A new 2-(2-phenylethyl)chromone derivative in Chinese agarwood ‘Qi-Nan’ from Aquilaria sinensis

Phytochemical analysis of the high quality Chinese agarwood ‘Qi-Nan’ originating from Aquilaria sinensis (Lour.) Glig led to the isolation of a new 2-(2-phenylethyl)chromone derivative, qinanones G (1), and four known 2-(2-phenylethyl)chromones (2–5). Their structures were elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. The NMR data of chromones 1–3 were first reported, and chromones 2 and 3 showed weak inhibitory activity against acetylcholinesterase.     

A new 2-(2-phenylethyl)chromone glycoside in Chinese agarwood “Qi-Nan” from Aquilaria sinensis

A new 2-(2-phenylethyl)chromone glycoside, 2-[2-(4-glucosyloxy-3-methoxyphenyl)ethyl]chromone (1), was isolated from the high-quality Chinese agarwood “Qi-Nan” originating from Aquilaria sinensis (Lour.) Glig. The structure including the absolute configuration of the sugar moiety was elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR), MS analysis, PMP-labeling HPLC analysis methods, as well as comparison with literature data. To the best of our knowledge, it is the first time that chromone glycoside was discovered in agarwood, or even in the whole Aquilaria plants.     

Anti-tumor activity of a lignanic compound from Schisandrapropinqua （Wall） Baill, var sinensis Oliv

AIM: To discover anti-tumor activity of a lignan from Schisandrapropinqua (Wall) Baill, varsinensis Oliv. METHODS: The cytotoxic activity of compound IE2503 was investigated on several cancer cell lines including solid tumor (HepG2), blood tumor (HL-60), drug resistant tumor (R-HepG2) and one normal cell line NIH3T3. To further prove the apoptosis and investigate the specific cell cycle distribution of HepG2 and     

Clinical evaluation of a new oral contraceptive, ‘Pregnon’

Summary

‘Pregnon’, a new oral contraceptive containing 1?mg. lynestrenol and 0.05?mg. ethinyl oestradiol, was administered cyclically to 639 women of fertile age over a total of 9,159 cycles.

There were no pregnancies. In most cases the withdrawal bleeding resembled normal menstruation. The incidence of metrorrhagia was relatively low and when it did occur it was usually confined to the early treatment cycles and was of very limited duration. The objective and subjective tolerance was excellent.     

The mesentery: an ADME perspective on a ‘new’ organ

Abstract

With the inclusion of mesentery, the total number of human organs has recently increased by one. The mesentery was formerly construed to be a complex, discontinuous anatomical structure simply serving as a support for organs in abdominal cavity. However, recent research has established the mesentery to be a far more simple and unfragmented organ. Newly emerging information on the mesentery has challenged some older pathophysiological concepts. This review briefly discusses the anatomy of the mesentery, historical perspective on the mesentery, embryology, drug metabolizing enzymes and transporters of the mesentery, and the mesentery’s role in diseases. The possible impact of the mesentery on absorption, distribution, metabolism, and excretion (ADME) is also discussed.     

Metabolic syndrome and new category ‘pre-hypertension’ in a Japanese population

SUMMARY

Objective: To examine whether insulin resistance and metabolic syndrome are associated with pre-hypertension, a new stage developed by the Joint National Committee on Prevention, Detection, Education and Treatment of High Blood Pressure (JNC-7).

Patients and methods: Subjects included 506 Japanese taking no anti-hypertensive medication. Subjects were divided into three groups according to blood pressure status using the JNC-7 criteria. Normotension (NTN) was defined as a Systolic Blood Pressure (SBP) < 120?mmHg and a Diastolic Blood Pressure (DBP) < 80?mmHg, pre-hypertension (PHT) as a SBP 120–139?mmHg or a DBP 80–89?mmHg and hypertension (HTN) as a SBP ≥ 140?mmHg or a DBP ≥ 90?mmHg. The metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III as modified for waist circumference criteria by the Regional Office for the Western Pacific Region of WHO. Insulin sensitivity was assessed by plasma glucose and insulin concentrations obtained at fasting or during a 75?g oral glucose tolerance test.

Results: There were no differences with respect to age, gender or glucose intolerance status among the three groups. The mean values of body mass index were similar between NTN and PHT, but were significantly higher in HTN than in other groups. The prevalence of the metabolic syndrome was 9.9% in NTN, 19.2% in PHT and 35.5% in HTN, respectively. The prevalence increased linearly with worsening of blood pressure status (?p < 0.0001). An increase in the number of metabolic syndrome components (MS score) was also associated with a progress in blood pressure status. Even in the non-obese persons, the prevalence of the metabolic syndrome and the MS score increased linearly with worsening in blood pressure status. The homeostasis model assessment of insulin resistance (HOMA-R) was significantly higher in PHT and HTN than in NTN and increased significantly with worsening in blood pressure status. Furthermore, the quantitative insulin sensitivity check index (QUICKI) and the insulin sensitivity index proposed by Stumvoll et al. decreased significantly with worsening in blood pressure status.

Conclusions: The metabolic syndrome is prevalent even in the pre-hypertensive stage in a Japanese population and insulin resistance contributes to the underlying mechanisms of these abnormalities.     

A comparative trial of a new,fast-release iron capsule (‘Eryfer’) and a slow-release tablet (‘Ferro-Gradumet’) in iron-deficiency anaemia

Summary

Sixty hospitalised patients receiving treatment for tuberculosis, diabetes or chronic bronchitis and who had iron-deficiency anaemia (Hb levels less than 12.5g.ll00 ml.) were entered in a between-patient comparative study of a new, fast-release iron capsule (‘Eryfer’) and a standard slow-release iron tablet (‘Ferro-Gradumet’).

Patients were allocated to either drug at random and received either 2 capsules (100?mg. elemental iron) or 1 tablet (105?mg. elemental iron) daily for 30 days. Haemoglobin levels and packed cell volume were measured before and at the end of the trial period. The results, analysed in 57 patients (28 on ‘Eryfer’ and 29 on the slow-release iron) indicate that treatment with ‘Eryfer’ produced a significantly more predictable response in haemoglobin regeneration, the response being dependent on the initial haemoglobin level. Both treatments, however, produced a highly significant increase in haemoglobin levels in the patients (mean increase: ‘Eryfer’ 1.09?g. and slow-release iron 0.76?g.). No side-effects were recorded with either treatment.     

Beyond a ‘post-cure’ world: Sketches for a new futurology of hepatitis C

Australia's recent investment in, and optimism about, direct-acting antivirals to treat hepatitis C brings with it the promise of new drug futures, including the possibility of a post-hepatitis C world and a revolution in the lives of people affected by the disease. But is the situation more complicated than we might assume? What expectations are being produced about post-cure lives? And what is being overlooked along the way? We argue that hepatitis C policy, practice and research can instantiate a problematic orientation towards medicine and ‘the future’ and explore ways of moving beyond these orientations. The essay then proceeds into two main stages. First, combining critiques from existing research with preliminary insights from a new study on hepatitis C ‘post-cure’ lives, we outline some of the key logics regarding cure and post-cure, and explain why such logics are problematic. We argue against the assumption that the availability of a medical cure will alone reverse the entrenched social, political and structural dynamics that drive infections and limit service access. To do so, we note, is to overlook the net of meanings and power relations that co-constitute hepatitis C and injecting drug use and render those associated with them marginalised and disenfranchised. Such optimism erases the legacy of laws and policies devised in a pre-cure world, and their role in generating and limiting new ways of being. Second, we introduce new ideas to the field and articulate a vision for what we call a ‘futurology’ of hepatitis C, designed to counter these assumptions and take us beyond problematic temporal logics. Our futurology is inspired by the work of Cuevas-Hewitt (2011) on the ‘futurology of the present’. Cuevas-Hewitt's approach discards linear temporalities, expectations of revolution and reform, and instead pays attention to multiplicities of becoming in the perpetual present. Taking up ideas from Cuevas-Hewitt, we introduce our own sketches for a ‘futurology of hepatitis C’. This is a set of practices for thinking, researching, writing about and otherwise engaging with hepatitis C, characterised by attention not to what an imagined, singular future might look like, or to assumptions about treatment as revolutionary, but to what Cuevas-Hewitt (2011) calls the multiple ‘perpetual presents’ already with us, and aims to foment hope for change.     

Cannabis ‘drugspeak’ from young people in Easterhouse,Glasgow

This qualitative study involved young people from an educational project in Easterhouse in Greater Glasgow. The main aim was to investigate how they would describe and explain onset and continued use of cannabis, with a focus on functional discourse and psychological issues. The range of ages reported for cannabis initiation was 11–15 years (modal age 13), with use taking place with friends or older siblings. Non-use was reportedly relatively rare in participants’ social circles. Participants appeared to accept cannabis use as a part of growing up in Easterhouse and were not motivated to explain in detail how their own use had come about. Some young people reported symptoms often associated with cannabis dependence, including daily use, increased tolerance and absence from school/project. They also spoke in contradictory terms about cannabis use, alternating between a hedonistic outlook and one that recognized problems with continued heavy use. Cannabis use commonly involved burning the drug in foil and inhalation through the use of improvised pipes or ‘buckets’ in places frequented primarily for smoking drugs. Language used could also be seen to mimic closely some aspects of heroin use. Questions are raised about the appropriateness of traditional images of ‘recreational’ cannabis-using behaviour in such settings.     

COVID-19 - Enacting a ‘new normal’ for people who use drugs

The COVID-19 crisis has magnified existing social, economic and political inequities. People who use drugs are particularly vulnerable due to criminalisation and stigma and often experience underlying health conditions, higher rates of poverty, unemployment and homelessness, as well as a lack of access to vital resources – putting them at greater risk of infection. On the other hand, COVID-19 presents an opportunity to confront the mistakes of the past and re-negotiate a new social contract. The International Network of People who use Drugs (INPUD) believe that this crisis must be an occasion to rethink the function of punishment, to reform the system and to work towards ending the war on drugs. This commentary presents a set of recommendations to UN agencies, governments, donor agencies, academics, researchers and civil society, challenging these actors to work alongside people who use drugs to enact a new reality based on solidarity and cooperation, protection of health, restoration of rights and dignity and most importantly to mobilise to win the peace.     

Neuroprotection for Parkinson’s disease: a new approach for a new millennium

Parkinson’s disease (PD) is the only neurodegenerative disorder in which pharmacological intervention has resulted in a marked decrease in morbidity and a significant delay in mortality. However, the medium to long-term efficacy of this pharmacotherapy, mainly consisting of dopaminomimetics like L-dopa and dopamine receptor agonists, suffers greatly from the unrelenting progression of the disease process underlying PD, i.e., the degeneration of neuromelanin-containing, dopaminergic neurones in the substantia nigra. Efforts concentrated on understanding the mechanisms of dopaminergic cell death in Parkinson’s disease have led to identification of a large variety of pathogenetic factors, including excessive release of oxygen free radicals during enzymatic dopamine breakdown, impairment of mitochondrial function, production of inflammatory mediators, loss of trophic support, and apoptosis. Therapeutic approaches aimed at correcting these abnormalities are currently being evaluated on their efficacy as neuroprotectants for PD. Here, we focus on the process of dopamine auto-oxidation, the chain of reactions leading to the formation of neuromelanin, as an often overlooked, yet obvious pathogenetic factor. In particular, we discuss the option of drug-mediated stimulation of endogenous mechanisms responsible for the detoxification of dopamine auto-oxidation products as a novel means of neuroprotection in Parkinson’s disease.     

‘Superbugs’: new antibacterials in the pipeline

‘Superbugs’ in the context discussed herein are Gram-positive pathogens that are multi-resistant to common antibiotic classes. Although many of these organisms were recently susceptible only to vancomycin, therapeutic options are now expanding with the recent approvals for the use of quinupristin-dalfopristin and linezolid against some of these pathogens. Compounds currently under development include cell-wall active agents, such as anti-MRSA cephalosporins, and the glycopeptide LY-333328 to treat resistant Gram-positive infections. More active topoisomerase inhibitors, such as gemifloxacin, sitafloxacin and non-fluoroquinolones, are being evaluated for treatment of multi-drug resistant streptococci, as is the penem faropenem. Novel protein synthesis inhibitors, such as new ketolides and the glycylcycline GAR-936, are also in development; in addition, the lipopeptides daptomycin and HMR-1043 are being evaluated. Safety and efficacy in the treatment of serious infections are two major issues that will determine the eventual success of these agents.     

Is ‘comfort’ care a ‘medical’ care? Observations on a neonatal population

The developments of science and medical technology have contributed to the survival of an increasing number of critically ill newborns. However, when the impossibility of survival becomes apparent, a new risk emerges: that of abandoning the patient. Infants diagnosed with congenital lethal conditions or terminally ill do not longer benefit traditional intensive care, therefore a different plan of medical care is warranted. A novel and personalized management for this population, defined ??comfort care??, is proposed. This paper offers some relevant observations arising from a 3-year experience of comfort care management in a tertiary Neonatal Intensive Care Unit, through clinical cases.     

The absolute stereochemistry of protoxylogranatin A – a new protolimonoid from the seeds of Chinese mangrove Xylocarpus granatum

A new protolimonoid, named protoxylogranatin A, has been isolated from the seeds of a Chinese mangrove Xylocarpus granatum. Its structure was elucidated on the basis of modern spectroscopic data. The absolute configuration was determined by the application of the modified Mosher MTPA ester method. The first complete assignments of ¹H and ¹³C NMR spectral data for this protolimonoid were achieved by means of 2D NMR techniques, including ¹H–¹H COSY, HSQC, HMBC and NOESY spectra.     

‘Ethnobotanicals’ and ‘Spice zombies’: new psychoactive substances in the mainstream media

Abstract

This paper observes and compares discursive framings of new psychoactive substances (NPS) in parts of the mainstream media in Romania and the United Kingdom. It assembles a corpus of about 800 news items and looks into samples of reporting from 2009 to 2017. In Romania, NPS or more generally ‘ethnobotanicals’ were first associated with gullible youths experimenting with what appeared to be synthetic cannabinoids only for public attention to briefly move on to stimulant powders displacing heroin among injecting users, later on. In the UK, the synthetic cathinone mephedrone was presented by tabloids as a ‘menace’ to teenagers and other young users, only for synthetic cannabinoids to eventually be linked with rough sleepers and other vulnerable groups. Through this, qualitative distinctions are shown in the portraying of a middle-class notion of naïve but ‘clean’ youth, valuable in itself, and the portraying of abject underclass users, mostly as a threatening and contagious presence. Beyond alarmism and exaggeration, drug news reporting thus also appears rooted in class politics and structural inequalities where NPS meet with the lived conditions and spoiled identities of disadvantaged groups.