Sesquiterpenoids lactones: benefits to plants and people

Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as pharmaceutical agents, due to their potential for the treatment of cardiovascular disease and cancer. This review highlights the role of sesquiterpene lactones endogenously in the plants that produce them, and explores mechanisms by which they interact in animal and human consumers of these plants. Several mechanisms are proposed for the reduction of inflammation and tumorigenesis at potentially achievable levels in humans. Plants can be classified by their specific array of produced sesquiterpene lactones, showing high levels of translational control. Studies of folk medicines implicate sesquiterpene lactones as the active ingredient in many treatments for other ailments such as diarrhea, burns, influenza, and neurodegradation. In addition to the anti-inflammatory response, sesquiterpene lactones have been found to sensitize tumor cells to conventional drug treatments. This review explores the varied ecological roles of sesquiterpenes in the plant producer, depending upon the plant and the compound. These include allelopathy with other plants, insects, and microbes, thereby causing behavioural or developmental modification to these secondary organisms to the benefit of the sesquiterpenoid producer. Some sesquiterpenoid lactones are antimicrobial, disrupting the cell wall of fungi and invasive bacteria, whereas others protect the plant from environmental stresses that would otherwise cause oxidative damage. Many of the compounds are effective due to their bitter flavor, which has obvious implications for human consumers. The implications of sesquiterpenoid lactone qualitiesfor future crop production are discussed.

Rapid-onset opioids and the management of episodic pain

This is the fourth in a short series of articles that focus on what GPs should consider when monitoring and prescribing specialist-initiated palliative-care medicines. Here, the authors summarise the key issues around the use of apid onset opioids in palliative care.

A conceptual framework of patient satisfaction with a pharmacy adherence service

Background Patients do not adhere to their medicines for a host of reasons which can include their underlying beliefs as well as the quality of their interactions with healthcare professionals. One way of measuring the outcome of pharmacy adherence services is to assess patient satisfaction but no questionnaire exists that truly captures patients' experiences with these relatively new services. Objective Our objective was to develop a conceptual framework specific to patient satisfaction with a community pharmacy adherence service based on criteria used by patients themselves. Setting The study was based in community pharmacies in one large geographical area of the UK (Surrey). All the work was conducted between October 2008 and September 2010. Methods This study involved qualitative non-participant observation and semi-structured interviewing. We observed the recruitment of patients to the Medicines Use Review (MUR) service and also actual MUR consultations (7). We also interviewed patients (15). Data collection continued until no new themes were identified during analysis. We analysed interviews to firstly create a comprehensive account of themes which had significance within the transcripts, then created sub-themes within super-ordinate categories. We used a structure-process-outcome approach to develop a conceptual framework relating to patient satisfaction with the MUR. Favourable ethical opinion for this study was received from the NHS Surrey Research Ethics Committee on 2nd June 2008. Results Five super-ordinate themes linked to patient satisfaction with the MUR service were identified, including relationships with healthcare providers; attitudes towards healthcare providers; patients' experience of health, healthcare and medicines; patients' views of the MUR service; the logistics of the MUR service. In the conceptual framework, structure was conceptualised as existing relationships, environment, and time; process was conceptualised as related to recruitment and consultation stages; and outcome as two concepts of immediate patient outcomes and satisfaction on reflection. Conclusion We identified and highlighted factors that can influence patient satisfaction with the MUR service and this led to the development of a conceptual framework of patient satisfaction with the MUR service. This can form the basis for developing a questionnaire for measuring patient satisfaction with this and similar pharmacy adherence services. Impact of findings on practice * Pharmacists and researchers can access the relevant ideas presented here in relation to patient satisfaction with pharmacy adherence services. * Researcher can use the conceptual framework as a basis for measuring the quality of pharmacy adherence services. * Community pharmacists can improve the quality of healthcare they provide by realizing concepts relevant to patient satisfaction with adherence services.

Stability of dobutamine 500 mg in 50 ml syringes prepared using a Central Intravenous Additive Service

Objectives A pharmacy Central Intravenous Additives Service (CIVAS) provides ready to use injectable medicines. However, manipulation of a licensed injectable medicine may significantly alter the stability of drug(s) in the final product. The aim of this study was to develop a stability indicating assay for CIVAS produced dobutamine 500 mg in 50 ml dextrose 1% (w/v) prefilled syringes, and to allocate a suitable shelf life. Methods A stability indicating high performance liquid chromatography (HPLC) assay was established for dobutamine. The stability of dobutamine prefilled syringes was evaluated under storage conditions of 4°C (protected from light), room temperature (protected from light), room temperature (exposed to light) and 40°C (protected from light) at various time points (up to 42 days). Results An HPLC method employing a Hypersil column, mobile phase (pH=4.0) consisting of 82:12:6 (v/v/v) 0.05 M KH2PO4:acetonitrile:methanol plus 0.3% (v/v) triethylamine with UV detection at λ=280 nm was specific for dobutamine. Under different storage conditions only samples stored at 40°C showed greater than 5% degradation (5.08%) at 42 days and had the shortest T95% based on this criterion (44.6 days compared with 111.4 days for 4°C). Exposure to light also reduced dobutamine stability. Discolouration on storage was the limiting factor in shelf life allocation, even when dobutamine remained within 5% of the initial concentration. Conclusions A stability indicating HPLC assay for dobutamine was developed. The shelf life recommended for the CIVAS product was 42 days at 4°C and 35 days at room temperature when protected from light.

Matching roots to their environment

Background Plants form the base of the terrestrial food chain and provide medicines, fuel, fibre and industrial materials to humans. Vascular land plants rely on their roots to acquire the water and mineral elements necessary for their survival in nature or their yield and nutritional quality in agriculture. Major biogeochemical fluxes of all elements occur through plant roots, and the roots of agricultural crops have a significant role to play in soil sustainability, carbon sequestration, reducing emissions of greenhouse gasses, and in preventing the eutrophication of water bodies associated with the application of mineral fertilisers. ● Scope This article provides the context for a Special Issue of Annals of Botany on ‘Matching Roots to Their Environment’. It first examines how land plants and their roots evolved, describes how the ecology of roots and their rhizospheres contributes to the acquisition of soil resources, and discusses the influence of plant roots on biogeochemical cycles. It then describes the role of roots in overcoming the constraints to crop production imposed by hostile or infertile soils, illustrates root phenotypes that improve the acquisition of mineral elements and water, and discusses high-throughput methods to screen for these traits in the laboratory, glasshouse and field. Finally, it considers whether knowledge of adaptations improving the acquisition of resources in natural environments can be used to develop root systems for sustainable agriculture in the future.

Cannabinoids and tremor induced by motor-related disorders: friend or foe?

Tremor arises from an involuntary, rhythmic muscle contraction/relaxation cycle and is a common disabling symptom of many motor-related diseases such as Parkinson disease, multiple sclerosis, Huntington disease, and forms of ataxia. In the wake of anecdotal, largely uncontrolled, observations claiming the amelioration of some symptoms among cannabis smokers, and the high density of cannabinoid receptors in the areas responsible for motor function, including basal ganglia and cerebellum, many researchers have pursued the question of whether cannabinoid-based compounds could be used therapeutically to alleviate tremor associated with central nervous system diseases. In this review, we focus on possible effects of cannabinoid-based medicines, in particular on Parkinsonian and multiple sclerosis-related tremors and the common probable molecular mechanisms. While, at present, inconclusive results have been obtained, future investigations should extend preclinical studies with different cannabinoids to controlled clinical trials to determine potential benefits in tremor.

Molecular targets of cannabidiol in neurological disorders

Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD’s beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular phar- macology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD’s relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeu- tics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent with modulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug’s action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excluding unlikely and implausible targets, the remaining molecular targets of CBD with plausible evidence for involvement in therapeutic effects in neurological disorders (e.g., voltage-dependent anion channel 1, G protein-coupled receptor 55, CaV3.x, etc.) are associated with either the regulation of, or responses to changes in, intracellular calcium levels. While no causal proof yet exists for CBD’s effects at these targets, they represent the most probable for such investigations and should be prioritized in further studies of CBD’s therapeutic mechanism of action.

Children’s physic: medical perceptions and treatment of sick children in early modern England, c. 1580-1720

Historians of medicine, childhood, and paediatrics, have often assumed that early modern doctors neither treated children, nor adapted their medicines to suit the peculiar temperaments of the young. Through an examination of medical textbooks and doctors’ casebooks, this article refutes these assumptions. It argues that medical authors and practising doctors regularly treated children, and were careful to tailor their remedies to complement the distinctive constitutions of children. Thus, this article proposes that a concept of ‘children’s physic’ existed in early modern England: this term refers to the notion that children were physiologically distinct, requiring special medical care. Children’s physic was rooted in the ancient traditions of Hippocratic and Galenic medicine: it was the child’s humoral makeup that underpinned all medical ideas about children’s bodies, minds, diseases, and treatments. Children abounded in the humour blood, which made them humid and weak, and in need of medicines of a particularly gentle nature.

Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation.

Biodiversity and green open space

Biodiversity has been defined as the totality of genes, species, and ecosystems that inhabit the earth with the field contributing to many aspects of our lives and livelihoods by providing us with food, drink, medicines and shelter, as well as contributing to improving our surrounding environment. Benefits include providing life services through improved horticultural production, improving the business and service of horticulture as well as our environment, as well as improving our health and wellbeing, and our social and cultural relationships. Threats to biodiversity can include fragmentation, degradation and deforestation of habitat, introduction of invasive and exotic species, climate change and extreme weather events, over-exploitation of our natural resources, hybridisation, genetic pollution/erosion and food security issues and human overpopulation. This chapter examines a series of examples that provide the dual aims of biodiversity conservation and horticultural production and service; namely organic horticultural cropping, turf management, and nature-based tourism, and ways of valuing biological biodiversity such as the payment of environmental services and bio-prospecting. Horticulture plays a major role in the preserving of biodiversity.

The Sick Child in Early Modern England, 1580-1720

The Sick Child in Early Modern England is a powerful exploration of the treatment, perception, and experience of illness in childhood, from the late sixteenth to the early eighteenth centuries. At this time, the sickness or death of a child was a common occurrence - over a quarter of young people died before the age of fifteen - and yet this subject has received little scholarly attention. Hannah Newton takes three perspectives: first, she investigates medical understandings and treatments of children. She argues that a concept of 'children's physic' existed amongst doctors and laypeople: the young were thought to be physiologically distinct, and in need of special medicines. Secondly, she examines the family's' experience, demonstrating that parents devoted considerable time and effort to the care of their sick offspring, and experienced feelings of devastating grief upon their illnesses and deaths. Thirdly, she takes the strikingly original viewpoint of sick children themselves, offering rare and intimate insights into the emotional, spiritual, physical, and social dimensions of sickness, pain, and death. Newton asserts that children's experiences were characterised by profound ambivalence: whilst young patients were often tormented by feelings of guilt, fears of hell, and physical pain, sickness could also be emotionally and spiritually uplifting, and invited much attention and love from parents. Drawing on a wide array of printed and archival sources, The Sick Child is of vital interest to scholars working in the interconnected fields of the history of medicine, childhood, parenthood, bodies, emotion, pain, death, religion, and gender.

Resource-dependent livelihoods and the natural resource base

The natural resource base, terrestrial and marine, provides rural households in lower-income countries with income, food, shelter, and medicines, which are variously gathered and hunted in common lands and waters. These resources may be actively managed, whether by the government or local community; or may be de facto open access, with little effort by governments to prevent what may be de jure illegal extraction. This paper provides an appraisal of the literature that encompasses the direct value of wild resources to rural households; the extent to which these resources mitigate poverty and inequality; and the importance of the institutional context. The literature is increasingly addressing competing demands on the resource base both to support nearby livelihoods, and to enhance ecosystem services such as biodiversity; and how initiatives such as community-based payments for ecosystem services are changing how people interact with the resource base.

Oral colonization by Candida species in AIDS pediatric patients

The aim of this study was to assess the prevalence of factors associated with oral colonization by Candida spp. in pediatric patients with AIDS. The sample comprised of 117 children. Clinical status, medicines in use, and laboratory findings were obtained from hospital records; sociodemographic data were given by relatives. A dental examination assessed the prevalence of dental caries. The prevalence of oral colonization by Candida was 62%. Only seven children presented clinical manifestation of oral candidosis despite their high viral load index and low-for-age CD4 count. Candida colonization was directly associated with frequent use of antibiotics (prevalence ratio [PR] = 1.44), sulfa drugs (PR = 1.23), alteration in the oral mucosa (PR = 1.55), and untreated dental caries (PR = 1.93). It was inversely associated with the use of antiretroviral therapies (PR = 0.65). Candida albicans was the most frequently detected species (80%); phenotypic tests did not detect C. dubliniensis strains. This study observed a low prevalence of Candida-related oral lesions in these patients, which is compatible with the hypothesis that antiretroviral medicines may have contributed to reducing oral manifestations from Candida infection. The high prevalence of Candida colonization in HIV+/AIDS children with untreated dental caries reinforces the importance of oral health care in interdisciplinary health units that assist these patients.

Overweight and obesity related factors in schoolchildren in Santa Catarina State, Brazil

The purpose of this study is to determine the correlation of socioeconomic, dietary, and anthropometric-nutritional variables of parents and their children to overweight (including obesity) in schoolchildren in Santa Catarina State, Brazil. This is a transversal study conducted on 4,964, 6 to 10-year-old schoolchildren registered in 345 Santa Catarina elementary schools. The following data were acquired: the children`s current weight and height, birth weight and length, duration of breastfeeding, age at which water, herbal tea and other foods were introduced to their diet; parental income, education level, age, weight and height were also obtained. The prevalence of overweight and obese children were estimated by point and by interval with a 95% confidence; prevalence rates were obtained based on the Poisson model. An hierarchical approach was used, in which variables were adjusted within blocks and included in the model when they presented p<0.05 at the outcome (overweight including obesity). The results indicate that 47.8% of the subjects were male. The prevalence of overweight and obese students was 15.4% (C195%: 14.4%-16.5%) and 6.1% (CI95%: 5.4%-6.7%) respectively and were statistically similar among sexes and age ranges. BMI values were higher in males and among older children (p<0.05). After adjustment within and among blocks, the variables per capita household income and parents` BM I values remained associated with overweight (including obesity). Overweight (including obesity) in schoolchildren is associated with a higher per capita household income and parental overweight and obesity.

Evaluation of Fungal Burden and Aflatoxin Presence in Packed Medicinal Plants Treated by Gamma Radiation

This study was developed to evaluate the fungal burden, toxigenic molds, and mycotoxin contamination and to verify the effects of gamma radiation in four kinds of medicinal plants stored before and after 30 days of irradiation treatment. Eighty samples of medicinal plants (Peumus boldus, Camellia sinensis, Maytenus ilicifolia. and Cassia angustifolia) purchased from drugstores, wholesale, and open-air markets in Sao Paulo city, Brazil, were analyzed. The samples were treated using a (60)Co gamma ray source (Gammacell) with doses of 5 and 10 kGy. Nonirradiated samples were used as controls of fungal isolates. For enumeration of fungi on medicinal plants, serial dilutions of the samples were plated in duplicate onto dichloran 18% glycerol agar. The control samples revealed a high burden of molds, including toxigenic fungi. The process of gamma radiation was effective in reducing the number of CFU per gram in all irradiated samples of medicinal plants after 30 days of storage, using a dose of 10 kGy and maintaining samples in a protective package. No aflatoxins were detected. Gamma radiation treatment can be used as an effective method for preventing fungal deterioration of medicinal plants subject to long-term storage.