Effectiveness of Amlodipine in the Control of 24-Hour Blood Pressure in Mild-to-Moderate Essential Hypertension: A Prospective, Multicenter, Observational Real-World Study from India.

Background Calcium-channel blockers (CCB) are a mainstay in the management of hypertension (HTN), and amlodipine is the preferred CCB due to its longer half-life and better safety. Patients and methods This practice-based, observational, real-world evidence study assessed the 24-hour ambulatory blood pressure (ABP) control in mild-to-moderate essential hypertensive patients (treatment naïve receiving amlodipine monotherapy, or as add-on therapy) in inadequately controlled blood pressure (BP goal not met after one month of existing therapy). One hundred four (62M/42F) patients between 18 and 65 years of age who received amlodipine 5/10 mg/day for >8 weeks were included after obtaining informed written consent. The primary outcome was a change from baseline in the mean 24-h SBP and DBP on ABP monitoring at eight (±1) weeks. Secondary outcomes were different from baseline in the mean morning, day-time, night-time, and last six-hour dosing interval period. Other outcomes assessed BP variability (dippers and non-dippers), and responder rates based on ABP monitoring and in-clinic trough cuff measurements. Safety outcomes included adverse effects reported, electrocardiogram, and laboratory abnormalities (hepatic and renal function). Changes in BP parameters in different sub-groups (age, gender, BMI, physical activity, occupation, duration of hypertension, the total daily dose of amlodipine, type of amlodipine therapy, and hypertension severity at baseline) were estimated. Results Of the 104 patients, 49 patients (completed eight weeks) were included in the per-protocol (PP) data for efficacy analysis. Safety analysis was done on the intent-to-treat (ITT) dataset. Significant reductions (p<0.0001) from baseline in all BP measurements on ABPM were observed at the end of eight weeks. Similar improvements were observed in office BP recordings. There was a marginal but non-significant (p>0.05) increase in the proportion of dippers and extreme dippers with amlodipine at the end of the eight-week treatment period. Conclusions Amlodipine 5/10 mg/day therapy used as monotherapy or adjuvant therapy provided significant reductions in both office BP and ambulatory BP over eight weeks.

Stereoselective Synthesis of the C1-C16 Fragment of the Purported Structure of Formosalide B.

The first stereoselective synthesis of the C1-C16 fragment possessing stereo-enriched fully substituted tetrahydropyran (THP) along with tetrahydrofuran (THF) rings of the proposed structure of formosalide B is described in 12 longest linear steps with 22% overall yield, starting from two cheap and commercially available 1,5-pentanediol and l-glutamic acid, following a convergent approach. The key steps involve in this synthesis are Horner-Wadsworth-Emmons reaction, Sharpless asymmetric dihydroxylation, and acid-mediated ketalization to assemble the substituted THP ring, one-pot Sharpless dihydroxylation-SN2-type cyclization, and Wittig homologation to construct the THF derivative.

Appropriate use of PCSK9 Inhibitors in India.

The burden of atherosclerotic cardiovascular (CV) disease is alarmingly high and increasing in our country. Dyslipidemia is one of the major modifiable risk factors, and INTERHEART study showed that dyslipidemia had the highest population attributable risk for myocardial infarction. In the management of dyslipidemia, low-density lipoprotein cholesterol (LDL-C) is the primary therapeutic target. In addition to therapeutic lifestyle changes, statins and ezetimibe effectively lower LDL-C and consequently improve CV outcomes. However, there are situations where these drugs fall short of achieving the target or they may not be well tolerated.

Synthesis and anticancer activity evaluation of novel azacalix[2]arene[2]pyrimidines.

A series of novel azacalix[2]arene[2]pyrimidines were synthesized, and evaluated for their antiproliferative activities against A549, MCF7, SH-SY5Y and CNE human cancer cell lines in vitro by using the CCK-8 assay. A number of compounds showed low micromolar antiproliferative activities against MCF7 cell line. Compound 4j, containing a pyrrolidine moiety, exhibited the strongest inhibitory activity with an IC50 value of 0.58 µM. Furthermore, breast cancer cells were used to explore the inhibition mechanism of these azacalix[2]arene[2]pyrimidines. The results suggested these compounds were involved in inducing cell apoptosis via up-regulation of caspase-3 and caspase-9 protein expression, and the cell cycle was arrested at the S phase. Our reports here represent the first studies on the biological activities of azacalix[2]arene[2]pyrimidines.