Sevoflurane vs. propofol in post-operative catheter-related bladder discomfort: a prospective randomized study.

BACKGROUND: Post-operative catheter-related bladder discomfort (CRBD) causes increased emergence agitation. Muscarinic receptor activation is a major mechanism in CRBD development. Experimental studies showed that sevoflurane has anti-muscarinic effects whereas propofol does not. Our hypothesis was that sevoflurane anaesthesia would reduce the incidence of CRBD following bladder surgery. METHODS: In total, 82 patients undergoing transurethral bladder tumour excision (TURBT) were assigned randomly to two groups according to the maintenance anaesthetic agent received: sevoflurane (n = 41) or propofol (n = 41). The incidence of CRBD was evaluated at 0, 1, 6 and 24 h post-operatively. The number of patients treated with a rescue medication (tramadol) for CRBD was noted. RESULTS: The incidence of CRBD at post-operative 1 h was lower in the sevoflurane group than that in the propofol group (59% vs. 85%; P = 0.007). The differences in CRBD were 27% and 22% at 0 and 6 h post-operatively (P = 0.008 and 0.047, respectively). CRBD occurred in 27 (66%) patients in the sevoflurane group vs. 38 (93%) in the propofol group from 0 to 24 h post-operatively (P = 0.005). The number of patients treated with tramadol was lower in the sevoflurane group (13 [22%] vs. 22 [54%]; P = 0.044). CONCLUSION: Sevoflurane, as a maintenance in general anaesthesia, decreased the incidence of early post-operative CRBD and tramadol requirements in patients undergoing TURBT, compared with propofol.

Effects of depression co-morbidity and treatment on quality of life in patients with acute coronary syndrome: the Korean depression in ACS (K-DEPACS) and the escitalopram for depression in ACS (EsDEPACS) study.

BACKGROUND: Depression is common after acute coronary syndrome (ACS) with adverse effects on prognosis. There is little evidence on whether depression treatment improves quality of life (QoL) in ACS patients. The aim of this study was to investigate the effects of co-morbid depression and its treatment on QoL in ACS. METHOD: In total, 1152 patients were recruited at baseline, 2-14 weeks after a confirmed ACS episode, and 828 were followed 1 year thereafter. Of 446 baseline participants with co-morbid depressive disorders, 300 were randomized to a 24-week double blind trial of escitalopram or placebo, while the remaining 146 received medical treatment only (MTO). QoL was measured by the World Health Organization Quality of Life -Abbreviated form (WHOQOL-BREF). RESULTS: At baseline, QoL was significantly lower in patients with co-morbid depressive disorder than those without. QoL improvement was significantly greater in those receiving escitalopram than those receiving placebo over the 24-week treatment period. In the 1-year follow-up, the better outcomes associated with escitalopram remained evident against both placebo and MTO. CONCLUSIONS: Depression was significantly associated with worse QoL even in patients with recently developed ACS. Depression treatment was associated with QoL improvement in ACS patients in the 24-week treatment period, the effects of which extended to 1 year.

A macrophage-specific synthetic promoter for therapeutic application of adiponectin.

Foam cell formation from macrophage is a major cause of atherosclerosis. An efficient macrophage-specific promoter is required for the targeting to macrophages. In this study, we develop a macrophage-specific synthetic promoter for the therapeutic application of adiponectin (APN), an antiatherogenic gene. Synthetic promoter-146 (SP146), registered on the NCBI website (http://www.ncbi.nlm.nih.gov/nuccore/DQ107383), was tested for promoter activities in two non-macrophage cell lines (293 T, HeLa) and a macrophage cell line (RAW264.7, bone marrow-derived macrophages). To enforce macrophage specificity, partial elements of p47(phox) including the PU.1 site with various lengths (-C1, -C2 and -C3) were inserted next to the synthetic promoters. SP146-C1 showed the highest specificity and efficacy in RAW264.7 cells and was selected for development of an APN-carrying macrophage-specific promoter. Green fluorescent protein (GFP)- or APN-expressing lentivirus under SP146-C1 (Lenti-SP-GFP or Lenti-SP-APN, respectively) showed the highest expression efficacy in RAW264.7 cells compared with the non-macrophage cell lines. APN overexpression in RAW264.7 cells successfully inhibited intracellular lipid accumulation, and atherosclerotic lesions and lipid accumulation were significantly reduced by Lenti-SP-APN in ApoE-/- atherosclerosis mice. In conclusion, the synthetic promoter SP146-C1, combined with a p47(phox) promoter element, was successfully developed to target macrophage, and macrophage-specific introduction of APN under SP146-C1 was shown to ameliorate the atherosclerotic pathology.

Efficient transfer of reporter gene-loaded nanoparticles to bone marrow stromal cells (D1) by reverse transfection.

Nucleic acids can be complexed with cationic polymer to form DNA nanoparticles (polyplex) which are then immobilized on the surface coated extracellular matrix protein (ECM), the process termed as reverse transfection. ECM-containing proteins provide a surface for cell attachment and sustain the release of polyplexes from their surface, thereby inducing transgene expression for prolonged period of time. Consequently, long-term expression of the desired protein can be achieved with the smaller amount of required DNA, as compared to bolus delivery. First of all, we investigated the different ECM components as a coating material and the range of optimal coating density in different ECM was examined for enhanced transfection to neighboring cells. Reporter genes such as luciferase (luc) and enhanced green fluorescent protein (eGFP) were initially used to quantitate transfection efficiencies from polyplex from the coated ECMs of Collagen type I (Col I), fetal bovine serum protein (FBS), bovine serum albumin (BSA). DNA was complexed with positively charged polyethyleneimine (PEI) at N/P ratio 9. Our initial work exhibited that, in the case of both NIH/3T3 cell line and bone marrow stromal (D1) cell line, Col I facilitated the greatest cell adhesion compared to the other coating proteins and 0.5 microg/cm2 of Col I coating density resulted in highest transfection efficiency. On the other hand, comparison of reverse delivery system with atelocollagen-I have shown that reverse delivery system to yield ten times higher transfection efficiency than atelocollagen-PEI/DNA delivery system and one hundred times higher than atelocollagen-naked plasmid delivery system. Moreover, the amount of DNA used for reverse delivery system was much lower than the other systems. This methodology would be applied to induce cellular differentiation in 3-dimensional scaffold after coating scaffolds with genes inducing the differentiation in the nanoparticle formulation. Our final goal is to search for the optimal conditions for the differentiation of stem cells to specific cell types.

Endophytic and endolichenic fungal diversity in maritime Antarctica based on cultured material and their evolutionary position among Dikarya.

Fungal endophytes comprise one of the most ubiquitous groups of plant symbionts. They live asymptomatically within vascular plants, bryophytes and also in close association with algal photobionts inside lichen thalli. While endophytic diversity in land plants has been well studied, their diversity in lichens and bryophytes are poorly understood. Here, we compare the endolichenic and endophytic fungal communities isolated from lichens and bryophytes in the Barton Peninsula, King George Island, Antarctica. A total of 93 fungal isolates were collected from lichens and bryophytes. In order to determine their identities and evolutionary relationships, DNA sequences of the nuclear internal transcribed spacer (ITS), nuclear ribosomal small subunit (nuSSU), nuclear large subunit (nuLSU), and mitochondrial SSU (mtSSU) rDNA were obtained and protein coding markers of the two largest subunit of RNA polymerase II (RPB1 and RPB2) were generated. Multilocus phylogenetic analyses revealed that most of the fungal isolates were distributed in the following six classes in the phylum Ascomycota: Dothideomycetes, Eurotiomycetes, Lecanoromycetes, Leotiomycetes, Pezizomycetes and Sordariomycetes. For the first time we report the presence of subphylum Mortierellomycotina that may belong to an undescribed order in endophytic fungi. Taken together, our results imply that lichens and bryophytes provide similar niches and harbour a selection of these fungi, indicating generalists within the framework of evolutionary adaptation.

The use of statins for the treatment of depression in patients with acute coronary syndrome.

This study aimed to investigate the effect of statins for the treatment of depression in individuals with acute coronary syndrome (ACS). We used 1-year follow-up data of a 24-week double-blind, placebo-controlled trial of escitalopram and a naturalistic prospective observational cohort study. Of 446 participants with comorbid depressive disorders and ACS at baseline, 300 participated in a randomised escitalopram trial and the remaining 146 participated in a naturalistic observational study. The participants in the two studies were approached for a 1-year follow-up investigation. Treatment response rates, defined as a ⩾ 50% reduction in the Hamilton Depression Rating Scale (HAM-D) and Beck Depression Inventory (BDI) scores, were used as the outcome variables. In the escitalopram trial, both HAM-D and BDI response rates were highest in patients taking escitalopram and statins together and lowest in patients receiving neither medication. Logistic regression analyses revealed that statin use was significantly associated with higher response rates on both the HAM-D and BDI at 1 year, whereas no such associations were found for escitalopram. In the naturalistic observational study, the response rates at 1 year did not differ significantly by statin use. Instead, the HAM-D response rate was significantly higher in patients taking lipophilic statins than in those who did not. In conclusion, statins may be effective for the treatment of depression independent of medical status and escitalopram use, and they may potentiate the antidepressant action of serotonergic antidepressants in patients with ACS.

Protein tyrosine kinase inhibitors modulate radiosensitivity and radiation-induced apoptosis in K562 cells.

We studied the modulating effect of protein tyrosine kinase inhibitors on the response of cells of the human chronic myelogenous leukemia cell line K562 to radiation. The radiosensitivity of the cells was increased by treatment with herbimycin A and decreased by treatment with genistein. This modulating effect of protein tyrosine kinase inhibitors on radiation sensitivity was associated with the alteration of the mode of radiation-induced cell death. After X irradiation, the cells arrested in the G(2) phase of the cell cycle, but these TP53(-/-) cells were unable to sustain cell cycle arrest. This G(2)-phase checkpoint deficit caused cell death. The morphological pattern of cell death was characterized by swelling of the cytoplasmic compartments, cytosolic vacuolation, disruption of the plasma membrane, less evident nuclear condensation, and faint DNA fragmentation, all of which were consistent with oncosis or cytoplasmic apoptosis. The nonreceptor protein tyrosine kinase inhibitor herbimycin A accelerated the induction of typical apoptosis by X irradiation, which was demonstrated by morphological assessments using nuclear staining and electron microscopy as well as oligonucleosomal fragmentation and caspase 3 activity. Herbimycin A is known to be a selective antagonist of the BCR/ABL kinase of Philadelphia chromosome-positive K562 cells; this kinase blocks the induction of apoptosis after X irradiation. Our results showed that the inhibition of protein tyrosine kinase by herbimycin A enhanced radiation-induced apoptosis in K562 cells. This effect was associated with the activation of caspase 3 and rapid abrogation of the G(2)-phase checkpoint with progression out of G(2) into G(1) phase. In contrast, the receptor-type protein tyrosine kinase inhibitor genistein protected K562 cells from all types of radiation-induced cell death through the inhibition of caspase 3 activity and prolonged maintenance of G(2)-phase arrest. Further investigations using this model may give valuable information about the mechanisms of radiation-induced apoptosis and about the radiosensitivity and radioresistance of chronic myelogenous leukemia cells having the Philadelphia chromosome.

Hemolytic mechanism of cytolysin produced from V. vulnificus.

The characteristics of hemolytic action of cytolysin produced from V. vulnificus were investigated in mouse erythrocytes. The cytolysin bound erythrocyte membranes in temperature-independent manner and then lysed cells temperature-dependently. Hemoglobin release by the cytolysin was completely inhibited by the presence of raffinose or melezitose, but K+ release was not affected. The cytolysin-induced hemolysis was always accompanied with the conversion of membrane-bound cytolysin into an oligomer of 210 kDa, corresponding to a tetramer of native cytolysins. Nonesterified cholesterol inactivated the cytolysin by converting active monomeric cytolysin into inactive oligomer. The results suggest that the cytolysin lyses erythrocytes due to the formation of small pores on erythrocyte membrane by cholesterol-mediated oligomerization of the cytolysin.

Szygium aromaticum (L.) Merr. Et Perry (Myrtaceae) flower bud induces apoptosis of p815 mastocytoma cell line.

This study was conducted to investigate SAFB-induced apoptosis of mast cells as it pertains to both its basic drug mechanism and the potential therapeutics of the pathologic conditions accompanying mast cell proliferation. SAFB induced many apoptotic manifestations as evidenced by changes in cell morphology, generation of DNA fragmentation, activation of caspase 3, and DNA hypoploidy. The reduction of mitochondrial membrane potential and the release of cytochrome c to cytosol were also demonstrated. However, reduction of mitochondrial membrane potential and cytochrome c release were not prevented by caspase inhibitor zVAD-fmk or PTP blockers such as bongkrekic acid and cyclosporin A. Expression levels of Bcl-2 and Fas remained unchanged following SAFB treatment. This results suggest that the clinical effect of SAFB may depend on the pharmacological mechanism regulating the demise of mast cells.

Arterial remodeling after experimental percutaneous injury is highly dependent on adventitial injury and histopathology.

BACKGROUND: The extent and nature of unfavorable geometric remodeling, especially related to the adventitia, has not been studied previously. The purpose of this study was to examine two methods of experimental arterial injury, characterize the extent of remodeling, and determine if remodeling is injury-specific. METHODS: Two methods for producing coronary stenoses in pigs were used: heat injury using thermal balloon angioplasty (resulting in adventitial fibrosis), and copper stent implantation (resulting in intense inflammation). Histomorphometric parameters included changes in neointimal thickness (delta neointima) from uninjured to injured sections, and differences in area circumscribed by the internal and external elastic laminas (delta internal elastic lamina area and delta external elastic lamina area, respectively). Remodeling was calculated for each lesion as the enlargement of the external elastic lamina area or internal elastic lamina area for incremental neointimal thickening, expressed as the slopes delta external elastic area/delta neointima and delta internal elastic lamina area/delta neointima. RESULTS: Remodeling indices for the heat lesions for the heat lesions were negative (delta internal elastic lamina area/delta neointima = 0.15, delta external elastic lamina area/delta neointima = 0.64) and indicated little remodeling in contrast to copper stent injury (delta internal elastic lamina area/delta neointima = 0.95, delta external elastic lamina area/delta neointima = 1.20). CONCLUSIONS: Remodeling in fibrotic compared to inflammatory lesions differs markedly, and may explain increased restenosis rates observed in thermal balloon angioplasty in patients. This formulation may be useful to study remodeling and restenosis following interventional technologies.

Ret finger protein inhibits muscle differentiation by modulating serum response factor and enhancer of polycomb1.

Skeletal myogenesis is precisely regulated by multiple transcription factors. Previously, we demonstrated that enhancer of polycomb 1 (Epc1) induces skeletal muscle differentiation by potentiating serum response factor (SRF)-dependent muscle gene activation. Here, we report that an interacting partner of Epc1, ret finger protein (RFP), blocks skeletal muscle differentiation. Our findings show that RFP was highly expressed in skeletal muscles and was downregulated during myoblast differentiation. Forced expression of RFP delayed myoblast differentiation, whereas knockdown enhanced it. Epc1-induced enhancements of SRF-dependent multinucleation, transactivation of the skeletal α-actin promoter, binding of SRF to the serum response element, and muscle-specific gene induction were blocked by RFP. RFP interfered with the physical interaction between Epc1 and SRF. Muscles from rfp knockout mice (Rfp(-/-)) mice were bigger than those from wild-type mice, and the expression of SRF-dependent muscle-specific genes was upregulated. Myotube formation and myoblast differentiation were enhanced in Rfp(-/-) mice. Taken together, our findings highlight RFP as a novel regulator of muscle differentiation that acts by modulating the expression of SRF-dependent skeletal muscle-specific genes.

Dichromated gelatin reflection holographic optical element derived from Kodak 649F plates.

The characteristics of diffraction efficiency and spectral bandwidth of dichromated gelatin reflection holograms formed by a modified processing method are presented.

Simplified processing method of dichromated gelatin holographic recording material.

We are concerned with new simplified procedures for obtaining sufficient initial bias hardness of dichromated gelatin film by inserting the dehydration process before exposure.

Mechanisms of biomaterial-induced superoxide release by neutrophils.

Biomaterial-centered infection is an important cause of the failure of prosthetic implants and organs. Because neutrophils mediate host defense against infection, the effect of biomaterials on neutrophil superoxide release and the mechanism of that effect were investigated using three materials commonly employed in surgical practice. The graft materials were expanded polytetrafluorethylene (PTFE), polyurethane and woven dacron. Polystyrene, a commonly used laboratory support vessel, was also studied. Both polystyrene and polyurethane were activating, but serum inhibitable, whereas PTFE was nonactivating, and woven dacron was not activating unless serum was present. The signaling mechanisms used by these materials demonstrated time and material dependency. Pertussis toxin inhibition of G protein-dependent activation had little or no effect on biomaterial induced activation, whereas FMLP-induced activation of the same biomaterial-associated cells was inhibited. Protein kinase C inhibition with staurosporine greatly inhibited polystyrene-induced activation, but had only a partial effect with polyurethane and even less effect with the activation associated with serum-treated woven dacron. These studies demonstrated that biomaterial contact-induced neutrophil activation differed from that described for cells in suspension, and showed that activation mechanisms on one material cannot be extrapolated to mechanisms on other materials.

Biomaterial-neutrophil interactions: dysregulation of oxidative functions of fresh neutrophils induced by prior neutrophil-biomaterial interaction.

Biomaterial-associated infection results in increased morbidity and mortality, and may occur because of nonproductive premature activation of neutrophils resulting in impaired phagocyte function at the biomaterial surface in the event of bacterial challenge. To further explore the effects of this premature activation, we evaluated the supernatants of biomaterial associated neutrophils to determine whether soluble mediators were released, and the likely role of these mediators. We show that these supernatants contain a chemoattractant and thereby induce chemotaxis by fresh neutrophils. No evidence of enhanced oxidative free radical production by either unstimulated neutrophils or a primed response to other mediators occurs when neutrophils were incubated with these supernatants. We also examined the effect of adding fresh neutrophils to a biomaterial surface containing a previous inoculum of neutrophils, and observed that the fresh cells did not become stimulated to release reactive oxygen intermediates (ROI) and also exhibited impaired killing of staphylococci. These studies suggest that not only does the biomaterial surface activate the initial wave of neutrophils but that subsequent waves of neutrophils exhibit an impaired host-defense function. These results are consistent with the known impairment of host defense in the presence of biomaterials, and provide evidence for a long-term down-regulation of neutrophil function at biomaterial surfaces.

Biomaterial-induced alterations of neutrophil superoxide production.

Because periprosthetic infection remains a vexing problem for patients receiving implanted devices, we evaluated the effect of several materials on neutrophil free radical production. Human peripheral blood neutrophils were incubated with several sterile, lipopolysaccharide (LPS)-free biomaterials used in surgically implantable prosthetic devices: polyurethane, woven dacron, and velcro. Free radical formation as the superoxide (O2-) anion was evaluated by cytochrome c reduction in neutrophils that were exposed to the materials and then removed and in neutrophils allowed to remain in association with the materials. Neutrophils exposed to polyurethane or woven dacron for 30 or 60 min and then removed consistently exhibited an enhanced release of O2- after simulation via receptor engagement with formyl methionyl-leucyl-phenylalanine. Enhanced reactivity to stimulation via protein kinase C with phorbol myristate acetate, however, was not consistently observed. The cells evaluated for O2- release during continuous association with the biomaterials showed enhanced metabolic activity during short periods of association (especially with polyurethane and woven dacron). Although O2- release by neutrophils in association with these materials decreased with longer periods of incubation, it was not obliterated. These studies, therefore, show that several commonly used biomaterials activate neutrophils soon after exposure and that this activated state diminishes with prolonged exposure but nevertheless remains measurable. The diminishing level of activity with prolonged exposure, however, suggests that ultimately a depletion of reactivity may occur and may result in increased susceptibility to periprosthetic infection.

Genistein induces apoptosis of RPE-J cells by opening mitochondrial PTP.

Although previous studies demonstrated that genistein-induced apoptosis of various cell types including RPE-J cells, the involvement of mitochondrial events in such types of apoptosis has not been demonstrated to date. In this investigation of genistein-induced apoptosis of RPE-J cells, genistein induced the reduction of the mitochondrial membrane potential and the release of cytochrome c to cytosol. A mitochondrial permeability transition pore (PTP) blocker bongkrekic acid prevented the reduction of the mitochondrial membrane potential and cytochrome c release, and consequently abolished caspase-3 activation, nuclear condensation, and DNA fragmentation. On the other hand, zVAD-fmk did not inhibit the mitochondrial event such as the reduction of the mitochondrial membrane potential and cytochrome c release although it prevented caspase-3 activation, nuclear condensation, and DNA fragmentation. Taken together, genistein induces apoptosis of RPE-J cells by opening the mitochondrial PTP, and the mitochondrial event in this type of apoptosis is caused independently of caspase.

Initial and late results of Freedom coronary stent.

OBJECTIVES: Initial and late results after implantation of Freedom stents, a balloon expandable stainless steel coil stents were evaluated. METHODS: From Jun. 1996 to Nov. 1997, we implanted 123 Freedom stents in 122 lesions in 117 patients and performed follow-up coronary angiograms at 7.0 +/- 3.6 months after stents placement. Clinical courses after stenting and follow-up coronary angiographic findings were evaluated. Comparison of clinical, angiographic, and procedural factors according to the presence or absence of restenosis was performed. RESULTS: In 117 patients who underwent stents implantation, major complications were not observed. Follow-up coronary angiograms were performed in 47 stents in 41 patients (35%). Among 47 stents, angiographic significant restenosis (percent diameter stenosis > 50%) was observed in 13 (28%). Mean age in 41 patients was 59 +/- 9 years, with 27 male patients (66%). Indications for stents implantation were de novo lesions in 18 (38%), suboptimal results after PTCA in 18 (38%), bail-out lesions in 4 (9%) and restenotic lesions in 7 (15%). Lesion types by AHA/ACC classification were A in 1 (1%), B1 in 10 (21%), B2 in 17 (36%), and C in 19 (40%). Average lesion length was 13.7 +/- 9.0 mm, stent diameter 3.0 +/- 0.3 mm, and stent length 24.6 +/- 9.0 mm. There were no significant differences of the clinical, angiographic, and procedural characteristics according to the presence or absence of restenosis. CONCLUSION: Freedom coronary stents implantation is safely performed in various morphology of coronary lesions and no significant predictive factors on restenosis in follow-up coronary angiogram were observed.

Predictive factors for the second restenosis after coronary interventions.

One of the major limitations in coronary intervention is restenosis. This study was aimed to identify clinical, angiographic, and procedural factors that may be related to the second restenosis (SR). We studied 101 patients who underwent more than two follow-up coronary angiograms after two coronary interventions between January 1996 and December 1998 in Chonnam University Hospital (out of 4,092 total coronary interventions in 3,030 patients during the same period). The patients were divided into two groups according to the evidence of SR. Fifty-two patients (group A: 57+/-10 years, M:F = 44:8) who had SR and the other 49 patients (group B: 54+/-9 years, M:F = 44:5) without SR were analyzed. Clinical features, angiographic characteristics, coronary interventional procedures, and other risk factors were compared between two groups by univariate analysis and multivariate stepwise logistic regression analysis was performed for the predictive factors for SR. The clinical variables of age, sex, clinical diagnosis, and risk factors were not different between two groups. The lesion severer than B(2) by AHA/ACC classification were associated with SR (P<0.05). Recurrent angina as an indication for follow-up angiography was associated with SR (P<0.01). Predictive factors associated with SR were patient's subjective symptom and lesion severer than type B(2) according to AHA/ACC classification.

Tsutsugamushi myocarditis with congestive heart failure and persistent atrial standstill.

Acute infectious myocarditis is primarily by viruses and bacteria, but sometimes by rickettsia. Tsutsugamushi disease is a febrile illness caused by Rickettsia tsutsugamushi, and has been prevalent in Korea since 1985. Characteristics of tsutsugamushi disease are fever, rash and eschar. Tsutsugamushi myocarditis is rare. Cardiac involvement may include ST-T changes, PR prolongation, mild mitral regurgitation, and perivascular inflammation with myocardial necrosis. We describe here a 50-year-old woman who complained of fever, orthopnea and chest pain. Work-up of the patient revealed abdominal scar, positive tsutsugamushi antibody, congestive heart failure with severe mitral and tricuspid regurgitation, persistent atrial standstill on electrophysiologic study, junctional rhythm and ST-T changes mimicking anterior myocardial infarction and myocardial inflammation with perivasculitis on endomyocardial biopsy. The patient's condition improved with doxycycline and inotropics. Persistent atrial standstill during was found at the one-year follow-up.