Search

What is known and objective Patients' poor adherence to medications is reported to be related to the individual patients' beliefs and cognitions and their trust of the medical staff. However, the causes of the two forms of non-adherence, intentional and unintentional behaviours, have yet to be clarified. This study compared psychological latent factors associated with intentional and unintentional non-adherence to chronic medication regimens, focusing on the potential effects of (i) patients' dissatisfaction with treatment and their relationships with the medical staff and (ii) patients' subliminal rational thinking processes, which weighed the positive values such as their expectations of benefits from treatment against negative values such as their dissatisfaction. Methods Two cross-sectional surveys were undertaken of patients given medications for chronic diseases, using a questionnaire developed and validated in this study. One survey was undertaken in three hospitals and the other survey, online throughout Japan. We scored the individual latent factors using the questionnaire and calculated the differential score between two negatively correlated latent factors to quantify patients' subliminal rational thinking process. We compared the adjusted odds ratio ( OR) of latent factors between intentional and unintentional non-adherence to medication in both surveys. Results and discussion Of the eligible subjects, 149 hospitalized patients and 524 survey participants completed the questionnaire. Intentional non-adherence was associated with patient dissatisfaction with treatment including interpersonal relationships with medical staff in both hospitalized patients and online survey participants (95% confidence interval of adjusted OR for Dissatisfaction, 1·20-16·26 in the hospital-based survey and 1·33-3·45 in the online survey). In both surveys, intentional non-adherence was significantly associated with the differential score between two negatively correlated latent factors, Willingness and Dissatisfaction ( P = 0·02 in the hospital-based survey and P < 0·001 in the online survey). However, these associations were not evident in unintentionally non-adherent patients. What is new and conclusions Patients' dissatisfaction and their resulting rational judgments are unique, consistent determinants of intentional non-adherence to medications, but not of unintentional non-adherence. [ABSTRACT FROM AUTHOR]

We have shown previously that mice lacking the adenosine A2A receptor (A2AR) generated on a CD1 background self-administer more ethanol and exhibit hyposensitivity to acute ethanol. We aimed to investigate if the increased propensity of A2A−/− mice to consume ethanol is associated with an altered sensitivity in the motivational properties of ethanol in the conditioned place preference (CPP) and conditioned taste aversion (CTA) paradigms and with an altered development of sensitization to the locomotor effects of ethanol. We also tested their sensitivity to the anxiolytic effects of ethanol. Our results show that A2A−/− mice produced on a CD1 background displayed a reduced ethanol-induced CPP and an increased sensitivity to the anxiolytic and locomotor-stimulant effects of ethanol, but they did not show alteration in ethanol-induced CTA and locomotor sensitization. Ethanol-induced CPP, ethanol consumption and the locomotor effects of ethanol were also tested in A2A−/− mice produced on a C57BL/6J background. Our results emphasized the importance of the genetic background because alteration in ethanol consumption and preference, ethanol-induced CPP and locomotor-stimulant effects were not found in knockout mice produced on the alcohol-preferring C57BL/6J genetic background. Finally, the A2AR agonist, 2-p-(2-carboxyethyl)-phenylethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680), reduced ethanol consumption and preference in C57BL/6J mice. In conclusion, A2AR deficiency in mice generated on a CD1 background leads to high ethanol consumption that is associated with an increased sensitivity to the locomotor-stimulant/anxiolytic effects of ethanol and a decrease in ethanol-induced CPP. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study investigated whether genetic polymorphisms in the tumor necrosis factor alpha (TNFalpha) gene's promoter region play a role in severe acute alcoholic hepatitis (AAH). METHODS: One-hundred and fifty patients (58 AAH patients, 45 cirrhosis group free-AAH, 47 healthy group) were genotyped for 3 TNFalpha polymorphisms (-238, -308, -863) using a polymerase chain reaction-restriction fragment length polymorphism technique. Serum TNFalpha levels were determined. RESULTS: The TNFalpha-308 allele A frequency was significantly lower in AAH group (0.09), than cirrhosis (0.28) (p < 0.001), and healthy groups (p < 0.001). The TNFalpha-308 A/G, A/A genotypes were significantly lower in AAH group, than cirrhosis (p = 0.005), and healthy groups (p < 0.001). For AAH group, there were no clinical, biological, and serum TNFalpha differences between the -308 G/G and A/G, A/A genotype patients, apart higher transaminase in the former group (p = 0.02). AAH and cirrhosis groups did not differ for the frequency of TNFalpha-238, -863 polymorphisms. The specific genotype did not appear to have any influence on the therapeutic response following corticotherapy or posttreatment 6-month survival. In the AAH group, nonsurvivors had higher TNFalpha levels than survivors (7.9 +/- 8.8 vs. 3.3 +/- 1.6 pg/ml, p = 0.01). CONCLUSIONS: These results attest to the involvement of TNFalpha-related genetic factors in susceptibility to AAH. [ABSTRACT FROM AUTHOR]

It has previously been reported that ischemia and reperfusion of the heart cause accumulation of lyophosphatidylcholine (LPC) within the myocardium. While it is known that LPC causes the transient increase of intracellular free Ca2+ concentration ([Ca2+]i) during contraction of cardiac cells, little is known about the mechanism for decreasing [Ca2+]i in cardiomyocytes during LPC accumulation. Since cumulative elevation in [Ca2+]i leads to irreversible injury to cardiomyocytes, elevated [Ca2+]i must be restored to an unstimulated level to maintain cell functions. In the present study, we therefore examined the effect of LPC on Ca2+ efflux from freshly isolated adult rat cardiomyocytes. LPC stimulated the efflux of 45Ca2+ from the cells in a concentration dependent manner (10–7 M – 10–5 M). Other lysophospholipids, which are generated from phopholipids of the cell membrane, failed to induce 45Ca2+ efflux from the cells. Dilazep and K 7259, which are known to inhibit the increase in [Ca2+]i caused by LPC, likewise reduced 45Ca2+ efflux caused by LPC addition. Furthermore, the LPC stimulated 45Ca2+ efflux was not affected by removal of extracellular Ca2+, but was dependent on the presence of extracellular Na+. On the other hand, inhibitors of Na+/Ca2+ exchange, amiloride and 5 (N,N dimethyl) amiloride, inhibited LPC induced 45Ca2+ efflux. These results suggest that LPC stimulates extracellular Na+ dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through Na+/Ca2+ exchange on the plasma membrane of cells. [ABSTRACT FROM AUTHOR]