Risk of microbial transmission by reusing gloves after alcohol-based hand hygiene.

BACKGROUND: Disinfection of gloves might reduce the workload of healthcare workers, protect the environment, and bring economic benefits. Thus, the safety of hand hygiene of gloved hands is an important issue. AIM: We aimed to evaluate the risk of microbial transmission by comparing residual micro-organisms after multiple patient contacts, with or without gloves, in clinical practice. METHODS: Researchers, two with gloved hands (single or double gloves) and one with bare hands, made rounds of patients, followed by alcohol-based hand rub. Hand imprints were obtained before and after the rounds and cultured. The number of colony-forming units (cfu) of gloved and bare hands was compared, and the colony distribution was evaluated semi-quantitatively by hand region. FINDINGS AND CONCLUSION: A total of 108 imprints were obtained after 10 rounds. The median cfu counts were significantly higher in the gloved hands (single and double) than in the bare hands (9.00 vs 3.50, P=0.028). The cfu counts of single- and double-gloved hands were higher after than before contact (P=0.044 and P=0.001, respectively). Carbapenem-resistant Acinetobacter baumannii was identified in a pair of double gloves after a round, which included patients with the same organism with identical antibiotic susceptibility results. The mean percentage of colony-growing compartments from gloved hands was significantly higher than that of bare hands in the finger and wrist regions (P=0.019 and P=0.049, respectively). Compared with bare hands, reuse of gloves increased residual microbial colonies and potential for transmission of multi-drug-resistant organisms, even after using alcohol-based hand rub.

Nosocomial person-to-person transmission of severe fever with thrombocytopenia syndrome.

OBJECTIVES: This study is an epidemiologic investigation of nosocomial severe fever with thrombocytopenia syndrome virus (SFTSV) transmission among healthcare workers (HCWs) after contact with an index patient. The aim of this study was to determine whether exposure to blood or bloody respiratory secretion is associated with human-to-human transmission of SFTSV. METHODS: Eleven days after the index patient died, two HCWs who had close exposure to the patient presented with typical symptoms of SFTS. An epidemiological investigation was conducted on all 25 HCWs who had been in close contact with the index patient. Clinical and laboratory data were collected, and transmission rate before and after the index patient had haemorrhagic manifestations was analysed. RESULTS: Among 25 HCWs who had direct contact with the index patient, five HCWs were confirmed to have SFTS. All five HCWs had contact to blood or bloody respiratory secretions of the index patient without adequate use of personal protective equipment (PPE). No HCW with contact before haemorrhagic manifestations of the index patient contracted SFTS. Overall, the transmission rate was higher for HCWs who had contact after the index patient had haemorrhagic manifestations (33.3%, five of 15 HCWs, vs. 0%, zero of ten HCWs, p 0.041). CONCLUSIONS: In HCWs who are inadequately protected, person-to-person transmission of SFTSV may be associated with contact with blood or bloody respiratory secretions. Therefore, universal precaution and full PPE is highly recommended for protection against SFTSV when there are signs of bleeding.

Distal hyperintense vessel sign is associated with neurological deterioration in acute ischaemic stroke.

BACKGROUND AND PURPOSE: The aim was to evaluate the relationship between distal hyperintense vessel sign (HVS) and early neurological deterioration (END) in acute ischaemic stroke with large vessel steno-occlusion. METHODS: Acute ischaemic stroke patients with symptomatic severe steno-occlusion in the middle cerebral artery or internal carotid artery were recruited within 24 h from symptom onset. Stroke outcomes were evaluated using the National Institutes of Health Stroke Scale (NIHSS) score at the time of admission and at 72 h and 7 days. END was defined as an increment of ≥1 in the motor NIHSS score or ≥2 in the total NIHSS score. Distal HVS was defined as hyperintensity on fluid-attenuated inversion recovery image, located distal to the Sylvian fissure. The extent of distal HVS was divided into absent, subtle and prominent. RESULTS: Amongst a total of 325 participants, END was found in 103 (32%) patients. END was associated with age, atrial fibrillation, initial NIHSS score, initial infarct volume, severe leukoaraiosis, hemorrhagic infarction and distal HVS. In multivariate analysis, distal HVS remained an independent predictor of END [adjusted odds ratio (aOR) 2.86, 95% confidence interval (CI) 1.65-4.97, P < 0.001]. Initial infarct volume (aOR = 1.01, 95% CI 1.01-1.02, P < 0.001) and severe leukoaraiosis (aOR = 3.16, 95% CI 1.77-5.65, P < 0.001) were also associated with END, independently of distal HVS. In the analysis of the burden of distal HVS and stroke outcomes, prominent distal HVS was associated with stroke severity and infarct volume in a dose-response manner. CONCLUSIONS: Distal HVS is associated with END in acute ischaemic stroke patients with large vessel steno-occlusion.

Antiangiogenic Effect of Bevacizumab: Application of Arterial Spin-Labeling Perfusion MR Imaging in a Rat Glioblastoma Model.

BACKGROUND AND PURPOSE: The usefulness of arterial spin-labeling for the evaluation of the effect of the antiangiogenic therapy has not been elucidated. Our aim was to evaluate the antiangiogenic effect of bevacizumab in a rat glioblastoma model based on arterial spin-labeling perfusion MR imaging. MATERIALS AND METHODS: DSC and arterial spin-labeling perfusion MR imaging were performed by using a 9.4T MR imaging scanner in nude rats with glioblastoma. Rats were randomly assigned to the following 3 groups: control, 3-day treatment, and 10-day treatment after bevacizumab injection. One-way analysis of variance with a post hoc test was used to compare perfusion parameters (eg, normalized CBV and normalized CBF from DSC MR imaging and normalized CBF based on arterial spin-labeling) with microvessel area on histology. The Pearson correlations between perfusion parameters and microvessel area were also determined. RESULTS: All of the normalized CBV from DSC, normalized CBF from DSC, normalized CBF from arterial spin-labeling, and microvessel area values showed significant decrease after treatment (P < .001, P < .001, P = .005, and P < .001, respectively). In addition, normalized CBV and normalized CBF from DSC and normalized CBF from arterial spin-labeling strongly correlated with microvessel area (correlation coefficient, r = 0.911, 0.869, and 0.860, respectively; P < .001 for all). CONCLUSIONS: Normalized CBF based on arterial spin-labeling and normalized CBV and normalized CBF based on DSC have the potential for evaluating the effect of antiangiogenic therapy on glioblastomas treated with bevacizumab, with a strong correlation with microvessel area.

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM.

Association of lipid parameters and insulin resistance with bone health in South Korean adolescents.

UNLABELLED: This study investigated the association between lipid profiles and insulin resistance and bone mineral content (BMC) in Korean adolescents and found that BMC was inversely associated with triglyceride (TG) and homeostasis model assessment of insulin resistance (HOMA-IR). This association did not differ according to obesity status in either boys or girls. INTRODUCTION: To prevent future osteoporosis, it is important to identify factors that affect bone health in adolescents as well as adults. This study aimed to examine the association between lipid profiles and insulin resistance and BMC in Korean adolescents. METHODS: Data from 706 boys and 621 girls, who participated in the Korea National Health and Nutrition Examination Survey from 2008 to 2011, were analyzed. Lipid profiles were measured, and HOMA-IR was calculated to assess insulin resistance. BMC was measured for the total femur, femur neck, and lumbar spine by using whole-body dual-energy X-ray absorptiometry (DXA). RESULTS: TG level and HOMA-IR were negatively correlated with BMC at all three sites in boys. In girls, TG level showed a negative correlation with BMC at the femur neck and lumbar spine, and HOMA-IR was negatively associated with BMC at the femur neck only. These inverse associations did not differ according to obesity status in either sex. Adjusted means of BMC at the three sites in boys tended to decrease in the higher tertile groups of TG and HOMA-IR, and the adjusted means of BMC for the total femur in girls tended to decrease in the higher tertile groups of TG and HOMA-IR. CONCLUSIONS: BMC was inversely associated with TG and HOMA-IR in Korean adolescents, and this association was more pronounced in boys. This association did not differ according to obesity status in either sex.

Correlation of Asymmetry Indices Measured by Arterial Spin-Labeling MR Imaging and SPECT in Patients with Crossed Cerebellar Diaschisis.

BACKGROUND AND PURPOSE: Crossed cerebellar diaschisis, not only a secondary result of supratentorial infarction but also an indicator of clinical outcomes, has frequently been reported on PET and SPECT but has been rarely described with arterial spin-labeling MR imaging. The purpose of this study was to determine the ability of arterial spin-labeling MR imaging to evaluate crossed cerebellar diaschisis compared with that of SPECT. To our knowledge, this is the first study to validate arterial spin-labeling in crossed cerebellar diaschisis by using SPECT as a reference standard. MATERIALS AND METHODS: This study included 16 patients in whom crossed cerebellar diaschisis was shown on SPECT and 10 control subjects in whom crossed cerebellar diaschisis was not shown on SPECT. During the qualitative analysis, asymmetric cerebellar perfusion on arterial spin-labeling was divided into 1 of the following 3 grades by 2 blinded observers: the affected cerebellum was isointense compared with the unaffected cerebellum (grade I), it was slightly hypointense (grade II), or it was markedly hypointense (grade III). In the quantitative analysis, asymmetry indices were calculated by using SPECT and arterial spin-labeling images. For statistical analysis, κ statistics, the interobserver correlation coefficient, the independent t test, Pearson correlation, and linear regression analysis were used. RESULTS: Almost all the diagnoses of crossed cerebellar diaschisis on SPECT were noted on arterial spin-labeling in both qualitative and quantitative analyses with good interobserver agreement (κ = 0.961; interobserver correlation coefficient, 0.806). The mean asymmetry index of arterial spin-labeling (26.06 ± 9.00) was significantly larger than that for SPECT (15.28 ± 5.34; P < .001). There was a significant positive correlation between the asymmetry indices obtained for SPECT and those for arterial spin-labeling (r = 0.77 [95% CI, 0.443-0.916]; P < .001). The relationship of asymmetry indices between SPECT and arterial spin-labeling (x, y) was calculated as y = 6.2131 + 1.2986x (R(2) = 0.592; P < .001). CONCLUSIONS: Arterial spin-labeling can be a noninvasive alternative to SPECT for evaluating crossed cerebellar diaschisis.

Cytoplasmic DRAK1 overexpressed in head and neck cancers inhibits TGF-ß1 tumor suppressor activity by binding to Smad3 to interrupt its complex formation with Smad4.

Head and neck squamous cell carcinoma (HNSCC) is an extremely aggressive cancer with a poor prognosis and low patient survival. Because chemotherapy for advanced HNSCC is often ineffective, discovering new therapeutic targets that are important for HNSCC development and progression and elucidating their molecular mechanisms are required. In the present study, we describe the role of DRAK1 (death-associated protein kinase-related apoptosis-inducing kinase 1) as a novel negative regulator of the transforming growth factor-ß (TGF-ß) tumor suppressor signaling pathway for the first time in human HNSCC cells. DRAK1 was significantly overexpressed in primary human HNSCCs and in HNSCC cell lines. Through gain- and loss-of-function experiments, we demonstrated that the DRAK1 expression level regulated TGF-ß1-induced transcriptional activity and expression of the tumor suppressor gene p21(Waf1/Cip1). DRAK1 depletion enhanced TGF-ß1-induced growth inhibition in vitro and suppressed tumorigenicity in xenograft models in vivo. Mechanistically, DRAK1 was predominantly localized in the cytoplasm and bound to Smad3, thereby interrupting Smad3/Smad4 complex formation, which is the core process for the induction of tumor suppressor genes by TGF-ß1. Thus, our findings suggest that cytoplasmic DRAK1 increases tumorigenic potential through inhibition of TGF-ß1-mediated tumor suppressor activity in HNSCC cells and may be a potential therapeutic target for HNSCCs.

Atherogenic dyslipidaemic profiles associated with the development of Type 2 diabetes: a 3.1-year longitudinal study.

AIMS: While there is thought to be an association between glucose and lipid metabolism, it is largely unknown whether apolipoprotein B and non-high density lipoprotein (HDL) cholesterol are associated with the development of Type 2 diabetes. It is also unknown whether these atherogenic dyslipidaemic profiles have a stronger association with diabetes risk compared with conventional lipid measurements. METHODS: A total of 118 429 subjects without diabetes (70 980 men and 47 449 women), aged 17-90 years (mean age 39.6 years), were enrolled in this study and followed for a mean duration of 3.1 years. RESULTS: Apolipoprotein B and non-HDL cholesterol levels showed a strong association with the development of Type 2 diabetes compared with conventional lipid measurements and their ratios [hazard ratio per 1 sd; 1.39 (95% CI 1.37-1.42) and 1.38 (95% CI 1.35-1.40), respectively; both P < 0.001]. The Kaplan-Meier survival curve demonstrated that Type 2 diabetes developed more frequently as apolipoprotein B or non-HDL cholesterol levels increased across quartiles (both P < 0.001). In multivariate Cox regression analyses, both apolipoprotein B and non-HDL cholesterol were associated with the development of Type 2 diabetes, independent of other risk factor including age, sex, waist circumference, family history of diabetes, fasting serum glucose and insulin levels, HbA1c , systolic blood pressure and other conventional lipid measurements [hazard ratio per 1 sd; 1.14 (95% CI 1.11-1.18) and 1.13 (95% CI 1.10-1.16), respectively; both P < 0.001]. CONCLUSIONS: Atherogenic dyslipidaemia was more strongly associated with the development of Type 2 diabetes than conventional lipid measurements, and this effect was independent of other well-established risk factor for diabetes.

Association of serum C1q/TNF-Related Protein-9 (CTRP9) concentration with visceral adiposity and metabolic syndrome in humans.

BACKGROUND: C1q/TNF-Related Protein (CTRP) family members are novel adipokines that have anti-inflammatory, immunomodulatory, glucose-regulating and vascular effects. However, the metabolic effects of CTRP9 remain unclear in humans. OBJECTIVES: The aims of this study were to investigate whether serum CTRP9 concentrations are associated with glucose tolerance, metabolic parameters and abdominal fat accumulation. In addition, the authors investigated whether the aforementioned effects of CTRP9 are independent of serum adiponectin levels. METHODS: A total of 221 subjects (140 men and 81 women), 25-72 years of age (mean age 46.0 years), were randomly selected from two different study populations. The normal glucose tolerance group (n=120) was selected from one study population and the prediabetes/type 2 diabetes group (n=101) was selected from the other study population. Serum CTRP9, total adiponectin concentrations and abdominal fat via computed tomography scan were measured in all subjects. RESULTS: Subjects in the lower serum CTRP9 tertile were older, had metabolically unhealthy profiles and had lower serum total adiponectin levels when compared with subjects in the middle or upper serum CTRP9 tertiles. In addition, serum CTRP9 concentration were inversely correlated with age, blood pressure, fasting glucose, homeostasis model assessment for insulin resistance, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels (all P<0.01) and positively correlated with serum total adiponectin levels (P=0.03). In terms of abdominal fat accumulation, serum CTRP9 concentrations were inversely correlated with visceral fat amount (P<0.01), but no correlation was observed with subcutaneous fat amount. Finally, serum CTRP9 was inversely associated with the presence of metabolic syndrome, independent of age, sex, body mass index, smoking status, total cholesterol, visceral fat and serum total adiponectin concentrations (odds ratio per 1 s.d. 0.47; 95% confidence interval 0.32-0.70; P<0.01). CONCLUSIONS: Serum CTRP9 concentrations were positively associated with favorable glucose or metabolic phenotypes and absence of metabolic syndrome, independent of serum total adiponectin concentrations.

Apolipoprotein A1 potentiates lipoxin A4 synthesis and recovery of allergen-induced disrupted tight junctions in the airway epithelium.

BACKGROUND: Asthma is characterized by chronic airway inflammation triggered by various allergens in the environment. Defects in the bronchial epithelial interface with the external environment are the hallmark of asthma. Apolipoprotein A-1 (ApoA1) or ApoA1 mimetics have demonstrated anti-inflammatory activity and preventive effects in mouse models. OBJECTIVE: We investigated airway levels of ApoA1 in asthmatics and the possible role of ApoA1 in protection of the bronchial epithelium and in resolution of inflammation in cellular and animal models of asthma. METHODS: ApoA1 levels were measured in bronchoalveolar lavage fluid (BALF) from asthmatics and healthy controls. With treatment of ApoA1, mouse model of house dust mite (HDM)-driven asthma and cultured primary bronchial epithelial cells obtained from asthmatics were examined. Tight junction (TJ) expression in the bronchial epithelial cells was assessed by using confocal microscopy and immunoblot. RESULTS: Asthmatics showed significantly lower ApoA1 levels in bronchoalveolar lavage fluid than did healthy controls. Local ApoA1 treatment significantly decreased lung IL-25, IL-33, and thymic stromal lymphopoietin levels in HDM-challenged mice and inhibited allergen-induced production of these cytokines in cultured primary bronchial epithelial cells. ApoA1 promoted recovery of disrupted TJ proteins zonula occludens-1 and occludin in cultured primary bronchial epithelium obtained from asthmatics. ApoA1-induced increases in the TJ proteins were dependent on increased production of lipoxin A4 (LX A4). CONCLUSIONS AND CLINICAL RELEVANCE: ApoA1 enhances resolution of allergen-induced airway inflammation through promoting recovery of damaged TJs in the bronchial epithelium. ApoA1 could be a therapeutic strategy in chronic airway inflammatory diseases that are associated with a defective epithelial barrier, including asthma.

Risk factors for 30-day mortality in adult patients with pneumococcal bacteraemia, and the impact of antimicrobial resistance on clinical outcomes.

The clinical impact of antimicrobial resistance on the outcome of pneumococcal bacteraemia has remained unclear. This study aimed to evaluate risk factors for mortality and determine the impact of antimicrobial resistance on clinical outcomes. A total of 150 adult patients with pneumococcal bacteraemia were identified over a period of 11 years at Seoul National University Hospital. Of the 150 patients, 122 (81.3%) had penicillin-susceptible (Pen-S) strains and 28 (18.7%) penicillin-non-susceptible (Pen-NS) strains; 43 (28.7%) had erythromycin-susceptible (EM-S) strains and 107 (71.3%) erythromycin-non-susceptible (EM-NS) strains. On multivariate analysis, elevated APACHE II score [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.14-1.34, P<0.001) and presence of solid organ tumour (OR 2.99, 95% CI 1.15-7.80, P=0.025) were independent risk factors for mortality. Neither erythromycin resistance nor penicillin resistance had a significant effect on clinical outcomes. However, for the 76 patients with pneumococcal pneumonia, the time required for defervescence was significantly longer in the EM-NS group than in the EM-S group (5.45 ± 4.39 vs. 2.93 ± 2.56, P=0.03 by log rank test). In conclusion, antimicrobial resistance does not have an effect on mortality in adult patients with pneumococcal bacteraemia.

The role of serum adipocyte fatty acid-binding protein on the development of metabolic syndrome is independent of pro-inflammatory cytokines.

BACKGROUND AND AIM: Adipocyte fatty acid-binding protein (FABP4) is abundantly expressed in adipocytes and plays a role in glucose homeostasis. We analysed the relationship between serum FABP4 levels and the progression of metabolic syndrome in healthy adults. METHODS AND RESULTS: A total of 465 subjects were selected from participants in a medical check-up programme at a Health Promotion Center. Baseline serum FABP4 levels were measured, and the subjects were evaluated for the presence of metabolic syndrome (MetS) according to the recommendations of the American Heart Association/National Heart, Lung, and Blood Institute. The subjects were re-evaluated 4 years later. Baseline FABP4 concentrations were significantly higher in subjects with MetS than in those without MetS (P<0.001). At the 4-year follow-up, subjects in the highest FABP4 tertile at baseline exhibited higher values for body mass index, fat mass and percent body fat, as well as blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, insulin, homeostasis model assessment of insulin resistance, monocyte chemoattractant protein-1 and tumor necrosis factor-α levels (all P<0.05). The subjects with higher FABP4 levels had lower HDL-cholesterol concentrations (P<0.05). After adjustment for age, sex, change in percent body fat and baseline values for other metabolic and inflammatory parameters, FABP4 levels at baseline were shown to be strongly associated with the development of MetS by year 4 (odds ratio (OR), 5.75; 95% confidence interval (CI), 2.71-12.23 for highest tertile vs. lowest tertile, P<0.001) CONCLUSION: Baseline serum FABP4 levels appear to be a significant predictor for the future development of MetS, independent of pro-inflammatory cytokines.

Kimura disease: CT and MR imaging findings.

BACKGROUND AND PURPOSE: KD is a rare chronic inflammatory disorder of unknown etiology. The purpose of this study was to evaluate the CT and MR imaging findings of KD in the head and neck. MATERIALS AND METHODS: We retrospectively reviewed the CT (n = 21) and MR (n = 9) images obtained in 28 patients (24 males and 4 females; mean age, 32 years; age range, 10-62 years) with histologically proved KD in the head and neck. RESULTS: In these 28 patients, CT and MR images demonstrated a total of 52 non-nodal lesions, 1-8 cm in greatest diameter, in the head and neck. The lesions were unilateral in 11 patients and bilateral in 17 patients. Eleven patients had a solitary lesion, and 17 patients had 2-4 lesions. The parotid and/or periparotid area was the most frequent location, with 36 lesions in 23 patients. The margin of the lesions was well-defined in 1 and ill-defined in 51 cases. Compared with the adjacent muscle, the MR signal intensity of all lesions was iso- to slightly hyperintense on T1-weighted images and hyperintense on T2-weighted images. Most of the lesions demonstrated mild or moderate enhancement on postcontrast CT scans and moderate or marked enhancement on postcontrast MR images. MR images also showed tubular signal-intensity voids in 7 of 13 lesions. Associated lymphadenopathy was demonstrated in 23 patients, usually bilaterally. CONCLUSIONS: Multiple ill-defined enhancing masses within and around the parotid gland with associated regional lymphadenopathy are characteristic CT and MR imaging findings of KD in the head and neck.

Pharmacokinetic comparison and bioequivalence of two leflunomide formulations in humans: a single dose, randomized, open-label, two-way crossover study.

BACKGROUND AND AIMS: Leflunomide is a disease-modifying antirheumatic drug (DMARD) with comparable efficacy to methotrexate in the treatment of rheumatoid arthritis. We compared the pharmacokinetic characteristics of two leflunomide formulations in healthy subjects and assessed whether these formulations were bioequivalent. SUBJECTS AND METHODS: A randomized, two-way, crossover study was conducted in 24 healthy male volunteers to compare the pharmacokinetics of two leflunomide formulations after administration of a single 20 mg dose of each drug with a 7 week washout period. Blood samples for the analysis of A77 1726, the main active metabolite of leflunomide, were obtained 624 h after drug administration. RESULTS: After administering a single dose of 20 mg of each leflunomide formulation, the mean AUC(0-t) and Cmax values of A771726 were 487.3 +/- 167.6 microg*h/ml and 2.24 +/- 0.85 microg/ml for the reference formulation and 468.5 +/- 148.6 microg*h/ml and 1.98 +/- 0.45 microg/ml for the test formulation, respectively. The 90% confidence intervals of the test/reference mean ratios for AUC(0-t), AUC(0-inf), and Cmax fell within the predetermined equivalence range of 0.8 - 1.25. No serious adverse events occurred during the study period. CONCLUSIONS: The two leflunomide formulations showed similar pharmacokinetic profiles in terms of A77 1726, and the test formulation was found to be bioequivalent to the reference formulation with respect to the rate and extent of leflunomide absorption.

High fat stores in ectopic compartments in men with newly diagnosed type 2 diabetes: an anthropometric determinant of carotid atherosclerosis and insulin resistance.

OBJECTIVE: The objective of this study was to analyze how fat partitioning in the liver, muscle and visceral compartments is altered by diabetes and age, and whether altered fat distribution is associated with a higher carotid artery intima-media thickness (C-IMT) and insulin resistance. METHODS: This was an observational study performed on 21 young healthy men (mean age + or - s.d., 28.6 + or - 3.8 years) and 73 men with newly developed type 2 diabetes (38 young (29.2 + or - 4.1 years) and 35 middle-aged (47.1 + or - 6.0 years) subjects). Abdominal visceral and subcutaneous fat areas, mid-thigh muscle attenuation and liver attenuation characteristics were determined; the mid-thigh muscle was divided into low- and normal-density muscle areas. RESULTS: The young and middle-aged diabetic subjects had higher visceral fat areas, higher liver attenuation and higher lipid-rich muscle (greater low-density muscle area and decreased muscle attenuation) when compared with healthy individuals; however, no differences were observed between the two diabetic groups. In contrast, the C-IMT increased with both age and diabetes. On the basis of multiple regression analyses, mid-thigh low-density muscle area and muscle attenuation were independently associated with the C-IMT, and the mid-thigh normal-density muscle area and muscle attenuation were independent factors of insulin resistance. CONCLUSIONS: High fat stores within ectopic compartments were observed at an early stage in the development of diabetes. Furthermore, altered lipid partitioning within muscle was independently associated with carotid atherosclerosis and insulin resistance.

Effects of bupivacaine and ropivacaine on field potential in rat hippocampal slices.

BACKGROUND: In spite of more than 20 yr of research, the mechanism whereby local anaesthetics act on the brain to mediate anaesthesia still remains unclear. Furthermore, the effect of local anaesthetics on neuronal excitability and synaptic transmission in the hippocampus has not been reported. Thus, the purpose of the present study was to find out the differences between the local anaesthetics, bupivacaine and ropivacaine, in their actions on synaptic transmission of brain in the context of hippocampal field potential. METHODS: Brains were removed from 3- to 4-week-old rats and transverse slices (300 microm thick) were prepared using a microslicer. A slice was then placed on the centre on a multielectrode dish probe. To record evoked field potentials at 64 sites, a pair of single planar microelectrodes delivering bipolar constant current pulses (45-90 microA, 0.1 ms) was applied. Electrophysiological recordings were measured using the 64-channel multielectrode dish. RESULTS: The amplitude of field potential in the rat CA1 region was inhibited by both bupivacaine and ropivacaine. The inhibitory effects of bupivacaine and ropivacaine on field potential amplitudes in CA1 were similar. For bupivacaine 10 microg ml(-1), inhibited field potentials were incompletely recovered; in contrast, for 10 ropivacaine microg ml(-1), inhibited field potentials were completely recovered after washing out with incubation solution. CONCLUSIONS: Inhibitory effects of bupivacaine and ropivacaine on hippocampal field potential amplitude and recovery rate after washout after bupivacaine or ropivacaine treatment represent the underlying mechanisms of the systemic toxicity of local anaesthetics.