Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

Effects of dipyrone on the digestive tract

Dipyrone (metamizole), acting through its main metabolites 4-methyl-amino-antipyrine and 4-amino-antipyrine, has established analgesic, antipyretic, and spasmolytic pharmacological effects, which are mediated by poorly known mechanisms. In rats, intravenously administered dipyrone delays gastric emptying (GE) of liquids with the participation of capsaicin-sensitive afferent fibers. This effect seems to be mediated by norepinephrine originating from the sympathetic nervous system but not from the superior celiac-mesenteric ganglion complex, which activates β2-adrenoceptors. In rats, in contrast to nonselective non-hormonal anti-inflammatory drugs, dipyrone protects the gastric mucosa attenuating the development of gastric ulcers induced by a number of agents. Clinically, it has been demonstrated that dipyrone is effective in the control of colic-like abdominal pain originating from the biliary and intestinal tracts. Since studies in humans and animals have demonstrated the presence of β2-adrenoceptors in biliary tract smooth muscle and β2-adrenoceptor activation has been shown to occur in dipyrone-induced delayed GE, it is likely that this kind of receptors may participate in the reduction of smooth muscle spasm of the sphincter of Oddi induced by dipyrone. There is no evidence that dipyrone may interfere with small bowel and colon motility, and the clinical results of its therapeutic use in intestinal colic appear to be due to its analgesic effect.

Acute exercise inhibits gastric emptying of liquids in rats: influence of the NO-cGMP pathway

We previously found that acute exercise inhibited the gastric emptying of liquid in awake rats by causing an acid-base imbalance. In the present study, we investigated the involvement of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, vasoactive intestinal peptide (VIP), and corticotropin-releasing factor (CRF) peptide in this phenomenon. Male rats were divided into exercise or sedentary group and were subjected to a 15-min swim session against a load (2.5 or 5% b.w.). The rate of gastric emptying was evaluated after 5, 10, or 20 min postprandially. Separate groups of rats were treated with vehicle (0.9% NaCl, 0.1 mL/100 g, ip) or one of the following agents: atropine (1.0 mg/kg, ip), the NO non-selective inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10.0 mg/kg, ip), or the selective cGMP inhibitor 1H-(1,2,4)oxadiazole[4,3-a]quinoxalin-1-one (ODQ; 5.0 mg/kg, ip), the i-NOS non-specific inhibitor (aminoguanidine; 10.0 mg/kg, ip), the corticotropin-releasing factor receptor antagonist (astressin; 100 µg/kg, ip), or the vasoactive intestinal peptide (VIP) receptor antagonist Lys1, Pro2,5, Arg3,4, Tyr6 (100 µg/kg, ip). Compared to sedentary rats, both the 2.5 and 5% exercise groups exhibited higher (P<0.05) values of blood lactate and fractional gastric dye recovery. Corticosterone and NO levels increased (P<0.05) in the 5% exercised rats. Pretreatment with astressin, VIP antagonist, atropine, L-NAME, and ODQ prevented the increase in gastric retention caused by exercise in rats. Acute exercise increased gastric retention, a phenomenon that appears to be mediated by the NO-cGMP pathway, CRF, and VIP receptors.

Dipyrone in association with atropine inhibits the effect on gastric emptying induced by hypoglycemia in rats

Atropine (AT) and dipyrone (Dp) induce a delay of gastric emptying (GE) of liquids in rats by inhibiting muscarinic receptors and activating β2-adrenergic receptors, respectively. The objective of the present study was to determine the effects of pretreatment with AT and Dp, given alone or in combination, on the effect of hypoglycemia in the liquid GE in rats. Male Wistar adult rats (280-310 g) were pretreated intravenously with AT, Dp, AT plus Dp or their vehicle and then treated 30 min later with iv insulin or its vehicle (n=8-10 animals/group). Thirty min after treatment, GE was evaluated by determining, in awake rats, the percent gastric retention (%GR) of a saline meal labeled with phenol red administered by gavage. The results indicated that insulin induced hypoglycemia in a dose-dependent manner resulting in a significant reduction in %GR of liquid only at the highest dose tested (1 U/kg). Pretreatment with AT significantly increased %GR in the rats treated with 1 U/kg insulin. Surprisingly, after pretreatment with AT, the group treated with the lowest dose of insulin (0.25 U/kg) displayed significantly lower %GR compared to its control (vehicle-treated group), which was not seen in the non-pretreated animals. Pretreatment with Dp alone at the dose of 40 mg/kg induced an increase in %GR in both vehicle and 0.25 U/kg-treated rats. A higher dose of Dp alone (80 mg/kg) significantly reduced the effect of a marked hypoglycemia induced by 1 U/kg of insulin on GE while in combination with AT the effect was completely abolished. The results with AT suggest that moderate hypoglycemia may render the inhibitory mechanisms of GE ineffective while Dp alone and in combination with AT significantly overcame the effect of hypoglycemia on GE.

Effect of selective beta-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

There is evidence for participation of peripheral β-adrenoceptors in delayed liquid gastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At). The present study aimed to determine whether β-adrenoceptors are involved in delayed GE induced by phenylpyrazole derivatives and the role of the prevertebral sympathetic nervous system in this condition. Male Wistar rats weighing 220-280 g were used in the study. In the first experiment rats were intravenously pretreated with vehicle (V), atenolol 30 mg/kg (ATE, β1-adrenergic antagonist), or butoxamine 25 mg/kg (BUT, β2-adrenergic antagonist). In the second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA, β3-adrenergic antagonist). In the third experiment, rats were subjected to surgical resection of the celiac-superior mesenteric ganglion complex or to sham surgery. The groups were intravenously treated with saline (S), 240 µmol/kg Dp, AA, or At, 15 min after pretreatment with the antagonists or V and nine days after surgery. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR (means±SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dp vs V+Dp: 35.0%±5.1% vs 56.4%±2.7%) and At (BUT+At vs V+At: 33.5%±4.7% vs 52.9%±2.6%) on GE, and significantly reduced (P<0.05) the effect of AA (BUT+AA vs V+AA: 48.0%±5.0% vs 65.2%±3.8%). ATE, SRA, and sympathectomy did not modify the effects of treatments. These results suggest that β2-adrenoceptor activation occurred in delayed liquid gastric emptying induced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, and antipyrine. Additionally, the released neurotransmitter did not originate in the celiac-superior mesenteric ganglion complex.

Potencialidades e fragilidades da rede de cuidado da pessoa com HIV/Aids / Potencialidades y fragilidades de la red de cuidado de las personas con VIH/SIDA / Potentialities and weaknesses in the care network of people with HIV/AIDS

RESUMOObjetivo:compreender as potencialidades e fragilidades da rede de cuidado da pessoa com HIV/Aids em um serviço de referência do Estado de Santa Catarina-SC.Método:participaram oito sujeitos e sua rede de cuidado, totalizando 18 participantes. Os dados foram coletados através de entrevistas e examinados por análise de conteúdo, sustentados teoricamente pelo interacionismo simbólico.Resultado:a análise resultou nas categorias: A rede ofertando o cuidado à pessoa com síndrome da imunodeficiência adquirida e Enfrentando Barreiras no cuidar, que refletem as potencialidades e fragilidades, na rede de cuidado. A primeira retrata a oferta de cuidado afetivo e humanizado e a segunda, uma rede pouco ampliada, constituída por profissionais de saúde e algum membro familiar.Conclusão:a rede de cuidado profissional é importante, mesmo diante do aumento dos atendimentos numa estrutura física e número de profissionais que já não comportam a crescente demanda.

RESUMENObjetivo:comprender las fortalezas y debilidades de la red de atención de la persona con VIH/SIDA en un centro de referencia en el estado de Santa Catarina-SC.Metodo:ocho participantes sujetos y su red de atención, por un total de 18 participantes. Los datos fueron recolectados a través de entrevistas y se examinaron mediante análisis de contenido, en teoría, con el apoyo de la interacción simbólica.Resultados:el análisis resultó en las siguientes categorías: La red de ofrecer atención a las personas con síndrome de inmunodefi ciencia adquirida y tropezando con obstáculos a la atención, que refl ejan las fortalezas y debilidades en la red de atención. El primero representa la prestación de atención emocional y humano y la segunda un poco más amplia, incluyendo la red de profesionales de la salud y un miembro de la familia.Conclusión:la red de atención profesional es importante, a pesar del aumento de las llamadas en una estructura física y el número de profesionales que ya no se comportan de la creciente demanda.

ABSTRACTObjective:to understand the strengths and weaknesses in the care network of people with HIV/AIDS in a referral center in the state of Santa Catarina-SC.Method:participants were eight subjects and their care network, totaling 18 participants. Data were collected through interviews and examined by content analysis, theoretically supported by symbolic interaction.Results:the analysis resulted in the following categories: The network offering care to people with acquired immunodefi ciency syndrome, and Facing Barriers in care, which refl ect the strengths and weaknesses in the care network. The fi rst depicts the provision of emotional and humanized care, and the second a restricted network formed by health professionals and a family member.Conclusion:the professional care network is important, despite the increased number of assistances in a physical structure and amount of professionals who no longer meet the growing demand.

GASTRIC RESIDUAL VOLUME BY MAGNETIC RESSONANCE AFTER INTAKE OF MALTODEXTRIN AND GLUTAMINE: a randomized double-blind, crossover study / Volume gástrico residual após ingestão de maltodextrina e glutamina: estudo randomizado, duplo-cego, cruzado

Context The addition of glutamine in preoperative drinks may enhance the benefits of carbohydrate alone. Objectives To evaluate the gastric residual volume after the intake of a beverage containing carbohydrate plus glutamine. Methods Eleven healthy volunteers (24-30 years-old) were randomized in a crossover fashion to intake 400 mL (4h before) and 200 mL (2h before) of a beverage containing either 12.5% maltodextrin (carbohydrate group) or 12.5% maltodextrin plus 15 g of glutamine (glutamine group) in two different moments 7 days apart. Magnetic ressonance was performed to measure the gastric residual volume (mL) 120 and 180 minutes after the last ingestion. Results Gastric residual volume similar to basal condition was found after 2h and 3h of the intake of beverages. There was no difference in the mean ±SD GRV (mL) found at 120 minutes (carbohydrate group: 22.9±16.6 and glutamine group: 19.7±10.7) and at 180 minutes (carbohydrate group: 21.5±24.1 and glutamine group: 15.1±10.1) between the two drinks. Conclusions Gastric emptying is efficient, and occurs in up to two hours after the intake of a beverage containing either carbohydrate alone or carbohydrate associated with glutamine. The addition of glutamine to carbohydrate-enriched drink seems to be safe for the use up to 2h before an operation. HEADINGS - Gastric emptying. Preoperative care. Carbohydrates. Glutamine. Magnetic resonance imaging. .

Contexto A adição de glutamina à bebidas de pré-operatório pode aumentar os benefícios do carboidrato isolado. Objetivos Avaliar o volume gástrico residual após ingestão de bebida contendo carboidrato mais glutamina. Métodos Onze voluntários saudáveis (de 24 à 30 anos) foram randomizados em um estudo cruzado para ingerirem 400 mL (4h antes) e 200 mL (2h antes) de bebida contendo 12,5% de maltodextrina (grupo carboidrato) ou 12,5% de maltodextrina mais 15 g de glutamina (grupo glutamina), em dois momentos distintos, com intervalo de 7 dias entres eles. A ressonância magnética foi realizada para medir o volume gástrico residual (mL) 120 e 180 minutos após a última ingestão. Resultados Foi encontrado um volume gástrico residual semelhante à condição basal de jejum após 2h e 3h da ingestão das bebidas. Não houve diferença na média ±DP do volume gástrico residual (mL) encontrada aos 120 minutos (grupo carboidrato: 22.9±16.6 e grupo glutamina: 19.7±10.7; P>0.05) e aos 180 minutos (grupo carboidrato: 21.5±24.1 e grupo glutamina: 15.1±10.1; P>0.05) entre as duas bebidas. Conclusões O esvaziamento gástrico é eficiente e ocorre em até 2h apos a ingesta de bebida contendo apenas carboidrato ou carboidrato associado à glutamina. Assim, a adição de glutamina à bebidas enriquecidas com carboidrato parece ser segura para uso até 2h antes da operação. DESCRITORES - Esvaziamento gástrico. Cuidados pré-operatórios. Carboidratos. Glutamina. Imagem por ressonância magnética. .

Evidence for the involvement of peripheral -adrenoceptors in delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

Dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At) delay liquid gastric emptying (GE) in rats. We evaluated adrenergic participation in this phenomenon in a study in male Wistar rats (250-300 g) pretreated subcutaneously with guanethidine (GUA), 100 mg·kg−1·day−1, or vehicle (V) for 2 days before experimental treatments. Other groups of animals were pretreated intravenously (iv) 15 min before treatment with V, prazosin (PRA; 1 mg/kg), yohimbine (YOH; 3 mg/kg), or propranolol (PRO; 4 mg/kg), or with intracerebroventricular (icv) administration of 25 µg PRO or V. The groups were treated iv with saline or with 240 µmol/kg Dp, AA, or At. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. %GR (mean±SE, n=8) indicated that GUA abolished the effect of Dp (GUA vs V=31.7±1.6 vs 47.1±2.3%) and of At (33.2±2.3 vs 54.7±3.6%) on GE and significantly reduced the effect of AA (48.1±3.2 vs 67.2±3.1%). PRA and YOH did not modify the effect of the drugs. %GR (mean±SE, n=8) indicated that iv, but not icv, PRO abolished the effect of Dp (PRO vs V=29.1±1.7 vs 46.9±2.7%) and At (30.5±1.7 vs 49±3.2%) and significantly reduced the effect of AA (48.4±2.6 vs 59.5±3.1%). These data suggest activation of peripheral β-adrenoceptors in the delayed GE induced by phenylpyrazolone derivatives.

Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats / Mucosite induzida pelo metotrexato retarda o esvaziamento gástrico e o trânsito gastrointestinal de líquidos em ratos acordados

CONTEXT: Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES: To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. METHODS: Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously) or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration). Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. RESULTS: After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. CONCLUSION: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.

CONTEXTO: Metotrexato e outros agentes anticâncer podem induzir uma mucosite intestinal, que é um dos fatores de limitante mais comum que limitam o aumento escalonado da dose do metotrexato. OBJETIVOS: Avaliar o esvaziamento gástrico e o trânsito gastrointestinal de líquidos na mucosite intestinal induzida por metotrexato. MÉTODOS: Ratos Wistar, receberam metotrexato (2.5 mg/kg/dia por 3 dias, subcutâneo) ou salina. Após 1, 3 ou 7 dias, secções do duodeno, jejuno e íleo foram retirados para análise morfométrica e dosagem da atividade de mieloperoxidase (marcador bioquímico da infiltração de neutrófilos). Outros ratos foram pré-tratados com metotrexato ou salina, após 3 ou 7 dias, foram alimentados mediante gavagem com uma refeição teste e sacrificados após 10, 20 e 30 minutos. As retenções fracionais do corante no estômago e em três segmentos do intestino delgado foram determinados por espectrofotometria. RESULTADOS: Após 3 dias do metotrexato, houve lesão do epitélio intestinal em todos os segmentos, com aumento da atividade de mieloperoxidase, no duodeno e íleo. Sete dias após o metotrexato, foi observada completa reversão da lesão intestinal. Observou-se ainda retardo no esvaziamento gástrico após 10 min, 20 min e 30 min, após 3 dias, mas não após 7 dias do tratamento com metotrexato. A retenção fracional dos segmentos do intestino foi reduzida no primeiro e segundo segmentos após 10 min, e no terceiro segmento após 30 min da administração da refeição, somente 3 dias após o tratamento com metotrexato. CONCLUSÃO: A mucosite intestinal induzida por metotrexato retarda o esvaziamento gástrico e o trânsito gastrointestinal de líquidos em ratos acordados.

Effect of baclofen on liquid and solid gastric emptying in rats / Efeito do baclofen no esvaziamento gástrico de líquido e de sólidos em rato

CONTEXT: Gamma-aminobutyric acid (GABA) is a potent inhibitory neurotransmitter. There is evidence that GABA B receptors located in the dorsal complex and in afferent fibers of the vagus nerve participate in the control of gastrointestinal motility. OBJECTIVE: To assess the intracerebroventricularly (ICV) and intravenously (IV) effect of baclofen, a GABA B receptor agonist, on liquid and solid gastric emptying in rats. METHODS: Adult male Wistar rats weighing 250-300 g (n = 6-8 animals) were used. Gastric emptying of liquid test meals labeled with phenol red was evaluated by the determination of percent gastric retention ( percentGR) 10 and 15 min after orogastric administration of saline and 10 percent glucose meals, respectively. Baclofen was injected ICV (1 and 2 µg/animal) through a tube implanted into the lateral ventricle of the brain and was injected IV (1 and 2 mg/kg) into a tail vein. The gastric emptying of liquid was determined 10 or 30 min after ICV and IV baclofen administration, respectively. The gastric emptying of the solid meal was assessed by the determination of percent gastric retention 2 h after the beginning of the ingestion of the habitual ratio by the animal, consumed over a period of 30 min. Baclofen was administered ICV (1 and 2 µg/animal) or IV (1 and 2 mg/kg) immediately after the end of the ingestion of the solid meal. The control groups received vehicle (sterile saline solution) ICV or IV. RESULTS: The group of animals receiving baclofen ICV (2 mg/animal) presented a significantly lower (P<0.05, Tukey test) percentGR (mean ± SEM) of the saline (18.1 ± 2.5 percent) compared to control (33.2 ± 2.2 percent). In the group receiving the drug IV, the gastric retention of the same test meal did not differ from control. ICV and IV administration of baclofen had no effect on the gastric emptying of the 10 percent glucose solution compared to control. ICV administration of 1 or 2 mg baclofen/animal significantly increased the gastric retention of the solid test meal (57.9 ± 6.5 percent and 66.6 ± 6.3 percent, respectively) compared to control (35.1 ± 4.4 percent). The same phenomenon was observed only with the IV dose of 2 mg/kg (71.9 ± 2.6 percent) compared to control (52.7 ± 2.8 percent). CONCLUSION: Baclofen administered: 1. ICV (2 µg/animal), but not IV, increased gastric emptying of a non-caloric isotonic liquid test meal (saline); 2. when administered ICV or IV, it had no effect of gastric emptying of a 10 percent glucose solution; 3) when administered ICV (1 and 2 mg/animal) and IV (2 mg/kg) it delayed the gastric emptying of the solid meal.

CONTEXTO: O ácido gama-aminobutírico (GABA) é um potente neurotransmissor inibitório. Há evidências que receptores GABA>B localizados no complexo dorsal do vago e em fibras aferentes do nervo vago participam no controle da motricidade gastrointestinal. OBJETIVO: Avaliar o efeito intracerebroventricular (ICV) e intravenoso (IV) do baclofen, um agonista para receptores GABA B, sobre o esvaziamento gástrico de líquidos e de sólidos em ratos. MÉTODOS: Foram utilizados ratos adultos Wistar, machos, de 250-300 g (n = 6-8 animais). O esvaziamento gástrico das refeições de prova líquidas, marcadas com fenol vermelho, foi avaliado através da determinação da por cento de retenção gástrica, 10 e 15 min após administração orogástrica das refeições salina e de glicose a 10 por cento, respectivamente. As injeções ICV de baclofen (1 e 2 µg/animal) foram feitas através de uma sonda implantada no ventrículo lateral do cérebro e as injeções IV de baclofen (1 e 2 mg/kg) numa veia da cauda. O esvaziamento gástrico das refeições de prova líquidas foi determinado 10 ou 30 min após a administração de baclofen ICV ou IV, respectivamente. O esvaziamento gástrico da refeição sólida foi avaliado através da determinação da por cento de retenção gástrica 2 h após o início da ingestão da ração habitual do animal, ingerida durante 30 min. As administrações de baclofen ICV (1 e 2 µg/animal) e IV (1 e 2 mg/kg) foram feitas imediatamente após o término da ingestão da refeição sólida. Os grupos controles receberam ICV ou IV veículo (solução salina estéril). RESULTADOS: O grupo de animais que recebeu baclofen 2 mg/animal ICV apresentou retenção gástrica (média ± SEM) de salina (18.1 ± 2.5 por cento) significantemente menor (P<0.05, teste de Tukey) em relação ao grupo controle (33.2 ± 2.2 por cento). No grupo com administração IV da droga, a retenção gástrica da mesma refeição de prova não diferiu do seu controle. As administrações ICV e IV de baclofen não tiveram qualquer efeito no esvaziamento gástrico da solução de glicose a 10 por cento, em relação aos seus controles. A administração ICV de 1 ou 2 µg/animal de baclofen aumentou significativamente as retenções gástricas da refeição de prova sólida (57.9 ± 6.5 por cento e 66.6 ± 6.3 por cento, respectivamente) em relação ao grupo controle (35.1 ± 4.4 por cento). O mesmo fenômeno somente foi observado com a dose IV de 2 mg/kg (71.9 ± 2.6 por cento) em relação ao grupo controle (52.7 ± 2.8 por cento). CONCLUSÃO: O baclofen administrado: 1. ICV (2 µg/animal), mas não IV, aumentou o esvaziamento gástrico de uma refeição de prova líquida isotônica não-calórica (salina); 2. ICV ou IV, não teve efeito sobre o esvaziamento da solução de glicose a 10 por cento; 3) ICV (1 e 2 µg/animal) e IV (2 mg/kg) retardou o esvaziamento gástrico da refeição sólida.

Endoscopic Evaluation of Gastric Emptying and Effect of Mosapride Citrate on Gastric Emptying

PURPOSE: Gastric emptying has been evaluated by scintigraphy in spite of its limitations of time consumption, cost, and danger of radioisotope. Endoscopy is a simple technique, however, its validation for gastric emptying and quantification of food has not yet been investigated. The aim of our study was to assess endoscopic gastric emptying compared with scintigraphy and radiopaque markers (ROMs) studies. We also investigated the effect of a single dose of mosapride on gastric emptying. MATERIALS AND METHODS: Fifteen healthy volunteers underwent scintigraphy. Next day, subjects received a standard solid meal with ROMs and underwent endoscopy and simple abdomen X-ray after 3 hrs. After one week, the same procedure was repeated after ingestion of mosapride (5 mg for group 1, n = 8; 10 mg for group 2, n = 7) 15 min before the meal. Quantification of gastric residue by endoscopy was scored from 0 to 3, and the scores were added up. RESULTS: All subjects completed the study without any complication. The gastric emptying rate [T1/2 (min)] was in normal range (65.6 +/- 12.6 min). Endoscopic gastric emptying was correlated significantly with gastric clearance of ROMs (r = 0.627, p = 0.012). Endoscopic gastric emptying and gastric clearance of ROMs after administration of mosapride showed significant differences in the 10 mg group (p < 0.05). CONCLUSION: Endoscopy can evaluate gastric emptying safely and simply on an outpatient basis. A 10 mg dose of mosapride enhanced gastric emptying, assessed by both endoscopy and ROMs.

Phenylpyrazolone derivatives inhibit gastric emptying in rats by a capsaicin-sensitive afferent pathway

Dipyrone (Dp), 4-aminoantipyrine (AA) and antipyrine (At) administered iv and Dp administered icv delay gastric emptying (GE) in rats. The participation of capsaicin (Cps)-sensitive afferent fibers in this phenomenon was evaluated. Male Wistar rats were pretreated sc with Cps (50 mg/kg) or vehicle between the first and second day of life and both groups were submitted to the eye-wiping test. GE was determined in these animals at the age of 8/9 weeks (weight: 200-300 g). Ten minutes before the study, the animals of both groups were treated iv with Dp, AA or At (240 μmol/kg), or saline; or treated icv with Dp (4 μmol/animal) or saline. GE was determined 10 min after treatment by measuring percent gastric retention (GR) of saline labeled with phenol red 10 min after orogastric administration. Percent GR (mean ± SEM, N = 8) in animals pretreated with Cps and treated with Dp, AA or At (35.8 ± 3.2, 35.4 ± 2.2, and 35.6 ± 2 percent, respectively) did not differ from the GR of saline-treated animals pretreated with vehicle (36.8 ± 2.8 percent) and was significantly lower than in animals pretreated with vehicle and treated with the drugs (52.1 ± 2.8, 66.2 ± 4, and 55.8 ± 3 percent, respectively). The effect of icv administration of Dp (N = 6) was not modified by pretreatment with Cps (63.3 ± 5.7 percent) compared to Dp-treated animals pretreated with vehicle (62.3 ± 2.4 percent). The results suggest the participation of capsaicin-sensitive afferent fibers in the delayed GE induced by iv administration of Dp, AA and At, but not of icv Dp.

Vincristine delays gastric emptying and gastrointestinal transit of liquid in awake rats

We evaluated the effects of vincristine on the gastrointestinal (GI) motility of awake rats and correlated them with the course of vincristine-induced peripheral neuropathy. Vincristine or saline was injected into the tail vein of male Wistar rats (180-250 g) on alternate days: 50 µg/kg (5 doses, N = 10), 100 µg/kg (2, 3, 4 and 5 doses, N = 49) or 150 µg/kg (1, 2, or 5 doses, N = 37). Weight and stool output were measured daily for each animal. One day after completing the vincristine treatment, the animals were fasted for 24 h, gavage-fed with a test meal and sacrificed 10 min later to measure gastric emptying (GE), GI transit and colon weight. Sensory peripheral neuropathy was evaluated by hot plate testing. Chronic vincristine treatments with total cumulative doses of at least 250 µg/kg significantly decreased GE by 31-59 percent and GI transit by 55-93 percent. The effect of 5 doses of vincristine (150 µg/kg) on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 µg/kg). Fecal output decreased up to 48 h after the fifth dose of vincristine (150 µg/kg). Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 µg/kg or after 3-5 doses of 150 µg/kg. This effect lasted for at least 2 weeks after the fifth dose. Chronic intravenous vincristine treatment delayed GE and GI transit of liquid. This effect correlated with the peak increase in colon weight but not with the pain threshold changes.

Sildenafil delays the intestinal transit of a liquid meal in awake rats

Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44) were treated (0.2 mL, iv) with sildenafil (4 mg/kg) or vehicle (0.01 N HCl). Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline) injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP) was monitored in a separate group of rats (N = 14). Data (medians within interquartile ranges) were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6) vs 2.9 (2.7-3.1); 3.8 (3.4-4.0) vs 2.9 (2.5-3.1), and 4.3 (3.9-4.5) vs 3.4 (3.2-3.7), respectively; P < 0.05). MAP was unchanged in vehicle-treated rats but decreased by 25 percent (P < 0.05) within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats.

Effect of 4-aminoantipyrine on gastric compliance and liquid emptying in rats

Dipyrone (Dp) delays gastric emptying (GE) in rats. There is no information about whether 4-aminoantipyrine (AA), one of its metabolites, has the same effect. The objectives of the present study were to assess the effects of AA and Dp on GE when administered intravenously (iv) and intracerebroventricularly (icv) (240 æmol/kg and 4 æmol/animal, respectively) and on gastric compliance when administered iv (240 æmol/kg). GE was determined in male Wistar rats weighing 250-300 g (5-10 per group) after icv or iv injection of the drug by measuring percent gastric retention (GR) of a saline meal labeled with phenol red 10 min after administration by gavage. Gastric compliance was estimated in anesthetized rats (10-11 per group), with the construction of volume-pressure curves during intragastric infusion of a saline meal. Compliance was significantly greater in animals receiving Dp (mean ± SEM = 0.26 ± 0.009 mL/mmHg) and AA (0.24 ± 0.012 mL/mmHg) than in controls (0.19 ± 0.009 mL/mmHg). AA and Dp administered iv significantly increased GR (64.4 ± 2.5 and 54.3 ± 3.8 percent, respectively) compared to control (34 ± 2.2 percent), a phenomenon observed only with Dp after icv administration. Subdiaphragmatic vagotomy reduced the effect of AA (GR = 31.4 ± 1.5 percent) compared to sham-treated animals. Baclofen, a GABA B receptor agonist, administered icv significantly reduced the effect of AA (GR = 28.1 ± 1.3 percent). We conclude that Dp and AA increased gastric compliance and AA delayed GE, with the participation of the vagus nerve, through a pathway that does not involve a direct action of the drug on the central nervous system.

Effect of antipyrine on the gastric emptying of liquid in rats

Antipyrine (At) and dipyrone (Dp) delay gastric emptying (GE) in rats. The objective of the present study was to assess the effects of intravenous (iv) and intracerebroventricular (icv) administration of At and Dp on the GE of liquid by rats. GE was assessed in male Wistar rats (5-10 in each group) 10 min after the icv or iv drug injection by measuring percent gastric retention ( percentGR) of a saline test meal labeled with phenol red 10 min after administration by gavage. The At iv group was significantly higher (64.4 ± 2.6 percent) compared to control (33.4 ± 1.5 percent) but did not differ from the Dp group (54.3 ± 3.8 percent). After icv administration of At, percentGR (34.2 ± 2 percent) did not differ from control (32.6 ± 1.9 percent), but was significantly higher after Dp (54.5 ± 2.3 percent). Subdiaphragmatic vagotomy significantly reduced percentGR in the At group (30.2 ± 0.7 percent) compared to the sham group, but was significantly higher than in the controls (23.0 ± 0.5 percent). In the animals treated with At iv, baclofen significantly reduced percentGR (28.3 ± 2.4 percent) compared to vehicle-treated animals (55.2 ± 3.2 percent). The same occurred in the animals treated iv with vehicle and icv with baclofen. Although vagotomy and baclofen reduced percentGR per se, the reduction was twice more marked in the animals treated with At. The results suggest that At administered iv, but not icv, delays GE of liquid in rats with the participation, at least in part, of the vagus nerve and that this phenomenon is blocked by the activation of GABA B receptors in the central nervous system.

Inducible nitric oxide synthase and tumor necrosis factor-alpha in delayed gastric emptying and gastrointestinal transit induced by lipopolysaccharide in mice

Gastrointestinal motility disturbances during endotoxemia are probably caused by lipopolysaccharide (LPS)-induced factors: candidates include nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß, and interleukin-6. Flow cytometry was used to determine the effects of LPS and these factors on gastric emptying (evaluated indirectly by determining percent gastric retention; percentGR) and gastrointestinal transit (GIT) in male BALB/c mice (23-28 g). NO (300 æg/mouse, N = 8) and TNF-alpha (2 æg/mouse, N = 7) increased (P < 0.01) GR and delayed GIT, mimicking the effect of LPS (50 æg/mouse). During early endotoxemia (1.5 h after LPS), inhibition of inducible NO synthase (iNOS) by a selective inhibitor, 1400 W (150 æg/mouse, N = 11), but not antibody neutralization of TNF-alpha (200 æg/mouse, N = 11), reversed the increase of GR ( percentGR 78.8 ± 3.3 vs 47.2 ± 7.5 percent) and the delay of GIT (geometric center 3.7 ± 0.4 vs 5.6 ± 0.2). During late endotoxemia (8 h after LPS), both iNOS inhibition (N = 9) and TNF-alpha neutralization (N = 9) reversed the increase of GR ( percentGR 33.7 ± 2.0 vs 19.1 ± 2.6 percent (1400 W) and 20.1 ± 2.0 percent (anti-TNF-alpha)), but only TNF-alpha neutralization reversed the delay of GIT (geometric center 3.9 ± 0.4 vs 5.9 ± 0.2). These findings suggest that iNOS, but not TNF-alpha, is associated with delayed gastric emptying and GIT during early endotoxemia and that during late endotoxemia, both factors are associated with delayed gastric emptying, but only TNF-alpha is associated with delayed GIT.

Efeito do lipopolissacarídio bacteriano sobre o esvaziamento gástrico de ratos: avaliação do pré-tratamento com Nw-nitro-L-arginine methyl ester (L-NAME) / The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using Nw-nitro-L-arginine methyl ester (L-NAME) / The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using Nw-nitro-L-arginine methyl ester (L-NAME)

RACIONAL: Há evidências de que o óxido nítrico participa do mecanismo de retardo do esvaziamento gástrico determinado pelo lipopolissacarídio bacteriano. OBJETIVO: Avaliar o efeito do pré-tratamento com Nw-nitro-L-arginine methyl ester, um inibidor competitivo das óxido nítrico-sintetases, sobre o fenômeno. MATERIAL E MÉTODOS: Utilizaram-se ratos, Wistar, machos, SPF ("specific-pathogen free"), adultos, adaptados às condições do laboratório, que após 24 horas de jejum alimentar foram pré-tratados endovenosamente com veículo (salina) ou Nw-nitro-L-arginine methyl ester nas doses de 0,5, 1, 2,5 e 5 mg/kg. No tratamento, administrou-se endovenosamente veículo (salina) ou lipopolissacarídio (50 µg/kg). O intervalo entre o pré-tratamento e o tratamento foi de 10 minutos, e entre este e a avaliação do esvaziamento gástrico foi de 60 minutos. O esvaziamento gástrico foi avaliado indiretamente através da determinação da retenção gástrica da solução salina marcada com fenol vermelho 10 minutos após administração por via orogástrica. RESULTADOS: Entre os animais pré-tratados com veículo, o tratamento com lipopolissacarídio determinou elevação significativa da retenção gástrica (média = 57 por cento) em relação aos tratados com veículo (38,1 por cento). O pré-tratamento com as diferentes doses de Nw-nitro-L-arginine methyl ester não modificou a retenção gástrica nos animais controles do tratamento. O pré-tratamento com Nw-nitro-L-arginine methyl ester com a dose de 1 mg/kg determinou redução discreta, mas significativa, na retenção gástrica (52 por cento) nos animais tratados com lipopolissacarídio, em relação ao observado naqueles com pré-tratamento e tratamento com veículo (35,9 por cento). Nos animais pré-tratados com 2,5 e 5 mg/kg de Nw-nitro-L-arginine methyl ester e tratados com lipopolissacarídio, houve aumento significante da retenção gástrica (74,7 por cento e 80,5 por cento, respectivamente) em relação aos seus controles pré-tratados com as mesmas doses...

BACKGROUND: There is evidence that nitric oxide plays a role in the decrease in gastric emptying induced by bacterial lipopolysaccharide. AIM: To evaluate the effect of pretreatment with Nw-nitro-L-arginine methyl to ester, one competitive inhibitor of the nitric oxide syntases, on the gastric emptying delay induced by lipopolysaccharide. MATERIAL AND METHODS: Male Wistar rats, SPF, were used after 24 h fast and 1 h-water withdrawn. The pretreatment was done intravenously with vehicle (saline) or Nw-nitro-L-arginine methyl to ester in the doses of 0.5, 1, 2.5 e 5 mg/kg. After 10 min, the animals were treated iv with lipopolysaccharide (50 mg/kg) or received vehicle (saline). The gastric emptying was evaluated 1 h after the lipopolysaccharide administration. A saline solution containing phenol red was used as the test meal. The gastric emptying was indirectly assessed by the determination of percent gastric retention of the test meal 10 min after orogastric administration. RESULTS: The animals pretreated with vehicle and treatment with lipopolysaccharide have significant rise of the gastric retention (average = 57 percent) in comparison with the controls receiving only vehicle (38.1 percent). The pretreatment with the different doses of Nw-nitro-L-arginine methyl to ester did not modify per se the gastric retention in comparison with the animals pretreated with vehicle. Pretreatment with Nw-nitro-L-arginine methyl to ester with the dose of 1 mg/kg determined a discrete but significant reduction in the gastric retention (52 percent) of animals treated with lipopolysaccharide in comparison with vehicle-pretreated rats. Paradoxically, animals pretreated with 2.5 or 5 mg of Nw-nitro-L-arginine methyl to ester/kg followed by treatment with lipopolysaccharide displayed a significantly higher gastric retention (74.7 percent and 80.5 percent, respectively) as compared to their controls, pretreated with the same doses of the inhibitor and treated with vehicle (40.5 percent and...

Evaluation of new gastro-intestinal prokinetic (ENGIP-I) study.

The ENGIP-I study was conducted to investigate the efficacy, and safety of itopride in patients of gastro-oesophageal reflux disease. There were significant reductions in heartburn frequency, heartburn severity, gastro-oesophageal regurgitation frequency at day 3 only. ENGIP-I study concluded that itopride was well tolerated by patients and appears to be the drug of choice in patients with gastro-oesophageal reflux disease.

Lack of effect of Helicobacter pylori on symptom improvement with a prokinetic medication, cisapride, in patients with non-ulcer dyspepsia.

OBJECTIVE: This study was undertaken to determine whether H. pylori infection has an effect on the improvement of dyspeptic symptoms in response to a prokinetic agent, cisapride, in patients with non-ulcer dyspepsia (NUD). MATERIAL AND METHOD: 35 NUD patients (16 M, 19 F) who had no underlying medical condition and negative upper endoscopy were included in the present study. Each patient received a 2-wk treatment of cisapride (Prepulsid, 10 mg, tid ac). H. pylori infection was determined using a rapid urease test (CLO test). Gastric emptying (GE) scintigraphy and dyspeptic symptom scores were evaluated before and at the end of the treatment. GE was evaluated in 22 healthy volunteers as normal controls. RESULTS: Half time (T1/2) GE of NUD patients was 90.9 +/- 28 min which was significantly longer than controls (77.6 +/- 14 min; p < 0.05) and was shortened to 73.6 +/- 22 min (p < 0.0001) at the end of the treatment. Cisapride significantly improved total dyspeptic symptom scores [7 (2-18) to 3 (0-11), p < 0.0001]. The symptom score improvement was not affected by H. pylori infection [H. pylori positive: 6 (2-18) to 2.5 (0-9), p < 0.0001; H. pylori negative: 9 (4-16) to 3 (0-11), p < 0.0001] or GE status [delayed GE: 10 (5-16) to 3 (15), p < 0.05; non delayed GE: 6 (2-18) to 2 (0-11); p < 0.0001]. CONCLUSIONS: Cisapride improves dyspeptic symptoms regardless of H. pylori and GE status. These results suggest that gastric emptying and H. pylori infection are not essential to determine prior to prescribing a prokinetic agent, cisapride, in patients with NUD.