Impact of Antihypertensive Medication Adherence on Blood Pressure Control in Hypertension: The COMFORT Study.

Impact of Antihypertensive Medication Adherence on Blood Pressure Control in Hypertension: The COMFORT Study.

QJM. 2013 May 20;
Matsumura K, Arima H, Tominaga M, Ohtsubo T, Sasaguri T, Fujii K, Fukuhara M, Uezono K, Morinaga Y, Ohta Y, Otonari T, Kawasaki J, Kato I, Tsuchihashi T,

BACKGROUND: It has not been fully elucidated whether antihypertensive medication adherence affects blood pressure control in hypertension cases. AIM: To investigate the association of adherence to antihypertensive-drug regimens and blood pressure control using data from the COMFORT study (Combination Pill of Losartan Potassium and Hydrochlorothiazide for Improvement of Medication Compliance Trial). DESIGN: An observational analysis from a randomized controlled trial. METHODS: A total of 203 hypertensive subjects were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/ hydrochlorothiazide 12.5 mg) or two pills, an angiotensin II receptor blocker and a thiazide diuretic. Medication adherence calculated based on pill counts and blood pressures were evaluated at 1, 3, and 6 months after randomization. RESULTS: The subjects were divided into three groups according to their adherence: i.e. relatively low-adherence (<90%; n=19), moderate-adherence (90-99%; n=71), and high-adherence (100%; n=113) groups. Clinical characteristics of the subjects including blood pressure, sex, randomized treatments, and past medical history did not differ significantly among the three groups. Achieved follow-up blood pressures over the 6-month treatment period, which were adjusted for age, sex, baseline blood pressure, and randomized treatment, were significantly higher in the low-adherence group (135/78 mmHg) compared with the high-adherence (130/74 mmHg; p=0.02/0.02) and the moderate-adherence (128/74 mmHg; p=0.003/0.02) groups. CONCLUSION: Low adherence to an antihypertensive-drug regimen was associated with poor blood pressure control. HubMed – drug


An integrin-binding-defective mutant of insulin-like growth factor-1 (R36E/R37E IGF1) acts as a dominant-negative antagonist of IGF1R and suppresses tumorigenesis, while the mutant still binds to IGF1R.

J Biol Chem. 2013 May 21;
Fujita M, Ieguchi K, Cedano Prieto D, Fong A, Wilkerson C, Chen JQ, Wu M, Lo SH, Cheung AT, Willson MD, Cardiff RD, Borowsky AD, Takada YK, Takada Y

Insulin-like growth factor-1 (IGF1) is a major therapeutic target for cancer. We recently reported that IGF1 directly binds to integrins (?v?3 and ?6?4) and induces ternary complex formation (integrin-IGF1-type I IGF receptor (IGF1R), and that the integrin-binding defective mutant of IGF1 (R36E/R37E) is defective in signaling and ternary complex formation. These findings predict that R36E/R37E competes with wt IGF1 for binding to IGF1R and inhibits IGF signaling. Here we describe that excess R36E/R37E suppressed cell viability increased by wt IGF1 in vitro in non-transformed cells. We studied the effect of R36E/R37E on viability and tumorigenesis in cancer cell lines. We did not detect the effect of wt IGF or R36E/R37E in cancer cells in anchorage-dependence. However, in anchorage-independence wt IGF1 enhanced cell viability and induced signals, while R36E/R37E did not. Notably, excess R36E/R37E suppressed cell viability and signaling induced by wt IGF1 in anchorage-independence. Using cancer cells that stably express wt IGF1 or R36E/R37E, we demonstrate that R36E/R37E suppressed tumorigenesis in vivo, while wt IGF1 markedly enhanced it. R36E/R37E suppressed the binding of wt IGF1 to the cell surface, and the subsequent ternary complex formation induced by wt IGF1. R36E/R37E suppressed activation of IGF1R by insulin. Wt IGF1, not R36E/R37E, induced ternary complex formation of IGF1R/ insulin receptor hybrid receptor. These findings suggest that 1) IGF1 induces signals in anchorage-independent conditions, and 2) R36E/R37E acts as a dominant-negative inhibitor of IGF1R (IGF1 decoy). Our results are consistent with a model in which ternary complex formation is critical for IGF signaling. HubMed – drug


Deprenyl Enhances the Teratogenicity of Hydroxyurea in Organogenesis Stage Mouse Embryos.

Toxicol Sci. 2013 May 21;
Schlisser AE, Hales BF

Hydroxyurea, an antineoplastic drug, is a model teratogen. The administration of hydroxyurea to CD1 mice on gestation day nine induces oxidative stress, increasing the formation of 4-hydroxy-2-nonenal (4-HNE) adducts to redox-sensitive proteins such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the caudal region of the embryo. GAPDH catalytic activity is reduced and its translocation into the nucleus is increased. Since the nuclear translocation of GAPDH is associated with oxidative stress-induced cell death, we hypothesized that this translocation plays a role in mediating the teratogenicity of hydroxyurea. Deprenyl (also known as selegiline), a drug used as a neuroprotectant in Parkinson’s disease, inhibits the nuclear translocation of GAPDH. Hence, timed pregnant CD1 mice were treated with deprenyl (10 mg/kg) on gestation day nine followed by the administration of hydroxyurea (400 or 600 mg/kg). Deprenyl treatment significantly decreased the hydroxyurea- induced nuclear translocation of GAPDH in the caudal lumbosacral somites. Deprenyl enhanced hydroxyurea-mediated caudal malformations, inducing specifically limb reduction, digit anomalies, tail defects and lumbosacral vertebral abnormalities. Deprenyl did not augment the hydroxyurea-induced inhibition of glycolysis or alter the ratio of oxidized to reduced glutathione. However, it did dramatically increase cleaved caspase 3 in embryos. These data suggest that nuclear GAPDH plays an important, region-specific, role in teratogen-exposed embryos. Deprenyl exacerbated the developmental outcome of hydroxyurea exposure by a mechanism that is independent of oxidative stress. While the administration of deprenyl alone did not affect pregnancy outcome, this drug may have adverse consequences when combined with exposures that increase the risk of malformations. HubMed – drug


Fatal poisonings in Finland during the years 2004-2009.

Hum Exp Toxicol. 2013 Jun; 32(6): 600-5
Lapatto-Reiniluoto O, Vuori E, Hoppu K, Ojanperä I

Fatal alcohol and drug poisonings in Finland during the years 2004-2009 were studied. Cases were divided into those that occurred outside the hospitals (the majority of cases) and those that occurred within the hospitals (the minority of cases). Differences and similarities between the two groups were analysed. The postmortem toxicological investigation of all sudden and unexpected deaths in Finland is centralised at the Department of Forensic Medicine, University of Helsinki. We examined each fatal poisoning separately and verified the cause and place of death as well as the age and sex of the deceased. Fatal poisonings, including suicides, have remained unchanged for many years from the same high level, that is, about 1200 cases annually (22/100,000 inhabitants). The number of patients dying in hospitals due to poisoning has also remained stable (55-70 patients/year). However, the toxic agents involved in such poisonings have changed and deaths due to opioids are now being more numerous. The number of fatal unintentional drug poisonings rose significantly from 191 to 341 (3-6/100,000 inhabitants, p < 0.001) during the study years, and the difference between poisonings caused by drugs or alcohol also changed significantly (p < 0.001). Diminishing substantially, the number of all fatal poisonings will be challenging because of the high percentage of suicides. However, a reduction in unintentional drug overdoses, which are presently on the rise, should be possible. HubMed – drug



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