Famotidine Repurposing for Novel Corona Virus Disease of 2019: A Systematic Review.

BACKGROUND: COVID-19 caused by SARS-CoV-2 was declared as a global pandemic by the WHO. Famotidine is a histamine-2 (H2) receptor antagonist which blocks the H2 receptors in the parietal cells, decreasing gastric acid secretion. Our review aims to study all the available scientific evidence on famotidine research outcomes systematically to introspect its clinical efficacy and probable mechanisms and clinical efficacy against SARS-CoV-2. METHODOLOGY: An electronic search of PubMed, Scopus and Google Scholar was performed using MeSH terms "SARS CoV-2" OR "COVID-19" AND"FAMOTIDINE". Relevant informationwas extracted from studies reporting the efficacy of famotidine in COVID-19. RESULTS: We found a total of 32 studies, out of which only 14 were relevant and were included in our review.Molecular computational studies showed that famotidine selectively acts on viral replication proteases papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro). Additionally, it acts via inverse-agonism on the H2 receptors present in neutrophils and eosinophils which leads to inhibition of cytokine release. Clinical study findings have pointed toward significant improvements in COVID-19 patient-reported symptoms in non-hospitalized patients and reduction in intubation or death in critically ill patients associated with the usage of famotidine. However,in one of the studies,famotidine has failed to show any significant benefit in reducing mortality due to COVID-19. CONCLUSION: Famotidine has the potential to answer the ongoing global challenge owing to its selective action on viral replication. Additionally, clinical findings in COVID-19 patients support its efficacy to reduce clinical symptoms of COVID-19.We suggest that further optimally powered randomized clinical trials should be carried out to come up with definitive conclusions.

Effect of lubiprostone on vinca alkaloid-induced constipation in patients with hematological malignancies: a propensity score-matched analysis.

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.

Informe diário de evidências COVID-19: busca realizada entre 6 e 8 de junho de 2020 / COVID-19 daily evidence report: search conducted between 6 and 8 June 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos.

The use of H2 antagonists in treating and preventing NSAID-induced mucosal damage.

Pain affects the quality of life for millions of individuals and is a major reason for healthcare utilization. As populations age, medical personnel will need to manage more and more patients suffering from pain associated with degenerative and inflammatory musculoskeletal disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective treatment for both acute and chronic musculoskeletal pain; however, their use is associated with potentially significant gastrointestinal (GI) toxicity. Guidelines suggest various strategies to prevent problems in those at risk for NSAID-associated GI complications. In this article, we review the data supporting one such strategy - the use of histamine type-2 receptor antagonists (H2RAs) - for the prevention of GI adverse events in NSAID users. Older studies suggest that high-dose H2RAs are effective in preventing upper GI ulcers and dyspepsia. This suggestion was recently confirmed during clinical trials with a new ibuprofen/famotidine combination that reduced the risk of ulcers by 50% compared with ibuprofen alone.

Comparison of adjuvant therapies by an H2-receptor antagonist and a proton pump inhibitor after endoscopic treatment in hemostatic management of bleeding gastroduodenal ulcers.

AIM: Upper gastrointestinal bleeding is often associated with a higher risk of serious blood loss. Both H2-receptor antagonists and proton pump inhibitors are commonly given intravenously for endoscopic hemostatic therapies. We compared the effects of a H2-receptor antagonist (famotidine) and a proton pump inhibitor (omeprazole) injected during the early phase (the first 3 days) on cessation of bleeding and prevention of its recurrence in patients who underwent endoscopic therapy for gastroduodenal ulcer bleeding. METHODS: Consecutive patients who were hospitalized at our clinic with bleeding gastroduodenal ulcers and underwent endoscopic therapy were randomly assigned to receive injections of famotidine, omeprazole, or both. Injection of acid suppressants was switched on the fourth day to the oral administration of omeprazole continued for 8 weeks. RESULTS: Over a 25-month period, 116 patients were enrolled. The overall success rate for endoscopic hemostasis was 115/116 (99.1%). The success rate of hemostasis and prevention of recurrent ulcer bleeding by type of acid suppressant following endoscopic hemostasis was 39/40 (97.5%) for Group 1 (3-day omeprazole administration), 35/37 (94.6%) for Group 2 (3-day famotidine administration), and 38/39 (97.4%) for Group 3 (1-day famotidine and then 2-day omeprazole administration), yielding an overall rate of 112/116 (96.6%). No significant difference in the hemostatic effect was observed among the groups. There were also no differences in the duration of hospital days and the number of fasting days between the three groups. CONCLUSION: Famotidine and omeprazole injected during the early phase of a bleeding ulcer may have similar effects to an adjuvant therapy for preventing rebleeding from endoscopically treated upper gastrointestinal bleeding in Japanese patients.

Double-blind randomized trials of single-tablet ibuprofen/high-dose famotidine vs. ibuprofen alone for reduction of gastric and duodenal ulcers.

OBJECTIVES: We performed two 24-week double-blind trials (REDUCE-1 and -2 (Registration Endoscopic Studies to Determine Ulcer Formation of HZT-501 Compared with Ibuprofen: Efficacy and Safety Studies)) to assess whether double-dose famotidine given in a single-tablet combination with ibuprofen (HZT-501) significantly reduces gastric and duodenal ulcers as compared with ibuprofen. METHODS: Patients (40-80 years) requiring daily non-steroidal anti-inflammatory drugs (NSAIDs) for ≥6 months with no prior ulcer complications, negative H. pylori stool test, and baseline endoscopy showing no ulcers and <5 erosions were randomly assigned in a 2:1 ratio to HZT-501 or identical-appearing ibuprofen 800 mg tablets thrice daily. Study endoscopies were done at 8, 16, and 24 weeks. After unblinding and initial analyses, 12 patients were found to be misclassified as having gastric ulcers based on the adjudication of endoscopy reports, and analyses were re-run. RESULTS: In REDUCE-1, the primary end point analysis of gastric ulcers at 24 weeks with HZT-501 vs. ibuprofen was 12.7% vs. 22.9% (P=0.0044) in the post-adjudication analysis. In REDUCE-2, the primary end point analysis of upper gastrointestinal (GI) ulcers was 13.0% vs. 20.5% (P=0.0587) in the post-adjudication analysis. Prespecified pooled analyses showed significantly fewer gastric (12.5% vs. 20.7%) and duodenal ulcers (1.1% vs. 5.1%) with HZT-501 vs. ibuprofen. Proportional hazards analysis of multiple potential risk factors showed the risk ratio of upper GI ulcers with HZT-501 vs. ibuprofen was 0.46, 95% confidence interval was 0.34-0.61. CONCLUSIONS: Combined results of the REDUCE studies indicate that double-dose famotidine plus ibuprofen, given as a combination tablet, decreases endoscopic upper GI ulcers as compared with ibuprofen alone.

[Modern approach to the prevention and treatment of NSAID-gastropathy].

The article presents the results of the first Russian open randomized comparative multicenter study on the effectiveness of Famotidine in the prevention of NSAID-gastropathy--Barrier. In addition, were showen the results of studies of the drugs effect used for prevention of NSAID gastropathy (Famotidine, Lansoprazole, Misoprostol) for the synthesis of prostaglandins in the gastric mucosa in patients with osteoarthritis. Was shown the impact of alternative anti-inflammatory drug on the basis of an extract of ginger as joint pain, and the mucous upper gastrointestinal tract in patients with osteoarthritis.

Physiological and clinical characteristics of gastroesophageal reflux after congenital diaphragmatic hernia repair.

BACKGROUND/PURPOSE: Gastroesophageal reflux (GER) is an important sequela of congenital diaphragmatic hernia (CDH) repair. This study investigated the physiological and clinical characteristics of GER in CDH survivors. METHODS: A total of 52 CDH survivors were investigated retrospectively. Esophageal acid exposure was evaluated with 24-h esophageal pH monitoring in all patients, and esophageal anatomical and motor functional abnormalities were examined with videomanometry in 16 patients. RESULTS: Fundoplication was necessary in 1 patient. Medical treatment with acid suppression or rikkunshito, a traditional Japanese medicine, was successful in nine patients, and the reflux symptoms were ameliorated at the age of 3 years. The percentage of total time the esophageal pH was below 4.0 (reflux index: RI) ranged from 0.1 to 44.3%. No patient with an RI < 10% had reflux symptoms requiring treatment. The basal lower esophageal sphincter (LES) tone ranged from 15 to 35 mmHg (median 25 mmHg). Esophageal peristalsis was preserved in all of the patients examined, except one who had failed peristalsis and poor clearance in the dilated esophagus. CONCLUSION: The motor function of the esophageal body and LES is usually preserved in CDH survivors despite the wide range of esophageal acid exposure in early infancy. Those with symptomatic GER outgrow it, unless associated with advanced respiratory distress or neurological impairment.

Should fundoplication be added at the time of gastrostomy placement in patients who are neurologically impaired?

BACKGROUND/PURPOSE: Patients who have advanced neurologic impairment (NI) and require gastrostomy placement (GP) frequently have symptomatic gastroesophageal reflux. We investigated the outcomes of GP without fundoplication in patients who had NI. METHODS: This was a retrospective review of 54 patients with NI (median, 7 years; range, 1-18 years) undergoing GP alone. The operative criteria included medically controllable or no reflux symptoms. The patients were divided into 2 groups based on the percentage of total esophageal time with a pH less than 4.0 (reflux index, or RI): group I (GI, n = 33), RI less than 5.0% (median age, 6 years; range, 2-15 years); group II (GII, n = 21), RI 5.0% or greater (median age, 10 years; range, 1-18 years). Data are expressed as medians and ranges. RESULTS: Nutritional management was successfully conducted after GP with or without the administration of lansoprazole, famotidine, or rikkunshito in all but 2 patients. One GI patient with alpha-thalassemia required fundoplication, and one GII patient with Cockayne syndrome required gastrojejunal tube feeding. The RI increased significantly in GI patients (2.1% [0%-4.8%] vs 4.5% [0.2%-11.4%], P = .004), whereas it decreased significantly in GII patients (11.2% [5.9%-41.6%] vs 9.8% [1.05-26.6%], P = .04). CONCLUSION: Gastroesophageal reflux and related symptoms rarely deteriorate to require additional treatment after GP in patients with NI. Gastrostomy placement is a less invasive and effective procedure for improving the quality of life in those patients.

Efficacy of omeprazole versus high-dose famotidine for prevention of exercise-induced gastritis in racing Alaskan sled dogs.

BACKGROUND: Omeprazole and famotidine both reduce severity of exercise-induced gastritis, but administering famotidine is easier than administering omeprazole during racing competition. HYPOTHESIS: Famotidine is more efficacious than no treatment in reducing severity of exercise-induced gastritis; and high-dose famotidine is more efficacious than omeprazole in reducing severity of exercise-induced gastritis. ANIMALS: Experiment 1: Randomized placebo-controlled study, 36 sled dogs (3-8 years); Experiment 2: Randomized positive-control study, 52 sled dogs (2-8 years). METHODS: Experiment 1: Equal numbers of dogs randomly assigned to famotidine (20 mg q24h) or no treatment groups. Gastroscopy was performed 24 hours after the dogs ran 330 miles. Mucosal appearance was blindly scored by previously described scoring system. Experiment 2: Equal numbers of dogs randomly assigned to omeprazole (20 mg q24h) or high-dose famotidine (40 mg q12h) groups. Gastroscopy was performed 48 hours before and 24 hours after the dogs ran 300 miles. Mucosal appearance was blindly scored by previously described scoring system. RESULTS: Famotidine reduced the prevalence of clinically relevant, exercise-induced gastric lesions compared with no treatment (7/16 versus 11/16, P = .031). Compared with high-dose famotidine, omeprazole significantly decreased the severity (0.4 versus 1.2, P = .0002) and prevalence (2/23 versus 7/21, P = .049) of gastric lesions. CONCLUSIONS AND CLINICAL RELEVANCE: Although famotidine provides some benefit in the prevention of exercise-induced gastric lesions, omeprazole is superior to famotidine in preventing gastritis in dogs running 300 miles. Routine administration of omeprazole is recommended to prevent stress-associated gastric disease in exercising and racing Alaskan sled dogs.

Pharmacological interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood.

BACKGROUND: Between 4% and 25% of school-age children complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with daily activities. For the majority no organic cause for their pain can be found on physical examination or investigation and although most children are likely managed by reassurance and simple measures, a large range of interventions have been recommended. OBJECTIVES: To determine the effectiveness of medication for recurrent abdominal pain in school-age children. SEARCH STRATEGY: The Cochrane Library (CENTRAL) 2006 (Issue 4), MEDLINE (1966 to Dec 2006), EMBASE (1980 to Dec 2006), CINAHL (1982 to Dec 2007), ERIC (1966 to Dec 2006), PsycINFO (1872 to Dec 2006), LILACS (1982 to Dec 2006), SIGLE (1980 to March 2005), and JICST (1985 to 06/2000) were searched with appropriate filters SELECTION CRITERIA: Studies on school age children with RAP (Apley or the Rome II criteria for gastrointestinal diseases) allocated by random or quasi-random methods to a drug treatment vs. placebo/ no treatment were included. DATA COLLECTION AND ANALYSIS: References identified by the searches were screened against the inclusion criteria by two independent reviewers. Data was extracted and analysed using RevMan 4.2.10. MAIN RESULTS: Three trials met the inclusion criteria. Symon et al report a cross-over trial comparing pizotifen and placebo in 16 children with "abdominal migraine". Data before cross-over was not available. Results for 14 children showed Mean fewer days in pain of 8.21 (95% CI 2.93, 13.48) while taking the active drug. Kline et al compared peppermint oil capsules with placebo in a randomised trial in 50 children with RAP and IBS. 42 children completed the study. OR for improvement was 3.33 (95% CI 0.93-12.1)See et al compared famotidine with placebo in a randomised cross-over trial in 25 children with RAP and dyspepsia. OR for improvement before cross-over was 11 (95%CI 1.6, 75.5). AUTHORS' CONCLUSIONS: This review provides weak evidence of benefit on medication in children with RAP. The lack of clear evidence of effectiveness for any of the recommended drugs suggests that there is little reason for their use outside of clinical trials. Clinicians may choose to prescribe drugs in children with severe symptoms that have not responded to simple management. However, if using drugs as a "therapeutic trial", clinicians should be aware that, RAP is a fluctuating condition and any "response" may reflect the natural history of the condition or a placebo effect rather than drug efficacy.

[Comparative study on Jinghua Weikang Capsule and famotidine in treating duodenal ulcer].

OBJECTIVE: To compare the effect and security of Jinghua Weikang Capsule (JWC) and famotidine in treating duodenal ulcer. METHODS: Two hundred patients with duodenal ulcer were randomly divided into the treated group treated with JWC, 160 mg 3 times per day and the control group treated with famotidine 20 mg twice per day, both by orally taking before meal for 4 weeks, 100 cases in each group. Changes of symptom score, adverse reaction, helicobacter pylori (Hp) infection and endoscopic figure before and after treatment were observed. RESULTS: The general remission rate and the ulcer healing rate in the treated group were equal to those in the control group respectively (both P > 0.05). Symptoms including belly ache, sour regurgitation and abdominal distension were ameliorated after therapy in both groups (all P < 0.05). The effect in relieving anorexia and eructation and Hp eradication rate were significantly higher in the treated group than those in the control group (all P< 0.05), while the incidence rate of adverse reaction in the treated group was remarkably lower than that in the control group (P < 0.05). CONCLUSION: JWC is an effective and safe remedy in treating duodenal ulcer, especially for symptom amelioration and Hp eradication, so it is worthy of expanding clinically.

Effects of Momordica charantia L. (Cucurbitaceae) on indomethacin-induced ulcer model in rats.

BACKGROUND/AIMS: Fruits of Momordica charantia L.-cucurbitaceae have been frequently used in folk medicine for rapid healing of cutaneous lesions and peptic ulcer, especially in Western Anatolia in Turkey. METHODS: The anti-ulcerogenic effect of the oily extract of Momordica charantia fruits was investigated in male Sprague-Dawley rats. Animals were separated into six groups. Distilled water (control group), famotidine (40 mg/kg), oily extracts (5 and 10 ml/kg), and vehicles (olive oil -5 and 10 ml/kg) were given orally (gavage). Thirty minutes later indomethacin (25 mg/kg) was administrated to all the groups. Six hours later, animals were killed with decapitation. For each stomach, ulcerated and total areas were measured (mm2). The ulcer indexes for each stomach and the ulcer inhibition rates for each group were calculated, after which the stomachs were evaluated pathologically (polymorphonuclear leukocytes infiltration). RESULTS: Ulcer inhibition rates were as follows: famotidine -91.54%, oily extract (5 ml/kg) -53.80%, oily extract (10 ml/kg) -98.04%, vehicle (olive oil -5 ml/kg) -18.40%, and vehicle (olive oil -10 ml/kg) -88.02%. According to polymorphonuclear leukocytes infiltration, oily extract (10 ml/kg) and vehicle (10 ml/kg) had similar effects to famotidine. CONCLUSIONS: The olive oil extract of M. charantia fruit did show a protective effect macroscopically.

Preventive therapy for non-steroidal anti-inflammatory drug-induced ulcers in Japanese patients with rheumatoid arthritis: the current situation and a prospective controlled-study of the preventive effects of lansoprazole or famotidine.

BACKGROUND: There is a lack of evidence for the efficacy of preventive medications for peptic ulcers (PUs) among long-term users of non-steroidal anti-inflammatory drugs (NSAIDs) in Japan. AIM: To estimate the preventive effect by normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID-induced ulcers. METHODS: We designed two different studies to assess the efficacy of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long term with NSAIDs. An investigative survey divided patients into those not taking anti-ulcer agents (non-medication group); those taking mucosal protective agents (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI group), or a prostaglandin E1 analog (PG) (PG group). The second study compared prospectively the preventive effects of either famotidine 20 mg bd (famotidine group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU scars. RESULTS: The prevalence of PU in the H2RA group was significantly lower compared to the mucosal protectant group (P < 0.05), and the mucosal protectant group was not significantly different to the non-medication group. The prospective study revealed that the PU onset rate of the famotidine group was 8% (1/13), and lansoprazole group was 15% (2/13), indicating no significant differences between the two. CONCLUSIONS: In Japan, normal-dose H2RA is expected to be a new PU preventive treatment strategy in patients requiring long-term NSAID therapy.

Antiinflammatory and antiulcer activities of phytic acid in rats.

Maximum antiinflammatory activity of phytic acid (PA) was seen at an oral dose of 150 mg/kg in the carrageenan induced rat paw edema model. Although PA showed ability to prevent denaturation of proteins, it showed less antiinflammatory activity than ibuprofen. Ability of PA to bring down thermal denaturation of proteins might be a contributing factor in the mechanism of action against inflammation. PA, at all the doses tested, showed significant protection from ulcers induced by ibuprofen, ethanol and cold stress, with a maximum activity at 150 mg/kg. There was a significant increase in gastric tissue malondialdehyde levels in ethanol treated rats but these levels decreased following PA pretreatment. Moreover, pretreatment with PA significantly inhibited various effects of ethanol on gastric mucosa, such as, reduction in the concentration of nonprotein sulfhydryl groups, necrosis, erosions, congestion and hemorrhage. These results suggested that gastro-protective effect of PA could be mediated by its antioxidant activity and cytoprotection of gastric mucosa.

Medicamentos disponibles en pediatría para el tratamiento de la enfermedad por reflujo gastroesofágico / Paediatric drugs available for the treatment of the gastroesophageal reflux disease

Se analiza la oferta del mercado farmacéutico español a la hora de cubrir el tratamiento de la Enfermedad por Reflujo Gastroesofágico (ERGE) en la población pediátrica. Para ello se realiza una revisión de las especialidades correspondientes a los grupos A03AF, A02BA y A02BC, a partir del catálogo de especialidades farmacéuticas del Consejo General de Colegios Farmacéuticos, en la que se atendió a: - Dosis indicada en el niño, en caso de ser un fármaco de uso pediátrico.- Formas farmacéuticas en que se presentan estos fármacos. A partir de esta revisión se establecen dos grupos: El 44 por ciento de los fármacos implicados en el tratamiento de la ERGE no se dispone de estudios en la población pediátrica. El 33 por ciento de los AH2 y el 40 por ciento de los IBP son utilizables en niños. Ningún IBP posee presentación correctamente diseñada para la población pediátrica. Se llega a la conclusión, de que el mercado actual no dispone de medicamentos correctamente diseñados para pediatría en las terapias más efectivas en el tratamiento de la ERGE (AU)

Systematic review of treatments for recurrent abdominal pain.

OBJECTIVE: To conduct a systematic review of evaluated treatments for recurrent abdominal pain (RAP) in children. METHODS: Online bibliographic databases were searched for the terms "recurrent abdominal pain," "functional abdominal pain," "children," or "alternative therapies" in articles classified as randomized controlled trials. The abstracts or full text of 57 relevant articles were examined; 10 of these met inclusion criteria. Inclusion criteria required that the study involve children aged 5 to 18 years, subjects have a diagnosis of RAP, and that subjects were allocated randomly to treatment or control groups. The methodology and findings of these articles were evaluated critically, and data were extracted from each article regarding study methods, specific interventions, outcomes measured, and results. RESULTS: Studies that evaluated famotidine, pizotifen, cognitive-behavioral therapy, biofeedback, and peppermint oil enteric-coated capsules showed a decrease in measured pain outcomes for those who received the interventions when compared with others in control groups. The studies that evaluated dietary interventions had conflicting results, in the case of fiber, or showed no efficacy, in the case of lactose avoidance. CONCLUSIONS: Evidence for efficacy of treatment of RAP in children was found for therapies that used famotidine, pizotifen, cognitive-behavioral therapy, biofeedback, and peppermint oil enteric-coated capsules. The effects of dietary fiber were less conclusive, and the use of a lactose-free diet showed no improvement. There seemed to be greater improvement when therapy (famotidine, pizotifen, peppermint oil) was targeted to the specific functional gastrointestinal disorder (dyspepsia, abdominal migraine, irritable bowel syndrome). The behavioral interventions seemed to have a general positive effect on children with nonspecific RAP. Many of these therapies have not been used widely as standard treatment for children with RAP. Although the mechanism of action for each effective therapy is not fully understood, each is believed to be safe for use in RAP.

Healing-promoting action of rhinax with dual action on chronic gastric and duodenal ulcers induced by acetic acid in rats.

Healing promoting actions of Rhinax, a multiconstituent herbal preparation, was investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine by gross of histological evaluation. Rhinax markedly promoted the well balanced healing of gastric ulcer at oral does of 25-100 mg/kg x 2 /day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connecitve tissue. Rhinax caused an increase in gastric mucosa secretion in all the regenerated mucosa around the gastric ulcers. Famotidine failed to promote the healing of gastric ulcers at 100 mg/kg x 2/ day p.o. Rhinax also significantly accelerated the healing of acetic acid -induced duodenal ulcers as well famotidine. These results indicate that Rhinax is characterised by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer action of Rhinax in rats.