Regression of macular edema with topical brinzolamide and nepafenac alone and identification of a novel gyrate atrophy mutation / Regressão de edema macular com o uso tópico de brinzolamida e nepafenac e identificação de uma nova mutação na atrofia girata

ABSTRACT Gyrate atrophy is a rare metabolic autosomal recessive disorder caused by ornithine aminotransferase enzyme deficiency that leads to characteristic progressive, degenerative chorioretinal findings. Patients complain mostly of low vision, night blindness, and peripheral vision loss. Posterior subcapsular cataract, myopia, choroid neovascularization, and intraretinal cysts may be accompanying factors related to vision loss. We encountered a patient with vision loss secondary to posterior subcapsular cataract and intraretinal cysts. After treatment with topical brinzolamide and nepafenac (and without any diet mo dification and/or supplementation), we observed 143- and 117-mm macular thickness resolutions with 2 and 1 Snellen lines of visual gain in his right and left eyes, respectively. Also, we detected a novel homozygous mutation in the ornithine aminotransferase gene: c.1253T>C (p.Leu418Pro). Carbonic anhydrase inhibitors and/or non-steroid anti-inflammatory drugs can control macular edema in patients with gyrate atrophy-associated intraretinal cysts. The genetic variants may also be a determinant in the responsiveness to the therapy type.

RESUMO A atrofia girata é um distúrbio autossômico recessivo metabólico raro causado pela deficiência da enzima ornitina ami notransferase, que leva a achados degenerativos coriorretinianos progressivos característicos. Os pacientes queixam-se principalmente de baixa visão, cegueira noturna e perda de vi são periférica. A catarata subcapsular posterior, a miopia, a neovascularização da coróide e os cistos intrarretinianos podem ser fatores associados à perda da visão. Encontramos um paciente com perda de visão secundária à catarata subcapsular posterior e cistos intrarretinianos. Após o tratamento com brinzolamida tópica e nepafenaco (e sem modificação e/ou suplementação da dieta), observamos resoluções de espessura macular de 143 e 117 mm e com 2 e 1 linhas de Snellen de ganho visual nos olhos direito e esquerdo, respectivamente. Além disso, detectamos uma nova mutação homozigótica no gene da ornitina aminotransfera se: c.1253T>C (p.Leu418Pro). Inibidores da anidrase carbônica e/ou drogas anti-inflamatórias não esteróides podem controlar o edema macular em pacientes com cistos intrarretinianos associados à atrofia girata. As variantes genéticas também podem ser determinantes na responsividade ao tipo de terapia.

Asociación entre edulcorantes no nutritivos y riesgo de obesidad en estudiantes universitarios de Latinoamérica / Association between non-nutritive sweeteners and obesity risk among university students in Latin America

Background: The association between non-nutritive sweeteners and obesity is controversial. Aim: To determine whether the consumption of non-nutritive sweeteners is related to higher risk for overweight or obesity among university students in Chile, Panama, Guatemala and Peru. Material and Methods: A total of 1,224 (472 from Chile, 300 from Panama, 248 from Guatemala and 204 from Peru) male and female university students aged between 18 and 26 years participated in the study. Each student reported their food intake (frequency of weekly consumption) in a survey that contained photos of foods containing non-nutritive sweeteners adapted for each country. Anthropometry was also measured. Results: More than 80% of students consumed at least one product containing non-nutritive sweeteners. Females who ate acesulfame potassium and sucralose had a lower risk of overweight or obesity with an odds ratio (OR) of 0.5 (confidence intervals (CI) = 0.3-0.9; p = 0.003) and OR = 0.4 (IC = 0.2-0.8; p = 0.01), respectively. Conclusions: In this sample of Latinamerican university students, consumption of non-nutritive sweeteners was associated with lower risk of overweight only in females.

Utilization of spray drying technique for improvement of dissolution and anti-inflammatory effect of meloxicam

Meloxicam [MLX] is a poorly water-soluble non steroidal anti-inflammatory drug [NSAID]. The main objective of the present work was to enhance the dissolution of MLX and thus its bioavailability by the aid of additives. The novelty of this work rises from the utilization of spray drying technology to produce micro particulates solid dispersion systems containing MLX in the presence of small amount of additives. Differential scanning calorimetry [DSC], Fourier transform infrared spectroscopy [FT-IR], and Scan Electron Microscope [SEM] were used for studying the physico-chemical and morphological properties of MLX samples. The dissolution of MLX samples was investigated in two different pH media. The morphology of MLX solid dispersion micro-particles was spherical in shape according to SEM. FT-IR profiles indicated that a complex was formed between MLX and the additives. DSC patterns of the MLX micro-particles suggested a reduction in the crystallinity of MLX and probability of presence of an interaction between MLX and the additives. The rate of dissolution of the spray-dried MLX enhanced as compared with the unprocessed MLX in both acidic and neutral media. It was found that 100% of the added MLX released within 5 min in phosphate buffer dissolution medium [pH 7.4] compared to that of the unprocessed MLX [15% in 60 min]. Such increase rate in the dissolution of the spray dried MLX could be attributed to the increase in wettability of MLX particles and the hydrophilic nature of the additives. The anti-inflammatory effect of the spray dried MLX was explored using formalin induced rat paw edema model. The spray-dried samples showed an increase in the anti-inflammatory activity of MLX as compared to the unprocessed MLX. This work reveals that the spray drying technique is suitable for preparation of micro-particles with improved dissolution and anti-inflammatory effect of MLX

La combinación de atorvastatina y meloxicam inhibe la neuroinflamación y atenúa el daño celular en la isquemia cerebral experimental por embolia arterial / Atorvastatin-meloxicam association inhibits neuroinflammation and attenuates the cellular damage in cerebral ischemia by arterial embolism.

Introducción. El accidente cerebrovascular es la segunda causa de muerte y la primera de discapacidad en el mundo, y más de 85 % es de origen isquémico. Objetivo. Evaluar en un modelo de infarto cerebral por embolia arterial el efecto de la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, sobre la respuesta neuronal, los astrocitos y la microglia. Materiales y métodos. Se sometieron ratas Wistar a embolia de la arteria carótida y a tratamiento con meloxicam y atorvastatina, administrados por separado y conjuntamente, a las 6, 24, 48 y 72 horas. Se evaluó la reacción de las proteínas COX-2, GFAP y OX-42 en las neuronas, los astrocitos y la microglia mediante inmunohistoquímica y estudios morfológicos y de densitometría. Los datos obtenidos se evaluaron por medio de un análisis de varianza y de pruebas no paramétricas de comparación múltiple. Resultados. La isquemia cerebral por embolia arterial incrementó significativamente (p<0,001) la reacción de los astrocitos y la microglia, en tanto que la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, la redujeron. La isquemia produjo acortamiento de las proyecciones de los astrocitos, engrosamiento celular, ruptura de las expansiones protoplásmicas (clasmatodendrosis) y cambios morfológicos en la microglia propios de diversas etapas de actividad. En las zonas circundantes del foco se incrementó la reacción inmunológica de la COX-2 y se redujo en el foco isquémico, en tanto que el meloxicam y la atorvastatina redujeron significativamente (p<0,001) la reacción inmunológica en la zona circundante del foco, restableciendo la marcación de la ciclooxigenasa en el foco isquémico. Conclusión. La combinación de meloxicam y atorvastatina atenúa la respuesta de los astrocitos y la microglia en el proceso inflamatorio posterior a la isquemia cerebral por embolia arterial, reduciendo la degeneración neuronal y restableciendo el equilibrio morfológico y funcional del tejido nervioso.

Introduction: Stroke is the second leading cause of death and the first cause of disability in the world, with more than 85% of the cases having ischemic origin. Objective: To evaluate in an embolism model of stroke the effect of atorvastatin and meloxicam on neurons, astrocytes and microglia. This evaluation was done administering each medication individually and in association. Materials and methods: Wistar rats were subjected to carotid arterial embolism and treatment with meloxicam and atorvastatin at 6, 24, 48 and 72 hours. Using immunohistochemistry, we evaluated the immunoreactivity of COX-2 protein, GFAP and OX-42 in neurons, astrocytes and microglia by densitometric and morphological studies. Data were evaluated by variance analysis and non-parametric multiple comparison. Results: Cerebral ischemia by arterial embolism increased significantly the reactivity of microglia and astrocytes (p<0.001), whereas it was reduced by atorvastatin, meloxicam and their association. Ischemia produced astrocytic shortening, cellular thickening, protoplasmic rupture expansions (clasmatodendrosis) and microglial morphological changes characteristic of various activity stages. In perifocal areas, immunoreactivity of COX-2 was increased and in the ischemic focus it was reduced, while meloxicam and atorvastatin significantly reduced (p<0.001) perifocal immunoreactivity, restoring the marking of cyclooxygenase in the ischemic focus. Conclusion: These results suggest that the meloxicam-atorvastatin association attenuates astrocytic and microglial response in the inflammatory process after cerebral ischemia by arterial embolism, reducing neurodegeneration and restoring the morphological and functional balance of nervous tissue .

The Effect of Combined Therapy with Tamsulosin Hydrochloride and Meloxicam in Patients with Benign Prostatic Hyperplasia Symptoms and Impact on Nocturia and Sleep Quality

Purpose We aimed to compare the effect and feasibility of a combined therapy with tamsulosin hydrochloride plus meloxicam, and tamsulosin hydrochloride alone in patients with benign prostate hyperplasia symptoms and impact on nocturia and sleep quality. Materials and Methods Four hundred male patients were included in this study between 2008 and 2011. Patients were randomly divided into two groups: one received tamsulosin hydrochloride 0.4 mg (Group 1, 200 patients) and the other tamsulosin hydrochloride 0.4 mg plus meloxicam 15 mg (Group 2, 200 patients) prospectively. Patients were evaluated for benign prostate hyperplasia (BPH) symptoms according to the American Urological Association clinical guidelines and sleep quality according to Pittsburgh Sleep Quality Index (PSQI). Patients were reevaluated after three months of treatment. The International Prostatic Symptom Score (IPSS), IPSS-Quality of Life (IPSS-QoL), maximal urinary flow rates (Qmax), average urinary flow rates (AFR), post void residual urine volumes (PVR), nocturia and Pittsburgh Sleep Quality Score (PSQS) were recorded at baseline and after three months. Results Mean age was 63.3 ± 6.6 and 61.4 ± 7.5 years in groups 1 and 2, respectively (p = 0.245). There were no statistically significant differences between both groups. Also, baseline prostate specific antigen (PSA), prostate volume, creatinine, International Prostatic Symptom Score (IPSS), IPSS-Quality of Life (IPSS-QoL), maximal urinary flow rates (Qmax), average urinary flow rates (AFR), post void residual urine volumes (PVR), nocturia and Pittsburgh Sleep Quality Score (PSQS) were similar in both groups. In addition, the total IPSS, IPSS-QoL, PVR, nocturia, and PSQS were significantly lower in Group 2 compared with Group 1 after treatment (p < 0.05). Qmax and AFR were higher significantly in Group 2 compared with Group 1 after treatment (p < 0.05). Conclusions Cyclooxygenase (COX)-2 inhibitors ...

Late administration of a specific COX-2 inhibitor does not treat and/or prevent progression of gastric tumors in rats submitted to duodenogastric reflux procedure

PURPOSE:To assess whether late introduction of a specific COX-2 inhibitor (Meloxicam) can treat and/or prevent the progression of tumors in the stomach of rats submitted to duodenogastric reflux. METHODS: Seventy five male Wistar rats, weighing 150 grams, were submitted to the induction of duodenogastric reflux through the pylorus. At 36 weeks of follow-up were established three experimental groups: DGR36 sacrificed immediately, DGR54 and DGR54MLX both sacrificed at 54th week of follow-up . The animals of the latter group were fed with a rat chow premixed with Meloxicam (2.0 mg/ kg feed; 0.3 mg / kg bw / day) and the other two with standard rat chow. The lesions found in the pyloric mucosa and gastrojejunal anastomosis were analyzed macroscopically and histologically. For statistical analysis was adjusted a generalized linear model assuming a binomial distribution with LOGIT link function. RESULTS: No significant differences were found when comparing the incidences of benign tumor lesions (Adenomatous Hyperplasia), p=0.4915, or malignant (Mucinous Adenocarcinoma), p=0.2731, among groups. CONCLUSION: Late introduction of specific COX-2 inhibitor (Meloxicam) did not treat and was not able to prevent the progression of tumoral lesions induced by duodenogastric reflux in the rat stomachs.

Efficacy of Combination of Meloxicam and Pregabalin for Pain in Knee Osteoarthritis

PURPOSE: Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients. MATERIALS AND METHODS: Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test. RESULTS: Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p0.05). CONCLUSION: Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.

In vitro effects of meloxicam on the number, Foxp3 expression, production of selected cytokines, and apoptosis of bovine CD25+CD4+ and CD25-CD4+ cells

The purpose of this study was to evaluate the effect of meloxicam (MEL) on selected immune parameters of bovine CD25highCD4+, CD25lowCD4+, and CD25-CD4+ cells. Peripheral blood mononuclear cells (PBMCs) collected from 12-month-old heifers were treated with MEL at a concentration corresponding to the serum level of this medication following administration at the recommended dose (MEL 5 x 10(-6) M) and at a concentration 10 times lower (MEL 5 x 10(-7) M). After 12 and 24 h of incubation with the drug, the percentage of CD25highCD4+ cells decreased; however, this disturbance was quickly reversed. Furthermore, the absolute number of CD25highCD4+ cells in the PBMC populations treated with MEL 5 x 10(-6) M for 48 and 168 h was increased. Prolonged (168 h) exposure to the drug increased the percentage of Foxp3+ cells in the CD25highCD4+ cell subpopulation. The higher dose of MEL was found to significantly increase the percentage of IFN-gamma+ cells among the CD25-CD4+ cells. These results indicated that MEL does not exert an immunosuppressive effect by depleting CD4+ cells and suppression of IFN-gamma+ production by these cells. Furthermore, IL-10 and TGF-beta production was not changed following exposure to MEL.

Meloxicam e prednisona: efeitos do tratamento oral de curto prazo sobre os níveis de pressão intraocular em cães / Meloxican and prednisone: the effects of orally short term treatment on the intra-ocular pressure levels in dogs

Para possível observação da hipertensão ocular com o uso de antiinflamatórios, foram selecionados 28 cães da raça Beagle. Para avaliação da pressão intra-ocular antes do tratamento, no dia 0 (zero) todos os animais tiveram a pressão intra-ocular avaliada às 08 horas e às 16 horas. No dia seguinte dez cães receberam meloxicam na dose de0,2 mg/kg, e 0,1mg/kg nos restantes quatro dias. Nove cães receberam prednisona na dose de 1,0 mg/kg durante cinco dias. Nove cães receberam somente porção de ração úmida. No quinto dia do tratamento todos os animais tiveram novamente a pressão intra-ocular avaliada às 08 horas e às 16 horas. Em todos os grupos, incluindo o grupo-controle, as maiores médias de pressão intra-ocular foram observadas no dia 5 (cinco). A diferença dos valores de pressão intra-ocular observada entre as medições das 08 horas e das 16 horas foi significativa, independente do tratamento e do dia considerado. O uso dos anti-inflamatórios esteroidal e não-esteroidal não foi capaz de causar hipertensão ocular e alguns fatores podem ser incriminados, como via de administração, dose e duração do tratamento utilizado, além da ausência de doença glaucomatosa nos cães selecionados

In order to observe a possible ocular hypertension associated with the use of anti-inflammatory drugs, 28 beagle dogs were selected. For evaluation of intraocular pressure before treatment, the totality of animals had their intraocular pressure measured at 8 a.m. and 4 p.m.on day 0 (zero). On the following day 10 animals received meloxican on dose of 0.2 mg/Kg and 0.1 mg/Kg on the four remaining days. Nine dogs received prednisone on dose of 1,0 mg/Kg during five days. Nine dogs received only wet feeding. On the fifth day of treatment the totality of dogs had their intraocular pressure measured at 8 a.m.and 4 p.m. For all groups, including control-group, the highest average values of intraocular pressure were observed on day 5 (five). The difference between the two evaluations of intra-ocular pressure (8a.m. and 4 p.m) was significant, independent of treatment and of the considered day. The use of both steroidal or non-steroidal antiinflammatory were not capable of causing ocular hypertension and some factors can be pointed out, such as route of administration, dosage and duration of therapy chosen, besides absence of glaucomatous disorder between the selected dogs

A comparative study of subsyde-CR versus meloxicam in rheumatic disorders.

A prospective, randomised comparative clinical study was conducted in adult patients of either sex presenting with articular and non-articular rheumatic conditions commonly encountered in clinical practice Rheumatoid arthritis, osteo-arthritis, cervical spondylosis, and lumbago/sciatica were the most frequent conditions encountered in both the groups, followed by others like tenosynovitis, frozen shoulder, prolapsed disc, fibrositis, myositis, sprains, strains and so on. The drugs that were employed for therapy were diclofenac in a controlled release formulation employing the DRCM technology (subsyde-CR) and meloxicam in a standard formulation marketed in our country. Both drugs were well tolerated and found to be effective in reducing the signs and symptoms of the disease entities throughout the study period, but subsyde-CR was observed to produce a somewhat greater reduction in signs and symptoms scores that meloxicam, a difference that could be possibly attributed to the greater efficacy of subsyde-CR in non-articular rheumatic conditions. On the basis of the available literature on diclofenac and meloxicam as well as the DRCM technology in formulating subsyde-CR, it is reasonable to conclude that a controlled release formulation of diclofenac based on the DRCM technology offers a safe and effective alternative to other non-steroidal anti-inflammatory drugs such as meloxicam.

Avaliaçäo comparativa da eficácia e tolerância de uma nova forma de administraçäo do Piroxicam (gotas) em afecçöes otorrinolaringológicas / Comparative evaluation of the efficacy and tolerance of new form of piroxicam (drops) in otorhinolaryngologic diseases

Piroxicam (Inflamene), conhecido antiinflamatório foi usado em estudo duplo-cego comparativo ao placebo, em 40 crianças, para observar a atividade terapêutica de sua nova apresentaçäo para uso em gotas. Após sete dias de tratamento, os Autores concluíram que piroxicam em gotas, pela sua ótima açäo analgésica e antiinflamatória, sua longa hemivida plasmática, e ausência de efeitos colateris importantes, deve ser incluído no arsenal terapêutico para tratamento de afecçöes otorrinolaringológicas em crianças

Pipotiazina de açäo prolongada e de administraçäo mensal no tratamento de manutençäo de esquizofrênicos em consultório particular com seguimento máximo de cinco anos / Prolonged action and monthly administration of pipothiazine in the treatment of schizophrenic patients in private clinic with maximum follow-up of 5 years

O objetivo deste trabalho foi avaliar a palmitato de pipotiazina no tratamento de manutençäo a longo termo em consultório particular. Quarenta e oito doentes foram seguidos por período de três a cinco anos. Interrupçäo do tratamento ocorreu em 44% dos casos, por motivos diversos e em maior proporçäo na fase inicial (<5 meses), confirmando deduçäo anterior sobre a importância da educaçäo contínua do doente e da família antes e no decorrer do tratamento. Os doentes que permaneceram em tratamento se beneficiaram com remissäo dos sintomas produtivos, melhora do relacionamento familiar e social, e muitos deles com a retomada das atividades. A dose média nas últimas quatro aplicaçöes foi de 53 mg IM. Reaçäo extrapiramidal ocorreu em baixa freqüência. O número de doentes utilizando antiparkinsoniano e seu consumo foram reduzidos no decorrer do tratamento. Amenorréia ocorreu em proporçäo elevada