Thoracoscopic management of empyema thoracis.

Appropriate management of empyema thoracis is dependent upon a secure diagnosis of the etiology of empyema and the phase of development. Minimal access surgery using video-assisted thoracoscopy (VATS) is one of many useful techniques in treating empyema. Complex empyema requires adjunctive treatment in addition to VATS.

Drug nanoparticles by antisolvent precipitation: mixing energy versus surfactant stabilization.

Organic itraconazole (ITZ) solutions were mixed with aqueous solutions to precipitate sub-300 nm particles over a wide range of energy dissipation rates, even for drug loadings as high as 86% (ITZ weight/total weight). The small particle sizes were produced with the stabilizer poloxamer 407, which lowered the interfacial tension, increasing the nucleation rate while inhibiting growth by coagulation and condensation. The highest nucleation rates and slowest growth rates were found at temperatures below 20 degrees C and increased with surfactant concentration and Reynolds number (Re). This increase in the time scale for growth reduced the Damkohler number (Da) (mixing time/precipitation time) to low values even for modest mixing energies. As the stabilizer concentration increased, the average particle size decreased and reached a threshold where Da may be considered to be unity. Da was maintained at a low value by compensating for a change in one variable away from optimum conditions (for small particles) by manipulating another variable. This tradeoff in compensation variables was demonstrated for organic flow rate vs Re, Re vs stabilizer concentration, stabilizer feed location (organic phase vs aqueous phase) vs stabilizer concentration, and stabilizer feed location vs Re. A decrease in the nucleation rate with particle density in the aqueous suspension indicated that secondary nucleation was minimal. A fundamental understanding of particle size control in antisolvent precipitation is beneficial for designing mixing systems and surfactant stabilizers for forming nanoparticles of poorly water soluble drugs with the potential for high dissolution rates.

Distinct transcriptional regulation of long-chain acyl-CoA synthetase isoforms and cytosolic thioesterase 1 in the rodent heart by fatty acids and insulin.

The molecular mechanism(s) responsible for channeling long-chain fatty acids (LCFAs) into oxidative versus nonoxidative pathways is (are) poorly understood in the heart. Intracellular LCFAs are converted to long-chain fatty acyl-CoAs (LCFA-CoAs) by a family of long-chain acyl-CoA synthetases (ACSLs). Cytosolic thioesterase 1 (CTE1) hydrolyzes cytosolic LCFA-CoAs to LCFAs, generating a potential futile cycle at the expense of ATP utilization. We hypothesized that ACSL isoforms and CTE1 are differentially regulated in the heart during physiological and pathophysiological conditions. Using quantitative RT-PCR, we report that the five known acsl isoforms (acsl1, acsl3, acsl4, acsl5, and acsl6) and cte1 are expressed in whole rat and mouse hearts, as well as adult rat cardiomyocytes (ARCs). Streptozotocin-induced insulin-dependent diabetes (4 wk) and fasting (

The intrinsic circadian clock within the cardiomyocyte.

Circadian clocks are intracellular molecular mechanisms that allow the cell to anticipate the time of day. We have previously reported that the intact rat heart expresses the major components of the circadian clock, of which its rhythmic expression in vivo is consistent with the operation of a fully functional clock mechanism. The present study exposes oscillations of circadian clock genes [brain and arylhydrocarbon receptor nuclear translocator-like protein 1 (bmal1), reverse strand of the c-erbaalpha gene (rev-erbaalpha), period 2 (per2), albumin D-element binding protein (dbp)] for isolated adult rat cardiomyocytes in culture. Acute (2 h) and/or chronic (continuous) treatment of cardiomyocytes with FCS (50% and 2.5%, respectively) results in rhythmic expression of circadian clock genes with periodicities of 20-24 h. In contrast, cardiomyocytes cultured in the absence of serum exhibit dramatically dampened oscillations in bmal1 and dbp only. Zeitgebers (timekeepers) are factors that influence the timing of the circadian clock. Glucose, which has been previously shown to reactivate circadian clock gene oscillations in fibroblasts, has no effect on the expression of circadian clock genes in adult rat cardiomyocytes, either in the absence or presence of serum. Exposure of adult rat cardiomyocytes to the sympathetic neurotransmitter norephinephrine (10 microM) for 2 h reinitiates rhythmic expression of circadian clock genes in a serum-independent manner. Oscillations in circadian clock genes were associated with 24-h oscillations in the metabolic genes pyruvate dehydrogenase kinase 4 (pdk4) and uncoupling protein 3 (ucp3). In conclusion, these data suggest that the circadian clock operates within the myocytes of the heart and that this molecular mechanism persists under standard cell culture conditions (i.e., 2.5% serum). Furthermore, our data suggest that norepinephrine, unlike glucose, influences the timing of the circadian clock within the heart and that the circadian clock may be a novel mechanism regulating myocardial metabolism.