Y Clement

Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice

The transcription factor NF‐E2‐related factor 2 (Nrf2) plays an essential role in the mammalian response to chemical and oxidative stress through induction of hepatic phase II detoxification enzymes and regulation of glutathione (GSH). Enhanced liver damage in Nrf2‐deficient mice treated with acetaminophen suggests a critical role for Nrf2; however, direct evidence for Nrf2 activation following acetaminophen exposure was previously lacking. We show that acetaminophen can initiate nuclear translocation of Nrf2 in vivo, with maximum levels reached after 1 hour, in a dose dependent manner, at doses below those causing overt liver damage. Furthermore, Nrf2 was shown to be functionally active, as assessed by the induction of epoxide hydrolase, heme oxygenase‐1, and glutamate cysteine ligase gene expression. Increased nuclear Nrf2 was found to be associated with depletion of hepatic GSH. Activation of Nrf2 is considered to involve dissociation from a cytoplasmic inhibitor, Kelch‐like ECH‐associated protein 1 (Keap1), through a redox‐sensitive mechanism involving either GSH depletion or direct chemical interaction through Michael addition. To investigate acetaminophen‐induced Nrf2 activation we compared the actions of 2 other GSH depleters, diethyl maleate (DEM) and buthionine sulphoximine (BSO), only 1 of which (DEM) can function as a Michael acceptor. For each compound, greater than 60% depletion of GSH was achieved; however, in the case of BSO, this depletion did not cause nuclear translocation of Nrf2. In conclusion, GSH depletion alone is insufficient for Nrf2 activation: a more direct interaction is required, possibly involving chemical modification of Nrf2 or Keap1, which is facilitated by the prior loss of GSH. (HEPATOLOGY 2004;39:1267–1276.)

Can green tea do that? A literature review of the clinical evidence

OBJECTIVE Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.

A gap between acceptance and knowledge of herbal remedies by physicians: The need for educational intervention

BackgroundThe unprecedented global increase in the use of herbal remedies is set to continue apace well into the foreseeable future. This raises important public health concerns, especially as it relates to safety issues including adverse effects and herb-drug interactions. Most Western-trained physicians are ignorant of the risks and benefits of this healthcare modality and assessment of acceptance and knowledge would identify appropriate intervention strategies to improve physician-patient communication in this area.MethodsA cross-sectional survey was done using an interviewer-administered pilot tested de novo questionnaire at six public hospitals in Trinidad between May–July 2004. The questionnaire utilized weighed questions to quantify acceptance (maximum score = 14 points) and knowledge (maximum score = 52 points). Acceptance and knowledge scores were analyzed using the ANOVA and Tukeys tests.ResultsOf 192 physicians interviewed, most (60.4%) believed that herbal remedies were beneficial to health. Respondents had relatively high acceptance levels (mean = 5.69 ± 0.29 points or 40% of total possible score) and poor knowledge (mean = 7.77 ± 0.56 points or 15% of total possible score). Seventy-eight physicians (40.6%) admitted having used herbs in the past, and 60 of these (76.9%) were satisfied with the outcome. Although 52 physicians (27.1%) recommended the use of herbs to their patients only 29 (15.1%) were able to identify at least one known herb-drug interaction.ConclusionThe use of herbal remedies is relatively high in Trinidad, as throughout the world, and most patients self-medicate with or without the knowledge of their attending physician. Surprisingly, we demonstrated relatively high acceptance levels and use of herbs among physicians in Trinidad. This interesting scenario of high acceptance levels and poor knowledge creates a situation that demands urgent intervention. We recommend educational intervention to narrow the gap between acceptance and knowledge so that physicians would be adequately equipped to communicate with their patients on this modality. The integration of herbal medicine into the curriculum of medical schools, continuing education programs and the availability of reputable pharmacopoeias for referencing at public health institutions are useful instruments that can be used to close this gap and promote improved physician-patient communication.

Medicinal herb use among asthmatic patients attending a specialty care facility in Trinidad

BackgroundThere is an increasing prevalence of asthma in the Caribbean and patients remain non-compliant to therapy despite the development of guidelines for management and prevention. Some patients may self-medicate with medicinal herbs for symptomatic relief, as there is a long tradition of use for a variety of ailments. The study assessed the prevalence of use and the factors affecting the decision to use herbs in asthmatic patients attending a public specialty care clinic in Trinidad.MethodsA descriptive, cross-sectional study was conducted at the Chest Clinic in Trinidad using a de novo, pilot-tested, researcher-administered questionnaire between June and July 2003.ResultsFifty-eight out of 191 patients (30.4%) reported using herbal remedies for symptomatic relief. Gender, age, ethnicity, and asthma severity did not influence the decision to use herbs; however, 62.5% of patients with tertiary level schooling used herbs, p = 0.025. Thirty-four of these 58 patients (58.6%) obtained herbs from their backyards or the supermarket; only 14 patients (24.1%) obtained herbs from an herbalist, herbal shop or pharmacy. Relatives and friends were the sole source of information for most patients (70.7%), and only 10.3% consulted an herbalist. Ginger, garlic, aloes, shandileer, wild onion, pepper and black sage were the most commonly used herbs.ConclusionsAmong patients attending the Chest Clinic in Trinidad the use of herbal remedies in asthma is relatively common on the advice of relatives and friends. It is therefore becoming imperative for healthcare providers to become more knowledgeable on this modality and to keep abreast with the latest developments.

Educational intervention for correct pressurised metered dose inhaler technique in Trinidadian patients with asthma

Correct pressurised metered dose inhalers (pMDI) usage is reportedly sub-optimal in patients and data for Caribbean populations is not available. We studied proficiency of inhaler use in Trinidadian patients, and determined sub-groups to be targeted for educational interventions. Inhaler use by 331 consecutive stable patients with airway disease (over 7 years) was observed and marked on a standard checklist. From direct observation only 41% of patients correctly inhaled, though 92% were confident of accurate technique. Few elderly patients (6%) received appropriate instructions on inhaler technique and only 35% (n = 23/66) understood the rationale for two different inhaler therapies (P < 0.001). More children (33%) and elderly patients (21%) reported escaping drug with use. Multiple regression analysis indicated the independent predictors of correct pMDI were age (P < 0.01) and correct understanding of different inhalers. Intensive patient education in Trinidadian children and elderly patients with airway disorders can enable active participation in disease management and maximal benefit from medication.

Effects of herbal and dietary supplements on cognition in menopause: A systematic review

OBJECTIVE Many postmenopausal women use herbal remedies and dietary supplements to counteract menopausal symptoms, including the decline in cognitive function. The aim of this systematic review is to evaluate the evidence regarding the efficacy of herbal and dietary supplements on cognition in menopause. DESIGN Randomized clinical trials (RCTs) of herbal medicines and dietary supplements were identified using the Medline, EMBASE, AMED, PsycINFO, CINAHL and The Cochrane Library 2010 (Issue 2) electronic databases and by hand searches. Data were independently extracted and evaluated by two reviewers. Risk of bias was assessed by two independent reviewers using the Cochrane Collaboration tool. RESULTS Twelve RCTs were included and five of these suggest that isoflavone, soy and Gingko biloba supplementation may improve cognition in postmenopausal women. However, most of the included studies had serious methodological flaws which demand a cautious interpretation of these findings. CONCLUSIONS The evidence that herbal and dietary supplements might positively affect the cognitive decline during the menopause is not compelling.

Silent cholinesterase gene in an Asian Indian family in Trinidad.

Cholinesterase activity was estimated in the serum of a Trinidadian female of Asian Indian descent. Her serum cholinesterase was pathologically low (0.17 U/ml) compared to the average reported for the population (10.59 ± 2.77 U/ml), and her dibucaine number could not be estimated. In a pedigree study her sister displayed similar enzyme activity and cholinesterase was 0.09 U/ml. Cholinesterase could not be detected in the sera of both sisters using electrophoresis. Among three generations of the family studied, the silent variant of the cholinesterase gene could be segregated in offspring of the maternal uncle (normal cholinesterase phenotype) whose spouses serum displayed an intermediate dibucaine number. The possible inheritance of the silent gene in the pedigree is discussed.