Lactobacillus paracasei IMC 502 ameliorates type 2 diabetes by mediating gut microbiota-SCFA-hormone/inflammation pathway in mice.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex and prevalent metabolic disease that seriously threatens human health. Numerous studies have shown that probiotics as dietary supplements have the potential to prevent and treat T2DM. However, the ability of various strains to improve diabetes symptoms and corresponding mechanisms are different. Thus, mechanistic investigation is required to validate the pharmacology of each probiotic strain for T2DM treatment. Lactobacillus paracasei IMC 502 was originally isolated from Italian elderly human feces and its probiotic attributes have been demonstrated. Here, the antidiabetic pharmacodynamics of L. paracasei IMC 502 on T2DM mice was explored. RESULTS: Lactobacillus paracasei IMC 502 significantly decreased blood glucose, HbA1c and lipid levels, improved insulin resistance and glucose intolerance, regulated the mRNA/protein expression of key hepatic enzymes associated with gluconeogenesis, de novo lipogenesis and PI3K/Akt pathway, and repaired pancreatic and hepatic tissue damage. This probiotic conferred beneficial outcomes in the gut microbiome of diabetic mice, which induced transformation of short-chain fatty acids (SCFAs) and further enhanced the secretion of downstream hormones, and ultimately ameliorated the inflammatory response. CONCLUSION: Lactobacillus paracasei IMC 502 prevents and alleviates T2DM by mediating the gut microbiota-SCFA-hormone/inflammation pathway. © 2022 Society of Chemical Industry.

Physiologically-Based Pharmacokinetic Modeling-Guided Dose Management of Oral Anticoagulants when Initiating Nirmatrelvir/Ritonavir (Paxlovid) for COVID-19 Treatment.

Patients with coronavirus disease 2019 (COVID-19) with cardiovascular diseases who are at higher risk of progressing to critical illness should be treated with nirmatrelvir/ritonavir (Paxlovid). Ritonavir, the booster in nirmatrelvir/ritonavir, modulates multiple drug metabolizing enzymes and transporters, complicating its use in real-world clinics. We aimed to apply physiologically-based pharmacokinetic (PBPK) modeling to simulate the complex drug-drug interactions (DDIs) of ritonavir with two anticoagulants, rivaroxaban and racemic warfarin, to address this important clinical conundrum. Simulations were implemented within Simcyp Simulator. Compound and population models were adopted from Simcyp and our previous studies. Upon verification and validation of the PBPK model of ritonavir, prospective DDI simulations with the anticoagulants were performed in both the general population (20-65 years) and geriatric subjects (65-85 years) with or without moderate renal impairment. Elevated rivaroxaban concentrations were simulated with nirmatrelvir/ritonavir treatment, where the impact was more profound among geriatric subjects with renal impairment. The overexposure of rivaroxaban was restored to normal range on day 4 post-discontinuation of nirmatrelvir/ritonavir, corroborating with the recovery of enzyme activity. A lower 10 mg daily dose of rivaroxaban could effectively maintain acceptable systemic exposure of rivaroxaban during nirmatrelvir/ritonavir treatment. Treatment of ritonavir marginally declined simulated S-warfarin concentrations, but substantially elevated that of R-warfarin, resulting in a decrease in the international normalized ratio (INR). As INR only recovered 2 weeks post-nirmatrelvir/ritonavir treatment, a longer surveillance INR for warfarin becomes important. Our PBPK-guided simulations evaluated clinically important yet untested DDIs and supports clinical studies to ensure proper anticoagulation management of patients with COVID-19 with chronic coagulative abnormalities when initiating nirmatrelvir/ritonavir therapy.

Individuals to Systems: Methodological and Conceptual Considerations for Addressing Mental Illness Stigma Holistically.

Mental illness stigma is a complex public health issue that creates barriers for clients needing access to quality mental health services. Most research focuses on interpersonal stigma with emerging research examining intrapersonal and structural stigma in the healthcare setting. This commentary focuses on how to address the gaps in the existing research to elicit greater organizational/structural change in healthcare systems and positive health outcomes. It describes key components of a 5-year multiphase study that aims to explore and address multiple levels of stigma holistically among stakeholders including physicians, nurses, protective services staff, and patients/families in an emergency department setting. Unique to this study is the inclusion of a patient research partner who will be positioned as a co-designer throughout the project. The goal of this study will be to explore, address, understand, and evaluate interventions that mitigate stigma in healthcare at both the individual and structural/organizational levels.

Inhibitory effect of Malaysian coastal plants on banana (Musa acuminata colla "Lakatan"), ginger (Zingiber officinale Roscoe) and sweet potato (Ipomoea batatas) polyphenol oxidase.

Undesired browning reaction catalyzed by polyphenol oxidase (PPO) has reduced the nutritional quality and customer acceptance of the products. The inhibitory effects of six coastal plants including Sonneratia alba, Rhizophora apiculata, Syzygium grande, Rhizophora mucronata, Hibiscus tiliaceus and Bruguiera gymnorhiza on PPO in banana, sweet potato and ginger were studied based on oxidation of pyrocatechol. Banana exhibited the highest PPO activity (141,600 U), followed by sweet potato (43,440 U) and ginger (26,880 U). Banana PPO was strongly inhibited by R. apiculata (70.87%) and sweet potato PPO was strongly inhibited by S. alba (82.00%). In general, most banana PPO was the most susceptible to inhibition with all inhibitors having inhibition higher than 60.00% at 0.5 mg/ml and ginger PPO was the least susceptible with all inhibitors showing less than 50.00% inhibition at 0.5 mg/ml. Coastal plant extracts are potentially to be developed as natural inhibitors for preventing enzymatic browning of fruits and vegetables.

An overview on the chemistry, pharmacology and anticancer properties of tetrandrine and fangchinoline (alkaloids) from Stephania tetrandra roots.

Tetrandrine (TET) and fangchinoline (FAN) are dominant bisbenzylisoquinoline (BBIQ) alkaloids from the roots of Stephania tetrandra of the family Menispermaceae. BBIQ alkaloids comprise two benzylisoquinoline units linked by oxygen bridges. The molecular structures of TET and FAN are exactly the same, except that TET has a methoxy (-OCH3) group, while FAN has a hydroxyl (-OH) group at C7. In this overview, the current knowledge on the chemistry, pharmacology and anticancer properties of TET and FAN have been updated. The focus is on colon and breast cancer cells, because they are most susceptible to TET and FAN, respectively. Against colon cancer cells, TET inhibits cell proliferation and tumor growth by inducing apoptosis and G1 cell cycle arrest, and suppresses adhesion, migration and invasion of cells. Against breast cancer cells, FAN inhibits cell proliferation by inducing apoptosis, G1-phase cell cycle arrest and inhibits cell migration. The processes involve various molecular mechanisms and signaling pathways. Some insights on the ability of TET and FAN to reverse multi-drug resistance in cancer cells and suggestions for future research are provided.

Phenolic constituents and anticancer properties of Morus alba (white mulberry) leaves.

Flavonoids are by far the most dominant class of phenolic compounds isolated from Morus alba leaves (MAL). Other classes of compounds are benzofurans, phenolic acids, alkaloids, coumarins, chalcones and stilbenes. Major flavonoids are kuwanons, moracinflavans, moragrols and morkotins. Other major compounds include moracins (benzofurans), caffeoylquinic acids (phenolic acids) and morachalcones (chalcones). Research on the anticancer properties of MAL entailed in vitro and in vivo cytotoxicity of extracts or isolated compounds. Flavonoids, benzofurans, chalcones and alkaloids are classes of compounds from MAL that have been found to be cytotoxic towards human cancer cell lines. Further studies on the phytochemistry and anticancer of MAL are suggested. Sources of information were PubMed, PubMed Central, ScienceDirect, Google, Google Scholar, J-Stage, PubChem and China National Knowledge Infrastructure.

Evaluation and Clinical Course of Keratomalacia With Descemetocele in a Child With Autism and Vitamin A Deficiency.

Autistic children with selective diets have an elevated risk for vitamin A deficiency. The authors present the case of a 7-year-old boy with keratomalacia resulting from dietary vitamin A deficiency. Optical coherence tomography and ultrasound biomicroscopy can provide useful details of the cornea and underlying structures. Vitamin A supplementation can result in significant resolution, obviating the need for surgical intervention. [J Pediatr Ophthalmol Strabismus. 2020;57:e1-e3.].

Ursolic acid: An overview on its cytotoxic activities against breast and colorectal cancer cells.

Ursolic acid (UA) is a pentacyclic triterpene of the ursane type. As a common chemical constituent among species of the family Lamiaceae, UA possesses a broad spectrum of pharmacological properties. This overview focuses on the anticancer properties of UA against breast cancer (BC) and colorectal cancer (CRC) that are most common among women and men, respectively. In vitro studies have shown that UA inhibited the growth of BC and CRC cell lines through various molecular targets and signaling pathways. There are several in vivo studies on the cytotoxic activity of UA against BC and CRC. UA also inhibits the growth of other types of cancer. Studies on structural modifications of UA have shown that the -OH groups at C3 and at C28 are critical factors influencing the cytotoxic activity of UA and its derivatives. Some needs for future research are suggested. Sources of information were from ScienceDirect, Google Scholar and PubMed.

Dose-Dependent Increase in Unconjugated Cinnamic Acid Concentration in Plasma Following Acute Consumption of Polyphenol Rich Curry in the Polyspice Study.

Spices that are rich in polyphenols are metabolized to a convergent group of phenolic/aromatic acids. We conducted a dose-exposure nutrikinetic study to investigate associations between mixed spices intake and plasma concentrations of selected, unconjugated phenolic/aromatic acids. In a randomized crossover study, 17 Chinese males consumed a curry meal containing 0 g, 6 g, and 12 g of mixed spices. Postprandial blood was drawn up to 7 h at regular intervals and plasma phenolic/aromatic acids were quantified via liquid chromatography tandem mass spectrometry (LC-MS/MS). Cinnamic acid (CNA, p < 0.0001) and phenylacetic acid (PAA, p < 0.0005) concentrations were significantly increased with mixed spices consumption, although none of the other measured phenolic/aromatic acids differ significantly between treatments. CNA displayed a high dose-exposure association (R² > 0.8, p < 0.0001). The adjusted mean area under the plasma concentration-time curve until 7 h (AUC0⁻7 h) for CNA during the 3 increasing doses were 8.4 ± 3.4, 376.1 ± 104.7 and 875.7 ± 291.9 nM.h respectively. Plasma CNA concentration may be used as a biomarker of spice intake.

Casticin from Vitex species: a short review on its anticancer and anti-inflammatory properties.

This short review provides an update of the anticancer and anti-inflammatory properties of casticin from Vitex species. Casticin is a polymethylflavone with three rings, an orthocatechol moiety, a double bond, two hydroxyl groups and four methoxyl groups. Casticin has been isolated from various tissues of plants in the Vitex genus: fruits and leaves of V. trifolia, aerial parts and seeds of V. agnus-castus and leaves of V. negundo. Studies have reported the antiproliferative and apoptotic activities of casticin from Vitex species. The compound is effective against many cancer cell lines via different molecular mechanisms. Studies have also affirmed the anti-inflammatory properties of casticin, with several molecular mechanisms identified. Other pharmacological properties include anti-asthmatic, tracheospasmolytic, analgesic, antihyperprolactinemia, immunomodulatory, opioidergic, oestrogenic, anti-angiogenic, antiglioma, lung injury protection, rheumatoid arthritis amelioration and liver fibrosis attenuation activities. Clinical trials and commercial use of the casticin-rich fruit extract of V. agnus-castus among women with premenstrual syndrome were briefly discussed.

Dronedarone-Induced Cardiac Mitochondrial Dysfunction and Its Mitigation by Epoxyeicosatrienoic Acids.

Dronedarone and amiodarone are structurally similar antiarrhythmic drugs. Dronedarone worsens cardiac adverse effects with unknown causes while amiodarone has no cardiac adversity. Dronedarone induces preclinical mitochondrial toxicity in rat liver and exhibits clinical hepatotoxicity. Here, we further investigated the relative potential of the antiarrhythmic drugs in causing mitochondrial injury in cardiomyocytes. Differentiated rat H9c2 cardiomyocytes were treated with dronedarone, amiodarone, and their respective metabolites namely N-desbutyldronedarone (NDBD) and N-desethylamiodarone (NDEA). Intracellular ATP content, mitochondrial membrane potential (Δψm), and inhibition of carnitine palmitoyltransferase I (CPT1) activity and arachidonic acid (AA) metabolism were measured in H9c2 cells. Inhibition of electron transport chain (ETC) activities and uncoupling of ETC were further studied in isolated rat heart mitochondria. Dronedarone, amiodarone, NDBD and NDEA decreased intracellular ATP content significantly (IC50 = 0.49, 1.84, 1.07, and 0.63 µM, respectively) and dissipated Δψm potently (IC50 = 0.5, 2.94, 12.8, and 7.38 µM, respectively). Dronedarone, NDBD, and NDEA weakly inhibited CPT1 activity while amiodarone (IC50 > 100 µM) yielded negligible inhibition. Only dronedarone inhibited AA metabolism to its regioisomeric epoxyeicosatrienoic acids (EETs) consistently and potently. NADH-supplemented ETC activity was inhibited by dronedarone, amiodarone, NDBD and NDEA (IC50 = 3.07, 5.24, 11.94, and 16.16 µM, respectively). Cytotoxicity, ATP decrease and Δψm disruption were ameliorated via exogenous pre-treatment of H9c2 cells with 11, 12-EET and 14, 15-EET. Our study confirmed that dronedarone causes mitochondrial injury in cardiomyocytes by perturbing Δψm, inhibiting mitochondrial complex I, uncoupling ETC and dysregulating AA-EET metabolism. We postulate that cardiac mitochondrial injury is one potential contributing factor to dronedarone-induced cardiac failure exacerbation.

Universal Health Coverage through Community Nursing Services: China vs. Hong Kong.

OBJECTIVE:: this article looks at how the development of community nursing services in China and Hong Kong can enhance universal health coverage. METHODS:: literature and data review have been utilized in this study. RESULTS:: nursing services have evolved much since the beginning of the nursing profession. The development of community nursing services has expanded the scope of nursing services to those in need of, not just hospital-level nursing care, but more holistic care to improve health and quality of life. CONCLUSION:: despite the one-country-two-systems governance and the difference in population and geography, Hong Kong and China both face the aging population and its complications. Community nursing services help to pave the road to Universal Health Coverage. OBJETIVO:: este artigo analisa a forma como o desenvolvimento de serviços de enfermagem comunitários na China e Hong Kong pode melhorar a cobertura universal de saúde. MÉTODOS:: literatura e revisão de dados foram utilizados neste estudo. RESULTADOS:: serviços de enfermagem têm evoluído muito desde o início da profissão de enfermagem. O desenvolvimento dos serviços de enfermagem da comunidade ampliou o escopo dos serviços de enfermagem, para aqueles que precisam não apenas de cuidados de enfermagem de nível de hospital, mas cuidados mais holísticos para melhorar a saúde e qualidade de vida. CONCLUSÃO:: apesar de ser "um-país-dois-sistemas" de governo, e as diferenças de população e geografia, Hong Kong e China enfrentam o envelhecimento da população e suas complicações. Os serviços de enfermagem da comunidade ajudam a pavimentar o caminho para a cobertura de saúde universal. OBJETIVO:: este artículo analiza cómo el desarrollo de los servicios de enfermería comunitaria en China y Hong Kong pueden expandir la cobertura universal de salud. MÉTODOS:: revisión de datos y literatura han sido utilizados en este estudio. RESULTADOS:: los servicios de enfermería han evolucionado mucho desde el comienzo de la profesión. El desarrollo de los servicios de enfermería comunitaria han ampliado el alcance de los servicios de enfermería a las personas que necesitan, no sólo en cuidados de enfermería en el hospital, sino también en una atención más integral para mejorar la salud y calidad de vida. CONCLUSIÓN:: a pesar del tipo de gobierno "un país, dos sistemas" y las diferencias de población y geografía, Hong Kong y China se enfrentan al envejecimiento de la población y sus complicaciones. Los servicios de enfermería comunitaria ayudan a allanar el camino hacia la cobertura universal de salud.

Universal Health Coverage through Community Nursing Services: China vs. Hong Kong / Cobertura Universal de Saúde através dos serviços de enfermagem comunitários: China vs. Hong Kong / Cobertura Universal de Salud a través de Servicios Comunitarios de Enfermería: China versus Hong Kong

ABSTRACT Objective: this article looks at how the development of community nursing services in China and Hong Kong can enhance universal health coverage. Methods: literature and data review have been utilized in this study. Results: nursing services have evolved much since the beginning of the nursing profession. The development of community nursing services has expanded the scope of nursing services to those in need of, not just hospital-level nursing care, but more holistic care to improve health and quality of life. Conclusion: despite the one-country-two-systems governance and the difference in population and geography, Hong Kong and China both face the aging population and its complications. Community nursing services help to pave the road to Universal Health Coverage.

RESUMO Objetivo: este artigo analisa a forma como o desenvolvimento de serviços de enfermagem comunitários na China e Hong Kong pode melhorar a cobertura universal de saúde. Métodos: literatura e revisão de dados foram utilizados neste estudo. Resultados: serviços de enfermagem têm evoluído muito desde o início da profissão de enfermagem. O desenvolvimento dos serviços de enfermagem da comunidade ampliou o escopo dos serviços de enfermagem, para aqueles que precisam não apenas de cuidados de enfermagem de nível de hospital, mas cuidados mais holísticos para melhorar a saúde e qualidade de vida. Conclusão: apesar de ser “um-país-dois-sistemas” de governo, e as diferenças de população e geografia, Hong Kong e China enfrentam o envelhecimento da população e suas complicações. Os serviços de enfermagem da comunidade ajudam a pavimentar o caminho para a cobertura de saúde universal.

RESUMEN Objetivo: este artículo analiza cómo el desarrollo de los servicios de enfermería comunitaria en China y Hong Kong pueden expandir la cobertura universal de salud. Métodos: revisión de datos y literatura han sido utilizados en este estudio. Resultados: los servicios de enfermería han evolucionado mucho desde el comienzo de la profesión. El desarrollo de los servicios de enfermería comunitaria han ampliado el alcance de los servicios de enfermería a las personas que necesitan, no sólo en cuidados de enfermería en el hospital, sino también en una atención más integral para mejorar la salud y calidad de vida. Conclusión: a pesar del tipo de gobierno “un país, dos sistemas” y las diferencias de población y geografía, Hong Kong y China se enfrentan al envejecimiento de la población y sus complicaciones. Los servicios de enfermería comunitaria ayudan a allanar el camino hacia la cobertura universal de salud.

A randomized placebo-controlled trial of traditional Chinese medicine as an add-on therapy to oral montelukast in the treatment of mild persistent asthma in children.

OBJECTIVES: Traditional Chinese medicine are commonly used for treatment of asthma. However, there are only very limited data about its efficacy in children. Therefore, we aimed to determine the efficacy of augmented Yu Ping Feng San (aYPFS) as an add-on to oral montelukast compared with montelukast alone for treatment of mild persistent asthma in children. DESIGN: A single centre, placebo-controlled, double-blinded, randomized control trial was carried out. Participants with age 6-18 years who had mild persistent asthma were randomized according to random number list to receive either aYPFS plus montelukast for 24 weeks or placebo plus montelukast for 24 weeks. Primary outcome measure was lung function parameters. Secondary outcome measures were Asthma Control Test™ (ACT™) and Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) scores, symptom-free days, short-acting ß2-agonist use, use of rescue oral corticosteroids, days of hospitalization for asthma and number of emergency consultation with GPs or AED department. RESULTS: Twenty-eight participants were randomized to aYPFS group and twenty-nine to placebo group. There was no significant difference in baseline characteristics. There was significant improvement in ACT™ score in aYPFS group (up to 6.9% change from baseline) (p=0.016) but not in the control group. There were no significant differences between groups in other primary and secondary outcome parameters. Dropout because of adverse effects is comparable in both groups. CONCLUSION: Traditional Chinese medicine aYPFS as an add-on to montelukast improved symptoms of asthma control. Further studies with larger sample size are needed to evaluate its efficacy and safety in childhood asthma.

Apocynaceae species with antiproliferative and/or antiplasmodial properties: a review of ten genera.

Apocynaceae is a large family of tropical trees, shrubs and vines with most species producing white latex. Major metabolites of species are triterpenoids, iridoids, alkaloids and cardenolides, which are known for a wide range of biological and pharmacological activities such as cardioprotective, hepatoprotective, neuroprotective, anti-inflammatory, anticancer and antimalarial properties. Prompted by their anticancer and antimalarial properties, the current knowledge on ten genera (Allamanda, Alstonia, Calotropis, Catharanthus, Cerbera, Dyera, Kopsia, Nerium, Plumeria and Vallaris) is updated. Major classes of metabolites are described using some species as examples. Species with antiproliferative (APF) and/or antiplasmodial (APM) properties have been identified. With the exception of the genus Dyera, nine genera of 22 species possess APF activity. Seven genera (Alstonia, Calotropis, Catharanthus, Dyera, Kopsia, Plumeria and Vallaris) of 13 species have APM properties. Among these species, Alstonia angustiloba, Alstonia macrophylla, Calotropis gigantea, Calotropis procera, Catharanthus roseus, Plumeria alba and Vallaris glabra displayed both APF and APM properties. The chemical constituents of these seven species are compiled for assessment and further research.

Phytochemistry, pharmacology, and clinical trials of Morus alba.

The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties.

Phytochemistry and pharmacology of ornamental gingers, Hedychium coronarium and Alpinia purpurata: a review.

In this review, the phytochemistry and pharmacology of two ornamental gingers, Hedychium coronarium (butterfly ginger) and Alpinia purpurata (red ginger), are updated, and their botany and uses are described. Flowers of H. coronarium are large, showy, white, yellow or white with a yellow centre and highly fragrant. Inflorescences of A. purpurata are erect spikes with attractive red or pink bracts. Phytochemical investigations on the rhizomes of H. coronarium generated research interest globally. This resulted in the isolation of 53 labdane-type diterpenes, with little work done on the leaves and flowers. Pharmacological properties of H. coronarium included antioxidant, antibacterial, antifungal, cytotoxic, chemopreventive, anti-allergic, larvicidal, anthelminthic, analgesic, anti-inflammatory, anti-urolithiatic, anti-angiogenic, neuro-pharmacological, fibrinogenolytic, coagulant and hepatoprotective activities. On the contrary, little is known on the phytochemistry of A. purpurata with pharmacological properties of antioxidant, antibacterial, larvicidal, cytotoxic and vasodilator activities reported in the leaves and rhizomes. There is much disparity in terms of research effort within and between these two ornamental gingers.

An investigation of the bioactivation potential and metabolism profile of Zebrafish versus human.

The zebrafish model has been increasingly explored as an alternative model for toxicity screening of pharmaceutical drugs. However, little is understood about the bioactivation of drug to reactive metabolite and phase I and II metabolism of chemical in zebrafish as compared with human. The primary aim of our study was to establish the bioactivation potential of zebrafish using acetaminophen as a probe substrate. Our secondary aim was to perform metabolite profiling experiments on testosterone, a CYP3A probe substrate, in zebrafish and compare the metabolite profiles with that of human. The glutathione trapping assay of N-acetyl-p-benzoquinone imine demonstrated that zebrafish generates the same reactive metabolite as humans from the bioactivation of acetaminophen. Zebrafish possesses functional CYP3A4/5-like and UDP-glucuronosyltransferase metabolic activities on testosterone. Differential testosterone metabolism was observed among the two species. In silico docking studies suggested that the zebrafish CYP3A65 was responsible for the bioactivation of acetaminophen and phase I hydroxylation of testosterone. Our findings reinforce the need to further characterize the drug metabolism phenotype of zebrafish before the model can fully achieve its potential as an alternative toxicity screening model in drug research.

Standardised herbal extract of chlorogenic acid from leaves of Etlingera elatior (Zingiberaceae).

BACKGROUND: Chlorogenic acid (CGA) or 5-caffeoylquinic acid, was found to be the dominant phenolic compound in leaves of Etlingera elatior (Zingiberaceae). The CGA content of E. elatior leaves was significantly higher than flowers of Lonicera japonica (honeysuckle), the commercial source. In this study, a protocol to produce a standardised herbal CGA extract from leaves of E. elatior using column chromatography was developed. MATERIALS AND METHODS: Freeze-dried leaves of E. elatior were extracted with 30% ethanol, and sequentially fractionated using Diaion HP-20 and Sephadex LH-20. RESULTS: The CGA fractions, which yielded extracts of 10% and 40% w/w purity, possessed antioxidant, tyrosinase inhibition, and antibacterial properties. The entire fractionation process took only 6.5 hours, using gravity flow. From 50 g of leaves, the final yield of CGA extract was 0.2 g (0.4%). The CGA content of the standardised herbal extract from leaves of E. elatior (40%) is 1.6 times that of commercial extracts from honeysuckle flowers (25%). CONCLUSION: With high CGA content, the standardised herbal extract has a great potential to be developed into functional food and other health products. Leaves of E. elatior, which currently have no economic value, could serve as an alternative source of CGA. Leaves are large, available in abundance, and harvesting is non-destructive to the plants.

A synopsis of current haemophilia care in Hong Kong.

OBJECTIVE: To provide a synopsis of current haemophilia care in Hong Kong. DESIGN: Retrospective survey. SETTING: All haematology units of the Hospital Authority in Hong Kong. PATIENTS: All patients with haemophilia A and haemophilia B. RESULTS: To date, there were 222 mild-to-severe haemophilia patients (192 type A, 30 type B) under regular public care in Hong Kong (43% were considered severe, 33% moderate, and 24% mild), which gave a crude prevalence of 6.8/100 000 male inhabitants. A total of 12.8 million units of Factor VIII and 3 million units of Factor IX were prescribed annually. This amounts to 1.83 units of FVIII per capita of the population, which is comparable to that of other developed countries. Leading causes of mortality were human immunodeficiency virus-related complications (10 cases) and cerebral bleeding (2 cases). The life expectancy of patients with severe haemophilia in Hong Kong is improving; currently the oldest patient is 60 years old. Such improved survival may be due to enhanced factor availability, prompt treatment of bleeding episodes at home, safer factor products, and better antiviral treatment. Primary prophylaxis is the accepted standard of care for severe and moderate cases, and "Factor First" has become hospital policy. However, 12 patients continue to present treatment challenges, due to the documented presence of factor inhibitors. In all, 28, 100, and 14 cases respectively were positive for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus; the youngest patients with the corresponding infections being 28, 13, and 22 years old. Comprehensive care with dedicated physiotherapy, surgical support, and radionucleotide synovectomy may reduce morbidity further. CONCLUSION: A multidisciplinary approach can further improve the future care for haemophilia patients in Hong Kong.