Riboflavin-mediated delivery of a macromolecule into cultured human cells

The effects of perivascular nerve stimulation and phenylephrine on osmolyte release were studied in the intact perfused rat liver and isolated liver parenchymal cells (PC) and nonparenchymal cells. In the perfused liver, electrical stimulation of perivascular nerves (20 Hz/2 ms/20 V) led to a phentolamine-sensitive increase of cell hydration by 6.5% +/- 1.2% (n = 3) and a transient phentolamine-sensitive stimulation of taurine and inositol, but not betaine, release. These nerve effects were mimicked by phenylephrine, but not prostaglandin F2alpha, and were not affected by sodium nitroprusside (SNP) or ibuprofen. Nerve stimulation-induced taurine, but not inositol, release was inhibited by 4, 4'-di-isothiocyanatostilbene-2,2'-disulphonic acid (DIDS) (50 micromol/L). Single-cell fluorescence studies with isolated liver PC, Kupffer cells (KC), sinusoidal endothelial cells (SEC), and hepatic stellate cells (HSC) revealed that phenylephrine induced an increase in cytosolic free Ca2+ only in PC and HSC, but not in KC and SEC, whereas extracellular uridine triphosphate (UTP) produced Ca2+ transients/oscillations in all liver cell types studied. Phenylephrine had no effect on osmolyte release from isolated KC and SEC, but increased taurine (but not inositol) release from PC and inositol (but not taurine) efflux from HSC. The data suggest that: 1) liver cell hydration and-consecutively-osmolyte content are modulated by hepatic nerves via an alpha-adrenergic mechanism, which does not involve eicosanoids or hemodynamic changes; 2) that PC and HSC are the primary targets for nerve-dependent alpha-adrenergic activation, whereas 3) KC and SEC probably do not express alpha-adrenoceptors coupled to Ca2+ mobilization or osmolyte efflux.     

Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and importance

The agar dilution MIC method was used to test the activity of cefminox, a beta-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. Other beta-lactams were less active, with respective MIC50s and MIC90s of 2.0 and 64.0 microg/ml for cefoxitin, 2.0 and 128.0 microg/ml for cefotetan, 2.0 and 64.0 microg/ml for moxalactam, 4.0 and > 128.0 microg/ml for ceftizoxime, 16.0 and > 128.0 microg/ml for cefotiam, 8.0 and >128.0 microg/ml for cefamandole, and 4.0 and 128.0 microg/ml for cefoperazone. The clindamycin MIC50 and MIC90 were 0.5 and 8.0 microg/ml, respectively, and the metronidazole MIC50 and MIC90 were 1.0 and 4.0 microg/ml, respectively. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4x the MIC and cefoperazone at 8x the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2 x the MIC produced the most rapid effect, with 90% killing of all strains.     

Aortic dissection: percutaneous management of ischemic complications with endovascular stents and balloon fenestration

PURPOSE: The purpose of this study was to evaluate endovascular stenting (EVS) and balloon fenestration (BF) of intimal flaps for the management of lower extremity, renal, and visceral ischemia in acute or chronic aortic dissection. METHODS: Twenty-two patients (16 male, 6 female) with a median age of 53 years (range 35 to 77 years) underwent percutaneous treatment for peripheral ischemic complications of 12 type A (five acute, seven chronic) and 10 type B (nine acute, one chronic) aortic dissections. RESULTS: Ten patients had leg ischemia, 13 had renal ischemia, and 6 had visceral ischemia. Sixteen patients were treated with EVS including 11 with renal, 6 with lower extremity, 2 with superior mesenteric artery, and 2 with aortic stents. Three patients had BF of the intimal flap, and three had BF in combination with EVS. Revascularization with clinical success was achieved in all 22 patients. Two patients died 3 days and 13.4 months after the procedure was performed, respectively. Of the remaining 20 patients, 1 is lost to follow-up, and 19 have persistent relief of clinical symptoms. Mean follow-up time is 13.7 months (range 1.1 to 46.5 months). One case was complicated by guidewire-induced perinephric hematoma. CONCLUSION: EVS and BF provide a safe and effective percutaneous method for managing peripheral ischemic complications of aortic dissection.