Protection of normal cells from irradiation bystander effects by silica-flufenamic acid nanoparticles.

The development of a myriad of nanoparticles types has opened new possibilities for the diagnostics and treatment of many diseases, especially for cancer. However, most of the researches done so far do not focus on the protection of normal cells surrounding a tumor from irradiation bystander effects that might lead to cancer recurrence. Gap-junctions are known to be involved in this process, which leads to genomic instability of neighboring normal cells, and flufenamic acid (FFA) is included in a new group of gap-junction blockers recently discovered. The present work explores the use of mesoporous silica nanoparticles MCM-41 functionalized with 3-Aminopropyltriethoxysilane (APTES) for anchoring the flufenamic acid for its prolonged and controlled release and protection from radiation bystander effects. MCM-41 and functionalized samples were structurally and chemically characterized with multiple techniques. The biocompatibility of all samples was tested in a live/dead assay performed in cultured MRC-5 and HeLa cells. HeLa cells cultured were exposed to 50 Gy of gamma-rays and the media transferred to fibroblast cells cultured separately. Our results show that MCM-41 and functionalized samples have high biocompatibility with MCR-5 and HeLa cells, and most importantly, the FFA delivered by these NPs was able to halt apoptosis, one of main bystander effects.

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.

Sensitivity equation for quantitative analysis with multivariate curve resolution-alternating least-squares: theoretical and experimental approach.

A new equation is derived for estimating the sensitivity when the multivariate curve resolution-alternating least-squares (MCR-ALS) method is applied to second-order multivariate calibration data. The validity of the expression is substantiated by extensive Monte Carlo noise addition simulations. The multivariate selectivity can be derived from the new sensitivity expression. Other important figures of merit, such as limit of detection, limit of quantitation, and concentration uncertainty of MCR-ALS quantitative estimations can be easily estimated from the proposed sensitivity expression and the instrumental noise. An experimental example involving the determination of an analyte in the presence of uncalibrated interfering agents is described in detail, involving second-order time-decaying sensitized lanthanide luminescence excitation spectra. The estimated figures of merit are reasonably correlated with the analytical features of the analyzed experimental system.

Adverse reaction of topical etofenamate: petechial eruption.

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.

Gap junction inhibitors modulate S100B secretion in astrocyte cultures and acute hippocampal slices.

Astrocytes sense, integrate, and respond to stimuli generated by neurons or neural injury; this response involves gap junction (GJ) communication. Neuronal vulnerability to injury increased when cocultures of astrocytes and neurons were exposed to GJ inhibitors. However, GJ uncoupling could limit the extension of a lesion. We investigated a possible link between GJ communication and S100B secretion. S100B is a calcium-binding protein of 21 kDa that is predominantly expressed and secreted by astrocytes, which has trophic paracrine activity on neurite growth, glial proliferation, and neuronal survival. GJ inhibitors were analyzed in isolated astrocytes in primary cultures from hippocampus, acute hippocampal slices, and C6 glioma cells, which were used as a negative control. Our data indicate that GJ blocking stimulates S100B secretion in astrocyte cultures and acute hippocampal slices. Different assays were used to confirm cell integrity during exposure to GJ inhibitors. S100B secretion was observed with different types of GJ inhibitors; the resulting event was dependent on time, the nature of the inhibitor, its putative molecular target of GJ blocking, and/or the cell preparation used. Only carbenoxolone induced a fast and persistent increase in S100B secretion in both preparations. Endothelin-1 increased S100B secretion in astrocyte cultures at 1 hr, but a decrease was observed at 6 hr or in acute hippocampal slices. Physiologically, a local GJ closure associated with release of S100B in injury conditions favors the idea of a common mechanism available to limit the extension of lesion and increase the chances of cell survival.

[Etofenamate and the analgesic effect in the management of acute pain from spine in the emergency room]. / Efecto analgésico del etofenamato en el manejo de las lumbalgias agudas en urgencias.

OBJECTIVE: To demonstrate that the application of etofenamate is effective in management of acute pain. MATERIAL AND METHODS: We conducted a prospective, longitudnal, 6 months trial, which included 22 women and 18 men with intense acute low back pain of mechanical or postural aetiology, patients who had pain of traumatic origin and needed radiographic studies by orthopaedic surgeon were excluded; the study subjects were treated with 1 g etofenamate intramuscularly and the analgesic effect was assessed by visual analog scale every 5 minutes for 30 minutes. RESULTS: Marked improvement in pain at 25 minutes in 35 subjects (87.5%). Pain did not improve in 5 subjects (four men, one woman, 12.5%) at 30 minutes. There were no adverse reactions to medication. DISCUSSION: The single dose of 1 g etofenamate is effective in the management of acute pain. Its use prevented 35 admissions with a cost savings of $70,000 pesos. Applying etofenamate caused satisfaction of the beneficiaries and emergency personnel, this drug could be an alternative treatment in medical services and first-level emergency.

Effects of riluzole and flufenamic acid on eupnea and gasping of neonatal mice in vivo.

The pre-Bötzinger complex (PBC), part of the ventral respiratory group that is responsible for inspiratory rhythm generation, contains at least two types of pacemaker neurons. In vitro studies have shown that bursting properties of one type of pacemaker relies on a riluzole-sensitive persistent sodium current, whereas bursting of a second type is sensitive to flufenamic acid (FFA), a calcium-dependent nonspecific cationic current blocker. In vitro, under control conditions, the PBC generates fictive eupneic activity that depends on both riluzole-sensitive and FFA-sensitive pacemaker neurons. During hypoxia the PBC generates fictive gasping activity and only riluzole-sensitive pacemaker neurons appear to be necessary for this rhythm. We carried out pharmacological experiments to test the role of respiratory pacemaker neurons in vivo by performing plethysmographic recordings on neonate mice. As reported in vitro, eupnea activity in vivo is abolished only if both FFA and riluzole are coadministered intracisternally, but not when either of them is administered independently. On the other hand riluzole, but not FFA, drastically reduced gasping generation and compromised the ability of mice to autoresucitate. Neither substance P nor forskolin was able to reestablish respiratory activity after riluzole and FFA coapplication. Our results confirm in vitro reports and suggest that eupnea generation in neonates requires a complex neuronal network that includes riluzole- and FFA-sensitive elements and that gasping activity depends mostly on a riluzole-sensitive mechanism.

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.

Influence of nanoencapsulation on human skin transport of flufenamic acid.

The effect of the inclusion of flufenamic acid in poly(lactide-co-glycolide) nanoparticles on the transport of flufenamic acid into excised human skin was investigated. Penetration and permeation data were acquired using two different in vitro test systems: the Saarbrucken penetration model, where the skin acts as its own receptor medium, and the Franz diffusion cell, where the receptor medium is a buffer solution. For the stratum corneum, no differences were found between nanoencapsulated and free drug. Drug accumulation in the deeper skin layers and drug transport across human epidermis were slightly delayed for the nanoencapsulated drug compared to the free drug after shorter incubation times (<12 h). In contrast, after longer incubation times (>12 h), the nanoencapsulated drug showed a statistically significantly enhanced transport and accumulation (p < 0.05). Additionally, nanoencapsulated flufenamic acid was visualized by multiphoton fluorescence microscopy. Particles were found homogeneously distributed on the skin surface and within the dermatoglyphs, but no nanoparticles were detected within or between the corneocytes.

[Comparative clinical multicenter study to evaluate analgesic effectiveness of intramuscular etofenamate and diclofenac in patients with post-surgical pain]. / Estudio multicéntrico comparativo para evaluar la eficacia analgésica de etofenamato y diclofenaco por vía intramuscular en pacientes con dolor postquirúrgico.

OBJECTIVE: The analgesic efficacy of intramuscular etofenamate (1 g/day) and intramuscular diclofenac (75 mg/day) was assessed in post-surgical pain relief during a period of 3 days. MATERIAL AND METHODS: One hundred ten hospitalized patients undergoing elective surgery were evaluated in an open-label, comparative, randomized, parallel-group, multicenter study. Fifty five patients received etofenamate and 55 patients diclofenac, 1 h before surgery. The doses were administered after 24 and 48 h. Baseline evaluations were carried out 30 min after anesthesia recovery and the clinical efficacy variables were assessed at 1, 6, 12, 24, 36, 48, 60 and 72 h. The efficacy variables were Pain Visual-Analogue Scale (VAS), Pain Analogous Verbal Scale (AVERS), and Well-Being Scale. Adverse events were documented. RESULTS: Patients in both groups showed similar values in post-surgical pain relief (VAS, AVERS). According to VAS, etofenamate at 24 h had a better analgesic action than diclofenac even though it was not statistically significant. Both drugs demonstrated to be safe. Patients in both groups reported nausea, vomiting, flatulence, and pain at injection site. CONCLUSIONS: We find that both etofenamate and diclofenac were safe, tolerable, and effective treatments for the relief of post-surgical pain.

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.

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.

Flufenamic acid as an inducer of mitochondrial permeability transition.

To assess the mechanism by which mitochondrial permeability transition (MPT) is induced by the nonpolar carboxylic acids, we investigated the effects of flufenamic acid (3'-trifluoromethyl diphenylamine-2-carboxylic acid, FA) on mitochondrial respiration, electrical transmembrane potential difference (delta psi), osmotic swelling, Ca2+ efflux, NAD(P)H oxidation and reactive oxygen species (ROS) generation. Succinate-energized isolated rat liver mitochondria incubated in the absence or presence of 10 microM Ca2+, 5 microM ruthenium red (RR) or 1 microM cyclosporin A (CsA) were used. The dose response-curves for both respiration release and delta psi dissipation were nearly linear, presenting an IC50 of approximately 10 microM and reaching saturation within 25-50 microM, indicating that FA causes mitochondrial uncoupling by a protonophoric mechanism. Within this same concentration range FA showed the ability to induce MPT in energized mitochondria incubated with 10 microM Ca2+, followed by delta psi dissipation and Ca2+ efflux, and even in deenergized mitochondria incubated with 0.5 mM Ca2+. ADP, Mg2+, trifluoperazine (TFP) and N-ethylmaleimide (NEM) reduced the extent of FA-promoted swelling in energized mitochondria by approximately one half, whereas dithiothreitol (DTT) slightly enhanced it. NAD(P)H oxidation and ROS generation (H2O2 production) by mitochondria were markedly stimulated by FA; these responses were partly prevented by CsA, suggesting that they may be implicated as both a cause and effect of FA-induced MPT. FA incubated with mitochondria under swelling assay conditions caused a decrease of approximately 40% in the content of protein thiol groups reacting with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). The present results are consistent with a ROS-intermediated sensitization of MPT by a direct or indirect FA interaction with inner mitochondrial membrane at a site which is in equilibrium with the NAD(P)H pool, namely thiol groups of integral membrane proteins.

The action of flufenamic acid and other nonsteroidal anti-inflammatories on sulfate transport in the isolated perfused rat liver.

The influence of flufenamic acid and other nonsteroidal anti-inflammatories on sulfate transport in the liver was investigated. The experimental system was the isolated perfused rat liver. Perfusion was accomplished in an open, nonrecirculating system. The perfusion fluid was Krebs/Henseleit-bicarbonate buffer (pH 7.4), saturated with a mixture of oxygen and carbon dioxide (95:5) by means of a membrane oxygenator and heated to 37 degrees C. Sulfate transport (equilibrium exchange) was measured by employing the multiple-indicator dilution technique with simultaneous injection (impulse input) of [35S]sulfate. [3H]sucrose (indicator for the distribution of the sinusoidal transit times), and [3H]water (indicator for the total aqueous space). Analysis was accomplished by means of a space-distributed variable transit time model. Flufenamic acid and other anti-inflammatories inhibited sulfate transport in the liver. For a concentration of 100 microM, the following decreasing series of potency could be established: flufenamic acid (53.4 +/- 2.9%) > niflumic acid (41.1 +/- 1.4%) > mefenamic acid (35.6 +/- 3.3%) > piroxicam (16.6 +/- 1.9%) > naproxen (13.5 +/- 8.4)%) nimesulide (11.6 +/- 5.8%). Inhibition of sulfate transport by flufenamic acid was clearly concentration dependent; 250 microM flufenamic acid produced more than 95% inhibition. Flufenamic acid in the range between 50 and 250 microM did not affect the mean transit times of tritiated water (t water) and [3H]sucrose (t suc), the same applying to all other anti-inflammatory agents (100 microM) tested in this work. This means that these agents do not affect vascular and cellular spaces, even when present at high concentrations. The ratio of the intra- to extracellular sulfate concentrations ([C]i/[C]e), generally between 0.4 and 0.5 under control conditions, was affected only by 250 microM flufenamic acid and 100 microM niflumic acid. In the first case, this phenomenon is possibly due to the high degree of transport inhibition (more than 95%), which does not allow a uniform tracer distribution over the whole cellular space during a single passage through the liver. The degree of inhibition of sulfate transport by 100 microM flufenamic acid was a function of the concentration of nontracer sulfate. With sulfate in the range between 1.2 and 25 mM, the inhibition degree increased linearly with the concentration. In the presence of flufenamic acid, the saturation curve of equilibrium exchange showed a substrate inhibition-like phenomenon, which was absent in the control curve. As inhibitors of sulfate transport in hepatocytes, flufenamic and niflumic acids are less active than in erythrocytes by a factor of 10(2). This observation is most probably indicative of structural differences between the hepatic sulfate carrier and the anion carrier of erythrocytes. It is unlikely that the action of flufenamic acid and its analogs on sulfate transport is a consequence of energy metabolism inhibition. Nimesulide is as active as flufenamic or niflumic acid in inhibiting energy metabolism but considerably less efficient as an inhibitor of sulfate transport. Our results as well as literature data reveal that the interactions of the nonsteroidal anti-inflammatories with the liver membranes and intracellular structures are ample and complex. Even at high concentrations, however, these interactions are not so intense as to change the vascular and cellular spaces.

Metabolic effects and distribution space of flufenamic acid in the isolated perfused rat liver.

The following aspects were investigated in the present work: (a) the action of flufenamic acid on hepatic metabolism (oxygen uptake, glycolysis, gluconeogenesis, uricogenesis and glycogenolysis), (b) the action of flufenamic acid on the cellular adenine nucleotide levels, and (c) the transport and distribution space of flufenamic acid in the liver parenchyma. The experimental system was the isolated perfused rat liver. Perfusion was accomplished in an open, non-recirculating system. The perfusion fluid was Krebs/Henseleit-bicarbonate buffer (pH 7.4), saturated with a mixture of oxygen and carbon dioxide (95:5) by means of a membrane oxygenator and heated to 37 degrees C. The distribution space of flufenamic acid was measured by means of the multiple-indicator dilution technique with constant infusion (step input) of [3H]water plus flufenamic acid. The results of the present work indicate that the metabolic effects of flufenamic acid are the consequence of an uncoupling of oxidative phosphorylation, a conclusion based on the following observations: (a) flufenamic acid increased oxygen uptake, a common property of all uncouplers; (b) the drug also increased glycolysis and glycogenolysis in livers from fed rats (these are expected compensatory phenomena for the decreased mitochondrial ATP formation); (c) flufenamic acid inhibited glucose production from fructose, an energy-dependent process; (d) the cellular ATP levels were decreased by flufenamic acid whereas the AMP levels were increased; and (e) the total adenine nucleotide content was decreased by flufenamic acid and uric acid production was stimulated. Indicator-dilution experiments with flufenamic acid revealed that this substance undergoes flow-limited distribution in the liver and that its apparent distribution space greatly exceeds the aqueous space of the liver. Flufenamic acid changed its behaviour when the portal concentration was increased from 25 to 50 microM. At 25 microM the initial upslope of the outflow profile clearly preceded that of all other concentrations. From the trend of the curves obtained with 50, 100 and 250 microM, one would expect an initial upslope situated at the right of the 50-microM curve. Furthermore, the time of appearance of flufenamic acid in the outflowing perfusate was practically the same irrespective of the portal concentration. For theoretical reasons one would expect progressively longer appearance times when the portal concentration was decreased. It is possible that the amount of flufenamic acid bound to the cell membranes during the early stages of the infusion produced changes that enabled these structures to bind a larger quantity of the drug than originally possible.

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