Retrospective evaluation of the effect of acid suppressant drugs on leukocyte ratios in dogs with mast cell tumors.

BACKGROUND: Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed. HYPOTHESIS: Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment. ANIMALS: Fifty-one dogs with mast cell tumors (MCTs). MATERIALS AND METHODS: Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine-2-receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre- and post-treatment time points, and between pre- and post-time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor. RESULTS: Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre- to post-treatment (3.429; range, 1.417-15 to 5.631; range, 2.654-92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups. CONCLUSIONS: A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs.

Development and in vitro/in vivo evaluation of famotidine hydrochloride bioadhesive sustained release suspension.

To develop a new kind of famotidine-resin microcapsule for gastric adhesion sustained release by screening out suitable excipients and designing reasonable prescriptions to improve patient drug activities to achieve the expected therapeutic effect. The famotidine drug resin was prepared using the water bath method with carbomer 934 used as coating material. Microcapsules were prepared using the emulsified solvent coating method and appropriate excipients were used to prepare famotidine sustained release suspension. Pharmacokinetics of the developed microcapsules were studied in the gastrointestinal tract of rats. The self-made sustained-release suspension of famotidine hydrochloride effectively reduced the blood concentration and prolonged the action time. The relative bioavailability of the self-made suspension of the famotidine hydrochloride to the commercially available famotidine hydrochloride was 146.44%, with an average retention time of about 5h longer, which indicated that the new suspension had acceptable adhesion properties. The findings showed that the newly developed famotidine-resin microcapsule increased the bioavailability of the drug with a significant sustained-release property.

Targeting of KOR by famotidine promotes OPC maturation differentiation and CNS remyelination via STAT3 signaling pathway.

This study aims to identify FDA-approved drugs that can target the kappa-opioid receptor (KOR) for the treatment of demyelinating diseases. Demyelinating diseases are characterized by myelin sheath destruction or formation that results in severe neurological dysfunction. Remission of this disease is largely dependent on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLGs) in demyelinating lesions. KOR is an important regulatory protein and drug target for the treatment of demyelinating diseases. However, no drug targeting KOR has been developed due to the long clinical trials for drug discovery. Here, a structure-based virtual screening was applied to identify drugs targeting KOR among 1843 drugs of FDA-approved drug libraries, and famotidine was screen out by its high affinity cooperation with KOR as well as the clinical safety. We discovered that famotidine directly promoted OPC maturation and remyelination using the complementary in vitro and in vivo models. Administration of famotidine was not only effectively enhanced CNS myelinogenesis, but also promoted remyelination. Mechanically speaking, famotidine promoted myelinogenesis or remyelination through KOR/STAT3 signaling pathway. In general, our study provided evidence of new clinical applicability of famotidine for the treatment of demyelinating diseases for which there is currently no effective therapy.

Effects of the histamine H2 receptor antagonist famotidine on the healing of colonic anastomosis in rats

BACKGROUND: Failure of anastomotic healing is one of the major complications in colorectal surgery. Because histamine plays an important role in immune and inflammatory reactions, we demonstrate the effects of famotidine on the healing of colonic anastomosis in rats. METHODS: Twenty-eight Sprague-Dawley rats were used in the study. Excision and end-to-end anastomosis was performed in the distal colon of the rat. The Famotidine Group received 2 mg/kg/day famotidine; the Control Group received the same amount of saline. Bursting pressure of anastomoses and hydroxyproline content of perianastomotic tissues were evaluated on the third and seventh days following surgery. RESULTS: Bursting pressures and hydroxyproline contents for the Famotidine Group were significantly lower than the equivalent parameters for the Control Group on both the third and seventh days post-surgery. CONCLUSIONS: According to our findings, famotidine exerts detrimental effects on the anastomotic bursting pressure and hydroxyproline content of perianastomotic tissues in the colon of rats.

Hernia hiatal gigante: reporte de un caso / Giant hiatal hernia: a case report

La hernia de hiato es una situación patológica que se da cuando parte del estómago se introduce hacia el tórax. El esófago entra en el abdomen desde el tórax a través de un agujero o hiato que se encuentra en el diafragma. El estómago protruye a través de este hiato debilitado y produce ardores (pirosis) y dolor torácico. La persistencia en el tiempo de esta hernia, puede provocar una metaplasia de la mucosa esofágica dando al lugar al esófago de Barret el cual puede malignizar produciéndose cáncer de esófago. (1) La hernia de hiato es relativamente frecuente, afectando hasta un 20 por ciento de la población. Del total de pacientes con el trastorno, cerca del 10 por ciento son asintomáticos, dependiendo del grado de protrución estomacal y de que tanto esté afectado el esfinter esofágico inferior (EEI). Un 40 por ciento de las hernias de hiato son hernias deslizantes, en las que el EEI protruye conjuntamente con una porción del estómago y solo un 5 por ciento son paraesofágicas, en la que solo una porción del estómago se hace intratorácica mientras tanto que el EEI permanece intraabdominal. Los síntomas más comunes de una hernia de hiato incluyen pirosis, dolor torácico, disfagia, palpitaciones y ocasionalmente regurgitación o reflujo gastroesofágico. El diagnóstico de una hernia hiatal comienza con el éxamen físico por razón de la sintomatología. Los estudios radiográficos y la endoscopia digestiva demuestran la hernia hiatal y ayudan a descartar otras causas de molestias digestivas altas. (2) Se recomienda un procedimiento quirúrgico conocida como fundoplicación de Nissen, (3) Cuando los síntomas causados por una hernia de hiato son tan severas que pueden resultar en lesiones al esófago o incluso cáncer del esófago. (6) Se trata de lactante mayor de seis meses de edad quien es natural de la localidad y procedente de Cordero, quien inicia enfermedad actual el día de hoy en la madrugada según refiere la madre, caracterizado por vómitos en número incontables.

Efeitos dos bloqueadores H2 sobre o espraiamento de macrófagos in vitro / Effects of H2 blockers on the spreading of macrophages in vitro

Verificar se a cimetifdina, ranitidina e a famotidina, quando injetadas por via ip em camundongo, promovem ativaçäo macrofágica e se esta é alterada com o uso prévio de tioglicolato sódico. Tipo de estudo - Experimental. Animais - Camundongos isogênicos, Balb/c, 19-21g. Intervençiao - Utilizados oito grupos com 10 animais cada. Os animais foram tratados, por via ip, com cimetidina (100mg/Kg), ranitidina (62,5mg/Kg) e famotidina (50mg/Kg), sendo comparados com um grupo controle (salina). Vinte e quatro horas após a inoculaçäo, foi aplicada a técnica do espraiamento de macrófagos. Em etapa posterior, o mesmo procedimento foi realizado, porém em grupos tratados previamente com tioglicolato sódico (15mg/Kg). Análise estatística - Através dos testes de KrusKal-Wallis e Mann-Whitney. Resultados e conclusäo - A inoculaçäo dos anti-H2 em cavidade peritoneal de camundongos aumenta significantemente o espraiamento macrofágico, independentemente do uso prévio de um irritante peritoneal