Drugs In Asia Research Articles

Tuberostemonine O from the Roots of Stemona tuberosa

Stemonae Radix is the dried root of Stemona species (Stemonaceae) including S. tuberosa Lour, S. japonica (Blume) Miquel, and S. sessilifolia (Miquel) Miquel. Stemonae Radix is a traditional medicine used as antitussive and anti-helminthic drugs in Asia. 1 Previous phytochemical studies on Stemona species have reported on the isolation of various types of alkaloids including croomine, protostemonine, stemoninine, maistemonine, tuberostemonine, and neotuberostemonine and led to a chemotaxonomic conclusion that each different characteristic alkaloids were distributed within each specific Stemona species. 2-4 There have been several reports that S. tuberosa containes stichoneurine- and croomine-types alkaloids such as tuberostemonine, neotuberostemonine, and stemoninine, while non-tuberosa group contains protostemonine type alkaloids. 2-5 Thus, Stemonae Radix used in the present study was identified as S. tuberosa since the stereoisomers of tuberostemonine were isolated in this study. The stereoisomers of tuberostemonine such as tuberostemonine A to N, which have differences in their relative configurations, have been identified as new constituents of S. tuberosa in its previous phytochemical studies. 3,7,9,11 In the present study, a new tuberostemonine, (2S*,7aR*,8R*,8aS*,11S*,11aS*,11bR*,11cS*)-8-ethyldodecahydro-11-methyl-2-[(2S*,4S*)-tetrahydro-4-methyl-5-oxo2-furanyl]-furo[2,3-h]pyrrolo[3,2,1-jk][1]benz-azepin-10(2H)one (tuberostemonine O) (1) (Figure 1) was isolated from the roots of S. tuberosa. The structure elucidation of compound 1 is described herein. Compound 1 was obtained as light yellow powder and assigned the protonated molecular formula of C22H34NO4 from its HRESIMS (m/z 376.2483) [M+H] + . In the 1 H-NMR spectrum, a primary methyl group appeared at δH 0.95 (3H, t, J = 7.4 Hz, H-17) and the secondary methyl groups were observed at δH 1.28 (3H, d, J = 7.2 Hz, H-22) and 1.32 (3H,

Counterfeit drugs and medical devices in developing countries.

The World Health Organization has reported that counterfeit medicines potentially make up more than 50% of the global drug market, with a significant proportion of these fake products being encountered in developing countries. This occurrence is attributed to a lack of effective regulation and a weak enforcement capacity existing in these countries, with an increase in this trade resulting from the growing size and sophistication of drug counterfeiters. In addition, due to both cost and lack of availability of medicines, consumers in developing countries are more likely to seek out these inexpensive options. The World Health Organization is mindful of the impact of counterfeit drugs on consumer confidence in health care systems, health professionals, the supply chain, and genuine suppliers of medicines and medical devices. Antibiotics, antituberculosis drugs, and antimalarial and antiretroviral drugs are frequently targeted, with reports of 60% of the anti-infective drugs in Asia and Africa containing active pharmaceutical ingredients outside their pharmacopoeial limits. This has obvious public health implications of increasing drug resistance and negating all the efforts that have already gone into the provision of medicines to treat these life threatening conditions in the developing world. This review, while focusing on counterfeit medicines and medical devices in developing countries, will present information on their impact and how these issues can be addressed by regulation and control of the supply chain using technology appropriate to the developing world. The complexity of the problem will also be highlighted in terms of the definition of counterfeit and substandard medicines, including gray pharmaceuticals. Although this issue presents as a global public health problem, outcomes in developing countries where counterfeit drugs to treat malaria, tuberculosis, and human immunodeficiency virus/acquired immunodeficiency syndrome not only result in drug resistance, but a number of deaths from the untreated disease, is in stark contrast with the developed world, where lifestyle drugs such as sildenafil (Viagra®) are most commonly counterfeited.

Incidence and Risk Factors for Incident Hepatitis C Infection Among Men Who Have Sex With Men With HIV-1 Infection in a Large Urban HIV Clinic in Tokyo

The epidemiology of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) who do not inject drugs in Asia remains unknown. The incidence and risk factors for incident HCV infection among HIV-infected MSM at a large HIV clinic in Tokyo were elucidated. Poisson regression compared the incidence of HCV seroconversion at different observation periods. Of 753 HIV-1 infected MSM patients negative for HCV antibody (HCVAb) at baseline and available follow-up HCVAb test, 21 patients (2.8%) seroconverted to HCVAb positive over 2246 person-years (PY), for an incidence of 9.35 per 1000 PY. The incidence increased over time from 0 per 1000 PY in 2005-2006, 3.0 per 1000 PY in 2007-2008, 7.7 per 1000 PY in 2009-2010, to 24.9 per 1000 PY in 2011-2012 (P = 0.012). Of 21 incident cases, only 4 (19%) were injection drug users, and sensitivity analysis that excluded injection drug users yielded similar findings. Multivariate analysis identified illicit drug use to be an independent risk for HCV infection (hazard ratio = 3.006; 95% confidence interval: 1.092 to 8.275; P = 0.033). Incident HCV infection is increasing among HIV-1-infected MSM noninjection drug users at resource-rich setting in Asia. Illicit drug use is an independent risk factor for incident HCV infection in this population.

Traditional Chinese medicine: a treasured natural resource of anticancer drug research and development.

To discover and develop novel natural compounds, active ingredients, single herbs and combination formulas or prescriptions in traditional Chinese medicine (TCM) with therapeutic selectivity that can preferentially kill cancer cells and inhibit the amplification of cancer without significant toxicity is an important area in cancer therapy. A lot of valuable TCMs were applied as alternative or complementary medicines in the United States and Europe. But these TCMs, as one of the main natural resources, were widely used to research and develop new drugs in Asia. In TCMs, some specific herbs, animals, minerals and combination formulas were recorded and exploited due to their active ingredients and specific natural compounds with antitumor activities. The article focused on the antitumor properties of natural compounds and combination formulas or prescriptions in TCMs, described its influence on tumor progression, angiogenesis, metastasis, and revealed its mechanisms of antitumor and inhibitory action. Among the nature compounds, triptolide, berberine, matrine, oxymatrine, kurarinone and deoxypodophyllotoxin (DPT) with specific molecular structures have been separated, purified, and evaluated their antitumor properties in vitro and in vivo. Cancer is a multifactorial and multistep disease, so the treatment effect of combination formulas and prescriptions in TCMs involving multi-targets and multi-signal pathways on tumor may be superior than that of agents targeting a single molecular target alone. Shi Quan Da Bu Tang and Yanshu injection, as well known combination formulas and prescriptions in TCMs, have shown an excellent therapeutic effect on cancer.

Stevens-Johnson syndrome / toxic epidermal necrolysis: an Asia-Pacific perspective

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCAR) to drugs which are associated with significant morbidity and mortality. High risk drugs in Asia are similar to those reported worldwide. Human leukocyte antigen (HLA)-related risk alleles for carbamazepine and allopurinol SCAR are unique to Asians. Although prognostic scoring systems like the SCORTEN have been used for more than a decade, pitfalls and caveats need to be recognized, in particular in patients with multiple medical co-morbidities and systemic features in SJS/TEN. In centres without a tertiary Burns Centre, SJS/TEN patients can still be managed successfully in general and dermatology wards with well-executed supportive/nursing care. Controversy remains regarding the effectiveness of immunomodulation in reducing SJS/TEN morbidity, mortality and hastening re-epithelialization. Despite paucity of robust evidence, intravenous immunoglobulins and ciclosporin remain the most commonly used modalities worldwide. Acute and long-term ocular effects are an important source of morbidity for which emerging ophthalmic therapies appear promising. Quality of life issues have now become an important outcome in patients with SJS/TEN as they often impact survivors' future attitudes towards pharmacotherapy. Even though pharmacogenetic testing for high-risk drugs appears to be the panacea for preventing carbamazepine- and allopurinol-induced SJS/TEN in ethnic Asians, many issues remain before health regulators in our region can conclusively determine whether testing should be made mandatory or highly recommended as standard of care.

Influences of musk administration on the doping test

Musk is widely used as a traditional drug in Asia for the treatment of stroke, tumour, and cardiopathy with an oral dosage of 0.03–0.1g per day. Because of the potential anabolic effect, musk preparations have been included in the list of medical products containing prohibited substances employed for doping. The application of musk pod formulation was regarded as the reason of some adverse analytical findings in the 2011 FIFA Women’s World Cup. In order to investigate the influence of musk administration on the doping test, we executed a chemical analysis and excretion study. The gas chromatography/mass spectrometry (GC–MS) analysis demonstrated the diversity of steroid concentrations in musk samples. Furthermore, the δ13C-values of steroids from wild deer musk showed more depleted than those of domestic deer musk by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) analysis. Because the steroids from some musk had δ13C-values in the range of naturally produced steroids in human body, the possible abuse of this kind of musk is very hard to be detected by isotope ratio mass spectrometry (IRMS) in doping control. Musk grains from wild and domestic deer were administrated for the excretion study respectively. Spot urine samples were collected from two male volunteers before and after 100mg musk grains administration. The profiles and carbon isotope ratios of urinary steroids were determined by GC–MS and GC/C/IRMS. The ingestion of either wild or domestic deer musk did not lead to the adverse analytical finding of doping control in the single dosage of 100mg.

Effect of ketamine on the development of Lucilia sericata (Meigen) (Diptera: Calliphoridae) and preliminary pathological observation of larvae

The estimation of postmortem interval (PMI) based on the growth patterns of necrophagous arthropods is the main mission of forensic entomology in practice. The larval development rates can be affected by various drugs or toxins, causing deviation in PMI estimate. Ketamine is a widely used anesthetic and recreational drug in Asia, which is rarely focused on in the previous entomotoxicological studies. The present work investigated the effect of ketamine on the development of Lucilia sericata (Meigen) (Diptera: Calliphoridae) by the measurement of body length and weight and the analysis of relationship between the ketamine effect and drug dosage or time interval, meanwhile the difference between ketamine effect on larval body length and weight was also analyzed. Additionally, the preliminary pathological observation of larvae was also employed for evaluating the drug effect in morphology. Significant differences were observed between control and treatment colonies of L. sericata at each life stage, and the effect of ketamine displayed a dosage-and-time-dependent manner, but no differences were noticed between the effects of ketamine on larval body length and weight, which provided a useful indication for larvae sample collection in practice. The pathological observation revealed that ketamine could promote the growth of trophocytes in fat body of L. sericata.

Substance Dependence Treatment Interventions: Why We Continue to Fail People Who Use Drugs in Asia

Introduction: Substance use disorders contribute to a large number of preventable deaths in Asia; a majority of the negative health consequences are associated with opioid use. User friendly and effective drug dependence treatment is limited. Scope: Factors mediating drug user treatment outcomes in Asia are explored, with a focus on opioid use. Individual, programmatic, and legal/political issues which reduce the impact of drug user treatment are noted. Discussion: Criminalization of drug users, inadequate insurance, chronic underinvestment, and an overall lack of therapeutic options create structural barriers for treatment for users and providers. The practice of detention as drug treatment serves to fracture the treatment alliance. At the individual level, extreme poverty and the lack of a social protection network mediate against the achievement of treatment goals. Conclusions: A range of factors has a bearing on processes and outcomes of drug user treatment. Acknowledging and addressing them, at each level, is fundamental to delivering useful interventions for people who use drugs.

PHP76 Evidence Requirements for Pricing and Reimbursement Decision Making for Orphan Drugs in Asia

PHP76 Evidence Requirements for Pricing and Reimbursement Decision Making for Orphan Drugs in Asia

The Role of Culinary-Medicinal Mushrooms on Human Welfare with a Pyramid Model for Human Health

Mushrooms are part of fungal biota characterized by wonder. They rise up from lignocellulosic wastes: yet they become so bountiful and nourishing. Mushrooms are environmentally friendly. They biosynthesize their own food from agricultural crop residues, which would otherwise cause health hazards. The extant records show the continued use of some mushrooms, e.g., Lentinus edodes, Ganoderma lucidum, and Cordyceps sinensis are now centuries old. This review presents a pyramid model for mushroom uses (industries), as food, dietary supplements (tonic), and medicine. A regular intake of mushrooms can make us healthier, fitter, and happier, and help us live longer. The sense of purpose and vision for the mushroom industries is also briefly discussed. A variety of mushrooms have been used traditionally in many different cultures for the maintenance of health and in the prevention and treatment of various diseases. A total of 126 medicinal functions are thought to be produced by medicinal mushrooms (MM) and fungi, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemia, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and anti-diabetic effects. Special attention is paid to mushroom polysaccharides. Many, if not all, higher Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, and cultured broth. The data on mushroom polysaccharides are summarized for approximately 700 species of higher Hetero- and Homobasidiomycetes. In particular, the most important for modern medicine are polysaccharides with antitumor and immunostimulating properties. Several of the mushroom polysaccharide compounds have proceeded through phase I, II, and III clinical trials and are used extensively and successfully as drugs in Asia to treat various cancers and other diseases. Mushrooms are superior sources of different types of dietary supplements (DSs) (tonics). The advantages of using mushroom-based DSs as a matter of safety (as opposed to herbal preparations) are: (1) The overwhelming majority of mushrooms used for production of DSs are cultivated commercially (and not gathered in the wild). (2) Mushrooms are easily propagated vegetatively and thus keep to one clone. The mycelium can be stored for a long time, and the genetic and biochemical consistency can be checked after a considerable time. (3) The main advantage, in our opinion, is that many mushrooms are capable of growing in the form of mycelial biomass in submerged cultures. In this review, we discuss legal and regulatory issues introducing and controlling DSs from MMs in different countries, including the United States, the European Community, Australia, New Zealand, Japan, and P.R. China, and guidelines of the World Health Organization. One of the targets of the present review is also to draw attention to many critically important unsolved problems in the future development of medicinal mushroom science in the 21st century.

Rare diseases, orphan drugs, and their regulation in Asia: Current status and future perspectives.

Rare diseases are an important public health issue and a challenge to medical care. Specific legislation to encourage research of rare diseases and development of orphan drugs has been adopted in the United States (US), the European Union (EU), and elsewhere. In recent years, much progress has been made in some parts of Asia, including Japan, South Korea, and Taiwan, with the enactment of legislation and accompanying regulation of rare diseases and orphan drugs. China is also actively promoting the regulation of rare diseases and orphan drugs. We describe the current status of the regulation of rare diseases and orphan drugs in Asia and we comparatively analyze the regulation of rare diseases and orphan drugs worldwide in order to examine the challenges to and future perspectives on promoting research on rare diseases and development of orphan drugs in China and other Asian countries.

Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action

Objectives Radix Bupleuri represents one of the most successful and widely used herbal drugs in Asia for treatment of many diseases over the past 2000 years. Thorough studies have been carried out on many species of this genus and have generated immense data about the chemical composition and corresponding biological activity of extracts and isolated secondary metabolites. In this work, we review the chemistry and pharmacology of the genus Bupleurum and explore the relationships between the pharmacological effects and the chemical composition of these drugs. Key findings Early studies on the genus Bupleurum had focused only on the traditional uses of the plants in the treatment of inflammatory disorders and infectious diseases. After chemical profiling, several groups of secondary metabolites were characterized with relevant biological activity: triterpene saponins (saikosaponins), lignans, essential oils and polysaccharides. As a result, present interest is now focused on the bioactivity of the isolated triterpene saponins acting as immunomodulatory, anti‐inflammatory and antiviral agents, as well as on the observed ant‐iulcer activity of the polysaccharides and anti‐proliferative activity of different lignans. Many saikosaponins exhibited very potent anti‐inflammatory, hepatoprotective and immunomodulatory activities both in vivo and in vitro. Conclusions Further investigations and screenings are required to explore other Bupleurum species, to evaluate the clinical safety and possible interactions with other drugs or herbs. Standardization of Bupleuri extracts is crucial for them being integrated into conventional medicine due to large chemical and biological variations between different species and varieties.

High Times on the Silk Road

In medieval times, traders carried jewels, spices, perfumes, and fabulous fabrics along the legendary Route through Central Asia. Today, the goods are just as valuable, but infinitely more dangerous. Weapons and equipment for American troops in Afghan istan travel from west to east, along the vital lifeline of the Northern Supply Route. In the other direction, an unadvertised, but no less deadly product travels along the same roads, generating billions of dollars in illicit profits. As much as 25 percent of Afghanistan's heroin production is exported through the former Soviet states of Central Asia, and the UN's drug experts express grave concerns. Antonio Maria Costa, head of the UN's Office of Drugs and Crime (UNODC), claims that the Silk Route, turned into a heroin route, is carving out a path of death and violence through one of the world's most strategic, yet volatile re gions. A report from his office asserts that there is a perfect storm spiraling into Cen tral Asia with drug trafficking funding ter rorist groups and insurgency, fostering in stability and conflict, and leaving a host of health problems behind. This should be a wake-up call to Central Asian governments. Yet, oddly, nobody seems to care very much. In theory, the United Nations is right to be worried. At first glance, drug trafficking seems like a major threat to the region, since it is so inextricably linked to violent crime and political instability in many other parts of the world. More people died in Mexican drug violence in 2009 than in Iraq. In Brazil, the government admits about 23,000 drug-related homicides each year? some ten times the number of civilians killed in the war in Afghanistan. And it's not just Latin America that suffers. On Afghanistan's border with Iran, there are regular clashes between Iranian counter narcotics units and drug smugglers. Hun dreds of border guards have been killed over the past decade in fights with heroin and opium traffickers. But Central Asia's drug trade looks rather different. A closer look reveals a

How much will it cost? Estimation of resource needs and availability for HIV prevention, treatment and care for people who inject drugs in Asia

As countries in Asia strive to meet their universal access targets, harm-reduction programmes are yet to be scaled up to reach effective levels of coverage. Resource tracking and estimation of resource needs and gaps is critical to inform the financing decisions of major donors of harm-reduction programmes in the region. This study aimed at estimating the financial resource needs and gaps for scaling-up harm reduction in the region, building on previous research conducted by the Independent Commission on AIDS in Asia. The overall resource need for achieving universal access in the target population in 2009 was US $0.5 billion, with NSP and OST accounting for nearly 70% of the overall regional resource need. A significant resource gap, approximately 90%, of the resource need in 2009, was identified for harm reduction in the region, representing less than 2% of the overall global resource need to address AIDS. Additional resources will be required to support the introduction and scaling-up of integrated, comprehensive harm-reduction programmes that provide a full range of services to reduce HIV transmission among people who inject drugs.

The rapid simultaneous tricyclic antidepressant determination by plasma deproteinization and liquid chromatography

Background: Imipramine, desipramine, amitriptyline and nortriptyline are widely prescribed antidepressant drugs in Asia because of their low price and high efficacy. The concentrations of these drugs in plasma need to be monitored for achieving efficient therapy. A simple, rapid and practical analytical method is required. Objective: To develop a plasma deproteinization process for rapid determination of imipramine, desipramine, amitriptyline or nortriptyline in plasma using high-performance liquid chromatography (HPLC). Methods: A deproteinizing agent, with an acceptable accuracy and sensitivity, to precipitate plasma protein containing imipramine, desipramine, amitriptyline and nortriptyline was investigated along with the HPLC condition for resolving each of these compounds. The developed method was verified by performing a bio-analytical method validation, and by analyzing plasma samples from volunteers who received imipramine or amitriptyline. Results: Using clomipramine as an internal standard, the concentrations of imipramine, desipramine, amitriptyline and nortriptyline in plasma could easily be determined by precipitating plasma protein with acetonitrile and concentrated aqueous potassium phosphate solution prior to HPLC analysis. The mobile phase comprised of acetonitrile and 70 mM phosphate buffer (pH 6.1) (60/40 v/v). A separation was achieved on a C 18 column, and the effluent was measured by UV absorption at 251 nm or by EC detection at +1.0 V of glassy carbon against silver/ silver chloride reference electrode. The chromatographic separation was excellent, without interference from endogenous plasma constituents. All compounds were resolved in a run time of 12 minutes. The method was suitable for quantifying drug concentrations in the ranges of 40-900 ng/ml for UV detection or 4-900 ng/mL for EC detection. The relative standard intra-day and inter-day deviations for each compound in the plasma were less than 8%. The percentage of bias was within ±4% which confirmed the accuracy of the method. The method proved to be efficient and practical for determining the plasma concentrations of each compound, following the administration of imipramine or amitriptyline to volunteers. Conclusion: This developed method is very simple, rapid and inexpensive and is practical for routine therapeutic drug monitoring and forensic toxicological screening.

Moving from a project to programmatic response: Scaling up harm reduction in Asia

The response to the HIV epidemics among people who inject drugs in Asia began to emerge in the early to mid 1990s, with the rather hesitant implementation of small-scale needle syringe programmes and community care initiatives aiming to support those who were already living with the virus. Since then Asia has seen a significant scaling up of harm reduction, despite very limited resources and difficult policy and legislative environments. One of the major reasons this has happened, is the utilisation of programme based approaches and the firm entrenchment of harm reduction thinking within national HIV/AIDS programmes and strategic plans—in most cases aided by multilateral and bilateral donors. Several models of scale up have been noted in Asia. The transition away from project based approaches, while on the whole positive, can also have a negative impact if the involvement of civil society and a client focussed approach is not protected. Also there are implications for which models of capacity building can be systematised for ongoing scale up. Most crucially, the tensions between drug policy, human rights and public health policies need to be resolved if harm reduction services are to be made available to the millions in Asia who are still unable to access these services.

The Golden Triangle: Inside Southeast Asia's Drug Trade

Review(s) of: The Golden Triangle: Inside Southeast Asia's Drug Trade, by Ko-Lin Chin, Ithaca: Cornell University Press, 2009. Includes references.

The golden triangle: inside Southeast Asia's drug trade

The golden triangle: inside Southeast Asia's drug trade

ArQule and Kyowa Hakko Kogya Sign Exclusive Licence Agreement for Cancer Drug in Asia

ArQule and Kyowa Hakko Kogya Sign Exclusive Licence Agreement for Cancer Drug in Asia

Untersuchungen zur in vitro Arzneimittelresistenz bei Malaria tropica in Bangladesch

Particularly in Southeast Asia drug resistance has become a major constraint in the treatment of falciparum malaria. So far relatively little is known about the current status of drug resistance in Bangladesh. The aim of this study was therefore to determine the in vitro drug susceptibility of Plasmodium falciparum in south-eastern Bangladesh. In the HRP2 in vitro drug sensitivity assay the tested isolates demonstrated a relatively high sensitivity to dihydroartemisinine (IC50 = 1.33 nM; 95% CI: 1.08-1.63; IC90 = 2.65 nM; 95% CI: 2.13-3.29), mefloquine (IC50 = 11.26 nM, 95% CI: 9.75-13.0; IC90 = 19.55 nM, 95% CI: 15.73-24.29) and quinine (IC50 = 73.24 nM, 95% CI: 65.26-82.21; IC90 = 157.75 nM, (95% CI: 134.16-185.5) thus being significantly more sensitive to mefloquine and quinine than isolates from Thailand. Chloroquine (IC50 = 93.06 nM, 95% CI: 80.38-107.76; IC90 = 214.76 nM, 95% CI: 175.64-262.62) sensitivity was highly compromised with inhibitory concentrations reaching levels comparable to Thailand. Therefore this drug should not be used in the treatment of falciparum malaria in this region. Despite compromised in vitro drug sensitivity to sulfadoxine/pyrimethamine, in clinical studies the combination of sulfadoxine (IC50 = 40.46 microM, 95% CI: 31.15-51.97; IC90 = 173.48 microM, 95% CI: 120.78-249.17) and pyrimethamine (IC50 = 1.7 microM, 95% CI: 1.25-2.3; IC90 = 4.83 microM, 95% CI: 3.17-7.37) with quinine proved to be an interesting option for treating uncomplicated falciparum malaria in Bangladesh.