Ranitidine as an adjuvant regulates macrophage polarization and activates CTLs through the PI3K-Akt2 signaling pathway.

Adjuvants are an indispensable component of vaccines, but there are few adjuvants for human vaccines. H2 receptor blockers, inhibiting gastric acid secretion, have immune enhancement effects. Ranitidine (RAN) is a water-soluble H2 receptor blocker, and whether it has an immune-enhancing effect is still unknown. In this study, flow cytometry, western blotting, and immunofluorescence methods were used to analyze whether RAN could activate macrophage polarization to the M1 phenotype in vivo and in vitro. Here, we found that the M1 inflammatory cytokine levels and surface markers in RAW264.7 cells were upregulated by NF-κB activation, possibly through the PI3K-Akt2 signaling pathway, after RAN treatment. Endocytic function was also enhanced by feedback regulation of Akt2/GSK3ß/Dynmin1 signaling. Furthermore, to evaluate the adjuvant function of RAN, we used OVA plus RAN as a vaccine to inhibit the growth of B16-OVA tumors in mice. We also found that in the RAN adjuvant group, macrophage polarization to M1, Th1 cell differentiation, and cytotoxic T lymphocyte (CTL) activation were significantly upregulated. The tumor growth of mice was inhibited, and the survival rate of mice was significantly improved. This study provides new evidence for the mechanism by which RAN activates the immune response and is expected to provide a new strategy for the research and development of tumor vaccine adjuvants.

Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study.

N-Nitrosodimethylamine (NDMA), a carcinogenic chemical, has recently been identified in ranitidine. We conducted a population-based study to explore ranitidine use and cancer emergence over time. Using the Taiwan National Health Insurance Research Database, a population-based cohort study was conducted. A total of 55,110 eligible patients who received ranitidine between January 2000 and December 2018 were enrolled in the treated cohort. We conducted a 1:1 propensity-score-matching procedure to match the ranitidine-treated group with the ranitidine-untreated group and famotidine controls for a longitudinal study. The association of ranitidine exposure with cancer outcomes was assessed. A multivariable Cox regression analysis that compared cancer risk with the untreated groups revealed that ranitidine increased the risk of liver (hazard ratio (HR): 1.22, 95% confidence interval (CI): 1.09-1.36, p < 0.001), lung (HR: 1.17, CI: 1.05-1.31, p = 0.005), gastric (HR: 1.26, CI: 1.05-1.52, p = 0.012), and pancreatic cancers (HR 1.35, CI: 1.03-1.77, p = 0.030). Our real-world observational study strongly supports the pathogenic role of NDMA contamination, given that long-term ranitidine use is associated with a higher likelihood of liver cancer development in ranitidine users compared with the control groups of non-ranitidine users treated with famotidine or proton-pump inhibitors.

Pharmacological interventions for prevention of weight gain in people with schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain is an extremely common problem in people with schizophrenia and is associated with increased morbidity and mortality. Adjunctive pharmacological interventions may be necessary to help manage antipsychotic-induced weight gain. This review splits and updates a previous Cochrane Review that focused on both pharmacological and behavioural approaches to this problem. OBJECTIVES: To determine the effectiveness of pharmacological interventions for preventing antipsychotic-induced weight gain in people with schizophrenia. SEARCH METHODS: The Cochrane Schizophrenia Information Specialist searched Cochrane Schizophrenia's Register of Trials on 10 February 2021. There are no language, date, document type, or publication status limitations for inclusion of records in the register. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that examined any adjunctive pharmacological intervention for preventing weight gain in people with schizophrenia or schizophrenia-like illnesses who use antipsychotic medications. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed the quality of included studies. For continuous outcomes, we combined mean differences (MD) in endpoint and change data in the analysis. For dichotomous outcomes, we calculated risk ratios (RR). We assessed risk of bias for included studies and used GRADE to judge certainty of evidence and create summary of findings tables. The primary outcomes for this review were clinically important change in weight, clinically important change in body mass index (BMI), leaving the study early, compliance with treatment, and frequency of nausea. The included studies rarely reported these outcomes, so, post hoc, we added two new outcomes, average endpoint/change in weight and average endpoint/change in BMI. MAIN RESULTS: Seventeen RCTs, with a total of 1388 participants, met the inclusion criteria for the review. Five studies investigated metformin, three topiramate, three H2 antagonists, three monoamine modulators, and one each investigated monoamine modulators plus betahistine, melatonin and samidorphan. The comparator in all studies was placebo or no treatment (i.e. standard care alone). We synthesised all studies in a quantitative meta-analysis. Most studies inadequately reported their methods of allocation concealment and blinding of participants and personnel. The resulting risk of bias and often small sample sizes limited the overall certainty of the evidence. Only one reboxetine study reported the primary outcome, number of participants with clinically important change in weight. Fewer people in the treatment condition experienced weight gains of more than 5% and more than 7% of their bodyweight than those in the placebo group (> 5% weight gain RR 0.27, 95% confidence interval (CI) 0.11 to 0.65; 1 study, 43 participants; > 7% weight gain RR 0.24, 95% CI 0.07 to 0.83; 1 study, 43 participants; very low-certainty evidence). No studies reported the primary outcomes, 'clinically important change in BMI', or 'compliance with treatment'. However, several studies reported 'average endpoint/change in body weight' or 'average endpoint/change in BMI'. Metformin may be effective in preventing weight gain (MD -4.03 kg, 95% CI -5.78 to -2.28; 4 studies, 131 participants; low-certainty evidence); and BMI increase (MD -1.63 kg/m2, 95% CI -2.96 to -0.29; 5 studies, 227 participants; low-certainty evidence). Other agents that may be slightly effective in preventing weight gain include H2 antagonists such as nizatidine, famotidine and ranitidine (MD -1.32 kg, 95% CI -2.09 to -0.56; 3 studies, 248 participants; low-certainty evidence) and monoamine modulators such as reboxetine and fluoxetine (weight: MD -1.89 kg, 95% CI -3.31 to -0.47; 3 studies, 103 participants; low-certainty evidence; BMI: MD -0.66 kg/m2, 95% CI -1.05 to -0.26; 3 studies, 103 participants; low-certainty evidence). Topiramate did not appear effective in preventing weight gain (MD -4.82 kg, 95% CI -9.99 to 0.35; 3 studies, 168 participants; very low-certainty evidence). For all agents, there was no difference between groups in terms of individuals leaving the study or reports of nausea. However, the results of these outcomes are uncertain given the very low-certainty evidence. AUTHORS' CONCLUSIONS: There is low-certainty evidence to suggest that metformin may be effective in preventing weight gain. Interpretation of this result and those for other agents, is limited by the small number of studies, small sample size, and short study duration. In future, we need studies that are adequately powered and with longer treatment durations to further evaluate the efficacy and safety of interventions for managing weight gain.

The Effect of Metformin on Ethanol- and IndomethacinInduced Gastric Ulcers in Rats.

BACKGROUND: Previous studies found metformin as an effective agent to suppress oxidative stress, inflammation, and apoptosis in various inflammatory diseases. The present study investigated the effect of metformin against 2 experimental gastric injury models in rats, using macroscopical, histopathological, biochemical, and immunostaining studies. METHODS: After 24 hours of fasting, male Sprague-Dawley rats (280-400 g) (n = 8 per group) received indomethacin (80 mg/kg; indo ulcer group) or absolute ethanol (5 mL/kg; ethanol ulcer group) or vehicle orally by gavage. Metformin (500 mg/kg) was given orally for 3 days prior to indomethacin or ethanol challenge. Ranitidine (50 mg/kg) was given orally for 3 days before indomethacin or ethanol administration as a positive control. On day 3, the animals were euthanized 6 hours after indo or 1 hour after ethanol challenge. Gastric samples were used for macroscopic scoring, histopathological examinations, and biochemical assays. Trunk blood was collected for the assessment of interleukin-1ß level. RESULTS: In both ethanol ulcer and indo ulcer groups, metformin decreased the extent of gastric lesions macroscopically and microscopically, improved the high chemiluminescence levels, and the percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with untreated ulcer groups. Gastric blood flow analysis revealed significant increases in both metformin-treated ulcer groups compared to untreated ulcer groups. CONCLUSION: The findings of the present work demonstrated the gastroprotective effect of metformin against the development of gastric mucosal lesions induced by ethanol and indomethacin in non-diabetic, normoglycemic rats via its antioxidant and anti-apoptotic properties and partly from its ability to restore blood flow.

Efficacy of Premedication Protocol without Ranitidine for Taxane Regimen: A Multicenter Non-Randomized Historical Controlled Study.

OBJECTIVE: To study the efficacy of the prevention of immediate hypersensitivity reactions (HSRs) from omitting ranitidine in the premedication protocol in patients who had chemotherapy with taxane regimen. METHODS: This was a Multicenter, Ambispective Non-Randomized Historical Controlled Cohort Study. The incidence of HSRs in the patients who had the modified premedication without ranitidine were collected to compare with the historical group who had the standard premedication protocol with ranitidine. The relationships of each HSRs in the experimental group were compared with the historical control group using a multilevel regression analysis with the random-effects model. RESULT: A total of 441 patients were enrolled and analyzed in this study. 221 patients received the modified premedication protocol compared with 220 patients who received the standard premedication protocol in the historical group. HSRs were observed in 6 of 768 cycles of chemotherapy (0.78%) in a group of patients with the modified premedication protocol. Moreover, it was found in 4 of 761 cycles of chemotherapy (0.52%) in a group of patients with the standard premedication protocol. When comparing the relationship of the HSRs incidence between the groups using multilevel regression analysis with the random-effects model, there were no differences with a statistical significance (regression coefficients = 0.008, p-value = 0.30). CONCLUSION: The results of the study comprised evidence-based medicine supporting the safety of omitting ranitidine from the premedication protocol for the patients who had a taxane regimen and had a similar rate of HSRs to the use of ranitidine.

Gastroprotective effect of topiramate on indomethacin-induced peptic ulcer in rats: Biochemical and histological analyses.

Topiramate is an anticonvulsant drug effective against a wide range of seizures and epilepsies. The present study was conducted to investigate the possible protective effect of topiramate on indomethacin-induced gastric mucosal damage in rats. The animals were randomly distributed into four experimental groups with 10 animals in each group. Group 1 was the control group received vehicle only (DMSO at 1:4 (w/v)), group 2 was the model group received indomethacin (50 mg/kg; i.p.), and groups 3 and 4 received topiramate (100 mg/kg; i.p.) and ranitidine (100 mg/kg; i.p.), respectively, 1 h before indomethacin (50 mg/kg; i.p.). The efficacy of topiramate was compared with ranitidine. Animals were euthanized 4 h after indomethacin administration, and gastric tissues were collected for macroscopical, histopathological, and biochemical analyses. The mucosal lesions in the gastric corpus were evaluated by pathological examinations. The results revealed that the administration of indomethacin caused evident gastric mucosal damage with morphological and histological manifestation, whereas topiramate pretreatment extensively ameliorated the gastric injuries. Topiramate pretreatment also reduced the contents of tissue malonaldehyde, enhanced ferric reducing antioxidant power value and glutathione levels, and increased the activity of superoxide dismutase, catalase, and glutathione peroxidase in gastric mucosa compared to the model group. Our results indicate that topiramate might possess a protective role against indomethacin-induced gastric ulcers by inhibition of oxidative stress in gastric tissue.

Hipocalcemia, hipomagnesemia y uso crónico de inhibidores de la bomba de protones / Hypocalcemia, hypomagnesemia, and chronic use of proton pump inhibitors

Introducción: Los inhibidores de la bomba de protones son fármacos usados en múltiples gastropatías. El omeprazol pertenece a este grupo de medicamentos y es aprobado y catalogado como indispensable por la Organización Mundial de la Salud. Esto ha causado que su uso se vuelva constante y hasta cierto punto equívoco. Pese a ser medicamentos seguros muestran efectos secundarios, dentro de los cuales uno ocasional es el trastorno hidroelectrolítico. Objetivo: Presentar un caso clínico en el cual se constató la presencia de efectos secundarios tras el uso de un fármaco de uso constante por la comunidad médica: el omeprazol. Caso clínico: Se presenta a continuación el caso clínico de un paciente masculino con antecedente de hipertensión arterial y gastropatía crónica que muestra uso por 8 años consecutivos de inhibidores de la bomba de protones, al cual se le diagnostica hipomagnesemia e hipocalcemia. Se obtuvieron resultados de laboratorio normales tras administración de suplementos orales y uso de ranitidina con supresión de terapéutica con omeprazol. Conclusiones: Un control constante de los fármacos que usan los pacientes crónicos es fundamental en atención primaria de salud. El uso de inhibidores de la bomba de protones se ha convertido en rutinario y es necesario corroborar siempre la dosis y el tiempo de uso de los fármacos además de la relación con otros medicamentos que use el paciente(AU)

Introduction: Proton-pump inhibitors are drugs used in multiple gastropathies. Omeprazole belongs to this group of medicines; it is approved and classified as essential by the World Health Organization. This has permitted for its use to become constant and, to some extent, misleading. Despite being safe drugs, they show side effects, among which an occasional one is fluid and electrolyte disorders. Objective: To present a clinical case in which the occurrence of side effects was verified after the administration of a drug constantly used by the medical community. Clinical case: The following is a clinical case of a male patient with a history of arterial hypertension and chronic gastropathy, characterized by the usage of proton-pump inhibitors for eight consecutive years, diagnosed with hypomagnesemia and hypocalcemia. Normal laboratory results were obtained after oral supplementation and usage of ranitidine with suppression of omeprazole therapy. Conclusions: Constant control of the drugs used by chronic patients is essential in primary health care. The usage of proton-pump inhibitors has become a routine. It is always necessary to check the dose and time for using the drugs as well as the relationship with other drugs used by the patient(AU)

The 'burn' of ranitidine recall: current insights and mitigation strategies.

Ranitidine was one of the most commonly used medications for the treatment of gastroesophageal reflux disease. On 1 April 2020, the US Food and Drug Administration requested all manufacturers to immediately withdraw ranitidine from the market because of concern of higher than acceptable levels of N-nitrosodimethylamine, a potential carcinogen. Herein, we highlight the reason for this recall, along with the effects of this recall on both the patients and healthcare practitioners, and offer insights on management strategies.

Anti-ulcerogenic effect of methanolic extract of Elaeagnus conferta Roxb. seeds in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant. AIM OF THE STUDY: Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta. MATERIALS AND METHODS: Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied. RESULTS: Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner. CONCLUSIONS: The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer.

Design and Synthesis of Ranitidine Analogs as Multi-Target Directed Ligands for the Treatment of Alzheimer's Disease.

The aggregation of amyloid ß (Aß) peptides and deposition of amyloid plaques are implicated in the pathogenesis of Alzheimer's disease (AD). Therefore, blocking Aß aggregation with small molecules has been proposed as one therapeutic approach for AD. In the present study, a series of ranitidine analogs containing cyclic imide isosteres were synthesized and their inhibitory activities toward Aß aggregation were evaluated using in vitro thioflavin T assays. The structure-activity relationship revealed that the 1,8-naphthalimide moiety provided profound inhibition of Aß aggregation and structural modifications on the other parts of the parent molecule (compound 6) maintained similar efficacy. Some of these ranitidine analogs also possessed potent inhibitory activities of acetylcholinesterase (AChE), which is another therapeutic target in AD. These ranitidine analogs, by addressing both Aß aggregation and AChE, offer insight into the key chemical features of a new type of multi-target directed ligands for the pharmaceutical treatment of AD.

The added value of H2 antagonists in premedication regimens during paclitaxel treatment.

BACKGROUND: Ranitidine, a histamine 2 blocker, is the standard of care to prevent hypersensitivity reactions (HSRs) caused by paclitaxel infusion. However, the added value of ranitidine in this premedication regimen is controversial. Therefore, we compared the incidence of HSRs during paclitaxel treatment between a standard regimen including ranitidine and a regimen without ranitidine. METHODS: This prospective, pre-post interventional, non-inferiority study compared the standard premedication regimen (N = 183) with dexamethasone, clemastine and ranitidine with a premedication regimen without ranitidine (N = 183). The primary outcome was the incidence of HSR grade ≥3. Non-inferiority was determined by checking whether the upper bound of the two-sided 90% confidence interval (CI) for the difference in HSR rates excluded the +6% non-inferiority margin. RESULTS: In both the pre-intervention (with ranitidine) and post-intervention (without ranitidine) group 183 patients were included. The incidence of HSR grade ≥3 was 4.4% (N = 8) in the pre-intervention group and 1.6% (N = 3) in the post-intervention group: difference -2.7% (90% CI: -6.2 to 0.1). CONCLUSIONS: As the upper boundary of the 90% CI does not exceed the predefined non-inferiority margin of +6%, it can be concluded that a premedication regimen without ranitidine is non-inferior to a premedication regimen with ranitidine. CLINICAL TRIAL REGISTRATION: www.trialregister.nl ; NL8173.

Acute Anisakiasis: Pharmacological Evaluation of Various Drugs in an Animal Model.

BACKGROUND: The accidental ingestion of the third larval stage of Anisakis can cause acute clinical symptoms, which are relieved via extraction of the larvae. Although this is a highly effective technique, it can only be practiced when the larvae are found in accessible areas of the gastrointestinal tract, and therefore instead the condition has often been treated using various different drugs. AIMS: This study evaluates the effectiveness of gastric acid secretion inhibitors (omeprazole and ranitidine), gastric mucosal protectants (sucralfate) and anthelmintics (mebendazole and flubendazole) in treating anisakiasis in Wistar rats. METHODS: Rats were infected with Anisakis-type I larvae and administered the drugs via a gastric probe. Data were recorded regarding the number of live and dead larvae, their location both within the animal and in its feces, and the presence of gastrointestinal lesions. Additionally, gastric pH was measured and histology performed. RESULTS: While rats in all experimental groups exhibited lesions; those treated with ranitidine and mebendazole showed significantly fewer lesions (50% and 35% of rats exhibited lesions, respectively). Histological examination of the gastric lesions revealed infection-induced changes, but no significant differences were observed between the treated and untreated rats. CONCLUSIONS: Mebendazole was found to be most efficacious in preventing gastrointestinal lesions, followed by ranitidine, which was the most effective antacid of those studied. Both these drugs could thus be considered as part of the conservative management of anisakiasis.

UPLC-qTOF-MS Phytochemical Profile and Antiulcer Potential of Cyperus conglomeratus Rottb. Alcoholic Extract.

Cyperus has been commonly used as a multi-use medicinal plant in folk medicine worldwide. The objectives of our study were to determine the different metabolites in the Cyperus conglomeratus Rottb. methanol extract, and to assess its in vivo gastroprotective effect in ethanol-induced gastric ulcer model in rats. Serum levels of galactin-3 and TNF-α were employed as biochemical markers. To pinpoint for active agents, comprehensive metabolites profiling of extract via UPLC-qTOF-MS/MS was employed. A total of 77 chromatographic peaks were detected, of which 70 were annotated. The detected metabolites were categorized into phenolic acids and their derivatives, flavonoids, stilbenes, aurones, quinones, terpenes, and steroids. Rats were divided into six groups; healthy control, ulcer control, standard drug group, and 25, 50, 100 mg/kg of C. conglomeratus treated rats. Pre-treatment with C. conglomeratus alcohol extract significantly reduced galactin-3, and TNF-α in ethanol-induced ulcer model at 25, 50, and 100 mg/kg. Further histopathological and histochemical studies revealed moderate erosion of superficial epithelium, few infiltrated inflammatory cells, and depletion of gastric tissue glycoprotein in the ulcer group. Treatment with the extract protected the gastric epithelial cells in a dose-dependent manner. It could be concluded that C. conglomeratus extract provides significant gastroprotective activity in ethanol-induced gastric ulcer and ought to be included in nutraceuticals in the future for ulcer treatment.

A short course of oral ranitidine as a novel treatment for toddler's diarrhea: a parallel-group randomized controlled trial.

BACKGROUND: The current paradigm for treating toddler's diarrhea comprises dietary modification and fluid restriction. Previous studies show that probiotics and proton-pump inhibitors (PPIs) or H2 blockers could control diarrhea associated with functional gastrointestinal disorders (FGIDs). This study aims to determine and compare the efficacy of a short course of oral ranitidine and a probiotic in the treatment of toddler's diarrhea. METHODS: This study was a parallel-group randomized controlled trial (RCT). We sequentially enrolled 40 patients who met the eligibility criteria. We randomly assigned 20 patients to the oral ranitidine group, ten patients to the probiotic group, and ten patients to the placebo group. In the oral ranitidine group, patients received oral ranitidine (3 mg/kg/day) once daily for 10 days; in the probiotic and placebo groups, they were administered 5 to 10 billion colony-forming units (CFUs) per day of lyophilized Lactobacillus rhamnosus and 50 mg of once-daily oral vitamin C tablet respectively for 10 days. Stool frequency and consistency on the 10th day of the interventions were recorded as the primary outcomes. We used the Student's t-test to determine if there were significant differences in the mean daily stool frequencies in the three intervention groups. A p-value < 0.05 was adopted as the level of statistical significance. RESULTS: In the ranitidine group, stool frequency decreased significantly from an average of five per day on the first day to an average of approximately one per day on the 10th day of intervention (t = 10.462, p <  0.001). Additionally, stool consistency normalized on the 10th day of intervention. In the probiotic group, there was a significant reduction in stool frequency from an average of five per day on the first day to four per day on the 10th day (t = 2.586, p = 0.041), although stool consistency remained loose. However, stool consistency and frequency were not significantly affected in the placebo group (t = 1.964, p = 0.072). CONCLUSION: Oral ranitidine is more effective than probiotics in reducing stool frequency and normalizing stool consistency in toddler's diarrhea. We recommend multi-center trials with appropriate study designs to confirm and validate this finding. TRIAL REGISTRATION: ISRCTN, ISRCTN10783996 . Registered 8 April 2016-Registered retrospectively.

Exploration of self-medication practice in Pokhara valley of Nepal.

BACKGROUND: Self-medication (SM) is the practice of consuming medication without the consultation of physician. The drugs most commonly self-medicated are paracetamol, analgesics, ranitidine, oral rehydration solution and antibiotics. The objective of the study was to assess the SM status and its causes in Pokhara valley of Nepal. METHOD: The study was conducted among the people residing in Pokhara metropolitan city. The study duration was of 4 months from April to July, 2018. The study population were patients attending health general and oral health screening programs at Baidam, Birauta, Hemja and Pame areas of Pokhara. Structured questionnaire was used to collect demographics of the patients and the details of the usage of self-medication. RESULT: Out of 201 patients, 38.2% patients were found to be self-medicating. The most common illness sought for SM was ache (headache, body ache) in 50% subjects followed by cough and cold in 31% and gastritis in 23%. Paracetamol was the drug consumed by 16 subjects followed by nimesulide by 11. Lack of knowledge about the disadvantages of SM led to self-medication in 65% of respondents. The personnel most commonly consulted for medication were pharmacists (60%). CONCLUSION: The trend of SM is high in Pokhara valley. The comedics were consulted most often for SM due to lack of knowledge of consultation to physicians. The public should be made aware about SM.

Ranitidine and finasteride inhibit the synthesis and release of trimethylamine N-oxide and mitigates its cardiovascular and renal damage through modulating gut microbiota.

Trimethylamine N-oxide (TMAO) leads to the development of cardiovascular and chronic kidney diseases, but there are currently no potent drugs that inhibit the production or toxicity of TMAO. In this study, high-fat diet-fed ApoE-/- mice were treated with finasteride, ranitidine, and andrioe. Subsequently, the distribution and quantity of gut microbiota in the faeces of the mice in each group were analysed using 16S rRNA sequencing of the V3+V4 regions. Pathological examination confirmed that both ranitidine and finasteride reduced atherosclerosis and renal damage in mice. HPLC analysis also indicated that ranitidine and finasteride significantly reduced the synthesis of TMAO and the TMAO precursor delta-Valerobetaine in their livers. The 16S rRNA sequencing showed that all 3 drugs significantly increased the richness and diversity of gut microbiota in the model mice. Bioinformatic analysis revealed that the faeces of mice treated with ranitidine and finasteride, had significant increases in the number of microbes in the families g_Helicobacter, f_Desulfovibrionaceae, Mucispirillum_schaedleri_ASF457, and g_Blautia, whereas the relative abundances of microbes in the families Enterobacter_sp._IPC1-8 and g_Bacteroides were significantly reduced. The microbiota metabolic pathways, such as nucleotide and cofactor and vitamin metabolism were also significantly increased, whereas the activities of metabolic signalling pathways related to glycan biosynthesis and metabolism and cardiovascular diseases were significantly reduced. Therefore, our study indicates that in addition to their known pharmacological effects, ranitidine and finasteride also exhibit potential cardiovascular and renal protective effects. They inhibit the synthesis and metabolism of TMAO and delay the deposition of lipids and endotoxins through improving the composition of the gut microbiota.

Use of Point-of-Care Gastric pH Testing to Assess the Efficacy of Acid Suppression Therapy in the Neonatal Intensive Care Unit.

OBJECTIVE: The use of acid suppression therapies in newborns lacks efficacy and is associated with adverse effects. Point-of-care (POC) assessment of gastric aspirate pH may provide an objective, noninvasive measure of gastric acidity in tube fed infants. We conducted the present study to characterize the POC gastric pH levels in gastric tube fed infants before and after initiation of enteral omeprazole or ranitidine. STUDY DESIGN: Retrospective cohort study of infants with gastric aspirate pH levels determined by POC pH strips. Gastric pH levels recorded during 7 days before and 14 days after medication initiation were compared using Wilcoxon's sign-rank tests. RESULTS: Among 307 evaluated infants, 284 (92%) had a median gastric pH level ≥4 in 7 days prior to ranitidine or omeprazole. In 14 days after medication initiation, the median gastric pH of infants with pretreatment median gastric pH < 4 increased to 4.5 and 5 (p < 0.01) in the ranitidine and omeprazole groups, respectively. There was no change in infants with pretreatment median gastric pH ≥4. CONCLUSION: Among infants receiving gastric tube feedings and enteral omeprazole or ranitidine, only those with a pretreatment gastric pH level <4 demonstrated a significant increase in gastric pH. Validation of our findings against esophageal pH multichannel intraluminal impedance testing is needed.

Mucoadhesive effect of Curcuma longa extract and curcumin decreases the ranitidine effect, but not bismuth subsalicylate on ethanol-induced ulcer model.

The study of pharmacological interactions between herbal remedies and conventional drugs is important because consuming traditional herbal remedies as supplements or alternative medicine is fairly common and their concomitant administration with prescribed drugs could either have a favorable or unfavorable effect. Therefore, this work aims to determine the pharmacological interactions of a turmeric acetone extract (TAE) and its main metabolite (curcumin) with common anti-ulcer drugs (ranitidine and bismuth subsalicylate), using an ethanol-induced ulcer model in Wistar rats. The analysis of the interactions was carried out via the Combination Index-Isobologram Equation method. The combination index (CI) calculated at 0.5 of the affected fraction (fa) indicated that the TAE or curcumin in combination with ranitidine had a subadditive interaction. The results suggest that this antagonistic mechanism is associated to the mucoadhesion of curcumin and the TAE, determined by rheological measurements. Contrastingly, both the TAE and curcumin combined with bismuth subsalicylate had an additive relationship, which means that there is no pharmacological interaction. This agrees with the normalized isobolograms obtained for each combination. The results of this study suggest that mucoadhesion of curcumin and the TAE could interfere in the effectiveness of ranitidine, and even other drugs.

Pharmacological antagonism of histamine H2R ameliorated L-DOPA-induced dyskinesia via normalization of GRK3 and by suppressing FosB and ERK in PD.

Parkinson's disease (PD) is often managed with L-3,4-dihydroxyphenylalanine (L-DOPA), which is still the gold standard to relieve the clinical motor symptoms of PD. However, chronic use of L-DOPA leads to significant motor complications, especially L-DOPA-induced dyskinesia (LID), which limit the therapeutic benefit. Few options are available for the pharmacological management of LID partly due to the inadequacy of our mechanistic understanding of the syndrome. We focused on the role of the histamine (HA) H2 receptor (H2R) in the striatum, which others have shown to be involved in the development of LID. We generated LID in a hemiparkinsonian mouse model and tested the signaling effects of ranitidine, an H2R antagonist. We used histidine decarboxylase deficient mice (Hdc-Ko) which lacks HA to study the role of G-protein-coupled receptor kinases (GRKs) in HA deficiency. Loss of HA in Hdc-Ko mice did not result in the downregulation of GRKs, especially GRK3 and GRK6, which were previously found to be reduced in hemiparkinsonian animal models. Ranitidine, when given along with L-DOPA, normalized the expression of GRK3 in the dopamine-depleted striatum thereby inhibiting LID in mice. The extracellular signal regulated kinase and ΔFosB signaling pathways were attenuated in the lesioned striatum when ranitidine was combined with L-DOPA than L-DOPA alone. These results demonstrate that ranitidine inhibits LID by normalizing the levels of GRK3, extracellular signal regulated kinase activation, and FosB accumulation in the dopamine-depleted striatum via HA H2R antagonism.