Clinical significance of prophylactic antibiotics in renal transplantation.

INTRODUCTION: The use of new selective immunosuppressants as well as the emergence of new antimicrobial resistances raise the use of prophylactic antibiotics as a matter of controversy. The purpose of this study was to retrospectively analyze the clinical significance of prophylactic antibiotics in kidney transplantation. METHODS: This retrospective study included 174 renal allograft recipients who were divided into two groups: group A including patients who received perioperative prophylactic antibiotics and group B, who did not receive them. We analyzed who the incidence of infectious complications as well as the causative micro-organisms and their antimicrobial resistance within 1 month after kidney transplantation. RESULTS: Overall bacterial infections were observed during the first postoperative month in 13 cases (7.4%): 6 (3.4%) surgical site 4 (2.3%) urinary tract, 2 (1.1%) bacteremic, and 1 (0.6%) central catheter infections. There was no respiratory infection. The incidence of bacterial infection was not significantly different between the two groups. The major micro-organisms isolated after kidney transplantation, were Staphylococcus aureus and Escherichia coli; both of which had already shown multidrug resistance at the initial time of infection. CONCLUSION: Not only did use of prophylactic antibiotics have little impact to prevent bacterial infections after kidney transplantation, but also it may induce antimicrobial resistance against the antibiotics used for prophylaxis. Moreover, the increased antibiotic resistance prior to kidney transplantation hampers the effectiveness of prophylactic antimicrobial agents. Guidelines for perioperative antibiotic prophylaxis should be therefore revised.

A comparison of consumption and recovery profiles according to anaesthetic circuit mode using a new multifunctional closed-circuit anaesthesia system during desflurane anaesthesia: a clinical study.

This clinical study compared induction time, consumed anaesthetic dose, and haemodynamic and recovery profiles when using a new type of multifunctional anaesthesia machine (Zeus) in semi-closed or closed circuit modes. Sixty female patients undergoing gynaecological surgery were randomly assigned to three groups and received desflurane anaesthesia through a semi-closed circuit (SCC) at fresh gas flow rates of 4 l/min (SCC 4 l/min) or 2 l/min (SCC 2 l/min), or through a closed circuit (CC). Anaesthesia was maintained at the minimum alveolar concentration for blocking the adrenergic response to painful stimulus (MAC(BAR)) (4.6% end-tidal desflurane) during each operation. The time required to reach MAC(BAR) was significantly shorter and the dose of desflurane was significantly smaller in the CC group compared with the other groups. There were no differences in haemodynamic and recovery profiles between the groups. It is concluded that the CC mode allowed a faster and more reliable induction, lower anaesthetic consumption and stable haemodynamic and recovery profiles.

Control of the haemodynamic response to surgical stimuli in semi-closed circuit or closed circuit anaesthesia using a multifunctional anaesthesia system.

This study compared the ability of the Zeus multifunctional anaesthesia system to control haemodynamic response to surgical stimulation in semi-closed (SCA) or closed circuit anaesthesia (CCA) modes. Fifty patients undergoing gynaecological surgery were randomly assigned to SCA or CCA. Anaesthesia was induced with 2 mg propofol and 0.9 mg/kg rocuronium, intravenously, and maintained using sevoflurane (minimum alveolar concentration [MAC], 1.0) using 2 l/min oxygen plus 2 l/min nitrous oxide (SCA 4 l/min group) or 50% oxygen plus 50% nitrous oxide (CCA group). An increase in mean arterial pressure (MAP) > 20% above baseline in response to surgical stimulation provoked a stepwise increase in sevoflurane (1.3 MAC and then 1.6 MAC), followed by fentanyl 1 pg/kg intravenously (rescue drug). The time required for MAP to return to within 10% of baseline was significantly shorter in the CCA group (6.4 +/- 3.6 min) compared with the SCA 4 l/min group (10.2 +/- 6.0 min). The percentage of patients requiring fentanyl was significantly greater in the SCA 4 l/min group than in the CCA group. In conclusion, CCA controlled acute haemodynamic responses to surgical stimuli more successfully and rapidly than SCA 4 l/min, using a multifunctional anaesthesia machine.

Outcomes after combined laparoscopic gastrectomy and laparoscopic cholecystectomy in gastric cancer patients.

BACKGROUND/AIMS: The purpose of this study was to determine the effect of performing laparoscopic cholecystectomy on patients undergoing laparoscopic-assisted gastrectomy for gastric cancer. METHODS: This single center study involved a retrospective review of a database of 400 patients who underwent consecutive laparoscopic-assisted gastrectomy for early gastric cancer from June 2003 to July 2007. Outcomes in 26 patients who underwent both laparoscopic-assisted gastrectomy and laparoscopic cholecystectomy were compared with outcomes from 364 patients who underwent laparoscopic-assisted gastrectomy without laparoscopic cholecystectomy. RESULTS: There were no postoperative 30-day mortalities in the combined cholecystectomy group. The mean surgery duration, time to first flatus and postoperative hospital stay for the laparoscopic gastric resection without combined operation were 181.7 min, 2.7 days and 9.7 days, respectively, and 196.7 min, 2.6 days and 8.8 days, respectively, for the combined cholecystectomy group. None of the postoperative complications was related to combined cholecystectomy. CONCLUSION: Performing a combined cholecystectomy prolonged the mean surgery duration by approximately 15 min, but had no effect on surgical outcomes. It appears that performing a cholecystectomy at the same time as laparoscopic gastric resection is safe and feasible in patients with both early gastric cancer and gallbladder disease.

Target-controlled propofol infusion for sedation in patients undergoing transrectal ultrasound-guided prostate biopsy.

The efficacy and safety of the routine use of target-controlled infusion of propofol for the sedation of patients undergoing transrectal ultrasound-guided prostate biopsy were assessed. The optimal level of sedation was also evaluated. A total of 250 patients were randomized into five groups according to sedation level determined by the Observer's Assessment of Alertness/Sedation (OAA/S) scale. As the level of sedation was increased, the overall pain and discomfort score decreased and the satisfaction rate tended to increase, although hypoxia meant that intervention occurred more frequently at higher sedation levels. Target-controlled infusion of propofol provided safe and effective sedation during transrectal ultrasound-guided prostate biopsy, particularly if moderate sedation (OAA/S score of 3) was achieved. The effect-site concentration of propofol for this level of sedation was about 1.5 microg/ml.

In vitro skin penetration and pharmacodynamic evaluation of prostaglandin E1 ethyl ester, a vasoactive prodrug of prostaglandin E1, formulated into alcoholic hydrogels.

Alcoholic hydrogels containing prostaglandin E1 ethyl ester (PGE1-EE), a prodrug of PGE1 as a therapeutic agent for erectile dysfunction, were formulated. The prodrug was stable against chemical hydrolysis in aqueous solution (pH 7.4), devoid of esterase activities, but was hydrolyzed to the parent drug in rat skin homogenates within 240 min. In the rat skin penetration study for 24 h, the steady-state flux values (microg/cm2/h) of PGE1-EE and PGE, from alcoholic hydrogels having 20% ethanol content were 7.6 and 1.8, respectively. PGE1-EE was superior to PGE, from a skin penetration point of view due to its increased lipophilicity. The fastest skin penetration rate was obtained for PGE1-EE in 20% alcoholic hydrogel together with limonene or cineole. These formulations increased the flux of PGE1-EE up to about 4-fold compared to control hydrogel in the absence of penetration enhancers. In the pharmacodynamic study using a cat, alcoholic hydrogel with limonene or cineole showed a significant effect in terms of increasing intracavernosal pressure compared to control hydrogel. Therefore, the transdermal alcoholic hydrogel formulation of PGE1-EE with limonene or cineole can be a promising transdermal delivery system to overcome inconvenience associated with frequent intracavernosal injections for the treatment of erectile dysfunction.

Thoracic epidural clonidine attenuates haemodynamic responses induced by endobronchial intubation.

Laryngoscopy and endobronchial intubation usually cause transient hypertension and tachycardia. We investigated whether thoracic epidurally injected 3 microg/kg clonidine attenuates cardiovascular responses to intubation compared with 2 microg/kg fentanyl and 1 mg/kg lidocaine. Epidural catheterization was performed at the T6-T7 or T7-T8 intervertebral space, and saline or clonidine in saline was injected 20 min before anaesthetic induction. Anaesthesia was induced using 5 mg/kg thiopental sodium and 0.1 mg/kg vecuronium. Laryngoscopy and endobronchial intubation were performed 2 min later. Mean blood pressure and heart rate were measured throughout anaesthetic induction. In the control group and the fentanyl group, mean blood pressure and heart rate 3 min after endobronchial intubation were elevated significantly compared with baseline. In the clonidine group, however, mean blood pressure and heart rate did not increase compared with baseline. The control group had higher mean blood pressure and heart rate than the clonidine group 3 min after endobronchial intubation. Thoracic epidural clonidine may attenuate the haemodynamic response to endobronchial intubation.

Association of the ERK1/2 and p38 kinase pathways with nitric oxide-induced apoptosis and cell cycle arrest in colon cancer cells.

To investigate the mechanism by which nitric oxide (NO) induces cell death in colon cancer cells, we compared two types of colon cancer cells with different p53 status: HCT116 (p53 wild-type) cells and SW620 (p53-deficient) cells. We found that S-nitrosoglutathione (GSNO), the NO donor, induced apoptosis in both types of colon cancer cells. However, SW620 cells were much more susceptible than HCT116 cells to apoptotic death by NO. We investigated the role of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 kinase on NO-induced apoptosis in both types of colon cancer cells. GSNO treatment effectively stimulated activation of the ERK1/2 and p38 kinase in both types of cells. In HCT116 cells, pretreatment with PD98059, an inhibitor of ERK1/2, or SB203580, an inhibitor of p38 kinase, had no marked effect on GSNO-induced apoptosis. However, in SW620 cells, SB203580 significantly reduced the NO-induced apoptosis, whereas PD098059 increases NO-induced apoptosis. Furthermore, we found evidence of cell cycle arrest of the G0/G1 phase in SW620 cells but not in HCT116 cells. Inhibition of ERK1/2 with PD098059, or of p38 kinase with SB203580, reduced the GSNO-induced cell cycle arrest of the G0/G1 phase in SW620 cells. We therefore conclude that NO-induced apoptosis in colon cancer cells is mediated by a p53-independent mechanism and that the pathways of ERK1/2 and p38 kinase are important in NO-induced apoptosis and in the cell cycle arrest of the G0/G1 phase.

An effective thermal conductivity model of nanofluids with a cubical arrangement of spherical particles.

The theoretical investigation of the effective thermal conductivities of nanofluids, a new class of solid-liquid suspensions, is important in both predicting and designing nanofluids with effective thermal conductivities. We have developed a new thermal conductivity model for nanofluids that is based on the assumption that monosized spherical particles are uniformly dispersed in the liquid and are located at the vertexes of a simple cubic lattice, with each particle surrounded by a liquid layer having a thermal conductivity that differs from that of the bulk liquid. This model nanofluid with a cubical arrangement of nanoparticles gives a more practical upper limit of thermal conduction than a model nanofluid with a parallel arrangement of nanoparticles. The new model unexpectedly shows a nonlinear relationship of thermal conductivity with particle concentration, whereas the conductivity-concentration curve changes from convex upward to concave upward with increasing volume concentration. The effects of particle and layer parameters on the effective thermal conductivities are also analyzed. A comparison of predicted thermal conductivity values and experimental data shows that the predicted values are much higher than the experimental data, a finding that indicates that there is a potential to further improve the effective thermal conductivities of nanofluids with more uniformly dispersed particles.

Structure-activity relationship studies of isoquinolinone type anticancer agent.

Substituted isoquinolin-1-ones (1) were synthesized to test their in vitro anticancer activity. 3-Biphenyl-N-methylisoquinolin-1-one (7) showed the most potent anticancer activity against five different human cancer cell lines.

Phytochemical constituents of Artemisia stolonifera.

Repeated column chromatographic separation of the CH2Cl2 extract of Artemisia stolonifera (Asteraceae) led to the isolation of a triterpene (I), a sesquiterpene (II), two aromatic compounds (III and IV) and a benzoquinone (V). Their structures were determined by spectroscopic means to be simiarenol (I), (1S,7S)-1beta-hydroxygermacra-4(15),5,10(14)-triene (II), 3'-methoxy-4'-hydroxy-trans-cinnamaldehyde (III), vanillin (IV) and 2,6-dimethoxy-1,4-benzoquinone (V), respectively. Among these products, compound V showed significant cytotoxicity against five human tumor cell lines in vitro, A549 (non small cell lung adenocarcinoma), SK-OV-3 (ovarian), SK-MEL-2 (skin melanoma), XF498 (CNS) and HCT15 (colon) with ED50 values ranging from 1.33-4.22 microg/ml.

Costunolide, a sesquiterpene from the stem bark of Magnolia sieboldii, inhibits the RAS-farnesyl-proteintransferase.

Costunolide, a germacrane sesquiterpene lactone isolated from the stem bark of Magnolia sieboldii demonstrated a significant inhibition upon the farnesylation process of human lamin-B by farnesyl-proteintransferase (FPTase), in a dose dependent manner in vitro (IC50 value was calculated as 20 microM). It was also found to exhibit an inhibition upon the proliferation of cultured human tumor cells, i.e., A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon), in vitro.

Antibacterial activity of S-methyl methanethiosulfinate and S-methyl 2-propene-1-thiosulfinate from Chinese chive toward Escherichia coli O157:H7.

S-Methyl methanethiosufinate (1) and S-methyl 2-propene-1-thiosulfinate (2) were easily seperated from Chinese chive (Allium tuberosum L.) using simple column chromatography. Both compounds showed significant antibacterial activities against E. coli O-157:H7 including spoilage microorganism in food. Structural assignment was based on Mass and NMR-spectroscopic methods.

Cytotoxic alkaloids from Houttuynia cordata.

Six bioactive alkaloids, aristolactam B(1), piperolactam A(2), aristolactam A(3), norcepharadione B(4), cepharadione B(5) and splendidine(6) were isolated by bioactivity-guided fractionation of a methanolic extract of the aerial part of Houttuynia cordata. Several of them exhibited significant cytotoxicity against five human tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF-498 and HCT-15) in vitro.

A new caffeoyl quinic acid from aster scaber and its inhibitory activity against human immunodeficiency virus-1 (HIV-1) integrase.

The phytochemical study of the aerial parts of Aster scaber Thunb. (Asteraceae) yielded a new caffeoyl quinic acid, (-) 3,5-dicaffeoyl-muco-quinic acid (2) and three known compounds, (-) 3,5-dicaffeoyl quinic acid (1), (-) 4,5-dicaffeoyl quinic acid (3), (-) 5-caffeoyl quinic acid (4). The structures were established by high resolution spectroscopic methods. The antiviral effects against HIV-1 integrase of the compounds was evaluated. (-) 3,5-Dicaffeoyl-muco-quinic acid (2) exhibited potent antiviral activity with an IC50 value of 7.0 +/- 1.3 microg/ml.

Cytotoxic peroxides from Artemisia stolonifera.

Two sesquiterpene endoperoxides, 1S, 4R, 6R-1, 4-endoperoxy-bisabola-2, 10-diene (I), 1R, 4S, 6R-1, 4-endoperoxy-bisabola-2, 10-diene (II), and a sesquiterpene hydroperoxide, 1beta-hydroperoxygermacra-4 (15), 5, 10 (14)-triene (III) were isolated from the aerial parts of Artemisia stolonifera (Compositae). Their chemical structures were assigned by spectral evidences. Compounds I and II exhibited cytotoxicity against five human tumor cell lines with their ED50 values ranging from 0.20 to 5.43 microg/ml and from <0.1 to 0.87 microg/ml, respectively.

New cytotoxic butanolides from Lindera obtusiloba BLUME.

Three new butanolides, 2-(1-methoxy-11-dodecenyl)-penta-2,4-dien-4-olide (1), (2Z,3S,4S)-2-(11-dodecenylidene)-3-hydroxy-4-methylbutano lide (2) and (2E,3R,4R)-2-(11-dodecenylidene)-3-hydroxy-4-methoxy-4-methylbu tanolide (3), were isolated from the stems of Lindera obtusiloba BLUME. Their chemical structures were assigned by spectroscopic evidence. They exhibited cytotoxicity against cultured human tumor cell lines with their ED50 values ranging from 3.19 to 14.63 microg/ml.

Effects of KR-30035, a novel multidrug-resistance modulator, on the cardiovascular system of rats in vivo and on the cell cycle of human cancer cells in vitro.

The present study was performed to evaluate the adverse effects of KR-30035, a multidrug-resistance modulator, on the cardiovascular system in vivo, along with its effect on paclitaxel-induced cell cycle arrest in cultured cancer cells. In anesthetized rats, KR-30035 was about 10-fold less potent than verapamil in lowering blood pressure (i.v. ED20: 0.320+/-0.052 and 0.034+/-0.005 mg/kg, respectively) and in producing electrocardiogram changes. In conscious spontaneously hypertensive rats, verapamil caused a significant antihypertensive effects at the doses tested (p.o. ED20, 7.8+/-4.0 mg/kg), whereas KR-30035 did not significantly change either the blood pressure or the heart rate at any doses tested (up to 100 mg/kg). The estimated i.v. LD50 values in mice were 5.9 and 48.9 mg/kg for verapamil and KR-30035, respectively. In the presence of 10 microM KR-30035, paclitaxel (1 microM) when added to cultures of HCT15/CL02 human cancer cells greatly shifted the cell population from the G0/G1 phases towards G2/M phases (from 42.4, 30.3 and 27.3 to 14.6, 21.5 and 63.9% for the G0/G1, S and G2/M phases, respectively), with a similar magnitude to that of 10 microM verapamil (14.0, 15.7 and 70.3%, respectively). These results suggest that KR-30035 has weaker in vivo effects on the cardiovascular system compared with verapamil, while potentiating the G2/M arresting effect of paclitaxel on the cell cycle.

Effect of substituents on benzenesulfonyl motif of 4-phenyl-1-arylsulfonylimidazolidinones for their cytotoxicity.

To explore the effect of substituents' on phenyl motif on sulfonyl function of novel anticancer 4-phenyl-1-benzenesulfonylimidazolidinones (1), electron donating or withdrawing substituents were introduced at 3 or 4-position and the analogs were tested against human lung (A549) and colon (HCT-15) cancer cell lines. Quantitative structure activity relationship of the 4-substituted series shows that only STERIMOL L values are well correlated. The increment of substituent's volume enhances the activity against both cell lines. The small substituent at 3-position additionally increases the activity. However naphthyl group in place of phenyl reduces the activity. Therefore the phenyl motif with sterically large substituent at 4-position and small substituent at 3-position may be important for their activity. Integration of these substituents' effects into the structural design led to discover the more potent analog, 4-phenyl-1-(N-acetylindoline-5-sulfonyl) imidazolidinone (1n).

Synthesis and biology of 3'-N-acyl-N-debenzoylpaclitaxel analogues.

The, 3'-N-acyl-N-debenzoylpaclitaxel analogues 1a-d were synthesized and evaluated on biological systems. Some of the analogues 1a-d exhibited higher cytotoxicities (up to 20-fold) and stronger abilities to induce apoptosis than paclitaxel. In an in vivo experiment against i.p. implanted B16 melanoma, the most cytotoxic compound 1b in vitro caused tumor growth inhibition more than paclitaxel.