Cross-sectional relations of urinary sodium excretion to cardiac structure and hypertrophy. The Framingham Heart Study

BACKGROUND: Increased sodium intake has been positively associated with high blood pressure (BP) and hypertensive target organ damage, but associations with cardiac structure in nonhypertensive individuals have yielded inconsistent results. We tested the hypothesis that sodium intake is associated with left ventricular (LV) mass and left ventricular hypertrophy (LVH), independent of BP, in the community. METHODS: We analyzed the cross-sectional relationships between urinary sodium excretion and LV measurements in a community-based sample of 2660 Framingham Offspring Study participants (mean age 58 years, 56% women and 44% men). Participants with known coronary artery disease, congestive heart failure, or renal failure as well as those using diuretics were excluded. Urinary sodium excretion was measured on a spot urine sample and was indexed to urinary creatinine. RESULTS: In sex-specific, multivariable linear regression models adjusting for covariates known to influence LV measurements, log urinary sodium was not associated with LV mass, wall thickness, end-diastolic dimensions, or left atrial size in either sex. Urinary sodium was not related to LVH defined as LV mass >/= sex-specific 80th percentile value. In analyses restricted to hypertensive individuals (n = 983, 470 women), urinary sodium was not associated with LV mass or LVH. CONCLUSIONS: In our large community-based sample, urinary sodium excretion was not related to LV mass, function, or hypertrophy.     

Safety and potential cost savings of same-setting electrophysiologic testing and placement of transvenous implantable cardioverter-defibrillators

BACKGROUND: Separately, electrophysiologic study (EPS) and placement of a transvenous implantable cardioverter-defibrillator (ICD) can be performed safely in the majority of patients. The safety and potential cost savings of same-setting procedures have not been evaluated. HYPOTHESIS: Electrophysiologic study and placement of transvenous ICDs can be performed safely in the same setting at reduced cost. METHODS: In all. 160 (mean age 65 +/- 10 years, 75% men) and 41 (mean age 66 +/- 11 years, 73% men) consecutive patients who underwent same- versus separate-setting procedures, respectively, were prospectively evaluated. RESULTS: The two groups had similar clinical characteristics and indications for EPS and ICD therapy. Complications occurred in eight patients (5.0%, 95% confidence interval [CI] 2.3-10.3) who had same-setting procedures (one hypotension during ICD testing, one pocket hematoma, two lead dislodgments, two pneumothoraces, one stroke, and one infection) and in two (4.9%, CI 0.60-16.5) who had separate-setting procedures (one pocket hematoma and one infection). There were no procedure-related deaths or long-term ICD-related complications in either group. The mean time from ICD implantation to hospital discharge was similar in the two groups (2.5 +/- 2.4 vs. 2.7 +/- 2.2 days, p = NS). The combined procedure cost was higher in patients who had separate-setting procedures ($12,403 +/- 1,386 vs. $10,242 +/- 2.256, p = < 0.001). who incurred an additional hospital cost of $2,121 +/- $2,125 for the waiting period (1.7 +/- 1.6 days) between EPS and ICD implantation. CONCLUSIONS: In patients deemed candidates for ICD therapy based on EPS results, placement of transvenous defibrillators in the same setting as EPS is as safe as separate-setting procedures and, if adopted, could further reduce the cost of providing ICD therapy.     

Ulcerogenicity devoid novel non-steroidal anti-inflammatory agents (NSAIDS): syntheses,computational studies,and activity of 5-aryliden-2-imino-4-thiazolidinones

A series of new 5-aryliden-2-imino-4-thiazolidinones (5a–e and 6a–e) were synthesized via a three-step reaction and characterized by physicochemical and spectral data. The uniqueness of the derivatives lies in the fact that none of them had an acidic group, like conventional NSAIDS, but exhibited significant in vivo activity in acute inflammation models. In particular, 5-(3-chlorobenzyliden)-2-(pyridin-2-yl-imino)-4-thiazolidinone(5a) and 5-(3-chlorobenzyliden)-2-(5-methylisoxazol-3-yl-imino)-4-thiazolidinone (6a) showed remarkable paw oedema inhibition (67.76 and 74.47 % oedema inhibition, respectively, after 3 h) comparable to that of Ibuprofen (74.56 % oedema inhibition, after 3 h) at half of the dose of the standard drug. Also, compounds 5a (72.86 %) and 6a (80.20 %) were found to possess significant inhibition of albumin denaturation when screened for in vitro anti-inflammatory activity. In addition, these compounds were docked into the known active site of COX-2 protein using Glide XP and QPLD algorithms, and the binding-free energy was calculated using Prime MM/GBSA simulation methods. The combined use of molecular docking and MM/GBSA methods gave a good correlation between the predicted binding-free energy and experimentally determined biological activities. It was also evident from the docking results that 2-methylisoxazolylimino or 2-(pyridin-2-yl-imino substitution and 3-chloro moiety on 5-benzylidin nucleus of these 4-thiazolidinone derivatives can easily occupy the COX-2 binding pocket, considered as the critical interaction for COX-2 inhibition. Moreover, pharmacokinetic properties of all the synthesized compounds were predicted, with good results. Further, the synthesized derivatives showed neither acute toxicity nor symptoms of gastric ulceration, at extended doses, owing to the absence of an acidic group.     

Nasal in-situ gels for delivery of rasagiline mesylate: improvement in bioavailability and brain localization

Abstract

Intranasal thermosensitive gel for rasagiline mesylate (RM) was developed for effective treatment of Parkinson’s disease. Intranasal gels were prepared by combination of poloxamer 407 and poloxamer 188 (1:1) with mucoadhesive polymers (carbopol 934?P and chitosan). The formulations were evaluated for sol–gel transition temperature, in-vitro drug release and in-vivo mucociliary transit time. Further, optimal intranasal gel formulations were tested for in-vivo pharmacokinetic behavior, nasal toxicity studies and brain uptake studies. It was found that optimal formulations had acceptable gelation temperature (28–33?°C) and adequate in-vitro drug release profile. Pharmacokinetic study in rabbits showed significant (p?<?0.05) improvement in bioavailability (four- to six-folds) of the drug from intranasal gels than oral solution. Chronic exposure studies in Wistar rats showed that these intranasal gels were non-irritant and non-toxic to rat nasal mucosa. Estimation of RM in rat brain tissue showed significant (p?<?0.01) improvement in uptake of RM form intranasal gel formulations than nasal solution.