45 resultados para Route of drug intake


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OBJECTIVE: Evidence suggests that TV viewing is associated with body mass index (BMI) and metabolic syndrome (MetS) in adolescents. However, it is unclear whether dietary intake mediates these relationships.

METHODS: A cross-sectional analysis was conducted in adolescents (12-19 years) participating in the 2003-2006 United States National Health and Nutrition Examination Survey. BMI z scores (zBMI) (n = 3,161) and MetS (n = 1,379) were calculated using age- and sex-specific criteria for adolescents. TV viewing (h/day) was measured via a self-reported questionnaire, and dietary intake was assessed using two 24-h recalls. Using the MacKinnon method, a series of mediation analyses were conducted examining five dietary mediators (total energy intake, fruit and vegetable intake, discretionary snacks, sugar-sweetened beverages and diet quality) of the relationships between TV viewing and zBMI and MetS.

RESULTS: Small positive relationships were observed between TV viewing and zBMI (β = 0.99, p < 0.001) and TV viewing and MetS (OR = 1.18, p = 0.046). No dietary element appeared to mediate the relationship between TV viewing and zBMI. However, sugar-sweetened beverage consumption and fruit and vegetable intake partially mediated the relationship between TV viewing and MetS, explaining 8.7% and 4.1% of the relationship, respectively.

CONCLUSIONS: These findings highlight the complexity of the relationships between TV viewing, dietary intake and cardiometabolic health outcomes, and that TV viewing should remain a target for interventions.

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Transcellular diffusion across the absorptive epithelial cells (enterocytes) of the small intestine is the main route of absorption for most orally administered drugs. The process by which lipophilic compounds transverse the aqueous environment of the cytoplasm, however, remains poorly defined. In the present study, we have identified a structurally diverse group of lipophilic drugs that display low micromolar binding affinities for a cytosolic lipid-binding protein—intestinal fatty acid-binding protein (I-FABP). Binding to I-FABP significantly enhanced the transport of lipophilic drug molecules across a model membrane, and the degree of transport enhancement was related to both drug lipophilicity and I-FABP binding affinity. These data suggest that intracellular lipid-binding proteins such as I-FABP may enhance the membrane transport of lipophilic xenobiotics and facilitate drug access to the enterocyte cytoplasm and cytoplasmic organelles.

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The adoption, in mid-1995, of the revised food Standard A9, which permits the more liberal addition of nutrients to a range of food products, highlighted the need to obtain information on nutrient intake from supplements to complement the i 995 National Nutrition Survey data on nutrient intake from food. This paper describes the method used to obtain quantitative information on nutrient supplement intake and reports on the prevalence of supplement use in different subgroups of the Australian population. Information on supplement intake was obtained in two Australian Bureau of Statistics Population Survey Monitor surveys in August 1995 and February 1996 using the Therapeutic Goods Administration (TGA) registration numbers to identify individual products. Approximately 18% of men and 29% of women aged 18 years and over reported consuming a nutrient supplement on the day before the survey and these proportions increased to 25% and 35% respectively for consumption during the two weeks before the survey. The prevalence of supplement intake increased with age, education level, socioeconomic status, employment status and with fruit and vegetable intake. The substantial proportion of Australian adults who consume nutrient supplements, and the rapidly changing composition of the Australian food supply in response to changes in food regulation, indicate that there is a need for regular monitoring of nutrient intake from supplements. The use of TGA registration numbers to identify supplements provides a practical way to address this need.

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The official public policy related to recreational drug use and abuse in Australia is harm minimization or harm reduction. Definitions of harm minimization vary but a general statement is that harm minimization is a policy or programme intended to decrease adverse health, social and economic consequences of drug use, even though the user may continue to use psychoactive drugs. This type of definition is most often compared to a zero-tolerance policy that aims to eliminate all recreational drug abuse by legal and other means. Sociologists have historically scoffed at this latter policy. Unfortunately, what this has meant is that harm minimization in all its forms has not been the object of analytical work on the part of sociologists.

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The oxazaphosphorines including cyclophosphamide (CPA), ifosfamide (IFO), and trofosfamide represent an important group of therapeutic agents due to their substantial antitumor and immuno-modulating activity. CPA is widely used as an anticancer drug, an immunosuppressant, and for the mobilization of hematopoetic progenitor cells from the bone marrow into peripheral blood prior to bone marrow transplantation for aplastic anemia, leukemia, and other malignancies. New oxazaphosphorines derivatives have been developed in an attempt to improve selectivity and response with reduced toxicity. These derivatives include mafosfamide (NSC 345842), glufosfamide (D19575, β-D-glucosylisophosphoramide mustard), NSC 612567 (aldophosphamide perhydrothiazine), and NSC 613060 (aldophosphamide thiazolidine). This review highlights the metabolism and transport of these oxazaphosphorines (mainly CPA and IFO, as these two oxazaphosphorine drugs are the most widely used alkylating agents) and the clinical implications. Both CPA and IFO are prodrugs that require activation by hepatic cytochrome P450 (CYP)-catalyzed 4-hydroxylation, yielding cytotoxic nitrogen mustards capable of reacting with DNA molecules to form crosslinks and lead to cell apoptosis and/or necrosis. Such prodrug activation can be enhanced within tumor cells by the CYP-based gene directed-enzyme prodrug therapy (GDEPT) approach. However, those newly synthesized oxazaphosphorine derivatives such as glufosfamide, NSC 612567 and NSC 613060, do not need hepatic activation. They are activated through other enzymatic and/or non-enzymatic pathways. For example, both NSC 612567 and NSC 613060 can be activated by plain phosphodiesterase (PDEs) in plasma and other tissues or by the high-affinity nuclear 3'-5' exonucleases associated with DNA polymerases, such as DNA polymerases and ε. The alternative CYP-catalyzed inactivation pathway by N-dechloroethylation generates the neurotoxic and nephrotoxic byproduct chloroacetaldehyde (CAA). Various aldehyde dehydrogenases (ALDHs) and glutathione S-transferases (GSTs) are involved in the detoxification of oxazaphosphorine metabolites. The metabolism of oxazaphosphorines is auto-inducible, with the activation of the orphan nuclear receptor pregnane X receptor (PXR) being the major mechanism. Oxazaphosphorine metabolism is affected by a number of factors associated with the drugs (e.g., dosage, route of administration, chirality, and drug combination) and patients (e.g., age, gender, renal and hepatic function). Several drug transporters, such as breast cancer resistance protein (BCRP), multidrug resistance associated proteins (MRP1, MRP2, and MRP4) are involved in the active uptake and efflux of parental oxazaphosphorines, their cytotoxic mustards and conjugates in hepatocytes and tumor cells. Oxazaphosphorine metabolism and transport have a major impact on pharmacokinetic variability, pharmacokinetic-pharmacodynamic relationship, toxicity, resistance, and drug interactions since the drug-metabolizing enzymes and drug transporters involved are key determinants of the pharmacokinetics and pharmacodynamics of oxazaphosphorines. A better understanding of the factors that affect the metabolism and transport of oxazaphosphorines is important for their optional use in cancer chemotherapy.

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[A focus on risk environments] helps to overcome the limits of individualism characterising most [drug] prevention interventions as well as to appreciate how drug-related harm intersects with health and vulnerability more generally.

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Intestinal fatty acid binding protein (I-FABP) is present at high levels in the absorptive cells of the intestine (enterocytes) where it plays a role in the intracellular solubilization of fatty acids (FA). However, I-FABP has also been shown to bind to a range of non-FA ligands, including some lipophilic drug molecules, albeit with generally lower affinity than FA. The significance of these lower affinity interactions with exogenous compounds is not known. In this manuscript, we describe further characterization of drug-rat I-FABP binding interactions using a thermal-shift assay. A structural explanation of the observed affinity of rat I-FABP for different drugs based on spectroscopic data and modeling experiments is presented. In addition, immunocytochemistry has been used to probe the expression of I-FABP in a cell culture model reflective of the absorptive cells of the small intestine. Taken together, these data suggest a possible role for I-FABP in the disposition of some lipophilic drugs within the enterocyte.

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In 'The normalization of 'sensible' recreational drug use' Parker, Williams and Aldridge (2002) present data on illegal drug use by adolescents and young adults in the UK. They argue that it is both widespread and largely socially benign - ie, normal. We contrast this 'normalisation' thesis with evidence of an increase in the introduction of drug policies - and drug testing - in British organisations. Such policies construct employee drug use as excessive enough to necessitate heightened management vigilance over workers, in order to preserve corporate interests. These contrasting representations of drug use inspire our discussion. We deploy the normal/ excessive couplet to unpick drug taking, to examine organisational drug policies and to comment upon emerging and potential resistance to these policies. Our contribution is to suggest that each of these activities can be understood as simultaneously normal and excessive, in an area where orthodox and critical analyses alike tend to be far more dualistic.

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Fish and PUFA consumption are thought to play a role in mental health; however, many studies do not take into account multiple sources of PUFA. The present study analysed data from a sample of 935 randomly selected, population-based women aged 20–93 years. A validated and comprehensive dietary questionnaire ascertained the consumption of n-3 and n-6 PUFA. Another assessed fish and energy intake and provided data for a dietary quality score. The General Health Questionnaire-12 (GHQ-12) measured psychological symptoms and a clinical interview (Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition) assessed depressive and anxiety disorders. Median dietary intakes of long-chain n-3 fatty acids (310 mg/d) were below suggested dietary target levels. The only PUFA related to categorical depressive and anxiety disorders was DHA. There was a non-linear relationship between DHA intake and depression; those in the second tertile of DHA intake were nearly 70 % less likely to report a current depressive disorder compared to those in the first tertile. The relationship of DHA to anxiety disorders was linear; for those in the highest tertile of DHA intake, the odds for anxiety disorders were reduced by nearly 50 % after adjustments, including adjustment for diet quality scores, compared to the lowest tertile. Those who ate fish less than once per week had higher GHQ-12 scores, and this relationship was particularly obvious in smokers. These are the first observational data to indicate a role for DHA in anxiety disorders, but suggest that the relationship between DHA and depressive disorders may be non-linear.

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Background
There is broad consensus that diets high in salt are bad for health and that reducing salt intake is a cost-effective strategy for preventing chronic diseases. The World Health Organization has been supporting the development of salt reduction strategies in the Pacific Islands where salt intakes are thought to be high. However, there are no accurate measures of salt intake in these countries. The aims of this project are to establish baseline levels of salt intake in two Pacific Island countries, implement multi-pronged, cross-sectoral salt reduction programs in both, and determine the effects and cost-effectiveness of the intervention strategies.

Methods/Design
Intervention effectiveness will be assessed from cross-sectional surveys before and after population-based salt reduction interventions in Fiji and Samoa. Baseline surveys began in July 2012 and follow-up surveys will be completed by July 2015 after a 2-year intervention period.

A three-stage stratified cluster random sampling strategy will be used for the population surveys, building on existing government surveys in each country. Data on salt intake, salt levels in foods and sources of dietary salt measured at baseline will be combined with an in-depth qualitative analysis of stakeholder views to develop and implement targeted interventions to reduce salt intake.

Discussion
Salt reduction is a global priority and all Member States of the World Health Organization have agreed on a target to reduce salt intake by 30% by 2025, as part of the global action plan to reduce the burden of non-communicable diseases. The study described by this protocol will be the first to provide a robust assessment of salt intake and the impact of salt reduction interventions in the Pacific Islands. As such, it will inform the development of strategies for other Pacific Island countries and comparable low and middle-income settings around the world.

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Tris(2,2'-bipyridine)ruthenium(II) chemiluminescence was investigated for the detection of 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds in street drug samples. Optimization using flow injection analysis showed that the selectivity of the reagent can be targeted towards the detection of secondary amines by altering the pH of the reaction environment. The greater selectivity of this mode of detection, compared to UV-absorbance, reduces the probability of false positive results from interfering compounds. The detection limit for MDMA under these conditions was 0.48 μM. A HPLC method incorporating post-column tris(2,2'-bipyridine)ruthenium(II) chemiluminescence detection was applied to the determination of MDMA in five street drug samples. The results obtained were in good agreement with quantification performed using traditional UV-absorbance detection, which demonstrates the viability of this method for confirmatory analysis of drug samples. This is the first report of tris(2,2'-bipyridine)ruthenium(II) chemiluminescence for the detection of MDMA and related amphetamine derivatives.

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BACKGROUND: Understanding the relationship between children's dietary consumption and health is important. As such, it is crucial to explore factors related to the accuracy of children's reports of what they consumed. OBJECTIVE: The objective was to evaluate factors related to the accuracy of self-reported dietary intake information elicited by interview methods from children aged 6 to 12 years. METHODS: A systematic review of English articles using PsycINFO, PsycARTICLES, PsycEXTRA, PsycBOOKS, CINAHL Complete, Global Health, and MEDLINE Complete was performed. Search terms included interview, diet, children, and recall; studies were limited to those published from 1970 onward. Additional studies were identified using the reference lists of published articles. Studies that assessed children's dietary intake using direct observation, doubly labeled water, or the double-portion method and compared it with their recall of that intake (unassisted by parents) using an interview were included. RESULTS: The 45 studies that met the inclusion criteria showed that specific interview techniques designed to enhance children's recall accuracy had little effect. Rather, the timing of the interview appeared most important: The shorter the retention interval between children's consumption and their recall, the more accurate their memories. Children's age, body mass index, social desirability, food preferences, and cognitive ability were also related to accuracy. CONCLUSIONS: Factors related to the accuracy of children's dietary reporting should be taken into consideration when asking about consumption. Further research is required to examine whether other interview techniques, such as those developed to enhance children's recall of repeated staged events, can improve children's dietary reporting accuracy.

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The relevance of drug and alcohol involvement to sentencing law and practice is one of the most perplexing and unsettled areas of sentencing law and practice.1 It is also one of the most important issues in the criminal justice system. Most crimes are committed by offenders who are substance involved, and nearly half of all crimes that are committed are done so by offenders who are intoxicated at the time of the offense. Substance involved individuals are grossly over-represented in the criminal courts. Addiction and intoxication impair sound judgment, and hence, it intuitively appears that intoxicated offenders are less culpable for their crimes. Moreover, there is often a sense that addiction and intoxication causes aberrant behavior and that curing the substance involvement will lead to more prudent (law-abiding) conduct.

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BACKGROUND: Cryptomarkets are digital platforms that use anonymising software (e.g. Tor) and cryptocurrencies (e.g. Bitcoin) to facilitate peer-to-peer (P2P) trade of goods and services. Their emergence has facilitated access to a wide range of high-quality psychoactive substances, according to surveys of users. In this paper, we ask the question 'How does changing access to drugs through cryptomarkets affect the drug use and harm trajectories of their users?'

METHODS: We conducted a digital ethnography spanning 2012-2014, a period that included the seizure of the original Silk Road marketplace and forum by law enforcement. Using encrypted online chat, we interviewed 17 people who reported using Silk Road to purchase illicit drugs. The interviews were in-depth and unstructured, and also involved the use of life history timelines to trace trajectories. Transcripts were analysed thematically using NVivo.

RESULTS: For some, Silk Road facilitated initiation into drug use or a return to drug use after cessation. Typically, participants reported experiencing a glut of drug consumption in their first months using Silk Road, described by one participant as akin to 'kids in a candy store'. There was evidence that very high availability reduced the need for drug hoarding which helped some respondents to moderate use and feel more in control of purchases made online. Cryptomarket access also appeared to affect solitary and social drug users differently. Most participants described using other cryptomarkets after the closure of Silk Road, albeit with less confidence.

CONCLUSION: In the context of high levels of drug access, supply and diversity occurring within a community regulated environment online, the impacts of cryptomarkets upon drug use trajectories are complex, often posing new challenges for self-control, yet not always leading to harmful outcomes. A major policy challenge is how to provide support for harm reduction in these highly volatile settings.

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The aim of this study was to determine the intake and food sources of potassium and the molar sodium:potassium (Na:K) ratio in a sample of Australian pre-school children. Mothers provided dietary recalls of their 3.5 years old children (previous participants of Melbourne Infant Feeding Activity and Nutrition Trial). The average daily potassium intake, the contribution of food groups to daily potassium intake, the Na:K ratio, and daily serves of fruit, dairy, and vegetables, were assessed via three unscheduled 24 h dietary recalls. The sample included 251 Australian children (125 male), mean age 3.5 (0.19) (SD) years. Mean potassium intake was 1618 (267) mg/day, the Na:K ratio was 1.47 (0.5) and 54% of children did not meet the Australian recommended adequate intake (AI) of 2000 mg/day for potassium. Main food sources of potassium were milk (27%), fruit (19%), and vegetable (14%) products/dishes. Food groups with the highest Na:K ratio were processed meats (7.8), white bread/rolls (6.0), and savoury sauces and condiments (5.4). Children had a mean intake of 1.4 (0.75) serves of fruit, 1.4 (0.72) dairy, and 0.52 (0.32) serves of vegetables per day. The majority of children had potassium intakes below the recommended AI. The Na:K ratio exceeded the recommended level of 1 and the average intake of vegetables was 2 serves/day below the recommended 2.5 serves/day and only 20% of recommended intake. An increase in vegetable consumption in pre-school children is recommended to increase dietary potassium and has the potential to decrease the Na:K ratio which is likely to have long-term health benefits.