Canine and Feline Diabetes Mellitus: Nature or Nurture?

There is evidence for the role of genetic and environmental factors in feline and canine diabetes. Type 2 diabetes is the most common form of diabetes in cats. Evidence for genetic factors in feline diabetes includes the overrepresentation of Burmese cats with diabetes. Environmental risk factors in domestic or Burmese cats include advancing age, obesity, male gender, neutering, drug treatment, physical inactivity, and indoor confinement. High-carbohydrate diets increase blood glucose and insulin levels and may predispose cats to obesity and diabetes. Low-carbohydrate, high-protein diets may help prevent diabetes in cats at risk such as obese cats or lean cats with underlying low insulin sensitivity. Evidence exists for a genetic basis and altered immune response in the pathogenesis of canine diabetes. Seasonal effects on the incidence of diagnosis indicate that there are environmental influences on disease progression. At least 50% of diabetic dogs have type 1 diabetes based on present evidence of immune destruction of P-cells. Epidemiological factors closely match those of the latent autoimmune diabetes of adults form of human type 1 diabetes. Extensive pancreatic damage, likely from chronic pancreatitis, causes similar to28% of canine diabetes cases. Environmental factors such as feeding of high-fat diets are potentially associated with pancreatitis and likely play a role in the development of pancreatitis in diabetic dogs. There are no published data showing that overt type 2 diabetes occurs in dogs or that obesity is a risk factor for canine diabetes. Diabetes diagnosed in a bitch during either pregnancy or diestrus is comparable to human gestational diabetes.

Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK

Objective: To evaluate the cost of atrial fibrillation (AF) to health and social services in the UK in 1995 and, based on epidemiological trends, to project this estimate to 2000. Design, setting, and main outcome measures: Contemporary estimates of health care activity related to AF were applied to the whole population of the UK on an age and sex specific basis for the year 1995. The activities considered ( and costs calculated) were hospital admissions, outpatient consultations, general practice consultations, and drug treatment ( including the cost of monitoring anticoagulant treatment). By adjusting for the progressive aging of the British population and related increases in hospital admissions, the cost of AF was also projected to the year 2000. Results: There were 534 000 people with AF in the UK during 1995. The direct'' cost of health care for these patients was pound 244 million (similar toE350 million) or 0.62% of total National Health Service ( NHS) expenditure. Hospitalisations and drug prescriptions accounted for 50% and 20% of this expenditure, respectively. Long term nursing home care after hospital admission cost an additional pound46.4 million (similar toE66 million). The direct cost of AF rose to pound459 million (similar toE655 million) in 2000, equivalent to 0.97% of total NHS expenditure based on 1995 figures. Nursing home costs rose to pound111 million (similar toE160 million). Conclusions: AF is an extremely costly public health problem.

Ventilatory responses of healthy subjects to intravenous combinations of morphine and oxycodone under imposed hypercapnic and hypoxaemic conditions

Aims Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. Methods A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1 : 2, 1 : 1, 2 : 1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography-MS/MS. Results 'Placebo' treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PETCO2 = 55 mmHg (V-E55) decreased to 74% of the subjects' before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. Conclusions Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management.

Voltage-dependent inhibition of recombinant NMDA receptor-mediated currents by 5-hydroxytryptamine

1 The effect of 5-HT and related indolealkylamines on heteromeric recombinant NMDA receptors expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp recording technique. 2 In the absence of external Mg2+ ions, 5-HT inhibited NMDA receptor-mediated currents in a concentration-dependent manner. The inhibitory effect of 5-HT was independent of the NR1a and NR2 subunit combination. 3 The inhibition of glutamate-evoked currents by 5-HT was use- and voltage-dependent. The voltage sensitivity of inhibition for NR1a+NR2 subunit combinations by 5-HT was similar, exhibiting an e-fold change per similar to20 mV, indicating that 5-HT binds to a site deep within the membrane electric field. 4 The inhibition of the open NMDA receptor by external Mg2+ and 5-HT was not additive, suggesting competition between Mg2+ and 5-HT for a binding site in the NMDA receptor channel. The concentration-dependence curves for 5-HT and 5-methoxytryptamine (5-MeOT) inhibition of NMDA receptor-mediated currents are shifted to the right in the presence of external Mg2+. 5 The related indolealkylamines inhibited glutamate-evoked currents with the following order of inhibitory potency: 5-MeOT = 5-methyltryptamine > tryptamine > 7-methyltryptamine > 5-HTmuch greater than tryptophan melatonin. 6 Taken together, these data suggest that 5-HT and related compounds can attenuate glutamate-mediated excitatory synaptic responses and may provide a basis for drug treatment of excitoxic neurodegeneration.

Studies on the mode of cytotoxicity of imidazotetraziones

The irnidazotetrazinones are a novel group of anti tumour agents which have demonstrated good activity against a range of murine tumours and human xenografts. They possess a structure activity relationship similar to the anti tumour triazenes, with the chloroethyl (mitozolomide) and methyl (temozolomide) analogues being active antitumour agents, whilst the ethyl (CCRG 82019) and higher homologues are inactive. This thesiS attempts to elucidate the biological mechanisms responsible for the strict structure-activity relationship observed amongst the imidazotetrazinones. Mitozolomide is the only agent chemically capable of cross-linking DNA , which has been suggested to be responsible fo r the cytotoxicity of this group of agents. Only mitozolomide and ternozolornide Exhibit a marked ditferential toxicity towards the 0 -alkylguanine-DNA alkyltransferase deficient GM892A (Mer-) cell line rather than the proficient Raji cell line (Mer+). The rate of uptake of imidazotetrazinones into cells is similar for all three agents in both cell lines, and does not explain the differing sensitivities to these agents. The effect of drug treatment on the incorporation of precursors into macromolecules, and their pool sizes, was examined. Temozolomide administration was found to alter de novo protein synthesis in both GM892A and Raji cells. Flow cytometric analysis revealed that temozolomide and CCRG 82019 block cells in late S/G2/M phase of the cell cycle , similar to that observed with mitozolomide. The extent of reaction of all three drugs with isolated macromolecules and cellular macromolecules was determined, and differences found, with cellular repair processes influencing the number of alkyl lesions remaining bound to macromolecules. The specific bases formed in calf thymus DNA after treatment with either temozolornide and CCRG 82019 was measured, and it was found that the types and relative amounts of lesions formed, differed, as well as the total level of alkylation. Whereas DNA extracted from imidazotetrazinone treated cells is not affected in its ability to support RNA polymerase activity, an effect is observed on the ability to extract DNA polymerase from drug treated cells. This may suggest that the alkylated DNA must be in intact chromatin for the lesion to manifest its effects. Temozolomide and methyl methanesulphonate do got appear to act with a synergistic mode of action. The 0 -position of guanine is suspected to be a critical site for the action of these types of drugs.

Social aspects of pharmaceutical innovation: heart disease

This study examines the invention, innovation, introduction and use of a new drug therapy for coronary heart disease and hypertension; beta-blockade. The relationships between drug introductions and changes in medical perceptions of disease are analysed, and the development and effects of our perception of heart disease through drug treatments and diagnostic technology is described. The first section looks at the evolution of hypertension from its origin as a kidney disorder, Bright's disease, to the introduction and use of effective drugs for its treatment. It is shown that this has been greatly influenced by the introduction of new medical technologies. A medical controversy over its nature is shown both to be strongly influenced by the use of new drugs, and to influence their subsequent use. The second section reviews the literature analysing drug innovation, and examines the innovation of the beta-blocking drugs, making extensive use of participant accounts. The way in which the development of receptor theory, the theoretical basis of the innovation,was influenced by the innovation and use of drugs is discussed, then the innovation at ICI, the introduction into clinical use, and the production of similar drugs by other manufacturers are described. A study of the effects of these drugs is then undertaken, concentrating on therapeutic costs and benefits, and changes in medical perceptions of disease. The third section analyses the effects of other drugs on heart disease, looking at changes in mortality statistics and in medical opinions. The study concludes that linking work on drug innovation with that on drug effects is fruitful, that new drugs and diagnostic technology have greatly influenced medical perceptions of the nature and extent of heart disease, and that in hypertension, the improvement in drug treatment will soon result in much of the population being defined as in need of it life-long.

Evaluating the evidence for targeting FOXO3a in breast cancer:a systematic review

Background: Tumour cells show greater dependency on glycolysis so providing a sufficient and rapid energy supply for fast growth. In many breast cancers, estrogen, progesterone and epidermal growth factor receptor-positive cells proliferate in response to growth factors and growth factor antagonists are a mainstay of treatment. However, triple negative breast cancer (TNBC) cells lack receptor expression, are frequently more aggressive and are resistant to growth factor inhibition. Downstream of growth factor receptors, signal transduction proceeds via phosphatidylinositol 3-kinase (PI3k), Akt and FOXO3a inhibition, the latter being partly responsible for coordinated increases in glycolysis and apoptosis resistance. FOXO3a may be an attractive therapeutic target for TNBC. Therefore we have undertaken a systematic review of FOXO3a as a target for breast cancer therapeutics. Methods: Articles from NCBI were retrieved systematically when reporting primary data about FOXO3a expression in breast cancer cells after cytotoxic drug treatment. Results: Increased FOXO3a expression is common following cytotoxic drug treatment and is associated with apoptosis and cell cycle arrest. There is some evidence that metabolic enzyme expression is also altered and that this effect is also elicited in TNBC cells. FOXO3a expression serves as a positive prognostic marker, especially in estrogen (ER) receptor positive cells. Discussion: FOXO3a is upregulated by a number of receptor-dependent and -independent anti-cancer drugs and associates with apoptosis. The identification of microRNA that regulate FOXO3a directly suggest that it offers a tangible therapeutic target that merits wider evaluation.

Pharmacogenetics and the print media:what is the public told?

Background: Pharmacogenetics is a rapidly growing field that aims to identify the genes that influence drug response. This science can be used as a powerful tool to tailor drug treatment to the genetic makeup of individuals. The present study explores the coverage of the topic of pharmacogenetics and its potential benefit in personalised medicine by the UK newsprint media. Methods: The LexisNexis database was used to identify and retrieve full text articles from the 10 highest circulation national daily newspapers and their Sunday equivalents in the UK. Content analysis of newspaper articles which referenced pharmacogenetic testing was carried out. A second researcher coded a random sample (21%) of newspaper articles to establish the inter-rater reliability of coding. Results: Of the 256 articles captured by the search terms, 96 articles (with pharmacogenetics as a major component) met the study inclusion criteria. The majority of articles over-stated the benefits of pharmacogenetic testing while paying less attention to the associated risks. Overall beneficial effects were mentioned 5.3 times more frequently than risks (p < 0.001). The most common illnesses for which pharmacogenetically based personalised medicine was discussed were cancer, cardiovascular disease and CNS diseases. Only 13% of newspaper articles that cited a specific scientific study mentioned this link in the article. There was a positive correlation between the size of the article and both the number of benefits and risks stated (P < 0.01). Conclusion: More comprehensive coverage of the area of personalised medicine within the print media is needed to inform public debate on the inclusion of pharmacogentic testing in routine practice.

The PHAR-QA project: competency framework for pharmacy practice—first steps, the results of the European Network Delphi round 1

PHAR-QA, funded by the European Commission, is producing a framework of competences for pharmacy practice. The framework is in line with the EU directive on sectoral professions and takes into account the diversity of the pharmacy profession and the on-going changes in healthcare systems (with an increasingly important role for pharmacists), and in the pharmaceutical industry. PHAR-QA is asking academia, students and practicing pharmacists to rank competences required for practice. The results show that competences in the areas of drug interactions, need for drug treatment and provision of information and service were ranked highest whereas those in the areas of ability to design and conduct research and development and production of medicines were ranked lower. For the latter two categories, industrial pharmacists ranked them higher than did the other five groups

The relative influence of social support, rehabilitation program participation, and inmate preincarceration characteristics on incarcerated substance abusers' perceptions of adjustment to community reintegration

This dissertation identifies, examines, and assesses the relative influence of identified empirically and conceptually relevant variables on incarcerated substance abusers' expectations of postrelease adjustment. A purposive sampling procedure was used to recruit 101 male and female substance-abusing offenders participating in prison- and jail-based drug treatment programs in south Florida. A 92-item survey questionnaire was used to collect basic demographic data; measure inmate preincarceration characteristics, social support, and rehabilitation program participation; and record archival data. Regression equations were developed utilizing ten different measures of the participants' expectations of their postrelease adjustment. Two equations yielded statistically significant F ratios; maintaining a stable living and maintaining abstinence. Twenty-two percent of the variance in respondents' expectations of maintaining a stable living was explained by preincarceration characteristics, social support, and rehabilitation program participation (F = 1.89; df = 13,87; p $<$.05). The only significant predictor variable was perception of social support (b = $-$.05; t = $-$3.6; p $<$.001). Twenty-three percent of the variance in respondents' expectations of maintaining abstinence from substances was explained by preincarceration characteristics, social support, and rehabilitation program participation (F = 2; df = 13,87; p $<$.05). Once again, the only significant predictor variable was perception of social support. The results of the analyses indicate that social support was the only important variable for understanding these respondents' efficacy expectations of postrelease abstinence and stable living. The results of this investigation demonstrate the complexity of the social support variable for prisoners, and identify social support as a potential rehabilitative resource for substance-abusing inmates. The results of this investigation underscore the importance of continued, detailed empirical study in order to understand and clarify how social support, efficacy expectations, and actual postrelease performance interrelate for this population of offenders.

Predictors of client retention in alternative -to -prison substance abuse programs

Increased treatment retention among substance abusing individuals has been associated with reduced drug use, fewer arrests, and decreased unemployment, as well as a reduction in health risk behaviors. This longitudinal study examined the predictors of client retention for alternative to prison substance abuse treatment programs through assessing the roles of motivational factors and the client-worker relationship. The sample was comprised of 141 male felony offenders who were legally mandated to community based long-term residential drug treatment programs. ^ The primary measures used in the study were the consecutive days a participant remained in treatment, Stages of Change Readiness Model and Treatment Eagerness Scale (SOCRATES), the Working Alliance Inventory (WAI), and The Readiness Ruler. Hierarchical multiple regression analysis was conducted for four hypotheses (a) participants who are more motivated to change at the time of entry will remain in treatment longer, (b) participants who have a strong therapeutic alliance will remain in treatment a greater number of consecutive days than participants who have weaker therapeutic alliance, (c) motivation to change, as measured at treatment entry, will be positively related to therapeutic alliance, (d) during the course of treatment variation in motivation to change will be predicted by the therapeutic alliance. ^ Results support the following conclusions: Among clients in alternative-to prison programs the number of days in treatment is positively related to their motivation to change. The therapeutic alliance is not a predictor of the number of days in treatment. Motivation to change, particularly recognition of a drug problem, is positively related to the therapeutic alliance. Changes in motivation to change in response to treatment are positively related to the therapeutic alliance among clients in an alternative to prison substance abuse treatment programs. These results carry forward prior research and have implications for social work practice, research, and social welfare policy. ^

Predictors of client retention in alternative to prison substance abuse programs

Increased treatment retention among substance abusing individuals has been associated with reduced drug use, fewer arrests, and decreased unemployment, as well as a reduction in health risk behaviors. This longitudinal study examined the predictors of client retention for alternative to prison substance abuse treatment programs through assessing the roles of motivational factors and the client-worker relationship. The sample was comprised of 141 male felony offenders who were legally mandated to community based long-term residential drug treatment programs. The primary measures used in the study were the consecutive days a participant remained in treatment, Stages of Change Readiness Model and Treatment Eagerness Scale (SOCRATES), the Working Alliance Inventory (WAI), and The Readiness Ruler. Hierarchical multiple regression analysis was conducted for four hypotheses (a) participants who are more motivated to change at the time of entry will remain in treatment longer, (b) participants who have a strong therapeutic alliance will remain in treatment a greater number of consecutive days than participants who have weaker therapeutic alliance, (c) motivation to change, as measured at treatment entry, will be positively related to therapeutic alliance, (d) during the course of treatment variation in motivation to change will be predicted by the therapeutic alliance. Results support the following conclusions: Among clients in alternative-to prison programs the number of days in treatment is positively related to their motivation to change. The therapeutic alliance is not a predictor of the number of days in treatment. Motivation to change, particularly recognition of a drug problem, is positively related to the therapeutic alliance. Changes in motivation to change in response to treatment are positively related to the therapeutic alliance among clients in an alternative to prison substance abuse treatment programs. These results carry forward prior research and have implications for social work practice, research, and social welfare policy.

Efeito do topiramato sobre o craving em usuários de crack

The study aims to analyze the effects of topiramato on the craving of crack users. It is an open crossover clinical trial involving users from the Psychosocial Care Center for Alcohol and Drugs (CAPSad) in city of Parnamirim, RN, approved by the CEP CAAE: 38710614.1.0000.5537, respecting the norms of the resolution n. 466/2012/CNS. The study produced preliminary two scientific papers: a theoretical essay and an integrative review, as a way of seeking the state of art. The first paper was based in the theoretical framework of Hinds, Chaves and Cypress, which focuses different contexts, from the issues of individual use to the coping policies in Brazil, highlighting that the situation and the complexity of the phenome requires coping strategies for the full attention to the user, family and society. As a result of the integrative review, among the 902 retrieved records, eight of them presented therapeutic schemes with positive effects for the craving of cocaine. They used nine different drugs. It is important to spot out that there was no result for the craving of crack. The data collection was conducted from December 2014 to July 2015 and has as sample predominantly single males. The sample was composed of 30 subjects who met the inclusion criteria: adults, age from 18 years, diagnosis of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for cocaine/crack; cognitive capacity preserved; attendance to the service, participated at least three visits in the 12 months prior to data collection; and accepted to be monitored in the proposed treatment. Data was analyzed using descriptive statistics from the Statistical Package of Support for Social Sciences (SPSS) on the instruments: 1) Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), pointing out, among other results, that only 14% used crack/cocaine weekly during treatment, while 83% used daily or weekly after the washout period; 2) Barratt Impulsiveness Scale, with an average of 80.23 and 77.47 with and without drug treatment, respectively. An analysis from the Student t test show no significant differences in impulsivity with or without the drug; and 3) Cocaine-Craving Questionnaire-Brief (CCK-B), indicating that the number of users with craving intensity level is significantly higher without drug treatment (86%) than with treatment (33%). The analysis between craving and level of impulsivity showed that there is a low correlation (Pearson) between these two variables during treatment and after the washout, demonstrating that impulsivity has low influence on the outcome of drug therapy. As conclusion, it was noted that the topiramate produces positive effect on reducing the craving for crack users and their use is a relevant strategy for efficacy in the treatment of crack users.

Efeito do topiramato sobre o craving em usuários de crack

The study aims to analyze the effects of topiramato on the craving of crack users. It is an open crossover clinical trial involving users from the Psychosocial Care Center for Alcohol and Drugs (CAPSad) in city of Parnamirim, RN, approved by the CEP CAAE: 38710614.1.0000.5537, respecting the norms of the resolution n. 466/2012/CNS. The study produced preliminary two scientific papers: a theoretical essay and an integrative review, as a way of seeking the state of art. The first paper was based in the theoretical framework of Hinds, Chaves and Cypress, which focuses different contexts, from the issues of individual use to the coping policies in Brazil, highlighting that the situation and the complexity of the phenome requires coping strategies for the full attention to the user, family and society. As a result of the integrative review, among the 902 retrieved records, eight of them presented therapeutic schemes with positive effects for the craving of cocaine. They used nine different drugs. It is important to spot out that there was no result for the craving of crack. The data collection was conducted from December 2014 to July 2015 and has as sample predominantly single males. The sample was composed of 30 subjects who met the inclusion criteria: adults, age from 18 years, diagnosis of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for cocaine/crack; cognitive capacity preserved; attendance to the service, participated at least three visits in the 12 months prior to data collection; and accepted to be monitored in the proposed treatment. Data was analyzed using descriptive statistics from the Statistical Package of Support for Social Sciences (SPSS) on the instruments: 1) Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), pointing out, among other results, that only 14% used crack/cocaine weekly during treatment, while 83% used daily or weekly after the washout period; 2) Barratt Impulsiveness Scale, with an average of 80.23 and 77.47 with and without drug treatment, respectively. An analysis from the Student t test show no significant differences in impulsivity with or without the drug; and 3) Cocaine-Craving Questionnaire-Brief (CCK-B), indicating that the number of users with craving intensity level is significantly higher without drug treatment (86%) than with treatment (33%). The analysis between craving and level of impulsivity showed that there is a low correlation (Pearson) between these two variables during treatment and after the washout, demonstrating that impulsivity has low influence on the outcome of drug therapy. As conclusion, it was noted that the topiramate produces positive effect on reducing the craving for crack users and their use is a relevant strategy for efficacy in the treatment of crack users.

Management of adult attention deficit hyperactivity disorder in UK primary care: a survey of general practitioners

Background: Compared to existing literature on childhood attention deficit hyperactivity disorder (ADHD), little published adult data are available, particularly outside of the United States. Using General Practitioner (GP) questionnaires from the United Kingdom, this study aimed to examine a number of issues related to ADHD in adults, across three cohorts of patients, adults who received ADHD drug treatment in childhood/adolescence but stopped prior to adulthood; adults who received ADHD drug treatment in childhood/adolescence and continued treatment into adulthood and adults who started ADHD drug treatment in adulthood.Methods: Patients with a diagnosis of ADHD and prescribed methylphenidate, dexamfetamine or atomoxetine were identified using data from The Health Improvement Network (THIN). Dates when these drugs started and stopped were used to classify patients into the three cohorts. From each cohort, 50 patients were randomly selected and questionnaires were sent via THIN to their GPs.GPs returned completed questionnaires to THIN who forwarded anonymised copies to the researchers. Datasets were analysed using descriptive statistics.Results: Overall response rate was 89% (133/150). GPs stated that in 19 cases, the patient did not meet the criteria of that group; the number of valid questionnaires returned was 114 (76%). The following broad trends were observed: 1) GPs were not aware of the reason for treatment cessation in 43% of cases, 2) patient choice was the most common reason for discontinuation (56%), 3) 7% of patients who stopped pharmacological treatment subsequently reported experiencing ADHD symptoms, 4) 58% of patients who started pharmacological treatment for ADHD in adulthood received pharmacological treatment for other mental health conditions prior to the ADHD being diagnosed.Conclusion: This study presents some key findings relating to ADHD; GPs were often not aware of the reason for patients stopping ADHD treatment in childhood or adolescence. Patient choice was identified as the most common reason for treatment cessation. For patients who started pharmacological treatment in adulthood, many patients received pharmacological treatment for comorbidities before a diagnosis of ADHD was made.