Efficacy and tolerability of lercanidipine in mild to moderate hypertension among Asians of different ethnic groups.

Introduction: Calcium channel blockers are well established modalities for the treatment of hypertension. However, in spite of the availability of many efficacious agents, hypertension control continues to be poor. One reason is poor tolerability due to adverse events. Racial differences also exist. Lercanidipine, a third-generation calcium channel blocker, is associated with better tolerability. However, it has not been studied in the Asian population. This study examines its efficacy and tolerability in Asian subjects of different ethnicities. Methods: This was an eight-week open label study of adults with mild to moderate hypertension. Blood pressure (BP), pulse rate, self-administered symptom check and laboratory evaluations were done at baseline. Patients were prescribed 10 mg lercanidipine, with up-titration to 20 mg if BP was not controlled at Week 4. Baseline evaluations were repeated at Week 8. Adverse events were also enumerated. Results: 27 patients (mean age 53.4 +/- 12.1 years) completed the study. The baseline systolic BP (SBP), diastolic BP (DBP) and heart rate was 159 +/- 12.2, 96.6 +/- 7.7 mmHg and 71 +/- 13/min, respectively. Three racial groups were represented. SBP and DBP decreased significantly after four weeks of therapy. A further reduction to 139 +/- 14.3 and 88 +/- 9.8 (p-value is less than 0.0001) was seen in Week 8. The absolute SBP and DBP reduction was 20.5 mmHg (95 percent confidence interval [CI] 16.5-24.5, p-value is less than 0.0001) and 9.3 mmHg (95 percent CI 6.2-12.5, p-value is less than 0.0001), respectively. All adverse symptoms, except for palpitations, were reduced at the end of the study. Conclusion: Lercanidipine is efficacious and well tolerated in Asians of different ethnicities. Its BP lowering effects and tolerability in Asians appear to be similar to other studies on Caucasians and other calcium channel blockers

Efficacy and tolerability of lercanidipine in mild to moderate hypertension among Asians of different ethnic groups

Introduction: Calcium channel blockers are well established modalities for the treatment of hypertension. However, in spite of the availability of many efficacious agents, hypertension control continues to be poor. One reason is poor tolerability due to adverse events. Racial differences also exist. Lercanidipine, a third-generation calcium channel blocker, is associated with better tolerability. However, it has not been studied in the Asian population. This study examines its efficacy and tolerability in Asian subjects of different ethnicities. Methods: This was an eight-week open label study of adults with mild to moderate hypertension. Blood pressure (BP), pulse rate, self-administered symptom check and laboratory evaluations were done at baseline. Patients were prescribed 10 mg lercanidipine, with up-titration to 20 mg if BP was not controlled at Week 4. Baseline evaluations were repeated at Week 8. Adverse events were also enumerated. Results: 27 patients (mean age 53.4 +/- 12.1 years) completed the study. The baseline systolic BP (SBP), diastolic BP (DBP) and heart rate was 159 +/- 12.2, 96.6 +/- 7.7 mmHg and 71 +/- 13/min, respectively. Three racial groups were represented. SBP and DBP decreased significantly after four weeks of therapy. A further reduction to 139 +/- 14.3 and 88 +/- 9.8 (p-value is less than 0.0001) was seen in Week 8. The absolute SBP and DBP reduction was 20.5 mmHg (95 percent confidence interval CI 16.5-24.5, p-value is less than 0.0001) and 9.3 mmHg (95 percent CI 6.2-12.5, p-value is less than 0.0001), respectively. All adverse symptoms, except for palpitations, were reduced at the end of the study. Conclusion: Lercanidipine is efficacious and well tolerated in Asians of different ethnicities. Its BP lowering effects and tolerability in Asians appear to be similar to other studies on Caucasians and other calcium channel blockers

Board level drop test reliability of IC packages

Proceedings - Electronic Components and Technology Conference1630-636PECC

SAR by kinetics for drug discovery in protein misfolding diseases

To develop effective therapeutic strategies for protein misfolding diseases, a promising route is to identify compounds that inhibit the formation of protein oligomers. To achieve this goal, we report a structure.activity relationship (SAR) approach based on chemical kinetics to estimate quantitatively how small molecules modify the reactive flux toward oligomers. We use this estimate to derive chemical rules in the case of the amyloid beta peptide (Aβ), which we then exploit to optimize starting compounds to curtail Aâ oligomer formation. We demonstrate this approach by converting an inactive rhodanine compound into an effective inhibitor of Aβ oligomer formation by generating chemical derivatives in a systematic manner. These results provide an initial demonstration of the potential of drug discovery strategies based on targeting directly the production of protein oligomers

CHARMM-GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides

A complex cell envelope, composed of a mixture of lipid types including lipopolysaccharides, protects bacteria from the external environment. Clearly, the proteins embedded within the various components of the cell envelope have an intricate relationship with their local environment. Therefore, to obtain meaningful results, molecular simulations need to mimic as far as possible this chemically heterogeneous system. However, setting up such systems for computational studies is far from trivial, and consequently the vast majority of simulations of outer membrane proteins still rely on oversimplified phospholipid membrane models. This work presents an update of CHARMM-GUI Martini Maker for coarse-grained modeling and simulation of complex bacterial membranes with lipopolysaccharides. The qualities of the outer membrane systems generated by Martini Maker are validated by simulating them in bilayer, vesicle, nanodisc, and micelle environments (with and without outer membrane proteins) using the Martini force field. We expect this new feature in Martini Maker to be a useful tool for modeling large, complicated bacterial outer membrane systems in a user-friendly manner