PMID: 

J Res Pharm Pract. 2019 Jul-Sep;8(3):123-128. Epub 2019 Oct 16. PMID: 31728342

Abstract Title: 

The Association between Proton Pump Inhibitors and Myocardial Infarction: What Do Food and Drug Administration Data Tell Us?

Abstract: 

Objective: There is limited and conflicting evidence on the association between proton pump inhibitors (PPIs) and myocardial infarction (MI). This study aims to examine the occurrence of MI associated with PPI use from the Food and Drug Administration (FDA) Adverse Event Reporting System database.Methods: This is a cross-sectional study using data from the FDA dated from December 2013 to April 2018. Standard descriptive statistics were used to describe demographic information. Logistic regression analyses were performed to investigate the association between the independent variables and MI.Findings: Among the 52,443 individuals who were taking a PPI and experienced an adverse event which was registered on the FDA database, 726 (1.38%) experienced MI. Of all the PPIs, esomeprazole had the largest proportion of users experiencing MI (1.81%). Compared to other PPIs, esomeprazole was associated with a significantly higher rate of MI (odds ratio [OR] =1.53,

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PMID: 

Eur J Intern Med. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31735546

Abstract Title: 

Use of proton pump inhibitors is associated with an increase in adverse cardiovascular events in patients with hemodialysis: Insight from the kids registry.

Abstract: 

BACKGROUND: Proton pump inhibitors (PPIs) are known to increase the risk of mortality and cardiovascular events in the general population. However, in patients with maintenance hemodialysis, PPI effects are under investigated.METHODS: We analyzed the risk of PPIs for cardiovascular events using the Kagoshima Dialysis (KIDS) registry, a prospective, multicenter, observational study in patients with maintenance hemodialysis in Japan.RESULTS: In all, 531 patients were enrolled from June 2015 to December 2018. One-year follow-up data were available for 376 patients (Use of PPIs at baseline (PPI group): 217 patients and without PPIs (No PPI group): 159 patients). The incidence of a composite outcome (all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke) was higher in patients in the PPI group than the No PPI group (15.2% vs. 4.4%; hazard ratio (HR): 3.65, 95% confidence interval (CI): 1.61-8.23, P = 0.002). In the multivariate analysis, even after adjustment for covariates, the use of PPIs was an independent risk factor for a composite outcome (HR: 2.38, 95% CI: 1.02-5.54, P = 0.045). We performed propensity score matching analysis as a sensitivity analysis, showing a consistent result. The incidence of bleeding showed no difference between the two groups (15.7% vs. 11.3%; HR: 1.46, 95% CI: 0.83-2.59, P = 0.19).CONCLUSIONS: These results indicate that the use of PPIs in patients with maintenance hemodialysis might increase mortality and cardiovascular events without decreasing the risk of bleeding. Therefore, it should always be analyzed if a patient truly needs PPIs.

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PMID: 

Eur J Clin Pharmacol. 2019 Nov 21. Epub 2019 Nov 21. PMID: 31748819

Abstract Title: 

Proton pump inhibitors use and dementia risk: a meta-analysis of cohort studies.

Abstract: 

PURPOSE: The aim of this study was to explore the relationship between proton pump inhibitors use and the risk of dementia.METHODS: A comprehensive literature search was conducted in English and Chinese databases from origination to December 2018. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. Cochran's Q test and the Istatistic were used to evaluate the heterogeneity. Publication bias was assessed by Begg's test and Egger's test.RESULTS: Six studies were included, which contained a total of 166,146 participants. The overall result demonstrated a significant increase in dementia risk with proton pump inhibitors use (HR = 1.29, 95% CI = 1.12-1.49). In subgroup analyses, a significant association was detected between proton pump inhibitors use and the risk of dementia in Europe (HR = 1.46, 95% CI = 1.23-1.73) and among participants aged ≥ 65 years (HR = 1.39, 95% CI = 1.17-1.65). For thefactor follow-up time ≥ 5 years, the pooled HR was 1.28 (95% CI = 1.12-1.46), demonstrating a 1.28-fold increase in the risk of dementia among proton pump inhibitors users. In the case of regional impact, participants from Europe showed an overall pooled HR estimate of 1.46 (95% CI = 1.23-1.73). There was no evidence of publication bias.CONCLUSIONS: The overall result of this meta-analysis supports the hypothesis that proton pump inhibitors increase the risk of dementia. Furthermore, high-quality cohort studies are needed to confirm these findings.

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PMID: 

Sci Rep. 2019 Nov 21 ;9(1):17280. Epub 2019 Nov 21. PMID: 31754136

Abstract Title: 

Proton-pump inhibitor use is associated with a broad spectrum of neurological adverse events including impaired hearing, vision, and memory.

Abstract: 

Proton-pump inhibitors, PPIs, are considered effective therapy for stomach acid suppression due to their irreversible inhibition of the hydrogen/potassium pump in the gastric parietal cells. They are widely prescribed and are considered safe for over-the-counter use. Recent studies have shown an association between PPI use and Alzheimer dementia, while others have disputed that connection. We analyzed over ten million United States Food and Drug Administration Adverse Event Reporting System reports, including over forty thousand reports containing PPIs, and provided evidence of increased propensity for memory impairment among PPI reports when compared to histamine-2 receptor antagonist control group. Furthermore, we found significant associations of PPI use with a wide range of neurological adverse reactions including, migraine, several peripheral neuropathies, and visual and auditory neurosensory abnormalities.

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PMID: 

Atherosclerosis. 2019 Nov 16 ;292:84-89. Epub 2019 Nov 16. PMID: 31785493

Abstract Title: 

Proton pump inhibitors and risk for recurrent ischemic events or death in outpatients with symptomatic artery disease.

Abstract: 

BAGKGROUND AND AIMS: The influence of proton pump inhibitors (PPIs) on outcome in patients with symptomatic artery disease remains controversial.METHODS: FRENA is a prospective registry of consecutive outpatients with symptomatic coronary (CAD), cerebrovascular (CVD) or peripheral artery disease (PAD). We compared the risk for subsequent ischemic events or death according to the use of PPIs.RESULTS: As of December 2016, 5170 patients were recruited: 1793 (35%) had CAD, 1530 (30%) CVD and 1847 (35%) had PAD. Overall, 2289 patients (44%) were regularly using PPIs. During a median follow-up of 36 months, 172 patients suffered a recurrent myocardial infarction, 139 had ischemic stroke, 71 underwent limb amputation and 267 died (cardiovascular death, 109). On multivariable analysis, patients using PPIs were at a lower risk for subsequent limb amputation (hazard ratio [HR]: 0.53; 95%CI: 0.30-0.94), a similar risk for myocardial infarction (HR: 0.78; 95%CI: 0.55-1.10) or stroke (HR: 0.93; 95%CI: 0.64-1.35) and at a higher risk of death (HR: 1.37; 95%CI: 1.04-1.79).CONCLUSIONS: Among stable outpatients with symptomatic artery disease, the use of PPIs was associated with a lower risk for subsequent ischemic events but a higher risk for death.

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PMID: 

Int J Mol Sci. 2019 Nov 25 ;20(23). Epub 2019 Nov 25. PMID: 31775230

Abstract Title: 

Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer.

Abstract: 

L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present inL., namely, cannabidiol (CBD) andΔ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.

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PMID: 

Int J Environ Res Public Health. 2019 Nov 12 ;16(22). Epub 2019 Nov 12. PMID: 31718076

Abstract Title: 

Cannabidiol Protects Dopaminergic Neuronal Cells from Cadmium.

Abstract: 

The protective effect of cannabidiol (CBD), the non-psychoactive component of, against neuronal toxicity induced by cadmium chloride (CdCl10μM) was investigated in a retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cell line. CBD (1 μM) was applied 24 h before and removed during cadmium (Cd) treatment. In differentiated neuronal cells, CBD significantly reduced the Cd-dependent decrease of cell viability, and the rapid reactiveoxygen species (ROS) increase. CBD significantly prevented the endoplasmic reticulum (ER) stress (GRP78 increase) and the subcellular distribution of the cytochrome C, as well as the overexpression of the pro-apoptotic protein BAX. Immunocytochemical analysis as well as quantitative protein evaluation by western blotting revealed that CBD partially counteracted the depletion of the growth associated protein 43 (GAP43) and of the neuronal specific class III β-tubulin (β3 tubulin) induced by Cd treatment. These data showed that Cd-induced neuronal injury was ameliorated by CBD treatment and it was concluded that CBD may represent a potential option to protect neuronal cells from the detrimental effects of Cd toxicity.

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PMID: 

Ther Adv Psychopharmacol. 2019 ;9:2045125319881916. Epub 2019 Nov 8. PMID: 31741731

Abstract Title: 

Cannabidiol as a potential treatment for psychosis.

Abstract: 

Psychotic disorders such as schizophrenia are heterogeneous and often debilitating conditions that contribute substantially to the global burden of disease. The introduction of dopamine D2 receptor antagonists in the 1950s revolutionised the treatment of psychotic disorders and they remain the mainstay of our treatment arsenal for psychosis. However, traditional antipsychotics are associated with a number of side effects and a significant proportion of patients do not achieve an adequate remission of symptoms. There is therefore a need for novel interventions, particularly those with a non-D2 antagonist mechanism of action. Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, has emerged as a potential novel class of antipsychotic with a unique mechanism of action. In this review, we set out the prospects of CBD as a potential novel treatment for psychotic disorders. We first review the evidence from the perspective of preclinical work and human experimental and neuroimaging studies. We then synthesise the current evidence regarding the clinical efficacy of CBD in terms of positive, negative and cognitive symptoms, safety and tolerability, and potential mechanisms by which CBD may have antipsychotic effects.

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PMID: 

Food Chem Toxicol. 2019 Nov 21:110992. Epub 2019 Nov 21. PMID: 31760075

Abstract Title: 

Concentrations of nine bisphenol analogues in food purchased from Catalonia (Spain): Comparison of canned and non-canned foodstuffs.

Abstract: 

The present study was aimed at assessing the exposure of an adult population to nine BPs analogues (BPA, BPS, BPF, BPB, BPAF, BPZ, BPE, BPAP and BPP) through a duplicate diet study. Up to 40 canned and non-canned food samples were purchased from Tarragona (Catalonia, Spain) and further analyzed. Three of the nine BPs – BPA, BPB and BPE – were detected in the food samples. BPA was found in 93% and 36% of canned and non-canned samples, respectively, with a mean concentration of 22.49 and 4.73 μg/kg, respectively. Only one sample of canned asparagus (88.66 μg/kg) exceeded the new threshold set by the European Commission (50 μg/kg). BPB was found in canned and non-canned chicken and olive oil samples, with lower levels for canned chicken and non-canned olive oil. Finally, BPE was detected in non-canned mushrooms and nuts (2.40 and 12.35 μg/kg, respectively). Based on the current results, dietary intake for BPA was estimated to be 24.9 and 3.11 μg/day for canned and non-canned groups, respectively. The unexpected occurrence of BPs in non-canned products highlights the ubiquity of these compounds along the food production chain, beyond to the packaging.

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PMID: 

Environ Int. 2019 Nov 25 ;134:105328. Epub 2019 Nov 25. PMID: 31778932

Abstract Title: 

Peroxisome proliferator-activated receptor gamma (PPARγ) activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models.

Abstract: 

Bisphenol A (BPA) and its replacement analog, bisphenol S (BPS), have been proposed as environmental obesogen to disrupt the lipid metabolism through regulating peroxisome proliferator-activated receptor gamma (PPARγ) receptor. However, there is a dearth of information on whether this biological effect can occur in human macrophage, a cell type which closely interacts with adipocytes and hepatocytes to control lipid metabolism. Here, we for the first time investigate the activity of BPA and BPS on PPARγ pathway in human macrophages. The results demonstrated that BPA and BPS served as activators of PPARγ in human macrophage cell line, and significantly induced the expression of lipid metabolism-related genes, including fatty acid binding protein 4 (FABP4), cluster of differentiation 36 (CD36) and nuclear receptor subfamily 1 group H member 3 (NRH). In PPARγ knockout cells, expression of these genes was down-regulated, suggesting that these genes are dependent on PPARγ. The underlying mechanisms were further investigated using an in vivo mouse model, and the results confirmed the induction of PPARγ and its respective target genes in mice followingexposure to BPA or BPS. Moreover, the observed alteration of PPARγ expression highly correlated with the disturbance of metabolism profiles in liver tissues as detected byH Nuclear Magnetic Resonance (NMR)-based metabonomics. Overall, this study provided the first evidence that BPA and BPS activated PPARγ and its target genes in human macrophages, and provided comprehensive information to confirm that BPA and BPS disturb the metabolism through targeting PPARγ via both in vitro assays and in vivo animal models.