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INDUSTRY NEWS
University of Ottawa Heart Institute Creates New Pfizer Chair in Hypertension Research $2.4 million partnership to support innovative research into a condition that affects approximately five million Canadians The University of Ottawa Heart Institute announced last month the creation of the Pfizer Chair in Hypertension Research.
The five-year agreement will advance the work of the Institute’s Hypertension Research Group in new and unexplored areas,such as brain function. The first recipient is Dr Frans Leenen, Director of the Hypertension Unit at the Ottawa Heart Institute.
The Heart Institute Foundation and Pfizer Canada will each invest $1 million, and the Canadian Institutes of Health Researchwill contribute $400,000. The total partnership will amount to $2.4 million in support of hypertension research.
The University of Ottawa Heart Institute is a global leader in the fight against heart disease. The Hypertension Research Group at the Heart Institute explores the brain’s role in hypertension. By assessing the impact of salt on brain function, theresearch team is able to target specific areas affecting the nervous system, and therefore, blood pressure. The researchersbelieve that a better understanding of these brain mechanisms will help explain genetic links to hypertension and may leadto more effective preventative measures and new therapies.
Abstracts #450, #625, #704, #827 and #832 were printed incorrectly in the Can J Cardiol 2003;19(Suppl A):140A,192A,215A,252A,253A. The authors have been corrected for these abstracts, which are reprinted below.
usefulness of B-type Natriuretic Peptide (BNP) in the management of DEPENDENCE OF THE ISCHEMIA-REPERFUSION
CHF patients. Though BNP was found to be supplemental in diagnosing INDUCED CHANGES IN CARDIAC FUNCTION UPON
CHF in an emergency setting, its role in an inpatient population is not ful- CORONARY ENDOTHELIUM
ly understood. Since its introduction, BNP continues to be used or per- D Prajapati, NS Dhalla, PK Chohan
haps overused in the management of CHF. The aim of this study was to Winnipeg, Manitoba
evaluate and compare the clinical and economic benefit of BNP determi-nation in the management of heart failure in a community setting.
BACKGROUND: Although ischemia-reperfusion (I/R) of the isolated
METHODS: In this retrospective study we compared and analyzed the
heart is known to depress cardiac performance, the mechanisms are not length of stay (LOS), therapeutic differences and investigational fully understood. In order to gain some information whether the approach in the management of CHF in two groups of inpatients admit- magnitude of I/R injury to the heart depends upon endothelial integrity, ted with a primary diagnosis of CHF. Group I (n=191, mean age 65.5 ± we compared the effects of I/R on changes in cardiac performance by 16.1, Male 89 and Females 102) included patients in whom BNP levels perfusing the hearts either at constant flow or constant pressure.
were not tested, while Group II (n=171, mean age 66.2 ± 15.6, Male 94, METHODS: Isolated rat hearts were either perfused at a constant flow
Female 77) included those patients in whom BNP levels were tested.
(10 ml/min) or at constant pressure (80 mm Hg). Hearts were subjected Both groups were matched for age, comorbidities and New York Heart to global ischemia followed by reperfusion for 60 min at either constant Association class (NYHA class III &IV). flow or constant pressure and the contractile parameters were recorded.
RESULTS: There were no significant difference in the LOS (4.71±6 and
RESULTS: In hearts perfused at constant flow after 15 and 30 min of
4.39±5 days: p= 0.397) and no significant difference in the medications ischemia, the recovery of contractile function was 70 and 25% of the con- (p=0.41) and investigations ordered (p=0.36) between the two groups. A trol, respectively. On the other hand, in hearts perfused at constant total of 190 BNP determinations were made in group II which consisted pressure after 30 and 60 min ischemia, the recovery of contractile func- of 171 patients with a mean LOS of 4.39 days. tion was 75 and 30%, respectively. The recovery of constant flow hearts CONCLUSION: The results indicate that BNP measurement did not
by reperfusion after 30 min ischemia was improved by 3 mM L-arginine, a influence the management of CHF patients with regards to the investiga- precursor of NO, whereas that of constant pressure hearts after 30 min tions, medications and interventions ordered in an inpatient setting. It ischemia was attenuated by 100 µM L−NAME, an inhibitor of NO also did not influence the length of stay. The lack of clinical benefit from BNP measurement indicates that its utilization is of limited value while CONCLUSIONS: Hearts perfused at constant flow are more sensitive to
managing CHF in an inpatient setting and undoubtedly increases the cost I/R induced changes in cardiac performance than those perfused at con- stant pressure and these differences appear to be dependent upon the abil- ity of coronary endothelium to generate NO.
DNCCIHR Group in Experimental Cardiology ADRIAMYCIN-INDUCED APOPTOSIS AND
HETERODIMERIC ACTIVATION OF RETINOIC ACID
RECEPTORS
CLINICAL AND ECONOMIC INFLUENCE OF BNP IN THE
I Danelisen, S Thangirala, H Lou, P Singal
MANAGEMENT OF HEART FAILURE
Winnipeg, Manitoba
JC Sebastian, G Kommareddy, SS Jacob, S Jacob, P Yelamanchili,
We have earlier shown that adriamycin-induced congestive heart failure R Borra, M Korman
and cardiac pathology in rats was associated with no significant change in Philadelphia, Pennsylvania
the total retinol (Vitamin A) levels in heart and plasma but 3H retinol BACKGROUND: An aging population and the increasing incidence of
was significantly increased in these tissues. This coincided with a signifi- congestive heart failure (CHF) drives the need for advancements in the cant decrease in the total retinol and retinol palmitate (storage form of management of heart failure. There has been mixed reviews regarding the retinol) levels in the liver. The cardiac pathology was associated with increased apoptosis stimulated by multiple factors. Retinoic acid, a meta- bolic product of retinol, is known to regulate the expression of number of CARDIOVASCULAR PROFILE OF TADALAFIL, A NEW PDE5
genes as well as it influences the process of apoptosis. In the current study INHIBITOR
on isolated adult cardiomyocytes, retinoic acid (1000M-10:M) in low con- G Brock, V Watkins, T Costigan, A Bedding, M Mitchell, J Emmick
centrations decreased apoptosis whereas at high concentration an opposite London, Ontario
effect was seen. Myocytes were also treated with adriamycin (10-40 :M) for PURPOSE: Tadalafil is a selective and potent inhibitor of PDE5, for
4 and 24 hours and protein levels of retinoic acid receptors RAR(∀,∃,() the treatment of men with erectile dysfunction (ED). As the mecha- and RXR (∀,∃,() in whole cell lysates were examined. Adriamycin treat- nism of action of tadalafil and other PDE5 inhibitors involves vascular ment resulted in a significant increase in RAR∀, RAR∃ and RAR( pro- smooth muscle relaxation, there is a potential for effects on the cardio- teins and RXR∃ was significantly decreased. These characteristic changes vascular (CV) system. As previously reported, tadalafil has been shown in the receptor proteins and in the heterodimeric nature of the activation to augment the hypotensive effects of nitrates. This finding is consistent of receptors in response to adriamycin may lead to proapoptotic state. Such with the combined effects of nitrates and tadalafil on the nitric a change in vivo may suggest a role of retinoic acid in adriamycin-induced oxide/cGMP pathway. This report summarizes the overall CV profile of tadalafil based on data from both clinical pharmacology and large-scale Supported by the Heart and Stroke Foundation of Manitoba METHODS/RESULTS: Administration of 20 mg tadalafil in healthy
subjects resulted in no significant difference, compared to placebo, in
standing systolic and diastolic blood pressure (mean maximal decrease of EVALUATION OF TADALAFIL IN MEN WITH ERECTILE
0.2/4.6 mm Hg, respectively), and no change in heart rate. The incidence DYSFUNCTION (ED) TAKING SINGLE OR MULTIPLE
rate of myocardial infarction in tadalafil-treated patients across all clinical CONCOMITANT ANTIHYPERTENSIVES
studies (n > 4000) was 0.39 per 100 patient-years, vs 1.1 in placebo-treatedpatients (n > 1200) vs the prior published rate of 0.6 in age-standardized G Brock, RW Lewis, J Denne, T Costigan, S Chang, JT Emmick
men (Sadovsky et al, Int J Clin Pract 2001;55:115-28). The phase 3 clini- London, Ontario
cal trials of tadalafil included patients with a wide variety of stable CV PURPOSE: ED and hypertension often coexist. We analyzed the efficacy
conditions, including patients taking multiple antihypertensive agents.
and safety of tadalafil in men with ED taking single or multiple antihyper- The table shows the incidence of CV adverse events (AEs) in phase 3 clin- ical trials involving 949 tadalafil-treated and 379 placebo-treated patients.
METHODS: Tadalafil doses of 10 mg and 20 mg and placebo (not all
Overall, the incidence of CV AEs was low and tadalafil was not associated treatments included in all studies) were evaluated in 7 randomized, with a significant increase in these AEs, compared to placebo.
double-blind, placebo-controlled, phase 3 studies. For this integrated Hypotension was reported in 1 placebo-treated patient compared to no analysis, patients were categorized by concomitant use of aHT as follows: 1) no aHT; 2) single aHT; or 3) multiple (≥ 2) aHT. Efficacy was assessed CONCLUSION: Tadalafil treatment has little effect on systemic arterial
by International Index of Erectile Function (IIEF) EF domain score and pressure and has not been associated with an increased incidence of CV percentage “yes” responses to Sexual Encounter Profile (SEP) diary ques- tions 2 and 3 (SEP data not shown). Safety was assessed by incidence oftreatment-emergent adverse events (AE) and potentially clinically signifi- CV AEs in Phase 3 Clinical Trialsa
cant changes in blood pressure (BP).
RESULTS: One thousand two hundred eighty-nine men with ED were
Tadalafil
(none statistically
randomized to placebo or tadalafil 10 mg or 20 mg. Tadalafil 10 mg and significant)
20 mg significantly improved EF vs placebo on all efficacy variables regard-less of aHT use. The incidences of commonly reported (≥ 5%) AE and car- diovascular AE were not increased in tadalafil-treated patients taking single and multiple aHT compared to tadalafil-treated patients not taking aHT. The incidence of potentially clinically significant changes in BP for patients taking single and multiple aHT was not increased in those treated a All treatment-emergent CV AEs that occurred in at least 0.5% of patients with tadalafil compared to those treated with placebo.
while on either placebo or tadalafil treatment; b Numbers of events too small DCSupported by an unrestricted educational grant from Eli Lilly Canada Inc.

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