Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Background: Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Patients and methods: Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. Results: A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. Conclusions: The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways.

BACKGROUND: Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine model of chronic oral PPI administration to verify whether PPIs caused bone metabolic impairment and investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 murine osteoblasts. METHODS: A lansoprazole-induced bone loss model was used to investigate the damaging effects of PPIs. In vivo, immunohistochemistry, Hematoxylin-Eosin (HE) staining, micro-CT analysis, and blood biochemical analyses were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects of lansoprazole and related signaling pathways in MC3T3-E1 cells were investigated by CCK-8 assays, EdU assays, flow cytometry, laser confocal microscopy, patch clamping, reverse transcription-quantitative polymerase chain reaction and Western blotting. RESULTS: After 6 months of lansoprazole gavage in ICR mice, the micro-CT results showed that compared with that in the vehicle group, the bone mineral density (BMD) in the high-dose group was significantly decreased (P < 0.05), and the bone microarchitecture gradually degraded. Biochemical analysis of bone serum showed that blood calcium and phosphorus were both decreased (P < 0.01). We found that long-term administration of lansoprazole impaired skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOCE pathway, effectively blocked increase in calcium caused by LPZ, thus protecting cell viability. CONCLUSIONS: Longterm administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium increases in osteoblasts in a concentration-dependent manner. Intracellular calcium ([Ca2+]i) persisted at a high concentration, thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblast apoptosis.

Helicobacter pylori: Perturbation and restoration of gut microbiome.

Alternate remedies with natural products provides unlimited opportunities for new drug development. These can be either as pure compounds or as standardized set of compounds. The phytochemicals and secondary metabolites are in great demand for screening bioactive compounds and plays an important role towards drug development. Natural products have many advantages over to synthetic chemical drugs. Helicobacter pylori (H. pylori) a Gram-negative bacteria has been classified as Class I carcinogen by World Health Organization in 1994. Current treatment regimens for H. pylori is 'triple therapy' administrated for two weeks which includes a combination of two antibiotics like Amoxicillin and Clarithromycin and a proton pump inhibitor (PPI) like Lansoprazole, and for 'quadruple therapy' in addition to antibiotics and a PPI, Bismuth is used. Antibiotic resistance can be named as the main factor for failure of treatment of H. pylori infection. The need of the hour is to develop a herbal remedy that could combat the growth of H. pylori. Probiotics can also be used as 'feasible' tool for H. pylori infection management. Present review is an attempt to briefly discuss about the pathogenicity, genetic predisposition, perturbation of gut microbiota due to antibiotic treatment and restoration of healthy gut microbiota with phytochemicals and probiotics.

Ten-day high-dose proton pump inhibitor triple therapy versus sequential therapy for Helicobacter pylori eradication.

BACKGROUND AND AIM: Eradication rates of Helicobacter pylori following standard triple therapy are declining worldwide, but high-dose proton pump inhibitor-based triple therapy (HD-PPI-TT) and sequential therapy (ST) have demonstrated higher cure rates. We aimed to compare the efficacy and tolerability of HD-PPI-TT and ST in H. pylori-associated functional dyspepsia (FD). METHODS: One hundred and twenty H. pylori-associated functional dyspepsia patients were randomized to receive 10-day HD-PPI-TT (60 mg lansoprazole/500 mg clarithromycin/1 g amoxicillin, each administered twice daily for 10 days) or 10-day ST (30 mg lansoprazole/1 g amoxicillin, each administered twice daily for 5 days followed by 30 mg lansoprazole/500 mg clarithromycin/400 mg metronidazole, each administered twice daily for 5 days). H. pylori status was determined in post-treatment week 4 by 14 C-urea breath test. Eradication and antibiotic resistance rates, dyspeptic symptoms, drug compliance, and adverse effects were compared. RESULTS: Intention-to-treat eradication rates were similar in the ST and HD-PPI-TT groups (85% vs. 80%; P = 0.47). However, the eradication rate was significantly higher following ST compared with HD-PPI-TT in per protocol analysis (94.4% vs. 81.4%; P = 0.035). ST achieved higher cure rates than HD-PPI-TT in clarithromycin-resistant H. pylori strains (100% vs. 33.3%; P = 0.02). Treatment compliance was similar in the HD-PPI-TT and ST groups, although nausea and dizziness were more common in the ST group. CONCLUSIONS: Sequential therapy achieved better H. pylori eradication than HD-PPI-TT in patients with FD. However, the eradication rate for ST fell from 94.4% in per protocol to 85% in intention-to-treat analysis. Adverse effects might result in poorer compliance and compromise actual ST efficacy (ClinicalTrials.gov: NCT01888237).

Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation.

BACKGROUND: QT interval-prolonging drug-drug interactions (QT-DDIs) may increase the risk of life-threatening arrhythmia. Despite guidelines for testing from regulatory agencies, these interactions are usually discovered after drugs are marketed and may go undiscovered for years. OBJECTIVES: Using a combination of adverse event reports, electronic health records (EHR), and laboratory experiments, the goal of this study was to develop a data-driven pipeline for discovering QT-DDIs. METHODS: 1.8 million adverse event reports were mined for signals indicating a QT-DDI. Using 1.6 million electrocardiogram results from 380,000 patients in our institutional EHR, these putative interactions were either refuted or corroborated. In the laboratory, we used patch-clamp electrophysiology to measure the human ether-à-go-go-related gene (hERG) channel block (the primary mechanism by which drugs prolong the QT interval) to evaluate our top candidate. RESULTS: Both direct and indirect signals in the adverse event reports provided evidence that the combination of ceftriaxone (a cephalosporin antibiotic) and lansoprazole (a proton-pump inhibitor) will prolong the QT interval. In the EHR, we found that patients taking both ceftriaxone and lansoprazole had significantly longer QTc intervals (up to 12 ms in white men) and were 1.4 times more likely to have a QTc interval above 500 ms. In the laboratory, we found that, in combination and at clinically relevant concentrations, these drugs blocked the hERG channel. As a negative control, we evaluated the combination of lansoprazole and cefuroxime (another cephalosporin), which lacked evidence of an interaction in the adverse event reports. We found no significant effect of this pair in either the EHR or in the electrophysiology experiments. Class effect analyses suggested this interaction was specific to lansoprazole combined with ceftriaxone but not with other cephalosporins. CONCLUSIONS: Coupling data mining and laboratory experiments is an efficient method for identifying QT-DDIs. Combination therapy of ceftriaxone and lansoprazole is associated with increased risk of acquired long QT syndrome.

Lansoprazole-induced hypomagnesaemia.

The introduction of proton pump inhibitors (PPIs) in the late 1980s optimised the medical treatment of acid-related disorders. They are potent medications and have a good safety profile. However, long-term therapy with PPIs may carry undesired side effects, one of which is hypomagnesaemia. This entity is likely to be under-reported. We present a clinical case which illustrates this important clinical problem. We present the case of a 73-year-old woman who was admitted to the hospital with supraventricular tachycardia due to hypomagnesaemia while using lansoprazole, followed by the literature review on this subject. In our patient after the intravenous magnesium replenishment, her arrhythmia resolved. After stopping her PPI her serum magnesium remained within reference values without oral supplementation. We believe that more attention towards this underdiagnosed side effect is required. Serum magnesium concentration should be checked in patients on PPIs if they are unwell or present with arrythmia.

Phlebosclerotic colitis that was difficult to distinguish from collagenous colitis.

Phlebosclerotic colitis is a rare and recently known disease entity and its etiology is still to be elucidated. Some phlebosclerotic colitis cases are difficult to distinguish from collagenous colitis because of the similarity of pathological findings. In all Japanese case reports of phlebosclerotic colitis in which an association with the use of Chinese herbal medicine is suspected, sansisi (gardenia fruit) was included, suggesting pathogenesis of this disease. We report a case of phlebosclerotic colitis that wasdifficult to be distinguished from collagenous colitis, and an association with the use of Chinese herbal medicine was suspected as the cause of the disease.