Associations between healthy food groups and platelet-activating factor, lipoprotein-associated phospholipase A2 and C-reactive protein: a cross-sectional study.

PURPOSE: To investigate the association between pro-inflammatory markers platelet-activating factor (PAF), lipoprotein-associated phospholipase A2 (Lp-PLA2), hsCRP, and intake of core food groups including fruit, cruciferous and other vegetables, grains, meat and poultry, fish and seafood, nuts and legumes, and dairy. METHODS: A cross-sectional study was conducted. 100 adults (49 ± 13 years, 31% male) with variable cardiovascular disease risk were recruited. Data were collected in 2021 and 2022. Fasting PAF, Lp-PLA2 activity, hsCRP and usual dietary intake (via a validated food frequency questionnaire) were measured. Intake of foods were converted into serves and classified into food groups. Correlations and multiple regressions were performed with adjustment for confounders. RESULTS: A one-serve increase in cruciferous vegetables per day was associated with 20-24% lower PAF levels. An increase of one serve per day of nuts and legumes was associated with 40% lower hsCRP levels. There were small correlations with PAF and Lp-PLA2 and cheese, however, these were not significant at the Bonferroni-adjusted P < 0.005 level. CONCLUSION: The lack of associations between PAF and Lp-PLA2 and other healthy foods may be due to confounding by COVID-19 infection and vaccination programs which prevents any firm conclusion on the relationship between PAF, Lp-PLA2 and food groups. Future research should aim to examine the relationship with these novel markers and healthy food groups in a non-pandemic setting.

Effect of a Standardized Ginger Root Powder Regimen on Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial.

BACKGROUND: There is substantial interest in the role of ginger as an adjuvant therapy for chemotherapy-induced nausea and vomiting (CINV). However, available evidence lacks robust methodology. OBJECTIVE: To assess the effect of adjuvant ginger compared with placebo on chemotherapy-induced nausea-related quality of life (QoL) and CINV-related outcomes. DESIGN: A parallel, double-blind, placebo-controlled randomized trial with 1:1 allocation was conducted. PARTICIPANTS/SETTING: One hundred three chemotherapy-naïve adults scheduled to receive moderately to highly emetogenic chemotherapy at two hospitals in Australia were enrolled and analyzed. INTERVENTION: Four standardized ginger capsules (totaling 84 mg/day active gingerols/shogaols), or placebo, were administered commencing the day of chemotherapy and continuing for 5 days for chemotherapy cycles 1 through 3. MAIN OUTCOME MEASURES: The primary outcome was chemotherapy-induced nausea-related QoL. Secondary outcomes were vomiting- and CINV-related QoL; anticipatory, acute, and delayed nausea and vomiting; fatigue; nutritional status; depression and anxiety; health-related QoL; and adverse events. STATISTICAL ANALYSES PERFORMED: Intention-to-treat analysis was performed. Mixed analysis of variance with repeated measures determined differences between groups. The null hypothesis was no difference between groups. After applying a Bonferroni multiple testing correction, evidence against the null hypothesis was considered at P= 0.003. RESULTS: One hundred three participants (ginger: n = 52; placebo: n = 51) were enrolled and analyzed. There was clinically relevant evidence against the null hypothesis, favoring ginger, in change scores for nausea-related QoL (F[df] = 9.34[1,101]; P = 0.003; partial η2 = 0.09), overall CINV-related QoL (F[df] = 12.26[1,101]; P < 0.001; partial η2 = 0.11), delayed nausea severity (F[df] = 9.46[1,101]; P = 0.003; partial η2 = 0.09), and fatigue (F[df] = 10.11[1,101]; P = 0.002; partial η2 = 0.09). There was a clinically meaningful lower incidence of delayed nausea and vomiting in the ginger group at Cycle 2 (53% vs 75%; P = 0.020 and 4% vs 27%; P = 0.001, respectively) and Cycle 3 (49% vs 79%; P = 0.002 and 2% vs 23%; P = 0.001, respectively). There was a clinically meaningful lower incidence of malnutrition in the ginger group at Cycle 3 (18% vs. 41%; P = 0.032) and in change scores for Patient-Generated Subjective Global Assessment (F[df)] = 4.32[1,100]; P = 0.040; partial η2 = 0.04). Change scores between groups favored ginger for vomiting-related QoL and number of vomiting episodes; however, findings were not clinically meaningful. There was no effect of ginger on anticipatory or acute CINV, health-related QoL, anxiety, or depression. No serious adverse events were reported. CONCLUSIONS: Ginger supplementation was a safe adjuvant to antiemetic medications for CINV that enhanced QoL during chemotherapy treatment. Future trials are needed to examine dose-dependent responses to verify optimal dosing regimens.

The association between dietary quality scores with C-reactive protein and novel biomarkers of inflammation platelet-activating factor and lipoprotein-associated phospholipase A2: a cross-sectional study.

Healthy dietary patterns are associated with lower inflammation and cardiovascular disease (CVD) risk and adherence can be measured using diet quality scores. Inflammation is traditionally measured with C-reactive protein (hsCRP), however there is interest in novel pro-inflammatory markers platelet-activating factor (PAF) and lipoprotein-associated phospholipase A2 (Lp-PLA2) that are specifically involved in endothelial dysfunction and inflammation. This cross-sectional study investigated the association between PAF, Lp-PLA2, hsCRP, and six diet scores. One hundred adults (49 ± 13 years, 31% male) with variable CVD risk were recruited. Fasting PAF, Lp-PLA2 and hsCRP and usual dietary intake were measured. Adherence to Dietary Approaches to Stop Hypertension (DASH), Dairy-adjusted DASH, Vegetarian Lifestyle Index, Healthy Eating Index for Australians (HEIFA), Mediterranean Diet Adherence Screener (MEDAS) and PREDIMED-Plus (erMedDiet) scores were calculated. Correlations and multiple regressions were performed. hsCRP, but not PAF, independently correlated with several diet scores. Lp-PLA2 independently correlated with Vegetarian Lifestyle Index only in unadjusted models. A one-point increase in adherence to the DASH Index, the Dairy-adjusted DASH Index and the Vegetarian Lifestyle Index was associated with a 30%, 30%, and 33% reduction in hsCRP levels, respectively. Smaller effects were seen with the other diet scores with a one-point increase in adherence resulting in a 19%, 22% and 16% reduction in hsCRP with HEIFA, MEDAS, erMedDiet scores, respectively. The lack of stronger associations between the novel markers of inflammation and diet scores may be due to confounding by COVID-19 infection and vaccination programs, which prevents any firm conclusion on the relationship between PAF, Lp-PLA2 and healthy dietary patterns. Future research should aim to examine the relationship with these novel markers and healthy dietary patterns in a non-pandemic setting.

Effect of Ginger Root Powder on Gastrointestinal Bacteria Composition, Gastrointestinal Symptoms, Mental Health, Fatigue, and Quality of Life: A Double-Blind Placebo-Controlled Trial.

BACKGROUND: Despite compositional alterations in gastrointestinal microbiota being purported to underpin some of the therapeutic effects of ginger, the effect of a standardized ginger supplement on gut microbiota has not been tested in humans. OBJECTIVES: To determine the effect of a standardized ginger (Zingiber officinale) root powder, compared to placebo, on gastrointestinal bacteria and associated outcomes in healthy adults. METHODS: A randomized double-blind placebo-controlled trial allocated participants aged 18 to 30 y to ginger or microcrystalline cellulose (MCC) placebo. The intervention comprised 1.2 g/d of ginger (4 capsules per day totaling 84 mg/d of active gingerols/shogaols) for 14 d following a 1-wk run-in period. Primary outcomes were gastrointestinal community composition, alpha and beta diversity, and differential abundance, measured using 16S rRNA gene sequencing of fecal samples. Secondary outcomes were gastrointestinal symptoms, bowel function, depression, anxiety, stress, fatigue, quality of life, and adverse events. RESULTS: Fifty-one participants were enrolled and analyzed (71% female; mean age 25 ± 3 y; ginger: n = 29, placebo: n = 22). There was a greater increase in relative abundance of phylum, Actinobacteria, observed following ginger supplementation compared to placebo (U: 145.0; z: -2.1; P = 0.033). Ginger was associated with a greater abundance of the genera Parabacteroides, Bacillus, Ruminococcaceae incertae sedis, unclassified Bacilli, families Defluviitaleaceae, Morganellaceae, and Bacillaceae as well as lower abundance of the genus Blautia and family Sphingomonadaceae (P < 0.05). An improvement in indigestion symptoms was observed with ginger supplementation (U: 196.0; z: -2.4; P = 0.015). No differences between ginger and placebo groups were found for alpha and beta diversity or other secondary outcomes. No moderate or severe adverse events were reported. CONCLUSIONS: Supplementation with ginger root powder was safe and altered aspects of gastrointestinal bacteria composition; however, it did not change alpha- or beta diversity, bowel function, gastrointestinal symptoms, mood, or quality of life in healthy adults. These results provide further understanding regarding the mechanisms of action of ginger supplementation. This trial was registered in the Australia New Zealand Clinical Trials Registry as ACTRN12620000302954p and the Therapeutic Goods Administration as CT-2020-CTN-00380-1.

Therapeutic health effects of ginger (Zingiber officinale): updated narrative review exploring the mechanisms of action.

Ginger (Zingiber officinale) has been investigated for its potentially therapeutic effect on a range of chronic conditions and symptoms in humans. However, a simplified and easily understandable examination of the mechanisms behind these effects is lacking and, in turn, hinders interpretation and translation to practice, and contributes to overall clinical heterogeneity confounding the results. Therefore, drawing on data from nonhuman trials, the objective for this narrative review was to comprehensively describe the current knowledge on the proposed mechanisms of action of ginger on conferring therapeutic health effects in humans. Mechanistic studies support the findings from human clinical trials that ginger may assist in improving symptoms and biomarkers of pain, metabolic chronic disease, and gastrointestinal conditions. Bioactive ginger compounds reduce inflammation, which contributes to pain; promote vasodilation, which lowers blood pressure; obstruct cholesterol production, which regulates blood lipid profile; translocate glucose transporter type 4 molecules to plasma membranes to assist in glycemic control; stimulate fatty acid breakdown to aid weight management; and inhibit serotonin, muscarinic, and histaminergic receptor activation to reduce nausea and vomiting. Additional human trials are required to confirm the antimicrobial, neuroprotective, antineoplastic, and liver- and kidney-protecting effects of ginger. Interpretation of the mechanisms of action will help clinicians and researchers better understand how and for whom ginger may render therapeutic effects and highlight priority areas for future research.

Interrelationships among platelet-activating factor and lipoprotein-associated phospholipase A2 activity and traditional cardiovascular risk factors.

Traditionally cardiovascular disease (CVD) risk has been assessed through blood lipids and inflammatory marker C-reactive protein (hsCRP). Recent clinical interest in novel pro-inflammatory markers platelet-activating factor (PAF) and lipoprotein-associated phospholipase A2 (Lp-PLA2 ) recognizes that vascular damage can exist in the absence of traditional risk factors. This cross-sectional study investigated the potential relationship between circulating PAF, Lp-PLA2 , hsCRP, and traditional risk factors for CVD. One hundred adults (49 ± 13 years, 31% male) with variable CVD risk were recruited. Fasting inflammatory markers PAF, Lp-PLA2 and hsCRP and total, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, and triglycerides were measured. Blood pressure, body mass index, and waist circumference were measured. Medical and physical activity data were self-reported. Linear and multiple regressions were performed. PAF, Lp-PLA2 , and hsCRP independently correlated with several CVD risk factors. PAF was correlated significantly with risk factors in an unexpected way; there was a medium positive correlation between PAF and HDL cholesterol (r = 0.394, p < 0.001) and medium negative correlations with Total:HDL cholesterol; (r = -0.436, p < 0.001) systolic blood pressure; (r = -0.307, p = 0.001); BMI (r = -0.381, p < 0.001); and waist circumference (r = -0.404, p < 0.001). There were large positive correlations between Lp-PLA2 and LDL (r = 0.525, p < 0.001) and non-HDL cholesterol (r = 0.508, p < 0.001). There were large positive correlations between hsCRP and Total:HDL cholesterol (r = 0.524, p < 0.001); BMI (r = 0.668, p < 0.001); and waist circumference (r = 0.676, p < 0.001). PAF, Lp-PLA2 , and hsCRP are implicated in the pathophysiology of inflammation in CVD; however, the relationships between each marker and traditional risk factors were different suggesting they may be involved in different atherogenic pathways.

Extra virgin olive oil improves HDL lipid fraction but not HDL-mediated cholesterol efflux capacity: a double-blind, randomised, controlled, cross-over study (OLIVAUS).

Olive oil (OO) polyphenols have been shown to improve HDL anti-atherogenic function, thus demonstrating beneficial effects against cardiovascular risk factors. The aim of the present study was to investigate the effect of extra virgin high polyphenol olive oil (HPOO) v. low polyphenol olive oil (LPOO) on the capacity of HDL to promote cholesterol efflux in healthy adults. In a double-blind, randomised cross-over trial, fifty participants (aged 38·5 (sd 13·9) years, 66 % females) were supplemented with a daily dose (60 ml) of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for 3 weeks. Following a 2-week washout period, participants crossed over to the alternate treatment. Serum HDL-cholesterol efflux capacity, circulating lipids (i.e. total cholesterol, TAG, HDL, LDL) and anthropometrics were measured at baseline and follow-up. No significant between-group differences were observed. Furthermore, no significant changes in HDL-cholesterol efflux were found within either the LPOO and HPOO treatment arms; mean changes were 0·54 % (95 % CI (0·29, 1·37)) and 0·10 % (95 % CI (0·74, 0·94)), respectively. Serum HDL increased significantly after LPOO and HPOO intake by 0·13 mmol/l (95 % CI (0·04, 0·22)) and 0·10 mmol/l (95 % CI (0·02, 0·19)), respectively. A small but significant increase in LDL of 0·14 mmol/l (95 % CI (0·001, 0·28)) was observed following the HPOO intervention. Our results suggest that additional research is warranted to further understand the effect of OO with different phenolic content on mechanisms of cholesterol efflux via different pathways in multi-ethnic populations with diverse diets.

Mobile phones are hazardous microbial platforms warranting robust public health and biosecurity protocols.

Advancements in technology and communication have revolutionised the twenty-first century with the introduction of mobile phones and smartphones. These phones are known to be platforms harbouring microbes with recent research shedding light on the abundance and broad spectrum of organisms they harbour. Mobile phone use in the community and in professional sectors including health care settings is a potential source of microbial dissemination. To identify the diversity of microbial genetic signature present on mobile phones owned by hospital medical staff. Twenty-six mobile phones of health care staff were swabbed. DNA extraction for downstream next generation sequencing shotgun metagenomic microbial profiling was performed. Survey questionnaires were handed to the staff to collect information on mobile phone usage and users' behaviours. Each of the 26 mobile phones of this study was contaminated with microbes with the detection of antibiotic resistance and virulent factors. Taken together the sum of microbes and genes added together across all 26 mobile phones totalised 11,163 organisms (5714 bacteria, 675 fungi, 93 protists, 228 viruses, 4453 bacteriophages) and 2096 genes coding for antibiotic resistance and virulent factors. The survey of medical staff showed that 46% (12/26) of the participants used their mobile phones in the bathroom. Mobile phones are vectors of microbes and can contribute to microbial dissemination and nosocomial diseases worldwide. As fomites, mobile phones that are not decontaminated may pose serious risks for public health and biosecurity.

Orally consumed ginger and human health: an umbrella review.

BACKGROUND: Emerging evidence supports the health benefits of ginger for a range of conditions and symptoms; however, there is a lack of synthesis of literature to determine which health indications are supported by quality evidence. OBJECTIVES: In this umbrella review of systematic reviews we aimed to determine the therapeutic effects and safety of any type of ginger from the Zingiber family administered in oral form compared with any comparator or baseline measures on any health and well-being outcome in humans. METHODS: Five databases were searched from inception to April 2021. Review selection and quality were assessed in duplicate using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) checklist and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method, with results presented in narrative form. RESULTS: Twenty-four systematic reviews were included with 3% overlap of primary studies. The strongest evidence was found for the antiemetic effects of ginger in pregnant women (effect size: large; GRADE: high), analgesic effects for osteoarthritis (effect size: small; GRADE: high), and glycemic control (effect size: none to very large; GRADE: very low to moderate). Ginger also had a statistically significant positive effect on blood pressure, weight management, dysmenorrhea, postoperative nausea, and chemotherapy-induced vomiting (effect size: moderate to large; GRADE: low to moderate) as well as blood lipid profile (effect size: small; GRADE: very low) and anti-inflammatory and antioxidant biomarkers (effect size: unclear; GRADE: very low to moderate). There was substantial heterogeneity and poor reporting of interventions; however, dosage of 0.5-3 g/d in capsule form administered for up to 3 mo was consistently reported as effective. CONCLUSIONS: Dietary consumption of ginger appears safe and may exert beneficial effects on human health and well-being, with greatest confidence in antiemetic effects in pregnant women, analgesic effects in osteoarthritis, and glycemic control. Future randomized controlled and dose-dependent trials with adequate sample sizes and standardized ginger products are warranted to better inform and standardize routine clinical prescription.

Extra virgin olive oil high in polyphenols improves antioxidant status in adults: a double-blind, randomized, controlled, cross-over study (OLIVAUS).

PURPOSE: Olive oil polyphenols have been associated with cardiovascular health benefits. This study examined the antioxidant and anti-inflammatory effect of extra-virgin high polyphenol olive oil (HPOO) vs. low polyphenol olive oil (LPOO) in healthy Australian adults. METHODS: In a double-blind cross-over trial, 50 participants (aged 38.5 ± 13.9 years, 66% females) were randomized to consume 60 mL/day of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for three weeks. Following a 2-week wash-out period, participants crossed-over to the alternate treatment. Plasma oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), high-sensitivity C-reactive protein (hs-CRP) and anthropometrics were measured at baseline and follow-up. RESULTS: Fourty-three participants completed the study. Although there were no significant differences between treatments in the total sample, plasma ox-LDL decreased by 6.5 mU/mL (95%CI - 12.4 to - 0.5) and TAC increased by 0.03 mM (95% CI 0.006-0.05) only in the HPOO arm. Stratified analyses were also performed by cardiovascular disease risk status defined by abdominal obesity (WC > 94 cm in males, > 80 cm in females) or inflammation (hs-CRP > 1 mg/L). In the subgroup with abdominal obesity, ox-LDL decreased by 13.5 mU/mL (95% CI - 23.5 to - 3.6) and TAC increased by 0.04 mM (95% CI 0.006-0.07) only after HPOO consumption. In the subgroup with inflammation, hs-CRP decreased by 1.9 mg/L (95% CI - 3.7 to -0.1) only in the HPOO arm. CONCLUSIONS: Although there were no significant differences between treatments, the changes observed after HPOO consumption demonstrate the antioxidant and anti-inflammatory effect of this oil, which is more pronounced in adults with high cardiometabolic risk (Clinical Trial Registration: ACTRN12618000706279).

The association between dietary patterns and the novel inflammatory markers platelet-activating factor and lipoprotein-associated phospholipase A2: a systematic review.

CONTEXT: Atherosclerosis is a disease of chronic inflammation. Recent research has identified 2 novel inflammatory biomarkers: platelet-activating factor (PAF) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Diet has been proposed as a mediator of inflammation, but to date, the focus for these novel biomarkers has been on individual foods and nutrients rather than overall dietary patterns. OBJECTIVE: To systematically review the literature on the association between dietary patterns and PAF and Lp-PLA2. DATA SOURCES: The PubMed, Embase, CINAHL, and Cochrane CENTRAL literature databases were searched. DATA ANALYSIS: Study quality was evaluated using the Quality Criteria Checklist. Sixteen studies (n = 4 observational and n = 12 interventional) were included and assessed for associations between dietary patterns and PAF and Lp-PLA2. CONCLUSION: Study quality varied from neutral (n = 10) to positive (n = 6). Mediterranean, heart healthy, and vegetarian dietary patterns were associated with improved levels of PAF and Lp-PLA2. Conversely, Western dietary patterns were less favorable. A range of well-established, healthier dietary patterns may lower inflammation and the risk of atherosclerosis. More well-designed studies are needed to confirm these findings and identify other dietary patterns that improve inflammation.

A pilot metagenomic study reveals that community derived mobile phones are reservoirs of viable pathogenic microbes.

There is increasing attention focussed on the risks associated with mobile phones possibly serving as 'Trojan Horse' fomites for microbial transmission in healthcare settings. However, little is reported on the presence of microbes on community derived mobile phones which in 2021, numbered in the billions in circulation with majority being used on a daily basis. Identify viable microbial organisms swabbed from smartphones on a university campus. Entire surfaces of 5 mobile phones were swabbed and examined for their microbial content using pre-agar-based growths followed by downstream DNA metagenomic next-generation sequencing analysis. All phones were contaminated with viable microbes. 173 bacteria, 8 fungi, 8 protists, 53 bacteriophages, 317 virulence factor genes and 41 distinct antibiotic resistant genes were identified. While this research represents a pilot study, the snapshot metagenomic analysis of samples collected from the surface of mobile phones has revealed the presence of a large population of viable microbes and an array of antimicrobial resistant factors. With billions of phones in circulation, these devices might be responsible for the rise of community acquired infections. These pilot results highlight the importance of public health authorities considering mobile phones as 'Trojan Horse' devices for microbial transmission and ensure appropriate decontamination campaigns are implemented.

Mobile phones of paediatric hospital staff are never cleaned and commonly used in toilets with implications for healthcare nosocomial diseases.

An ever-increasing number of medical staff use mobile phones as a work aid, yet this may pose nosocomial diseases. To assess and report via a survey the handling practices and the use of phones by paediatric wards healthcare workers. 165 paediatric healthcare workers and staff filled in a questionnaire consisting of 14 questions (including categorical, ordinal and numerical data). Analysis of categorical data used non-parametric techniques such as the Chi-squared test. Although 98% of respondents (165 in total) report that their phones may be contaminated, 56% have never cleaned their devices. Of the respondents that clean their devices, 10% (17/165) had done so with alcohol swabs or disinfectant within that day or week; and an additional 12% respondents (20/165) within that month. Of concern, 52% (86/165) of the respondents use their phones in the bathroom, emphasising the unhygienic environments in which mobile phones/smartphones are constantly used. Disinfecting phones is a practice that only a minority of healthcare workers undertake appropriately. Mobile phones, present in billions globally, are therefore Trojan Horses if contaminated with microbes and potentially contributing to the spread and propagation of micro-organisms as per the rapid spread of SARS-CoV-2 virus in the world.

The role of mobile phones as a possible pathway for pathogen movement, a cross-sectional microbial analysis.

INTRODUCTION: Mobile phones are used the world over, including in healthcare settings. This study aimed to investigate the viable microbial colonisation of mobile phones used by healthcare personnel. METHODS: Swabs collected on the same day from 30 mobile phones belonging to healthcare workers from three separate paediatric wards of an Australian hospital were cultured on five types of agar plate, then colonies from each phone were pooled, extracted and sequenced by shotgun metagenomics. Questionnaires completed by staff whose phones were sampled assisted in the analysis and interpretation of results. RESULTS AND DISCUSSION: All phones sampled cultured viable bacteria. Overall, 399 bacterial operational taxonomic units were identified from 30 phones, with 1432 cumulative hits. Among these were 58 recognised human pathogenic and commensal bacteria (37 Gram-negative, 21 Gram-positive). The total number of virulence factor genes detected was 347, with 1258 cumulative hits. Antibiotic resistance genes (ARGs) were detected on all sampled phones and overall, 133 ARGs were detected with 520 cumulative hits. The most important classes of ARGs detected encoded resistance to beta-lactam, aminoglycoside and macrolide antibiotics and efflux pump mediated resistance mechanisms. CONCLUSION: Mobile phones carry viable bacterial pathogens and may act as fomites by contaminating the hands of their users and indirectly providing a transmission pathway for hospital-acquired infections and dissemination of antibiotic resistance. Further research is needed, but meanwhile adding touching mobile phones to the five moments of hand hygiene is a simple infection control strategy worth considering in hospital and community settings. Additionally, the implementation of practical and effective guidelines to decontaminate mobile phone devices would likely be beneficial to the hospital population and community at large.

Renal artery responses to trace amines: Multiple and differential mechanisms of action.

PURPOSE: The rise in consumption of dietary supplements containing the trace amines p-tyramine, p-synephrine and p-octopamine has been associated with cardiovascular side effects. Since renal blood flow plays an important role in blood pressure regulation, this study investigated the mechanisms of action of these trace amines on isolated porcine renal arteries. MAIN METHODS: Contractile responses to amines were investigated in noradrenaline-depleted rings of porcine main renal arteries in the absence and presence of the α1-adrenoceptor antagonist, prazosin (1 µM), ß-adrenoceptor antagonist, propranolol (1 µM), or the trace amine-associated receptor (TAAR-1) antagonist, EPPTB (RO-5212773; 100 nM or 100 µM). KEY FINDINGS: All three amines induced constrictor responses of similar magnitude and potency. However, their mechanisms of action on the renal artery appeared to differ. Depleting endogenous noradrenaline stores significantly reduced maximum responses to tyramine and synephrine, but less for octopamine. When direct responses were examined after depleting tissues of noradrenaline, responses to synephrine and octopamine, but not tyramine, were reduced in the presence of prazosin(1 µM) and potentiated in the presence of propranolol (1 µM) or L-NNA (100 µM). Generally, vasoconstrictor responses remaining after noradrenaline-depletion and α-adrenoceptor blockade were not affected by the TAAR-1 antagonist EPPTB (0.1-100 µM), although responses to low concentration of synephrine and octopamine were enhanced by this antagonist. SIGNIFICANCE: Tyramine appears to mediate constriction of the renal artery mainly via an indirect sympathomimetic mechanism, whereas synephrine and octopamine exert additional direct effects on α1-adrenoceptors and possibly contractile TAAR (not TAAR-1). The two amines also activate simultaneous inhibitory responses via ß-adrenoceptors, TAAR-1 and nitric oxide release.

Racemic synephrine found in Citrus aurantium-listing pre-workout supplements suggests a non-plant-based origin.

Multi-ingredient pre-workout supplements (MIPS) contain Citrus aurantium as a source of bioactive amines such as p-synephrine, but concerns regarding the authenticity of ingredients in some supplements as well as adverse effects from consumption have been raised. R-(-)-Synephrine is the predominant enantiomer in Citrus aurantium extracts while synthetic preparations are often racemic. The aims of this study were to develop a screening method to determine the ratio of synephrine enantiomers in pre-workout supplements listing Citrus aurantium and to assess the ingredient authenticity by directly comparing their ratios to that found in Citrus aurantium standardised reference materials (SRMs). Quantification of enantiomers in the supplements and SRMs was achieved using a validated, high-performance liquid chromatography-single quadrupole mass spectrometry (HPLC-UV-QDa) direct enantioseparation method with a cellobiohydrolase (CBH) column (100 × 4.0 mm, 5 µM) and UV detection at 225 nm. Citrus aurantium SRMs were found to have an average enantiomeric ratio of 94:6 (R:S) with total synephrine ranging from 5.7 to 90.2 mg/g. Within the pilot sample of pre-workout supplements tested, only 42% (5/12) had enantiomeric ratios consistent with the SRMs with total synephrine ranging from 0.03 to 91.2 mg/g. For the remaining supplements, four had racemic ratios of synephrine (0.14 to 5.4 mg/g), two lacked any detectable levels of synephrine, and one had solely the S-(+)-enantiomer (0.15 mg/g). These results bring the authenticity of labelling of some pre-workout supplements into question and highlight the need for more stringent labelling regulations and testing for dietary supplements.

"It's natural so it shouldn't hurt me": Chemotherapy patients' perspectives, experiences, and sources of information of complementary and alternative medicines.

BACKGROUND AND PURPOSE: Minimal evidence regarding the safety and efficacy of complementary and alternative medicine (CAM) use during chemotherapy is accompanied with a high prevalence of use and nondisclosure to health professionals. This study aimed to explore patients' perspectives, experiences, support needs, and sources of information regarding CAM use during chemotherapy. MATERIALS AND METHODS: Semi-structured interviews with ten adult participants who recently completed chemotherapy treatment at a large hospital in Australia were transcribed verbatim. Three investigators thematically analysed the interviews. RESULTS: These participants receiving chemotherapy valued CAMs as a natural complement to chemotherapy to improve wellbeing, with their use most strongly influenced by past experiences rather than expert advice. CONCLUSION: Health professionals would benefit from education on how to best inform patients of the potential risks, harms and lack of efficacy for CAM use during chemotherapy in a way that does not lead to patient non-disclosure of CAM use.

6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) from Wasabia japonica alleviates inflammatory bowel disease (IBD) by potential inhibition of glycogen synthase kinase 3 beta (GSK-3ß).

Inflammatory bowel disease (IBD) describes a set of disorders involving alterations to gastrointestinal physiology and mucosal immunity. Unravelling its complex pathophysiology is important since many IBD patients are refractory to or suffer adverse side effects from current treatments. Isothiocyanates (ITCs), such as 6-(methylsulfinyl)hexyl ITC (6-MITC) in Wasabia japonica, have potential anti-inflammatory activity. We aimed to elucidate the pathways through which 6-MITC alleviates inflammation by examining its role in the nuclear factor-kappa B (NF-κB) pathway through inhibition of glycogen synthase kinase 3 beta (GSK-3ß) using a chemically induced murine model of IBD, cell-based and in silico techniques. The effects of 6-MITC and two NF-κB inhibitors, sulfasalazine (SS), pyrrolidine dithiolcarbamate (PDTC) were investigated on a dextran sulfate sodium (DSS)-induced murine mouse model of acute and chronic colitis using macroscopic measurements and pro-inflammatory markers. The effect of 6-MITC on NF-κB induction was assessed using a murine macrophage cell line. Complexes of GSK-3ß-6-MITC and GSK-3ß-ATP were generated in silico to elucidate the mechanism of 6-MITC's direct inhibition of GSK-3ß. Changes in pro-inflammatory markers, inducible nitric oxide synthase (iNOS) (increased) and interleukin-6 (IL-6) (decreased) demonstrated that iNOS regulation occurred at the translational level. Intraperitoneal (ip) injection of 6-MITC to the colitis-induced mice ameliorated weight loss whereas oral administration had negligible effect. Fecal blood and colon weight/length ratio parameters improved on treatment with 6-MITC and the other NF-κB inhibitors. Levels of NF-κB decreased upon addition of 6-MITC in vitro while structural studies showed 6-MITC acts competitively to inhibit GSK-3ß at the ATP binding site. In this study we demonstrated that 6-MITC inhibits NF-κB signaling via GSK-3ß inhibition ameliorating fecal blood, colonic alterations and DSS-induced weight loss indirectly indicating reduced intestinal stress. Taken together these results suggest a role for 6-MITC in the treatment of IBD acting to alleviate inflammation through the GSK-3ß/NF-κB pathway. Furthermore, the GSK-3ß-6-MITC model can be utilized as a basis for development of novel therapeutics targeting GSK-3ß for use in other disorders including cancer.

HPLC-UV-QDa analysis of Citrus aurantium-labelled pre-workout supplements suggest only a minority contain the plant extract.

Bitter orange (Citrus aurantium) is a common ingredient in pre-workout supplements with purported weight-loss and performance-enhancing effects. Supplements listing Citrus aurantium or p-synephrine have been associated with reports of adverse cardiovascular events attributed to the active biogenic amines, p-synephrine, p-octopamine or p-tyramine. Additionally, questions have been raised as to the authenticity of the plant-derived active components listed on the supplement labels. The aim of this study was to determine the quantities of these amines in a sample of pre-workout supplements which specifically listed Citrus aurantium, and assess the authenticity of plant material by comparing the ratios of amines found to that found in Citrus aurantium standardized reference materials (SRM). The quantities of amines in the supplements and SRMs were determined using a validated high-performance liquid chromatography-single quadrupole mass spectrometry (HPLC-UV-QDa) method. In the Citrus aurantium SRMs the quantities of trace amines found ranged from 5.30 to 38.00 mg/g (synephrine) 0.14-0.35 mg/g (octopamine) and 0.15-1.90 mg/g (tyramine) with an average ratio of 100:1:5 (synephrine: octopamine: tyramine). Only 42 % (5/12) of the supplements tested had ratios consistent with that found in the SRMs. The average trace amine ratio in those supplements was 100:1:3 while the quantities of trace amines found ranged from 0.35 to 31.31 mg/g (synephrine); 0.005 - 0.10 mg/g (octopamine) and 0.01-1.51 mg/g (tyramine). For the remaining supplements, some did not contain any detectable levels of trace amines or only synephrine was detected with concentrations ranging from 0.003 - 0.95 mg/g. These results suggest a role for authenticity/quality assurance testing of pre-workout supplements and more stringent regulation of pre-workout supplements.