Protective Effect of Mormodica balsamina Leaf Extract on the Gastric Morphology of Experimental Rats Against Ethanol Induced Gastric Ulcers / Efecto Protector de los Extractos de Hojas de Mormodica balsamina en la Morfología Gástrica de Ratas Experimentales Contra Úlceras Gástricas Inducidas por Etanol

SUMMARY: Mormodica balsamina is a valuable medicinal plant that is used to treat wounds and inflammation; its leaves are also used as an antibiotic and in the treatment of stomach pain. This study was conducted to determine the anti-ulcer activity of methanolic leaf extract of Mormodica balsamina on ethanol-induced ulcer in albino rats. A total of 32 rats were used for the study. Groups I and II served as the baseline and negative controls respectively, while groups III-VII served as the test groups. Group I was untreated, while group II received 1ml/kg body weight of the vehicle (2 % DMSO). Three test groups (III - V) received methanol extracts (75 mg, 150 mg, 300 mg/kg body weight respectively) while the other three test groups (VI - VIII) received aqueous extracts (75 mg, 150mg, 300 mg/kg body weight respectively) via oral gavage for seven days prior to ulcer induction. The rats were sacrificed, stomachs excised and ulcers scored. Histological sections were produced and examined. Findings revealed that M. balsamina extracts protected the rats' gastric epithelia from ethanol induced ulceration to varying degree with the high dose (150 and 300 mg/kg) of both extracts offering the best preservation (42 % and 50 % ulcer protective index respectively) when compared to untreated animals. Histological findings correlated with calculated ulcer indices, with treated animals having less severe gastric mucosal lesions. In conclusion, extracts of M. balsamina may possess reasonable antiulcer activities in rats against ethanol induced gastric ulcer.

Mormodica balsamina es una valiosa planta medicinal que se utiliza para tratar heridas e inflamaciones; sus hojas también se utilizan como antibiótico y en el tratamiento del dolor de estómago. Este estudio se realizó para determinar la actividad antiulcerosa del extracto metanólico de hojas de Mormodica balsamina sobre la úlcera inducida por etanol en ratas albinas. Se utilizaron un total de 32 ratas para el estudio. Los grupos I y II sirvieron como referencia y controles negativos respectivamente, mientras que los grupos III-VII sirvieron como grupos de prueba. El grupo I no se trató, mientras que el grupo II recibió 1 ml/kg de peso corporal del vehículo (2% de DMSO). Tres grupos de prueba (III - V) recibieron extractos de metanol (75 mg, 150 mg, 300 mg/ kg de peso corporal respectivamente) mientras que los otros tres grupos de prueba (VI - VIII) recibieron extractos acuosos (75 mg, 150 mg, 300 mg/kg de peso corporal respectivamente) por sonda oral durante siete días antes de la inducción de la úlcera. Se sacrificaron las ratas, se extirparon los estómagos y se puntuaron las úlceras. Se realizaron y examinaron secciones histológicas. Los resultados revelaron que los extractos de M. balsamina protegieron el epitelio gástrico de las ratas de la ulceración inducida por etanol en diversos grados, y la dosis alta (150 y 300 mg/kg) de ambos extractos ofreció la mejor conservación (42 % y 50 % de índice de protección contra úlceras, respectivamente) en comparación con los animales no tratados. Los hallazgos histológicos se correlacionaron con los índices de úlcera calculados, y los animales tratados tenían lesiones de la mucosa gástrica menos graves. En extractos de M. balsamina puede poseer actividades antiulcerosas razonables en ratas contra la úlcera gástrica inducida por etanol.

Análise da utilização de inibidores de bomba de prótons em pacientes internados em um hospital universitário do interior de São Paulo / Analysis of the use of proton pump inhibitors in patients admitted to a university hospital in interior of São Paulo

Introdução: A crença de que o uso de Inibidores de Bomba de Prótons (IBPs) apresenta baixo risco de toxicidade, resultou em um aumento significativo na sua prescrição em nível mundial, esse fator juntamente com a baixa divulgação de orientações, têm contribuído para o aumento das indicações desnecessárias de inibidores de bomba de prótons em nível hospitalar, principalmente para profilaxia. Objetivo: Analisar a utilização dos inibidores de bomba de prótons em pacientes internados nas enfermarias de clínica médica de um Hospital Universitário, visando avaliar suas indicações, tempo de uso, efeitos adversos e impacto financeiro gerado pelo uso inadequado. Métodos: Foram analisados prontuários de pacientes que estiveram internados nas enfermarias de clínica médica do Hospital Municipal Universitário de Taubaté (HMUT) durante os meses de maio a julho de 2020. As indicações adequadas do uso de inibidores de bomba de prótons foram baseadas em diretrizes internacionais do American Journal of Gastroenterology e do American Society of Health-System Pharmacy. Resultados: Identificamos que 297 pacientes (79,6%) usaram inibidores de bomba de prótons em algum momento da internação. O uso desse medicamento foi adequadamente prescrito em 49,8% dos casos. Foi encontrado maior prevalência de pneumonia e diarreia nos pacientes que fizeram uso de inibidores de bomba de prótons a longo prazo. O custo anual associado as prescrições indevidas foram de R$24.736,40. Conclusão: Observamos alta prevalência de indicações incorretas dos inibidores de bomba de prótons em ambiente hospitalar, ocasionando gasto desnecessário e possíveis complicações. Faz-se necessário, portanto, elaboração de novos protocolos e maior rigidez nas indicações desses medicamentos no Hospital Municipal Universitário de Taubaté.

Introduction: The belief that the use of Proton Pump Inhibitors (PPIs) presents a low risk of toxicity, resulted in a significant increase in its prescription worldwide, this factor combined with the low disclosure of guidelines, have contributed to the increase in unnecessary indications of at the hospital level, especially for prophylaxis. Objective: To analyze the use of proton pump inhibitors in patients hospitalized in the medical clinic wards of a University Hospital, in order to evaluate their indications, time of use, adverse effects and financial impact generated by inadequate use. Methods: Medical records of patients who were admitted at the Municipal University Hospital of Taubaté during the months of May to July 2020 were analyzed. The appropriate indications for the use of proton pump inhibitors were based on the international guidelines of the American Journal of Gastroenterology and the American Society of Health-System Pharmacy. Results: We identified that 297 patients (79.6%) used proton pump inhibitors at some point in hospitalization. The use of this drug was adequately prescribed in 49.8% of the cases. A higher prevalence of pneumonia and diarrhea was found in patients who used proton pump inhibitors in the long term. The annual cost associated with undue prescriptions was R$24,736.40. Conclusion: We observed a high prevalence of incorrect indications of proton pump inhibitors s in the hospital environment, causing unnecessary expenses and possible complications. It is necessary, therefore, the elaboration of new protocols and greater rigidity in the indications of these drugs at the Municipal University Hospital of Taubaté.

Ulceración esofágica por ingestión de doxiciclina / Doxycycline induced esophageal ulceration

La ulceración esofágica por ingestión de doxiciclina es una de las causas más frecuentes de lesión esofágica. Ha sido subdiagnosticada y escasamente reconocida en dermatología. El dolor retroesternal, la odinofagia de aparición brusca y el antecedente de ingesta de doxiciclina u otros fármacos son características que facilitan su diagnóstico. Puede presentar complicaciones serias, como hemorragias, estenosis y mediastinitis.

Esophageal ulceration due to ingestion of doxycycline is one of the most frequent causes of esophageal injury. It has been underdiagnosed and scarcely recognized in dermatology. Retrosternal pain, sudden odynophagia and a history of doxycycline or other drugs intake are some of the characteristics that lead to diagnosis. It may cause severe complications such as bleeding, stenosis and mediastinitis.

Omeprazole prescriptions for older adults in health care units in Curitiba, Brazil: an analysis based on Beers Criteria / Prescrições de omeprazol para idosos em unidades de saúde de Curitiba: análise segundo os Critérios de Beers

OBJECTIVE: To evaluate omeprazole prescriptions for older adults based on the Beers Criteria, with an analysis of indications and duration of use longer than eight weeks. METHODS: In this retrospective cross-sectional study, data were collected from the electronic medical records of older adults with an omeprazole prescription seen at two health care units in Curitiba, Brazil, between June and August 2019. Data were subjected to descriptive statistical analysis, Student t and χ2 tests. RESULTS: Medical records of 386 patients were analyzed, and 69.95% were female. The mean age was 71 (SD, 8.15) years. Most patients had incomplete primary education (50.52%) and income level ranging from one to two Brazilian minimum monthly wages (39.90%). No indication for omeprazole prescription was found in 23.83% of medical records. Use longer than eight weeks was predominant for all indications in 96.60% of medical records. Duration of use more extended than the Beers Criteria recommendation was independent of sex (p = 0.327), education (p = 0.805), and income level (p = 0.629). A relationship between polypharmacy and long-term drug use was demonstrated (p < 0.001). CONCLUSION: The results of this study suggest the need for periodic review of omeprazole prescriptions considering deprescribing when they appropriate.

OBJETIVO: Avaliar as prescrições de omeprazol para idosos de acordo com os Critérios de Beers, por meio das indicações e do tempo de uso do medicamento por período superior a oito semanas. METODOLOGIA: Estudo transversal, retrospectivo, no qual foram coletados dados dos prontuários eletrônicos de idosos com prescrição de omeprazol atendidos entre junho e agosto de 2019 em duas unidades de saúde em Curitiba. Os dados foram submetidos à análise estatística descritiva e aos testes t de Student e do χ2 . RESULTADOS: Foram analisados prontuários de 386 usuários, sendo 69,95% do sexo feminino. A média de idade foi de 71 anos (DP, 8,15). A maioria dos usuários tem ensino fundamental incompleto (50,52%) e faixa de renda de um a dois salários mínimos (39,90%). Não foi encontrada a indicação para a prescrição de omeprazol em 23,83% dos prontuários. O uso por período superior a oito semanas foi predominante, para todas as indicações, em 96,60% dos prontuários. Demonstrou-se que o tempo de uso superior ao recomendado nos Critérios de Beers independe do sexo (p = 0,327), da escolaridade (p = 0,805) e da faixa de renda (p = 0,629). Evidenciou-se a relação entre polifarmácia e uso do medicamento por períodos prolongados (p < 0,001). CONCLUSÃO: Os resultados deste estudo apontam para a necessidade de revisão periódica das prescrições de omeprazol, considerando-se a desprescrição quando apropriado.

Perfil fitoquímico e atividade gastroprotetora dos frutos de Eugenia mattosii / Phytochemical profile and gastroprotective activity of eugenia mattosii fruits

ABSTRACT BACKGROUND: Extracts obtained from plants and fruits provide a relatively safe and practical alternative for the conventional medicine of gastrointestinal diseases. The specie Eugenia mattosii, popularly known in Brazil as "cerejinha", belongs to Myrtaceae family. Species of this family present pharmacological properties, and can be used in the treatment of gastrointestinal disorders. OBJECTIVE: The aim of this study was to determine the phytochemical profile and evaluate the gastroprotective activity of Eugenia mattosii fruits. METHODS: Phytochemical analysis was carried out by thin layer chromatography and gastroprotective assays were performed using two experimental models: acute ulcer model induced by ethanol/HCl and acute ulcer model induced by non-steroidal anti-inflammatory drug (indomethacin). Total lesion area (mm2) and relative lesion area (%) were determined. RESULTS: The results of the phytochemical analysis indicated that the bark and pulp and seeds of E. mattosii present phenolic compounds, terpenes and/or steroids. In gastric ulcer model induced by ethanol was evidenced significant reduction of damaged areas for doses of 50 and 250 mg/ kg of seeds methanol extract, while in the indomethacin-induced ulcer model, all parts of the fruit presented defense capability of the gastric mucosa by reducing lesions at doses of 50, 125 and 250 mg/kg. CONCLUSION: The results demonstrate that the specie E. mattosii has bioactive compounds that provide gastroprotective activity, presenting possible therapeutic potential.

RESUMO CONTEXTO: Extratos obtidos de plantas e frutos fornecem uma alternativa relativamente segura e prática para os remédios convencionais de doenças gastrointestinais. A espécie Eugenia mattosii, popularmente conhecida no Brasil como "cerejinha", pertence à família Myrtaceae. Espécies desta família apresentam propriedades farmacológicas e podem ser utilizadas no tratamento de distúrbios gastrointestinais. OBJETIVO: O objetivo deste estudo foi determinar o perfil fitoquímico e avaliar a atividade gastroprotetora dos frutos de Eugenia mattosii. MÉTODOS: A análise fitoquímica foi realizada por cromatografia em camada delgada e dois modelos experimentais foram utilizados para avaliação da atividade gastroprotetora em camundongos: modelo de úlcera gástrica induzida por anti-inflamatório não-esteroidal (indometacina) e modelo de úlcera gástrica induzida por etanol/HCl. RESULTADOS: Os resultados da análise fitoquímica indicaram que a casca e polpa e as sementes de E. mattosii apresentam compostos fenólicos, terpenos e/ou esteroides. No modelo de úlcera gástrica induzido pelo etanol, foi evidenciada redução significativa de áreas danificadas para doses de 50 e 250 mg/kg do extrato das sementes, enquanto no modelo de úlcera induzida por indometacina, todas as partes do fruto apresentaram capacidade de defesa da mucosa gástrica ao reduzir as lesões nas doses de 50, 125 e 250 mg/kg. CONCLUSÃO: Os resultados demonstram que a espécie E. mattosii possui compostos bioativos com atividade gastroprotetora, apresentando possível potencial terapêutico.

Flavonoids and anti-oxidant activity mediated gastroprotective action of leathery murdah, terminalia coriacea (roxb.) Wight & arn. Leaf methanolic extract in rats / A ação gastroprotetora antioxidante e flavonoide de extrato metanólico de folhas de Leathery Murdah, Terminalia coracea (Roxb.) Wight & Arn. em ratos

ABSTRACT BACKGROUND Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. from family Combretaceae is used in Ayurveda and Siddha traditional systems of medicine to heal ulcers. OBJECTIVE The present study was conducted to assess the gastroprotective effect and understand the fundamental mechanism of action of Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. Leaf Methanolic Extract. METHODS The test extract was screened for anti-ulcer activity by Aspirin induced ulcerogenesis in pyloric ligation and ethanol induced gastric ulcers at three doses - 125, 250, and 500 mg/kg, p.o. using Ranitidine 50 mg/kg and Misoprostol 100 μg/kg as standard drug in respective models. Seven parameters were carefully examined, that is, ulcer index, total protein, mucin, catalase, malondialdehyde, and superoxide dismutase levels and histopathology. High Performance Liquid Chromatographic - Ultra Violet profiling and Liquid Chromatography - Mass Spectral analysis of crude Terminalia coriacea leaves methanolic extract were carried out as a part of chemical characterization to identify bioactive compounds. RESULTS All the test doses exhibited significant gastroprotective function, particularly the higher doses demonstrated improved action. The results revealed a significant increase in the levels of catalase, superoxide dismutase, and Mucin with reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also illustrated the gastroprotective effect of Terminalia coriacea leaves methanolic extract. CONCLUSION Terminalia coriacea leaves methanolic extract exhibited strong anti-oxidant and anti-secretory activities mediated gastroprotection besides inducing the gastric mucosal production. The observed pharmacological response can be attributed to the flavonoidal compounds namely - Quercetin-3-O-rutinoside, Luteolin-7-O-glucoside, Myricetin hexoside, Quercetin-3-O-glucoside, Isorhamnetin-3-O-rhamnosylglucoside and Isorhamnetin-3-O-glucoside identified in the extract for the first time with High Performance Liquid Chromatographic - Ultra Violet and Liquid Chromatography - Mass Spectral analysis.

RESUMO CONTEXTO Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. da família Combretaceae é usada nos tradicionais sistemas da medicina Ayurveda e Siddha para cicatrização de úlceras. OBJETIVOS O presente estudo foi realizado para avaliar o efeito gastroprotetor e para esclarecer o mecanismo fundamental da ação do extrato metanólico de folhas de Leathery Murdah, Terminalia coracea (Roxb.) Wight & Arn. MÉTODOS O extrato teste foi testado para ação antiulcerogênica induzida pela Aspirina através da ligação pilórica e úlceras gástricas induzidas por etanol em três doses - 125, 250 e 500 mg/kg, via oral, utilizando-se Ranitidina 50 mg/kg e Misoprostol 100 μg/kg como drogas padrão nos respectivos modelos. Sete parâmetros foram cuidadosamente analisados tais como índice ulcerogênico, níveis de proteínas totais, de mucina, de catalase, de malondialdeído e de superoxido dismutase, além da histopatologia. A análise do perfil espectroscópico pela Cromatografia Líquida de Alta Eficiência - Ultravioleta e análise crua pela Cromatografia Líquida - Espectrometria de Massas foram realizadas como parte da caracterização química para identificar os componentes bioativos. RESULTADOS Todas as doses utilizadas exibiram função gastroprotetora, em particular as doses mais elevadas. Os testes revelaram aumentos significantes de catalase, superóxido dismutase e mucina, com diminuição do índice ulcerogênico, dos níveis de proteínas totais, e de malondialdeído. As observações histopatológicas também ilustraram o efeito gastroprotetor do extrato metanólico de folhas de Terminalia coracea. CONCLUSÃO O extrato metanólico de folhas de Terminalia coracea mostrou forte atividade antioxidante e antissecretória além de induzir a produção de mucosa gástrica. A resposta farmacológica observada pode ser atribuída aos compostos flavonoides denominados Quercetin-3-O-rutinosideo, Luteolin-7-O-glucosideo, Myricetin hexosideo, Quercetin-3-O-glucosideo, Isorhamnetin-3-O-rhamnosylglucosideo e Isorhamnetin-3-O-glucosideo, identificados no extrato pela primeira vez pelas análises de Cromatografia Líquida de Alta Eficiência - Ultravioleta e Cromatografia Líquida - Espectrometria de Massas.

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.

Is it necessary to increase the dose of levothyroxine in patients with hypothyroidism who use omeprazole? / É necessário aumentar a dose de levotiroxina em pacientes com hipotireoidismo que usam omeprazol?

Objective It is believed that gastric pH interferes in levothyroxine absorption. Omeprazole, which acts by blocking the secretion of gastric acid, might interfere in hypothyroidism control in patients using levothyroxine and this effect could be dose dependent. The present study aimed to investigate this possibility. Subjects and methods Twenty-one patients with primary hypothyroidism who had been using a stabilized levothyroxine dosage for at least one year were selected and randomly assigned to take omeprazole at the dosage of 40 mg or 20 mg per day. The mean levels of thyroid-stimulating hormone (TSH) before and 3 months after omeprazole usage were compared in the entire sample and in each group. Results Ten patients concluded the entire treatment protocol in the 20 mg group and nine patients in the 40 mg group. There was no significant difference in TSH levels before and 3 months after omeprazole treatment in the entire patient sample (median levels: 2.28 vs. 2.30 mU/L, respectively: p = 0.56). Analysis of each subgroup (20 and 40 mg) showed no significant variation in TSH levels before and 3 months after omeprazole treatment (median levels: 2.24 vs. 2.42 mU/L, p = 0.62, and 2.28 vs. 2.30 mU/L, p = 0.82, respectively). No significant difference in the absolute (p = 0.93) or relative (p = 0.87) delta were observed between the two subgroups. Conclusion Omeprazole in the dosage of 20 or 40 mg/day does not interfere in a clinically relevant manner in the treatment of patients with hypothyroidism that was previously under control. .

Objetivo Acredita-se que o pH gástrico possa interferir na absorção de levotiroxina. O omeprazol, ao inibir a secreção de ácido gástrico, poderia interferir no controle do hipotireoidismo em pacientes em uso de levotiroxina de forma dose-dependente. O presente estudo tem como objetivo investigar essa hipótese. Sujeitos e métodos Vinte e um pacientes em uso de dose estável de levotiroxina por no mínimo um ano foram incluídos e aleatoriamente selecionados para iniciar o uso de omeprazol na dose de 40 mg ou 20 mg por dia. Foram comparados os níveis médios de hormônio tireoestimulante (TSH) antes e 3 meses após o uso de omeprazol, na amostra total e em cada grupo. Resultados Dez pacientes concluíram o protocolo de tratamento no grupo de 20 mg e nove, no grupo de 40 mg. Não houve diferença significativa nos níveis de TSH antes e 3 meses após terapia com omeprazol na amostra total de pacientes (média: 2,28 vs. 2,30 mU/L, respectivamente: p = 0,56). A análise de cada subgrupo (20 e 40 mg) não demonstrou variação significativa nos níveis de TSH antes e 3 meses após terapia com omeprazol (média: 2,24 vs. 2,42 mU/L, p = 0,62 e 2,28 vs. 2,30 um/L, p = 0,82, respectivamente). Não houve diferença significativa no delta absoluto (p = 0,93) ou relativo (p = 0,87) entre os dois subgrupos. Conclusão Omeprazol na dose de 20 ou 40 mg/dia não interfere de forma clinicamente relevante no tratamento de pacientes com hipotireoidismo previamente bem controlados. .

Preventive Efficacy and Safety of Rebamipide in Nonsteroidal Anti-Inflammatory Drug-Induced Mucosal Toxicity

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.

Controlled delivery of ranitidine in the stomach using magnetic field / Administración controlada de ranitidina en el estómago usando campos magnéticos

An attempt has been made to localize ranitidine loaded microspheres in the stomach by magnetic means. Since ranitidine undergoes metabolism by microbial enzymes in the intestine, it is ideal to localize the controlled drug delivery system within the stomach to get uniform release and absorption of the drug for the desired period. Gelatin magnetic microspheres loaded with 9.1, 17.9, 26.3 and 33.3% w/w of ranitidine hydrochloride were prepared by emulsification-cross linking technique. The formulated microspheres were characterized by magnetite content, particle size and in vitro drug release. The efficiency of microspheres to be localized in the stomach is tested in vivo in rats. The prepared microspheres were spherical and had a size distribution from 10 to 105 µm. The in vitro study revealed the capability of microspheres to release the drug over a period of 8 to 12 hours, depending on drug loading. The release was found to be diffusion controlled and followed fickian diffusion principle. The in vivo study showed the efficiency of microspheres to be retained in the stomach over a period of 8 hours.

Se ha hecho el intento por localizar las microesferas cargadas de ranitidina en el estómago mediante medios magnéticos. Como que la ranitidina experimenta metabolismo mediante enzimas microbianas en el intestino, resulta ideal localizar el sistema de administración del medicamento controlado dentro del estómago para alcanzar la liberación y absorción uniformes del medicamento por el período deseado. Microesferas de gelatina magnética cargadas con 9.1, 17.9, 26.3 y 33.3% p/p de hidrocloruro de ranitidina, fueron preparadas mediante una técnica de emulsificación-entrecruzamiento. Las microesferas formuladas se caracterizaron por su contenido de magnetita, el tamaño de las partículas y la liberación del medicamento in vitro. La eficiencia de las microesferas a ser localizadas en el estómago se prueba in vivo en ratas. Las microesferas preparadas eran esféricas y tenían una distribución de tamaño de 10 a 105 µm. El estudio in vitro reveló la capacidad de las microesferas para liberar la droga en un período de 8 a 12 horas, en dependencia de la carga de la droga. Se halló que la liberación estaba sujeta difusión controlada y seguía la ley de Fick para la difusión. El estudio in vivo mostró la eficiencia de las microesferas para ser retenidas en el estómago por un período de 8 horas.

A comparative study between the efficacy of systemic meglumine antimoniate therapy with standard or low dose plus oral omeprazole in the treatment of cutaneous leishmaniasis.

BACKGROUND & OBJECTIVES: Pentavalent antimony compounds are the first line of drugs in the treatment of cutaneous leishmaniasis. However, because of their potential toxic effects, many investigations are performed to find an effective and safe treatment for cutaneous leishmaniasis patients. Our objective in this investigation was to compare the effect of oral omeprazole and low dose systemic meglumine antimoniate (MA) and standard dose of systemic MA in the treatment of cutaneous leishmaniasis. METHODS: This was a randomized double-blinded clinical trial. In 150 patients with cutaneous leishmaniasis who were randomly divided into three groups and were treated with: (i) MA 60 mg/kg/day/ IM and oral placebo for three weeks; (ii) MA 30 mg/kg/day/IM and oral omeprazole 40 mg/day for three weeks; and (iii) MA 30 mg/kg/day/IM and oral placebo for three weeks. All the patients were visited every two weeks from the beginning of the trial up to six weeks and then at 8 and 12 weeks. The effectiveness of the treatment was classified in three levels as complete response, partial response and no response. Data were analyzed by SPSS 10 using KI square, Mann-Whitney, Kaplan-Mayer and ANOVA tests. RESULTS: Rate of complete response for three months (12 weeks) after starting the treatments was 93% for the group treated with standard dose of glucantime and placebo, 89% for the group treated with omeprazole and low dose glucantime and 80% for the group treated with low dose glucantime and placebo and these differences were significant (p < 0.05). The highest response rate was for the group treated with standard dose of glucantime and placebo. INTERPRETATION & CONCLUSION: Although oral omeprazole and low dose of systemic MA showed less efficacy in comparison to standard dose of systemic MA in the treatment of cutaneous leishmaniasis, it still can be considered as a replacement therapy in high risk patients (such as patients with heart, kidney and/or liver disease) under close supervision of physician.

Gastric atrophy and intestinal metaplasia in a patient on long-term proton pump inhibitor therapy.

We report the case of a patient with gastroesophageal reflux disease who developed gastric atrophy and intestinal metaplasia (IM) while on 20-year treatment with proton pump inhibitors. This is perhaps the first report in human beings. A 74-year-old man, who presented with heartburn, showed abnormally high gastric pH (average 6.57) on 24-hour dual channel pH-metry even after discontinuing acid suppressive drugs for one month. No significant esophageal acid exposure was noted, which may be related to an impairment of the acid secreting capacity of the stomach (percentage time esophageal pH<4 during 24-h period 0.3%). Upper gastrointestinal endoscopy was normal except for the prominent submucosal vessels in the body and fundus suggesting gastric atrophy. Histopathological examination of multiple biopsies from the body and antrum of stomach showed signs of gastric atrophy and IM. Rapid urease test and histopathology of gastric biopsies were negative for Helicobacter pylori. Anti-H.pylori IgG ELISA however, was positive. Patient was asked to stop all anti-secretory drugs and only prokinetics were prescribed following which his symptoms markedly improved. On follow-up, in April 2007, he developed symptoms of peripheral neuropathy; serum vitamin 812 level was low. He responded to parenteral vitamin 812 therapy. 24-h dual channel pH-metry repeated after one and a half years showed persistently high gastric pH (average pH 6.76). The patient remained well after discontinuing proton pump inhibitors and continuing prokinetics and vitamin B12 injections.

Effect of single oral dose of sodium rabeprazole on the intragastric pH & volume in patients undergoing elective surgery.

BACKGROUND & OBJECTIVE: While evaluating the effectiveness of drugs used for the prophylaxis of acid aspiration of gastric contents, the impact of duodeno-gastric reflux on gastric contents has not been studied earlier. This study was carried out to evaluate the effect of preanaesthetic oral administration of sodium rabeprazole on pH and volume of gastric contents in adult patients undergoing elective surgery by excluding cases contaminated with duodeno-gastric refluxate. METHODS: The patients in group C (control) in the triple blind placebo controlled trial received placebo while group S sodium rabeprazole 20 mg orally at 2100 h, a night before elective surgery. Next day, gastric contents were aspirated with a large bore, multi-orifices gastric tube passed through an endotracheal tube placed blindly in oesophagus after tracheal intubation and analyzed for the presence of bile salts, pH and volume. The pH and volume of gastric contents were the primary and duodeno-gastric reflux secondary outcome measures of the study. RESULTS: The pH and volume of group S-2 were 3.97+/-1.78 and 9.48+/-8.39 ml respectively compared with 1.90+/-0.47 and 19.60+/-18.56 ml of group C-2. Sodium rabeprazole, after excluding contaminated cases with duodeno-gastric refluxate, significantly increased the pH (P<0.001), decreased the volume of gastric contents (P<0.005) and the proportion of the patients (30.76 vs 2.63%) considered at risk compared with placebo (P<0.001) according to the criteria defined (pH < 2.5 and volume > 25 ml). Thirty nine samples (33.33%) out of 117 were contaminated with duodenal contents. Duodenogastric reflux significantly (P<0.001) affected pH and volume of gastric in both groups C-1 vs C-2 and S-1 vs S-2. INTERPRETATION & CONCLUSION: Sodium rabeprazole 20 mg given orally a night before surgery provided adequate prophylaxis for acid aspiration syndrome at the time of induction of anaesthesia and duodeno-gastric reflux significantly affected both the pH and volume of gastric contents.

Estudo de utilização de anti-ulcerosos na população idosa de Porto Alegre, RS, Brasil / Study of antiulcerous utilization in the elderly population of Porto Alegre, RS, Brazil

O aumento gradativo da longevidade destaca-se como uma das mais importantes mudanças demográficas das últimas décadas. A incidência de usuários de anti-ulcerosos vem aumentando nessa parcela da população, e com isso, a necessidade do fortalecimento na relação profissional-usuário. Objetivos: Descrever a terapia anti-ulcerosa utilizada pela população idosa de Porto Alegre, RS, Brasil e analisar a necessidade de implementação de um programa de atenção farmacêutica a esses pacientes. Métodos: Estudo transversal exploratório e observacional. O instrumento utilizado para a coleta de dados foi uma ficha de seguimento farmacoterapêutico testada e validada. Os dados foram tabulados e analisados com o uso do programa SPSS 14,0. Resultados: Do total de 514 pacientes entrevistados, 13,2% utilizavam medicamentos para terapia das doenças ácido-pépticas. Os inibidores da bomba de prótons foram a subclasse de medicamentos mais utilizadas, seguidos pelos antagonistas de receptores H2. Foi observada grande presença de polifarmácia. Apenas 32,2% dos idosos se automedicam, em contrapartida, 71,2% não entendem a receita médica e 81,4% esquecem de ingerir seus medicamentos com freqüência. Conclusão: A grande variabilidade farmacocinética e farmacodinâmica dessa população evidenciam a importância deste estudo, a fim de evitar erros farmacoterapêuticos que poderão ocasionar interações farmacológicas e reações adversas. Portanto, é justificada a implementação de um programa de atenção farmacêutica ao paciente idoso que utiliza anti-ulcerosos.

The gradual increase of the longevity is distinguished as one of the most important demographic changes of the last decades. The incidence of antiulcerous users is increasing in this age group, and this strengthens the necessity of the professional-user relation. Objectives: To describe the antiulcerous therapy used by the elderly population of Porto Alegre, RS, Brazil and to analyze the implementation necessity of a pharmaceutical care program to these patients. Methods: Cross-sectional, observational and exploratory study. The instrument used for the data collection was a validated pharmacotherapy questionnaire tabulated and analyzed by the SPSS 14.0 computer program. Results: Of the total of 514 interviewed patients, 13.2% use medicines to acid-peptic illnesses. The inhibitor of proton pump was the medicine subclass more used, followed by the histamine 2 receptor (H2R) antagonist. Great presence of polypharmacy was observed. Only 32.2% of the elderly use self-medication. On the other hand, 71.2% do not understand the medical prescription and 81.4% forget their medicines. Conclusion: The great pharmacokinetic and pharmacodynamic variability of this population evidences the importance of this study, in order to prevent errors that can cause drugs interactions and side effects. Therefore, the implementation of a pharmaceutical care program to the elderly patient who use antiulcerous is justified.

Role of Anti-secretory Treatment in Addition to Helicobacter pylori Eradication Triple Therapy in the Treatment of Peptic Ulcer / 대한소화기학회지

BACKGROUND/AIMS: It is not clear whether the anti-secretory therapy should be continued for symptomatic relief and ulcer healing before or after the eradication of H. pylori in patients with peptic ulcer disease. The aim of this study was to evaluate the effectiveness of additional anti-secretory therapy before or after H. pylori eradication in peptic ulcer disease. METHODS: Thirty eight patients with H. pylori-positive active peptic ulcer were included. Patients were randomly allocated into 3 groups; standard 1-week triple therapy followed by omeprazole (20 mg, qd) for 3 weeks (group A), standard 1-week triple therapy only (group B), and omeprazole (20 mg, qd) for 3 weeks followed by 1-week triple therapy (group C). Endoscopy with the rapid urease test and histology for H. pylori was performed 4-8 weeks after the completion of treatment. The symptom was scored by a visual analog scale. RESULTS: Of the 38 patients, 10 were excluded from the per-protocol analysis of this study. The H. pylori eradication rates were 87.5% (group A), 80.0% (group B) and 90.0% (group C) respectively. The peptic ulcer healing rates were 100% in group A, 70.0% in group B, and 90.0% in group C. There was no difference in H. pylori eradication rates and ulcer healing rates among three groups (p>0.05). Symptom score differences between pre-treatment and post-treatment group were not significantly different (p>0.05). CONCLUSIONS: The standard one week triple therapy with or without 3-weeks anti-secretory treatment with omeprazole before or after the therapy does not affect H. pylori eradication rates, peptic ulcer healing rates, and symptom score improvement.

Extraesophageal Manifestations of Gastroesophageal Reflux Disease / 대한소화기학회지

Gastroesophageal reflux disease (GERD) often presents as typical symptoms such as heartburn or acid regurgitation. However, a subgroup of patients presents a collection of symptoms and signs that are not directly related to esophageal damage. These are known collectively as the extraesophageal manifestations of GERD, such as non-cardiac chest pain, laryngitis, chronic cough, hoarseness, asthma or dental erosion. They have a common pathophysiology, involving microaspiration of acid into the larynx and pharynx, and vagally mediated bronchospasm and laryngospasm. The role of extraesophageal reflux in such disorders is underestimated due to often silent symptoms and difficult confirmation of diagnosis. Endoscopy and pH monitoring are insensitive and therefore not useful in many patients as diagnostic modalities. Thus, anti-secretory therapy by proton pump inhibitor is used as both a diagnostic trial and as a therapy in the majority. Attention to optimizing therapy and judicious use of endoscopy and reflux monitoring are needed to maximize treatment success.

Comparison of Helicobacter pylori Eradication Rate in Patients with Non-ulcer Dyspepsia and Peptic Ulcer Diseases according to Proton Pump Inhibitors / 대한소화기학회지

BACKGROUND/AIMS: Conflicting results have been reported whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H. pylori) eradication treatment compared with patients with peptic ulcer diseases (PUD). The aim of this study was to evaluate any difference in H. pylori eradication rates between patients with NUD and PUD according to each proton pump inhibitor (PPI). METHODS: From September, 2004 to April, 2007, we retrospectively reviewed 2,297 patients with NUD (1,050 patients) or PUD (1,247 patients) infected with H. pylori. All patients received a standard 1 week triple therapy comprising of one of the five PPIs (pantoprazole, esomeprazole, omeprazole, lansoprazole, rabeprazole), clarithromycin and amoxicillin. The follow-up H. pylori test was performed 4 weeks after the completion of therapy. RESULTS: There was no significant difference in the eradication rates between the two groups. In comparison of eradication rates according to PPI, omeprazole- based triple therapy group showed higher eradication rate than other groups in patients with NUD, but not in patients with PUD. CONCLUSIONS: This study failed to show any difference in H. pylori eradication rate between patients with NUD and PUD. There is no convincing evidence that the eradication rate may be affected by different PPI.

Effectiveness of 10 Day-sequential Therapy for Helicobacter pylori Eradication in Korea / 대한소화기학회지

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. Proton pump inhibitor (PPI)-based triple therapy is the most preferred regimen in clinical practice. However, a critical fall in the H. pylori eradication rate has been observed in the recent years. A novel 10 day-sequential therapy consists of five days of dual therapy followed by five days of triple therapy regimen has recently been described. We aimed to evaluate whether 10 day-sequential therapy eradicated H. pylori infection better than the PPI-based triple therapy in Korea. METHODS: 158 patients with proven H. pylori infection were randomized to receive either 10 day-sequential therapy (20 mg of omeprazole, 1.0 g of amoxicillin, each administered twice daily for the first 5 days, followed by 20 mg of omeprazole, 500 mg of clarithromycin, 500 mg of metronidazole, each administered twice daily for the remaining 5 days) or PPI-based triple therapy (20 mg of omeprazole, 1.0 g of amoxicillin, 500 mg of clarithromycin, each administered twice daily for 1 week). Outcome of eradication therapy was assessed 8 weeks after the cessation of treatment. RESULTS: Eradication rates of 10 day-sequential therapy and PPI-based triple therapy were 77.9% (60/77) and 71.6% (58/81) by intention to treat analysis, respectively (p=0.361). By per protocol analysis, eradication rates of 10 day-sequential therapy and triple therapy were 85.7% (60/70) and 76.6% (58/76), respectively (p=0.150). There were no significant differences in adverse event rates and treatment compliance between two groups. CONCLUSIONS: The 10 day-sequential therapy regimen failed to achieve significantly higher eradication rates than PPI-based triple therapy.