity of Interstitial Cells of Cajal from the Mouse Small Intestine / 전남의대학술지

Purinergic receptors play an important role in regulating gastrointestinal (GI) motility. Interstitial cells of Cajal (ICCs) are pacemaker cells that regulate GI smooth muscle activity. We studied the functional roles of external adenosine 5′-triphosphate (ATP) on pacemaker activity in cultured ICCs from mouse small intestines by using the whole-cell patch clamp technique and intracellular Ca²⁺ ([Ca²⁺]ᵢ) imaging. External ATP dose-dependently depolarized the resting membrane and produced tonic inward pacemaker currents, and these effects were antagonized by suramin, a purinergic P2 receptor antagonist. ATP-induced effects on pacemaker currents were suppressed by an external Na⁺-free solution and inhibited by the nonselective cation channel blockers, flufenamic acid and niflumic acid. The removal of external Ca²⁺ or treatment with thapsigargin (inhibitor of Ca²⁺ uptake into endoplasmic reticulum) inhibited the ATP-induced effects on pacemaker currents. Spontaneous [Ca²⁺]ᵢ oscillations were enhanced by external ATP. These results suggest that external ATP modulates pacemaker activity by activating nonselective cation channels via external Ca²⁺ influx and [Ca²⁺]ᵢ release from the endoplasmic reticulum. Thus, it seems that activating the purinergic P2 receptor may modulate GI motility by acting on ICCs in the small intestine.

Adverse reaction of topical etofenamate: petechial eruption / Reacción adversa del etofenamato tópico: erupción petequial

Etofenamate is a non-steroidal anti-inflammatory drug (NSAID). Clinical findings caused by etofenamate are uncommon. Allergic contact dermatitis is the most common cutaneous reaction reported. But petechial eruption due to etofenamate had not been reported yet. This report concerns an 11-year old male with petechial eruption after application of topical etofenamate. Physicians need to be aware that patients can develop an asymptomatic purpuric eruption when etofenamate is ordered.

El etofenamato es un antiinflamatorio no esteroideo (AINE). Los hallazgos clínicos sobre los efectos del etofenamato son poco comunes. La dermatitis alérgica por contacto es la reacción cutánea más comúnmente reportada. En cambio, la erupción petequial a causa del etofenamato no se había reportado hasta ahora. Este reporte trata de un varón de 11 años de edad con erupción petequial tras la aplicación del etofenamato tópico. Es necesario que los médicos tomen conciencia de que los pacientes pueden desarrollar una erupción púrpura asintomática, a la hora de prescribir el etofenamato.

Uso del etofenamato en el manejo del dolor postoperatorio en comparación con ketoprofeno: Hospital Universitario "Dr. Angel Larralde" Valencia estado Carabobo / Using etofenamato in postoperative pain management compared with ketoprofen: Hospital Universitario Dr. Angel Larralde Valencia state Carabobo

El etofenamato es un compuesto derivado del  cido flufenámico, sus características fisicoquímicas y farmacológicas proporcionan analgesia prolongada. Nos planteamos realizar un estudio comparativo donde se evalúen las características analgésicas y tiempo de inicio de la dosis de analgésico en el dolor postoperatorio, utilizando etofenamato intramuscular o ketoprofeno endovenoso previo acto quirúrgico. Previa aprobación por el comité de ética, se realizó un estudio prospectivo, comparativo, al azar con cien pacientes de 18 y 60 años, ASA I-II, intervenidos quirúrgicamente (cirugía abdominal, urológica, ortopédica). Se dividieron en dos grupos: grupo K (n=50) ketoprofeno 100 mg endovenoso 60 minutos antes de la intervención, grupo E (n=50) etofenamato intramuscular 60 minutos previo a la intervención. El dolor postoperatorio fue evaluado con: Escala visual análogo del dolor; Escala verbal análogo del dolor: Escala de bienestar, a la hora, 2,4, 6,8,10,12,18 y 24 horas. A las 2 horas el grupo K reportó EVA 9 (74 porciento), el grupo E reportó un EVA 3 (84 porciento) (P<0,001), el tiempo de dosis adicional fue: grupo K 74 por ciento a los 125,5 + 6,9 min, el grupo E 68 por ciento 841,6 + 10,1 min (P<0,001). La escala de bienestar reportó a las 24 horas: el grupo E 60 por ciento sentirse bien, el grupo K 36 por ciento reportó sentirse mal (P<0,001). El etofenamato proporciona analgesia postoperatoria eficaz y segura por mayor tiempo, en comparación con el ketoprofeno.

Non-selective cation channels and oxidative stress-induced cell swelling

Necrosis is considered as a non-specific form of cell death that induces tissue inflammation and is preceded by cell swelling. This increase in cell volume has been ascribed mainly to defective outward pumping of Na+ caused by metabolic depletion and/or to increased Na+ influx via membrane transporters. A specific mechanism of swelling and necrosis driven by the influx of Na+ through nonselective cation channels has been recently proposed (Barros et al., 2001a). We have characterized further the properties of the nonselective cation channel (NSCC) in HTC cells. The NSCC shows a conductance of approximately 18 pS, is equally permeable to Na+ and K+, impermeant to Ca2+, requires high intracellular Ca2+ as well as low intracellular ATP for activation and is inhibited by flufenamic acid. Hydrogen peroxide induced a significant increase in cell volume that was dependent on external Na+. We propose that the NSCC, which is ubiquitous though largely inactive in healthy cells, becomes activated under severe oxidative stress. The ensuing Na+ influx initiates via positive feedback a series of metabolic and electrolytic disturbances, resulting in cell death by necrosis

Etofenamato: características farmacológicas y clínicas de la formulación intramuscular / Etophenamate. Pharmacological and clinical characteristics and of the intramuscular formulation

El etofenamato es un compuesto derivado del ácido flufenámico, que pertenece a los compuestos derivados del ácido antranílico. Éste se utilizó originalmente, como formulación para administración vía oral y, posteriormente, como crema o gel para administración tópica. Sin embargo, las características farmacológicas fueron mejoradas al hacer una combinación con triglicéridos de cadena media, generando un compuesto de administración intramuscular que mejoró el perfil terapéutico de este anti inflamatorio no esteroideo; destaca no sólo por inhibir la vía de las ciclooxigenasa sino que, en forma paralela, inhibe también la vía de la lipooxigenasa. Las características fisico-quirnicas, farmacológicas y clínicas son revisadas en este artículo.

The mechanism of t-butylhydroperoxide-induced apoptosis in IMR-32 human neuroblastoma cells

Apoptosis has been implicated in the pathophysiological mechanisms of various neurodegenerative diseases. In a variety of cell types, oxidative stress has been demonstrated to play an important role in the apoptotic cell death. However, the exact mechanism of oxidative stress-induced apoptosis in neuronal cells is not known. In this study, we induced oxidative stress in IMR-32 human neuroblastoma cells with tert-butylhydroperoxide (TBHP), which was confirmed by significantly reduced glutathione content and glutathione reductase activity, and increased glutathione peroxidase activity. TBHP induced decrease in cell viability and increase in DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. TBHP also induced a sustained increase in intracellular Ca2+ concentration, which was completely prevented either by EGTA, an extracellular Ca2+ chelator or by flufenamic acid (FA), a non-selective cation channel (NSCC) blocker. These results indicate that the TBHP-induced intracellular Ca2+ increase may be due to Ca2+ influx through the activation of NSCCs. In addition, treatment with either an intracellular Ca2+ chelator (BAPTA/AM) or FA significantly suppressed the TBHP-induced apoptosis. Moreover, TBHP increased the expression of p53 gene but decreased c-myc gene expression. Taken together, these results suggest that the oxidative stress-induced apoptosis in neuronal cells may be mediated through the activation of intracellular Ca2+ signals and altered expression of p53 and c-myc.

Influence of fluorine atom on certain pharmaceutical properties of flufenamic acid

The purpose of the present study was to investigate the effect of fluorine atom on certain pharmaceutical properties of flufenamic acid [F] using mefenamic acid [M] as a control. Both drugs have been anthranilic acid derivatives with 3 fluorine atoms in the former. The pharmaceutical properties studied were flowability [angle of repose], bulk density, porosity, and wettability [sinking time]. Dissolution and release studies of both drugs from capsules and ointment bases were also carried out

Two colorimetric methods for the assay of six nonsteroidal anti-inflammatory drugs in their pure and dosage forms

This paper described two new colorimetric methods for estimation of six nonsteroidal anti-inflammatory drugs; namely, piroxicam, tenoxicam, mefenamic acid, flufenamic acid, ibuprofen and ketoprofen in their pure forms and pharmaceutical preparations. The first method depends on scanning the azodyes resulting from the reaction of piroxicam and tenoxicam with diazonium salts of benzocaine, p-amino-N- methylbenzamide and sulfadiazine. The second procedure is based on colorimetric determination of the blue colored complexes yielded from the reaction of methylene blue with drugs under investigation. The different conditions for the proposed methods were studied. The methods have been applied for the analysis of pharmaceutical preparations containing these drugs and the results obtained were compared with those of pharmacopoeial or published methods. The methods are simple, precise and reproducible

Reduçäo da dose de antiinflamátorios näo hormonais orais pela administraçäo percutânea do etofenamato gel em pacientes com afecçöes reumáticas: estudo bicêntrico, resultados preliminares / Reduction of dose of non-hormonal oral anti-infammatory agents by percutaneous administration of etofenamate gel in patients with rheumatic disorders: bicenter study preliminary results

Em estudo aberto, näo controlado e näo comparativo, foram estudados 60 pacientes portadores de distintas afecçöes reumáticas localizadas, que utilizavam antiinflamatórios näo hormonais, em dose de manutençäo por mais de 30 dias, procurando-se avaliar a possibilidade da diminuiçäo ou da retirada gradativa destes fármacos, através do uso percutâneo (quatro doses diárias) do etofenamato gel, empregado associadamente. Dois centros participaram desta investigaçäo clínica, cujos resultados preliminares, obtidos através de metodologia simplificada, mostraram respostas favoráveis: diminuiçäo do consumo de antiinflamatórios näo-hormonais orais de 21,5% na primeira semana, 52,4% na segunda semana e 61,1% no final da terceira semana (o período de estudo foi de três semanas). Os melhores resultados foram observados em pacientes com afecçöes extra-articulares ou de partes moles e, em apenas um caso, apareceram efeitos adversos locais (hipersensibilidade cutânea) correlacionados com o etofenamato gel, durante a terceira semana de tratamento; um paciente piorou de suas manifestaçöes clínicas durante o estudo, obrigando a interrupçäo da terapêutica. Apenas nestes dois casos, näo foi conseguida a reduçäo da medicaçäo oral, concluindo-se pela ineficácia desta modalidade de tratamento. Deste modo, observou-se que, ao lado da boa aceitaçäo do etofenamato gel pelos pacientes, é possível associar este medicamento a outros fármacos antiinflamatórios orais, ao se procurar minimizar os freqüentes efeitos indesejáveis que estas substâncias apresentam, principalmente do ponto de vista gastrintestinal. No entanto, acreditam os autores, torna-se necessário novos e controlados estudos, para propiciarem dados mais conclusivos

Reduçäo do uso de anti-reumáticas orais pelo uso tópico de Etofenamato gel / Saving of oral antirheumatics agents by local use of Etofenamate gel

Um estudo multicêntrico com 3.584 pacientes foi realizado por clínicos gerais, especialistas em medicina interna e ortopedistas. Esse estudo tinha como objetivo responder a seguinte questäo: o tratamento combinado com aplicaçöes cutâneas de Etofenamato (Bayro Gel*) tornaria possível a reduçäo de doses orais de agentes anti-reumáticos? Entre as principais patologias estavam processos articulares como artrite reumatóide, doença de Bechterew, artrose e espondilartrose, especialmente aqueles com comprometimento dos tecidos periarticulares (um terço dos casos foi de afecçöes das partes moles). As doenças - a maioria das quais tinham uma evoluçäo bastante constante - foram tratadas com agentes anti-reumáticos orais livremente escolhidos por cada médico e mantidos através de todo o estudo sem serem combinados com outros agentes terapêuticos básicos e/ou fisioterapia. Durante o primeiro período de teste de 1-2 semanas de duraçäo, o tratamento anti-reumático oral foi mantido com uma dosagem constante. Durante o subseqüente período de teste de, novamente, 1-2 semanas de duraçäo, os pacientes receberam, concomitantemente, Bayro Gel quatro vezes ao dia. Ao mesmo tempo, a dosagem do anti-reumático oral foi reduzida gradualmente até o mínimo possível. Em média, foi possível reduzir a medicaçäo oral em aproximadamente 40% quando se aplica a Bayro Gel em doenças reumáticas inflamatórias, em 50% nas condiçöes degenerativas, e em até mais nas afecçöes de partes moles. A taxa de efeitos colaterais foi significativamente reduzida e as queixas além de diminuírem, em muitos casos, deixaram de ser referidas. Torna-se evidente com os resultados desse estudo, que é possível reduzir os antiinflamatórios orais e minimizar seus efeitos colaterais, ao se associar Bayro Gel aos antiinflamatórios orais nas indicaçöes acima mencionadas