Author Correction: mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis.

mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation. Evidence in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate response element binding protein (ChREBP) activity, histone acetylation, and gluco-lipogenic gene expression. Substrate utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate through acetyl-CoA synthetase 2 (ACSS2). These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-CoA synthesis.

Prognostic nutritional index is correlated with disease activity in patients with systemic lupus erythematosus.

The prognostic nutritional index (PNI), which is calculated using serum albumin level and total lymphocyte count in the peripheral blood, is regarded as an index that reflects the immunonutritional status of patients. PNI was calculated in 217 systemic lupus erythematosus (SLE) patients according to the following formula: 10 × serum albumin value (g/dL) + 0.005 × peripheral lymphocyte count (/mm3). Pearson's correlation analysis was used to elucidate the correlation between continuous variables. Linear and logistic regression analyses were performed to assess the correlation between laboratory variables and SLE Disease Activity Index-2000 (SLEDAI-2 K) and to differentiate between active and inactive SLE. Ninety-three patients were classified as active SLE (SLEDAI-2 K ≥ 5) and 124 as inactive SLE. Patients with active SLE exhibited lower median PNI than those with inactive SLE (39.0 vs. 49.1, p < 0.001). Multivariable logistic regression analysis revealed PNI as an independent predictor of active SLE. Multivariable linear regression analysis revealed that PNI was significantly correlated with laboratory variables of SLEDAI-2 K, erythrocyte sedimentation rate, C-reactive protein and SLEDAI-2 K. Furthermore, in patients who switched from active to inactive SLE after treatment ( n = 55), PNI increased as disease activity improved ( p < 0.001), which suggests that PNI may be useful for estimating SLE activity.

Renal outcome after kidney-transplantation in Korean patients with lupus nephritis.

We investigated renal outcome of kidney-transplantation in 19 Korean recipients with biopsy-proven lupus nephritis and compared it with 18 Korean age- and gender-matched recipients without lupus nephritis who were diagnosed with end-stage renal disease caused by renal diseases other than lupus nephritis in a single centre. We reviewed histological findings of kidneys and calculated cumulative dose of immunosuppressive agents. We assessed renal flare of systemic lupus erythematosus, recurrence of lupus nephritis and graft failure as prognosis. The mean age of recipients with lupus nephritis was 43.5 years and all patients were female. Six patients had class III, 10 had class IV and three had class V. There were no meaningful differences in demographic data, renal replacement modality, cumulative doses of immunosuppressants and prognosis between recipients with and without lupus nephritis. Eight patients experienced renal flare of systemic lupus erythematosus, but there were no cases of recurrence of lupus nephritis or graft failure in recipients with lupus nephritis. Kidney-recipients with class IV lupus nephritis exhibited a lower cumulative renal flare of systemic lupus erythematosus free survival rate than those with class III lupus nephritis. In conclusion, renal outcome of kidney-transplantation in patients with lupus nephritis is similar to that in those without lupus nephritis, and class IV was associated with renal flare of systemic lupus erythematosus.

Platelet collagen receptor Glycoprotein VI-dimer recognizes fibrinogen and fibrin through their D-domains, contributing to platelet adhesion and activation during thrombus formation.

Essentials Glycoprotein VI (GPVI) binds collagen, starting thrombogenesis, and fibrin, stabilizing thrombi. GPVI-dimers, not monomers, recognize immobilized fibrinogen and fibrin through their D-domains. Collagen, D-fragment and D-dimer may share a common or proximate binding site(s) on GPVI-dimer. GPVI-dimer-fibrin interaction supports spreading, activation and adhesion involving αIIbß3. SUMMARY: Background Platelet collagen receptor Glycoprotein VI (GPVI) binds collagen, initiating thrombogenesis, and stabilizes thrombi by binding fibrin. Objectives To determine if GPVI-dimer, GPVI-monomer, or both bind to fibrinogen substrates, and which region common to these substrates contains the interaction site. Methods Recombinant GPVI monomeric extracellular domain (GPVIex ) or dimeric Fc-fusion protein (GPVI-Fc2 ) binding to immobilized fibrinogen derivatives was measured by ELISA, including competition assays involving collagenous substrates and fibrinogen derivatives. Flow adhesion was performed with normal or Glanzmann thrombasthenic (GT) platelets over immobilized fibrinogen, with or without anti-GPVI-dimer or anti-αIIbß3. Results Under static conditions, GPVIex did not bind to any fibrinogen substrate. GPVI-Fc2 exhibited specific, saturable binding to both D-fragment and D-dimer, which was inhibited by mFab-F (anti-GPVI-dimer), but showed low binding to fibrinogen and fibrin under our conditions. GPVI-Fc2 binding to D-fragment or D-dimer was abrogated by collagen type III, Horm collagen or CRP-XL (crosslinked collagen-related peptide), suggesting proximity between the D-domain and collagen binding sites on GPVI-dimer. Under low shear, adhesion of normal platelets to D-fragment, D-dimer, fibrinogen and fibrin was inhibited by mFab-F (inhibitor of GPVI-dimer) and abolished by Eptifibatide (inhibitor of αIIbß3), suggesting that both receptors contribute to thrombus formation on these substrates, but αIIbß3 makes a greater contribution. Notably, thrombasthenic platelets showed limited adhesion to fibrinogen substrates under flow, which was further reduced by mFab-F, supporting some independent GPVI-dimer involvement in this interaction. Conclusion Only dimeric GPVI interacts with fibrinogen D-domain, at a site proximate to its collagen binding site, to support platelet adhesion/activation/aggregate formation on immobilized fibrinogen and polymerized fibrin.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein can reflect systemic lupus erythematosus activity.

Serum Mac-2-binding protein (M2BP) is elevated in various chronic inflammatory diseases, and evidence suggests that glycosylation of M2BP induces discrete biological effects. However, the role of serum M2BP in systemic lupus erythematosus (SLE) is still unclear. Recently, a Wisteria floribunda agglutinin-positive-M2BP (WFA+-M2BP) immunoassay has shown promise in detecting highly glycosylated M2BP. In this study, by using WFA+-M2BP immunoassay, we measured serum M2BP in 203 SLE patients and evaluated its clinical significance. Eighty patients were classified as having active SLE and 123 patients as having inactive SLE. The median serum M2BP was higher in patients with active SLE than in those with inactive SLE (2.1 vs. 0.9, p < 0.001). In multivariate linear regression analysis, serum M2BP, anti-dsDNA, C3 and erythrocyte sedimentation rate (ESR) were associated with SLEDAI-2K. Serum M2BP also strongly correlated with laboratory variables related to SLEDAI-2K, ESR and C-reactive protein. Furthermore, multivariate logistic regression analysis demonstrated that serum M2BP was useful in predicting active SLE. Finally, following immunosuppressive treatment, elevated serum M2BP significantly decreased along with improvement in disease activity. These findings suggest that serum M2BP might contribute to the inflammatory process in SLE, and measuring serum M2BP might be a useful marker to assess SLE disease activity.

Clustering of glycoprotein VI (GPVI) dimers upon adhesion to collagen as a mechanism to regulate GPVI signaling in platelets.

Essentials Dimeric high-affinity collagen receptor glycoprotein VI (GPVI) is present on resting platelets. Spatio-temporal organization of platelet GPVI-dimers was evaluated using advanced microscopy. Upon platelet adhesion to collagenous substrates, GPVI-dimers coalesce to form clusters. Clustering of GPVI-dimers may increase avidity and facilitate platelet activation SUMMARY: Background Platelet glycoprotein VI (GPVI) binding to subendothelial collagen exposed upon blood vessel injury initiates thrombus formation. Dimeric GPVI has high affinity for collagen, and occurs constitutively on resting platelets. Objective To identify higher-order oligomerization (clustering) of pre-existing GPVI dimers upon interaction with collagen as a mechanism to initiate GPVI-mediated signaling. Methods GPVI was located by use of fluorophore-conjugated GPVI dimer-specific Fab (antigen-binding fragment). The tested substrates include Horm collagen I fibers, soluble collagen III, GPVI-specific collagen peptides, and fibrinogen. GPVI dimer clusters on the platelet surface interacting with these substrates were visualized with complementary imaging techniques: total internal reflection fluorescence microscopy to monitor real-time interactions, and direct stochastic optical reconstruction microscopy (dSTORM), providing relative quantification of GPVI cluster size and density. Confocal microscopy was used to locate GPVI dimer clusters, glycoprotein Ib, integrin α2 ß1 , and phosphotyrosine. Results Upon platelet adhesion to all collagenous substrates, GPVI dimers coalesced to form clusters; notably clusters formed along the fibers of Horm collagen. dSTORM revealed that GPVI density within clusters depended on the substrate, collagen III being the most effective. Clusters on fibrinogen-adhered platelets were much smaller and more numerous; whether these are pre-existing oligomers of GPVI dimers or fibrinogen-induced is not clear. Some GPVI dimer clusters colocalized with areas of phosphotyrosine, indicative of signaling activity. Integrin α2 ß1 was localized to collagen fibers close to GPVI dimer clusters. GPVI clustering depends on a dynamic actin cytoskeleton. Conclusions Platelet adhesion to collagen induces GPVI dimer clustering. GPVI clustering increases both avidity for collagen and the proximity of GPVI-associated signaling molecules, which may be crucial for the initiation and persistence of signaling.

Acute toxicity of organic antifouling biocides to phytoplankton Nitzschia pungens and zooplankton Artemia larvae.

The toxicity of the antifouling biocides Irgarol 1051, Diuron, Chlorothalonil, Dichlofluanid, Sea-nine 211, Copper pyrithione, Zinc pyrithione, Ziram and Zineb were evaluated on Nitzschia pungens and Artemia larvae. Results showed that EC50 for Irgarol 1051 was 0.586µgl-1 was the strongest effect on N. pungens following by Copper pyrithione (4.908µgl-1), Ziram (5.421µgl-1), Zinc pyrithione (5.513µgl-1), Diuron (6.640µgl-1), Zineb (232.249µgl-1), Sea-nine 211(267.368µgl-1), Chlorothalonil (360.963µgl-1) and Dichlofluanid (377.010µgl-1) in 96h. In Artemia larvae, the biocides were evaluated the LC50 for larval survivals at 48h. Sea-nine 211 and Copper pyrithione were 0.318 and 0.319mgl-1. Chlorothalonil, Zinc pyrithione and Ziram were 2.683, 3.147 and 4.778mgl-1. Irgarol 1051, Diuron, Zineb and Dichlofluanid were 9.734, 30.573, 41.170 and 154.944mgl-1. These results provide baseline data concerning the toxicity of antifouling biocides against marine environment.

External validation of the prognostic index in acute paraquat poisoning.

OBJECTIVE: Some studies have evaluated the prognostic indicators associated with acute paraquat (PQ) poisoning. In this study, we externally validated the Yamaguchi index, which showed a good prognostic relevance in predicting the outcome of PQ poisoning. METHODS: A retrospective analysis of 297 patients was performed. The Yamaguchi index was calculated using the following equation: Eq1 = (K(+) × HCO3(-))/(Creatinine × 0.088)(mEq/L) against time from PQ ingestion (T). The patients were divided into three groups: group A: Eq1 > 1500 - 399 × log T, group B: 930 - 399 × log T < Eq1 ≤ 1500 - 399 × log T, and group C: Eq1 ≤ 930 - 399 × log T). RESULTS: The overall mortality rate was 65.3% (194 of 297). The mortality rates of the three groups stratified by the Yamaguchi index were 7.1% (2 of 28), 22.4% (15 of 67), and 87.6% (177 of 202). The area under the receiver-operating characteristic curve for predicting mortality from the external validation of the Yamaguchi index was 0.842 (95% confidence interval: 0.795-0.882). CONCLUSION: The Yamaguchi index is a reliable prognostic factor and could be helpful in predicting mortality due to PQ poisoning.

Lupus cystitis in Korean patients with systemic lupus erythematosus: risk factors and clinical outcomes.

This study was performed to investigate the clinical characteristics of lupus cystitis and determine the risk factors and clinical outcomes of lupus cystitis in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed 1064 patients at Seoul St. Mary's Hospital in Seoul, Korea, from 1998 to 2013. Twenty-four patients had lupus cystitis. Lupus cystitis was defined as unexplained ureteritis and/or cystitis as detected by imaging studies, cystoscopy, or bladder histopathology without urinary microorganisms or stones. Three-fourths of patients with lupus cystitis had concurrent lupus mesenteric vasculitis (LMV). The initial symptoms were gastrointestinal in nature for most patients (79.2%). High-dose methylprednisolone was initially administered to most patients (91.7%) with lupus cystitis. Two patients (8.3%) died of urinary tract infections. Sixty-five age- and sex-matched patients with SLE who were admitted with other manifestations were included as the control group. Patients with lupus cystitis showed a lower C3 level (p = 0.031), higher SLE Disease Activity Index score (p = 0.006), and higher ESR (p = 0.05) upon admission; more frequently had a history of LMV prior to admission (p < 0.001); and less frequently had a history of neuropsychiatric lupus (p = 0.031) than did patients with SLE but without lupus cystitis. The occurrence of lupus cystitis was associated with a history of LMV (OR, 21.794; 95% CI, 4.061-116.963). The median follow-up period was 3.4 years, and the cumulative one-year mortality rate was 20%. Complications developed in 33.3% of patients with lupus cystitis and were related to survival (log-rank p = 0.021). Our results suggest that the possibility of lupus cystitis should be considered when a patient with SLE and history of LMV presents with gastrointestinal symptoms or lower urinary tract symptoms. Development of complications in patients with lupus cystitis can be fatal. Thus, intensive treatment and follow-up are needed, especially in the presence of complications.

Pregnancy and patients with preexisting lupus nephritis: 15 years of experience at a single center in Korea.

We investigated obstetric outcomes and comorbidities during pregnancy in females with preexisting lupus nephritis (LN) and identified predictors for renal flare. In cases of renal flare during pregnancy, we assessed the long-term post-delivery renal outcome. We performed a retrospective analysis of 183 systemic lupus erythematosus (SLE) pregnancies including blood chemistry, urinalysis, urinary protein, and disease activity recorded at prepregnancy, during pregnancy, and at one month, six months, and one year post-delivery. Pregnancies with preexisting LN had a greater frequency of adverse obstetric outcomes and maternal comorbidity. Renal flares occurred in 50.7% of pregnancies with preexisting LN, 89.2% of which were reactivations. Renal flare among pregnancies with SLE was predicted based on preexisting lupus nephritis (OR 17.73; 95% CI, 5.770-54.484), an active disease prior to pregnancy (OR 2.743; 95% CI, 1.074-7.004), and prepregnancy eGFR < 90 ml/min/1.73 m(2) (OR 11.151; 95% CI, 3.292-37.768). Persistent LN one year after delivery was observed in 33.3% of pregnancies. The median follow-up time after delivery was 5.9 (3.1-9.7) years and chronic kidney disease (CKD) occurred in 21.4% of pregnancies with renal flare. In patients with renal flare, failing to achieve a ≥ 50% reduction in urine protein levels within six months, longer total duration of renal flare, and acute kidney injury at renal flare was associated with CKD development. Females with preexisting LN should achieve remission before pregnancy. When patients experience renal flares during pregnancy, it is important to reduce the proteinuria level by >50% within six months and to achieve early remission for excellent long-term renal outcomes.

Osteonecrosis of the hip in Korean patients with systemic lupus erythematosus: risk factors and clinical outcome.

OBJECTIVE: The objective of this paper is to identify the risk factors for development of symptomatic osteonecrosis (ON) and predictors of total hip replacement (THR) among systemic lupus erythematosus (SLE) patients in Korea. METHODS: The medical records of 1051 patients with SLE were reviewed, and 73 patients with symptomatic ON were identified. Among them, 64 patients were eligible for the analysis. Sixty-four age- and sex-matched SLE patients without apparent ON were included as disease controls. The risk factors for development of symptomatic ON were identified by logistic regression analyses. The predictors of THR were determined by Cox proportional hazards regression analyses. RESULTS: Among 64 patients with ON, 59 had ON of the hip and 36 underwent THR. Independent risk factors for development of symptomatic ON included Cushingoid body habitus (OR 21.792 (95% confidence interval (CI) 2.594-183.083)), use of cyclophosphamide (OR 2.779 (95% CI 1.106-6.981)) and azathioprine (OR 2.662 (95% CI 1.143-6.200)). In the Cox proportional hazards model, only advanced radiological stage of ON (Association for Research on Osseous Circulation (ARCO) stage) was a statistically significant predictor of THR. In subgroup analysis with stage I-III ON, multivariate Cox regression analysis showed neuropsychiatric SLE (NPSLE) (HR 6.295 (95% CI 2.178-18.192)) and cumulative prednisolone dose in the first six months after ON diagnosis > 0.9 g (HR 3.238 (95% CI 1.095-9.58)) to be independent predictors. CONCLUSIONS: Advanced ARCO stage at the onset of ON is an independent risk factor for THR in SLE patients with ON. In ARCO stage I-III ON, patients with NPSLE and those receiving > 0.9 g prednisolone during the first six months after the ON diagnosis are likely to require THR.

Posterior reversible encephalopathy syndrome in Korean patients with systemic lupus erythematosus: risk factors and clinical outcome.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon neurologic condition associated with systemic lupus erythematosus (SLE). This study aimed to demonstrate the risk factors and clinical outcome of PRES in patients with SLE. Fifteen patients with SLE were diagnosed with PRES by characteristic clinical manifestations and magnetic resonance imaging (MRI) features from 2000 to 2012. Clinical profiles and outcomes were assessed for this study population. Additionally, 48 SLE patients with neurologic symptoms who underwent brain MRI were included for comparative analyses. The median age and duration of SLE in patients with PRES was 27 and 6.1 years, respectively. Comparison between patients with and without PRES revealed significant differences in the presentation of hypertension and seizure, lupus nephritis with renal insufficiency, treatment with high-dose steroid and cyclophosphamide, recent transfusion, and lupus activity measured by SLE disease activity index. Renal failure was the single independent factor with a high odds ratio of 129.250 by multivariate analysis. Of 15 patients, four experienced relapse and two died of sepsis during hospitalization. Our results suggest that lupus nephritis with renal dysfunction and other related clinical conditions can precede the occurrence of PRES in patients with SLE. It is important to perform early brain imaging for a timely diagnosis of PRES when clinically suspected.

The phenotypic characteristic of liver-derived stem cells from adult human deceased donor liver.

Liver transplantation is the only effective treatment for end-stage liver disease. Because of the limited donor availability, attention has been focused on the possibility to restore liver mass and function through cell transplantation. Stem cells are a promising source for liver repopulation after cell transplantation, but whether or not the adult liver contains hepatic stem cells is highly controversial. Several studies have suggested the presence of stem cells in the adult normal human liver. However, a population with stem cell properties has not yet been isolated. The purpose of this study was to identify and characterize progenitor cells in normal adult human liver. We isolated and expanded human liver stem cells (HLSCs) from a donated liver not suitable for liver transplantation or characterizing them by fluorescence-activated cell sorter, polymerase chain reaction, and immunofluorescence assay. HLSCs expressed the mesenchymal stem cell markers CD29, CD73, CD44, CD90, CD105, and CD166 but not the hematopoietic stem cell markers CD34, CD45, and CD117. HLSCs were also positive for vimentin and nestin, a stem cell marker. The absence of staining for cytokeratin-19, CD117, and CD34 indicated that HLSCs were not oval stem cells. In addition, HLSCs expressed CD26, and in a small percentage of cells, cytokeratin-8 and cytokeratin-18, indicating a partial commitment to hepatic cells. We concluded that HLSCs expressed several mesenchymal but not hematopoietic stem cell markers as well as CD26 and CK18, indicating a partial commitment to hepatic cells.

Differentiation and major histocompatibility complex antigen expression in human liver-derived stem cells.

Stem cells are a promising source for liver repopulation after cell transplantation, but whether the adult liver contains hepatic stem cells is controversial. The purpose of this study was to characterize the properties and expression profile of major histocompatibility complex (MHC) antigens on the surface of human-derived stem cells. Human liver-derived stem cells (HLSC7) were isolated from the nontumorous tissue of a patient who underwent a resection of an hepatic hemangioendothelioma. We characterized HLSC7 using a fluorescence-activated cell sorter, polymerase chain reactions, and immunofluorescence assays. HLSC7 expressed mesenchymal but not hematopoietic stem cell markers. HLSC7 underwent osteogenic, chondrogenic, and hepatogenic differentiation when cultured in appropriate differentiation media. However, HLSC7 did not differentiate into adipocytes. In addition, HLSC7 did not express MHC class II (HLA-DP, -DQ, and -DR) antigens. However, they did express MHC class I antigens. These results suggest that human liver-derived stem cells express MHC class I antigens and thus may be rejected on transplantation. Therefore, in addition to studies on stem cell differentiation, one must overcome immunologic barriers for successful clinical application of this therapy.

Live cell-imaging perfusion culture system of liver sinusoidal endothelial cells to mimic stem cell engraftment in liver.

Hepatocyte and various hepatic stem cell transplantations have been studied as alternative therapies to orthotopic liver transplantation for liver injury. The engraftment of transplanted cells into the parenchyma requires transmigration through sinusoidal endothelial cells (SECs), the only cellular barrier. In this study, we constructed a SEC-imaging perfusion culture system that mimics sinusoids with respect to hemorheologic properties. SECs were successfully maintained for 24 hours. Human liver stem cells (HLSCs) were used as a model of transplanted cells for in vitro engraftment to SECs under perfusion culture conditions. Conditions of high shear stress perfusion with 0.34 dyne/cm(2) significantly reduced cell adhesion in contrast to lower shear stress conditions of 0.1 and 0.03 dyne/cm(2). Among the biologic perfusion fluids, namely, fetal bovine serum (FBS), pig plasma, and 5% human albumin solution, HLSCs showed significantly greater attachment to SECs when perfused with FBS, which is well known to contain abundant amounts of adhesion molecules. This biomimetic SEC perfusion culture system may provide a useful tool to study engraftment mechanisms and to evaluate the effects of various enhancers as an alternative to animal models.

Predicted effect-site concentration of propofol and sufentanil for gynecological laparoscopic surgery.

BACKGROUND: this study was to estimate the predicted effect-site concentration of propofol administered by a target-controlled infusion (TCI) for maintenance of anesthesia based on the bispectral (BIS) index as a measure of hypnosis in laparoscopic surgery. METHOD: one-hundred and sixty unpremedicated patients undergoing gynecologic laparoscopy were assigned randomly to receive one of the target effect-site concentrations of propofol 2.0, 2.5, 3.0, 3.5 and 4.0 microg/ml during TCI with propofol and sufentanil. The dose-response relationship of propofol for the maintenance of adequate anesthesia based on BIS, movement and hemodynamic response was investigated using a fixed effect-site concentration of sufentanil (0.2 ng/ml). The BIS values, hemodynamic variables, time course during emergence and intraoperative awareness were also assessed. RESULTS: the predicted effect-site propofol concentrations for adequate anesthesia at the skin incision in 50% (EC(50) ) and 95% (EC(95) ) of patients undergoing gynecologic laparoscopy were 2.2 and 3.7 microg/ml, respectively. The predicted propofol EC(50) and EC(95) to maintain adequate anesthesia in these patients were 2.6 microg/ml (95% CI 2.3-2.7 microg/ml) and 3.6 microg/ml (95% CI 3.3-4.0 microg/ml), respectively. The BIS values, effect-site concentration of propofol, hemodynamic data and time course during emergence and post-operative adverse events were comparable in each group. There were no reports of intraoperative awareness in the post-anesthetic care unit. CONCLUSION: based on the anesthetic depth assessed by the clinical signs and BIS monitoring, the predicted effect-site propofol concentrations for the maintenance of anesthesia in patients undergoing gynecologic laparoscopy were similar in those administered adequate anesthesia at the skin incision during TCI.

Impaired skin wound healing in lumican-null mice.

BACKGROUND: Previous studies have demonstrated that the lack of lumican delayed corneal wound healing in lumican-null (Lum(-/-) ) mice. This defect is rescued by the addition of glycosylated lumican core protein to the injured corneas. OBJECTIVES: We examined the hypothesis that lumican is also required for the healing of cutaneous wounds using Lum(-/-) mice. METHODS: We demonstrated the basic thinner skin phenotypes in Lum(-/-) mice at different time points and the changes in arrangement of collagen fibres by transmission electron microscopy (TEM). A full skin thickness wound was generated by punch biopsy (6 mm diameter) in experimental Lum(-/-) and wild-type mice. The closure of injured skin was measured after various periods of time (3, 6, 12, 18 days). Specimens of injured and uninjured skin (serving as control) were then subjected to morphological examination with haematoxylin and eosin and Masson trichrome stains, and by TEM. Immunohistochemical staining with anti-CD68 antibody was used to assess the presence of macrophages in injured skin healing for various periods of time. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to elucidate the transforming growth factor (TGF)-ß1-induced myofibroblast phenotypic genes. RESULTS: Skin of adult Lum(-/-) mice (3 months and older) was much thinner (40% less) than that of age-matched wild-type mice. This phenomenon was aggravated in older mice. TEM revealed disoriented and irregular collagen fibrils in the dermis of Lum(-/-) mice. Delayed wound healing with an increase in inflammatory macrophages was compatible with the delayed response of the expression of TGF-ß1, type I collagen α1 and fibronectin at the mRNA level by semiquantitative RT-PCR in the Lum(-/-) mice. CONCLUSIONS: Our data demonstrate that lumican plays pivotal roles in skin collagen fibrillogenesis and wound healing.

Intravenous anti-obsessive agents: a review.

Oral antidepressants are currently the first-line pharmacotherapy for obsessive-compulsive disorder (OCD), but response rates can often be low and with delayed onset of therapeutic action. Some reports have suggested that intravenous (i.v.) anti-obsessive agents may have faster onset of action and greater efficacy. A Medline search was conducted for all reports pertaining to the use of i.v. antidepressants for OCD. Search terms included: 'intravenous', 'clomipramine', 'selective serotonin reuptake inhibitor', 'tricyclic', 'citalopram', 'sertraline', 'paroxetine', 'fluvoxamine', 'SSRIs' and 'intravenous antidepressants'. Relevant articles mainly investigated clomipramine (CMI) with one open trial examining citalopram. Intravenous agents appear to be well-tolerated, particularly in those who have failed oral agents, and may act more rapidly to produce initial clinical response, although this advantage is often lost over time. Preliminary evidence suggests subgroups of patients with severe treatment-refractory OCD may benefit from i.v. anti-obsessive agents, CMI and citalopram. Larger, controlled trials are needed for more definitive conclusions.

Implementation and performance evaluation of mobile ad hoc network for Emergency Telemedicine System in disaster areas.

So far we have developed Emergency Telemedicine System (ETS) which is a robust system using heterogeneous networks. In disaster areas, however, ETS cannot be used if the primary network channel is disabled due to damages on the network infrastructures. Thus we designed network management software for disaster communication network by combination of Mobile Ad hoc Network (MANET) and Wireless LAN (WLAN). This software maintains routes to a Backbone Gateway Node in dynamic network topologies. In this paper, we introduce the proposed disaster communication network with management software, and evaluate its performance using ETS between Medical Center and simulated disaster areas. We also present the results of network performance analysis which identifies the possibility of actual Telemedicine Service in disaster areas via MANET and mobile network (e.g. HSDPA, WiBro).