-
1.
Efficacy and safety of Chinese herbal medicine for patients with postmenopausal hypertension: A systematic review and meta-analysis.
Xiong, X, Yang, X, Li, X, Yue, G, Xing, Y, Cho, WC
Pharmacological research. 2019;:481-500
Abstract
Chinese herbal medicine has been increasingly used for patients with postmenopausal hypertension in China. A comprehensive literature search was performed in 7 electronic databases from their inception up to December 17, 2017 to examine the efficacy and safety of Chinese herbal medicine for postmenopausal hypertension. Thirty-nine randomized controlled trials involving 3, 823 participants were included. Meta-analyses favored Chinese herbal medicine plus antihypertensive drugs on blood pressure, blood pressure variability, postmenopausal symptoms, quality of life, and hormone levels compared with antihypertensive drugs. No severe adverse effects were identified. Er-xian decoction was the most frequently prescribed herbal formula, while Rehmannia glutinosa Libosch. was the most commonly used single herb. Chinese herbal medicine as complementary therapy maybe beneficial for postmenopausal hypertension. However, the effectiveness and safety of the decoction are still uncertain due to methodological shortcomings. Well-conducted trials are warranted to resolve the issue.
-
2.
Serum dietary fatty acids and coronary heart disease risk - A nested case-control-study within the CARLA cohort.
Medenwald, D, Kluttig, A, Lacruz, ME, Schumann, J
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2019;(2):152-158
Abstract
BACKGROUND AND AIMS Diet is known to play a decisive role in the development of coronary heart disease (CHD). One factor believed to decrease lifetime risk of CHD is the consumption of omega-3 fatty acids. Yet, conclusive evidence regarding the potential cardioprotective effects of fatty acids is far from being reached. The present study aimed to provide further evidence on the association of serum fatty acid profiles with CHD risk. METHODS AND RESULTS The CARdio-vascular Disease, Living and Ageing in Halle study (CARLA study) is an observational cohort study comprising an older adult's general population with a high level of cardiovascular risk factors. In a matched case-control design the serum fatty acid concentrations of 73 subjects with an incident fatal or nonfatal CHD event were compared to 146 controls matched for sex and age. Our data show that the participants of the CARLA study are underserved in unsaturated fatty acids with respect to current dietary recommendations. In addition, the ratio of omega-6 to omega-3 fatty acids was determined to be 8:1 which underlines the consumption of a Western-style diet enriched in omega-6 fatty acids. There were no significant differences in fatty acid patterns between cases and controls. Thus, no clear association of particular serum fatty acid levels with cardiovascular risk was found. CONCLUSION Our results support the conclusion that in populations with a homogenous low level of omega-3 polyunsaturated fatty acids consumption, serum fatty acid levels are not associated with CHD risk.
-
3.
Genotoxic Effects of Tributyltin and Triphenyltin Isothiocyanates, Cognate RXR Ligands: Comparison in Human Breast Carcinoma MCF 7 and MDA-MB-231 Cells.
Hunakova, L, Horvathova, E, Majerova, K, Bobal, P, Otevrel, J, Brtko, J
International journal of molecular sciences. 2019;(5)
Abstract
The cytotoxicity of two recently synthesized triorganotin isothiocyanate derivatives, nuclear retinoid X receptor ligands, was tested and compared in estrogen-receptor-positive MCF 7 and -negative MDA-MB-231 human breast carcinoma cell lines. A 48 h MTT assay indicated that tributyltin isothiocyanate (TBT-ITC) is more cytotoxic than triphenyltin isothiocyanate (TPT-ITC) in MCF 7 cells, and the same trend was observed in the MDA-MB-231 cell line. A comet assay revealed the presence of both crosslinks and increasing DNA damage levels after the 17 h treatment with both derivatives. Differences in cytotoxicity of TBT-ITC and TPT-ITC detected by FDA staining correspond to the MTT data, communicating more pronounced effects in MCF 7 than in the MDA-MB-231 cell line. Both derivatives were found to cause apoptosis, as shown by the mitochondrial membrane potential (MMP) depolarization and caspase-3/7 activation. The onset of caspase activation correlated with MMP dissipation and the total cytotoxicity more than with the amount of active caspases. In conclusion, our data suggest that the DNA damage induced by TBT-ITC and TPT-ITC treatment could underlie their cytotoxicity in the cell lines studied.
-
4.
The Effect of Food on the Pharmacokinetics of Sildenafil after Single Administration of a Sublingual Testosterone and Oral Sildenafil Combination Tablet in Healthy Female Subjects.
Bloemers, J, Gerritsen, J, van Rooij, K, de Leede, L, van der Geest, R, Frijlink, HW, Koppeschaar, HPF, Olivier, B, Tuiten, A
The journal of sexual medicine. 2019;(9):1433-1443
Abstract
INTRODUCTION Female sexual interest/arousal disorder (FSIAD) affects many women worldwide, but pharmacological treatment options are scarce. A new medicine being developed for FSIAD is an on-demand, dual-route, dual-release drug combination product containing 0.5 mg testosterone (T) and 50 mg sildenafil (S), referred to here as T+S. AIM: The aim of this study was to compare the effect of a fed and a fasted state on the pharmacokinetics of sildenafil following administration of T+S. METHODS Eighteen healthy women were administered T+S under fed and fasted conditions during 2 separate overnight visits in this randomized, open-label, balanced, 2-period, 2-treatment, 2-sequence crossover study. MAIN OUTCOME MEASURES The pharmacokinetics of sildenafil and its active metabolite N-desmethyl sildenafil were determined over a 24-hour period. Total testosterone was assessed only at a limited number of time points for quality purposes, as sublingual uptake is not expected to be affected by food intake. RESULTS The observed geometric mean ratios (GMRs) and 90% confidence intervals of sildenafil were not all contained within the prespecified bounds (0.80, 1.25). The GMR (90% CI) for plasma AUC0-last was 1.2753 (0.9706-1.6755); for AUC0-14h, it was 1.7521 (1.0819-2.8374); and for Cmax, it was 1.5591 (0.8634-2.8153). Only lower limits of the CIs fell within the bounds. For N-desmethyl sildenafil, the GMR (90% CI) for AUC0-last was 0.8437 (0.6738-1.0564); for AUC0-10h, it was 1.0847 (0.7648-1.5383); and for Cmax, it was 1.0083 (0.6638-1.5318). Only the GMRs were contained within bounds. No differences were observed between plasma testosterone Cmax and Tmax under fed and fasted conditions, which is in line with expectations for a sublingual administration. CLINICAL IMPLICATIONS The T+S combination tablet ruptures too late when taken in a fasted state and should therefore not be taken on an empty stomach. STRENGTHS & LIMITATIONS This is a well-controlled study that provides important insights into the performance characteristics of the delayed-release coating of the combination tablet. The higher variability of the pharmacokinetic parameters in the fasted state was caused by severely delayed rupture in one-third of the women. A reason for this is proposed but the present data do not explain this phenomenon. CONCLUSION The pharmacokinetics of sildenafil from this modified-release tablet are more robust under fed conditions as compared to the artificial fasted condition where no food is consumed 10 hours prior to and 4 hours after dosing. The dosing situation under the tested fasting condition does not represent the expected common use of this product. Patients should, however, be instructed not to take the tablet on an empty stomach. Bloemers J, Gerritsen J, van Rooij K, et al. The Effect of Food on the Pharmacokinetics of Sildenafil After Single Administration of a Sublingual Testosterone and Oral Sildenafil Combination Tablet in Healthy Female Subjects. J Sex Med 2019; 19:1433-1443.
-
5.
Novel Oral Anticoagulant Based Versus Vitamin K Antagonist Based Double Therapy Among Stented Patients With Atrial Fibrillation: Insights From the PIONEER AF-PCI Trial.
Kerneis, M, Yee, MK, Mehran, R, Nafee, T, Bode, C, Halperin, JL, Peterson, ED, Verheugt, FWA, Wildgoose, P, van Eickels, M, et al
Circulation. Cardiovascular interventions. 2019;(11):e008160
Abstract
BACKGROUND Among stented patients with atrial fibrillation, double therapy with a novel oral anticoagulant plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular rehospitalizations compared with a vitamin K antagonist (VKA) based triple therapy regimen. A recent study demonstrated that apixaban based double therapy reduced bleeding compared with VKA based double therapy. However, it remains unknown whether rivaroxaban based double therapy is superior to a VKA based double therapy. METHODS Patient with stented atrial fibrillation (n=2124) were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y12 inhibitor (Group 1, n=709); rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (DAPT; Group 2, n=709); and warfarin plus DAPT (Group 3, n=706). Before randomization, subjects were stratified according to a prespecified duration of DAPT (1, 6, or 12 months). After the prespecified DAPT duration, subjects in Group 2 were switched to rivaroxaban 15 mg plus low dose aspirin, and those in Group 3 were switched to VKA plus low dose aspirin. The Wei, Lin, and Weissfeld time to multiple events method was used to compare the occurrence of all bleeding and cardiovascular rehospitalizations among subjects on a novel oral anticoagulant versus VKA based double therapy. RESULTS A total of 906 subjects were prespecified to a 1 or 6 months DAPT duration and received at least one dose of study drug. Twenty subjects (3.3%) assigned to novel oral anticoagulant+SAPT, and 15 (5.1%) subjects assigned to VKA+SAPT experienced multiple rehospitalizations. In total, 124 (20.3%) events occurred among subjects on novel oral anticoagulant+SAPT compared with 87 (29.6%) among subjects on VKA+SAPT (hazard ratio=0.65 [95% CI, 0.45-0.93], P=0.008). CONCLUSIONS Among stented patients with atrial fibrillation, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and cardiovascular rehospitalization. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT01830543.
-
6.
Effects of Burdock tea on recurrence of colonic diverticulitis and diverticular bleeding: An open-labelled randomized clinical trial.
Mizuki, A, Tatemichi, M, Nakazawa, A, Tsukada, N, Nagata, H, Kinoshita, Y
Scientific reports. 2019;(1):6793
Abstract
Colonic diverticular bleeding (CDB) and acute colonic diverticulitis (ACD) show high recurrence rates. The establishment of optimal strategies that prevent the recurrence of CDB and ACD is a major concern among gastroenterologists. This study aimed to assess the efficacy of burdock tea for preventing CDB and ACD recurrences. Newly diagnosed patients with CDB (n = 91) or ACD (n = 70) were randomly assigned into two groups. The experimental group received 1.5 g of burdock tea three times a day, whereas the control group did not receive any treatment. The median (interquartile range) of observation for recurrence of CDB or ACD was 22.0 (14.1) months and 30.3 (18.6), respectively. The burdock tea treatment showed significant preventive effects on recurrence of ACD. A lower ACD recurrence rate (5/47 [10.6%] vs. 14/44 [31.8%]) and longer recurrence-free duration was observed in the burdock tea group (59.3 months [95% CI: 54.0-64.7] vs. 45.1 months [95% CI: 37.1-53.0] by the Kaplan-Meier analysis; p = 0.012 by log rank test) than in the control group, although there was no significant preventive effects on the CDB recurrence. This randomized clinical trial demonstrated that daily intake of burdock tea could be an effective strategy for prevention of ACD recurrence, but not for CDB recurrence.
-
7.
Sugar reduction without compromising sensory perception. An impossible dream?
Hutchings, SC, Low, JYQ, Keast, RSJ
Critical reviews in food science and nutrition. 2019;(14):2287-2307
Abstract
Sugar reduction is a major technical challenge for the food industry to address in response to public health concerns regarding the amount of added sugars in foods. This paper reviews sweet taste perception, sensory methods to evaluate sugar reduction and the merits of different techniques available to reduce sugar content. The use of sugar substitutes (non-nutritive sweeteners, sugar alcohols, and fibres) can achieve the greatest magnitude of sugar and energy reduction, however bitter side tastes and varying temporal sweet profiles are common issues. The use of multisensory integration principles (particularly aroma) can be an effective approach to reduce sugar content, however the magnitude of sugar reduction is small. Innovation in food structure (modifying the sucrose distribution, serum release and fracture mechanics) offers a new way to reduce sugar without significant changes in food composition, however may be difficult to implement in food produced on a large scale. Gradual sugar reduction presents difficulties for food companies from a sales perspective if acceptability is compromised. Ultimately, a holistic approach where food manufacturers integrate a range of these techniques is likely to provide the best progress. However, substantial reduction of sugar in processed foods without compromising sensory properties may be an impossible dream.
-
8.
Early Detection and Treatment of Patients with Alzheimer's Disease: Future Perspectives.
Guest, FL
Advances in experimental medicine and biology. 2019;:295-317
Abstract
Alzheimer's disease affects approximately 6% of people over the age of 65 years. It is characterized as chronic degeneration of cortical neurons, with loss of memory, cognition and executive functions. As the disease progresses, it is accompanied by accumulation of amyloid plaques and neurofibrillary tangles in key areas of the brain, leading to a loss of neurogenesis and synaptic plasticity in the hippocampus, along with changes in the levels of essential neurotransmitters such as acetylcholine and glutamate. Individuals with concomitant diseases such as depression, diabetes and cardiovascular disorders have a higher risk of developing Alzheimer's disease, and those who have a healthier diet and partake in regular exercise and intellectual stimulation have a lower risk of developing the disorder. This chapter describes the advances made in early diagnosis of Alzheimer's disease as this could help to improve outcomes for the patients by facilitating earlier treatment.
-
9.
The Pharmacology of Bile Acids and Their Receptors.
Fiorucci, S, Distrutti, E
Handbook of experimental pharmacology. 2019;:3-18
Abstract
This review provides a historical perspective of bile acids and their receptors as therapeutic targets. Bile acids are atypical steroids generated by the liver from cholesterol and have been used for almost half a century for treating liver and biliary disorders. Since the early 1970s of the last century, chenodeoxycholic acid (CDCA), a primary bile acid, and ursodeoxycholic acid (UDCA), a secondary bile acid and the 7βepimer of CDCA, have been shown effective in promoting the dissolution of cholesterol gallstones. However, lack of activity and side effects associated with the use of CDCA, along with the advent of laparoscopic cholecystectomy, have greatly reduced the clinical relevance of this application. At the turn of the century, however, the discovery that bile acids activate specific receptors, along with the discovery that those receptors are placed at the interface of the host and intestinal microbiota regulating physiologically relevant enterohepatic and entero-pancreatic axes, has led to a "bile acid renaissance." Similarly to other steroids, bile acids bind and activate both cell surface and nuclear receptors, including the bile acid sensor farnesoid X receptor (FXR) and a G-protein-coupled bile acid receptor, known as GPBAR1 (TGR5). Both receptors have been proved druggable, and several highly potent, selective, and nonselective ligands for the two receptors have been discovered in the last two decades. Currently, in addition to obeticholic acid, a semisynthetic derivative of CDCA and the first in class of FXR ligands approved for clinical use, either selective or dual FXR and GPBAR1 ligands, have been developed, and some of them are undergoing pre-approval trials. The effects of FXR and GPBAR1 ligands in different therapeutic area are reviewed.
-
10.
Increasing the proportion of healthier foods available with and without reducing portion sizes and energy purchased in worksite cafeterias: protocol for a stepped-wedge randomised controlled trial.
Reynolds, JP, Kosīte, D, Rigby Dames, B, Brocklebank, LA, Pilling, M, Pechey, R, Hollands, GJ, Marteau, TM
BMC public health. 2019;(1):1611
Abstract
BACKGROUND Overconsumption of energy from food contributes to high rates of overweight and obesity in many populations. A promising set of interventions tested in pilot studies in worksite cafeterias, suggests energy intake may be reduced by increasing the proportion of healthier - i.e. lower energy - food options available, and decreasing portion sizes. The current study aims to assess the impact on energy purchased of i. increasing the proportion of lower energy options available; ii. combining this with reducing portion sizes, in a full trial. METHODS A stepped-wedge randomised controlled trial in 19 worksite cafeterias, where the proportion of lower energy options available in targeted food categories (including main meals, snacks, and cold drinks) will be increased; and combined with reduced portion sizes. The primary outcome is total energy (kcal) purchased from targeted food categories using a pooled estimate across all sites. Follow-up analyses will test whether the impact on energy purchased varies according to the extent of intervention implementation. DISCUSSION This study will provide the most reliable estimate to date of the effect sizes of two promising interventions for reducing energy purchased in worksite cafeterias. TRIAL REGISTRATION The study was prospectively registered on ISRCTN (date: 24.05.19; TRN: ISRCTN87225572; doi: https://doi.org/10.1186/ISRCTN87225572).