Cardiovascular risk in fire academy instructors during live-fire simulation activity.

Firefighting is an extreme occupation with a risk of cardiovascular disease and sudden cardiac death due to strenuous physical exertion and psychological stress during fire suppression activity. This study aimed to investigate the vital signs (hemodynamic status) and biomarkers related to cardiac disease during live firefighting activity. In this pilot case-controlled study, seven firefighting training instructors performed a live-fire simulation for 40 min in a multi-storey training tower at the Gyenoggi-do Fire Service Academy Institute. Seven participants in the control group undertook similar exercises while wearing personal protective equipment. Cardiovascular evaluation, including vital signs and related biomarkers, was done before and after simulation until 24 h later. Nonparametric statistics were used to compare between the two groups and within the simulation group. After live-fire simulation, pulse pressure, heart rate (HR) and body temperature (BT) in the simulation group were higher than in the control group (pulse pressure 74.6 mmHg vs. 53.3 mmHg, HR 110 beats per minute (bpm) vs. 77 bpm, and BT 37.6 °C vs. 36.0 °C, P < 0.05 for all). Inflammatory cytokines (IL- 6), coagulation protein (fibrinogen), and stress hormones (cortisol, adrenocorticotrophic hormone) were elevated immediately after live-fire simulation, and IL-6 and fibrinogen remained elevated until 24 h after the simulation (all P < 0.05). Our exploratory analysis found increased altered hemodynamic status and stress-related biomarkers in live-fire firefighting simulations compared to controls. These markers have the potential to be used to decrease cardiovascular risk for firefighters, and warrant further investigation.

L'attaque de feu est une activité épuisante physiquement et psychologiquement stressante augmentant le risque cardio-vasculaire dont la mort subite. Cette étude pilote cas-témoin avait pour but d'étudier l'état hémodynamique et les biomarqueurs de pathologie cardiaque pendant l'attaque de feu. Elle a été menée sur 7 instructeurs de l'institut de formation du service d'incendie de la province de Gyenoggi-do, pendant un exercice de 40 mn en conditions réelles dans la tour d'entraînement. Le groupe contrôle effectuait un effort similaire, avec la même tenue, hors incendie. Les évaluations clinique et biologique étaient réalisées préalablement puis pendant 24 h. Des tests non paramétriques ont été utilisés pour les comparaisons entre groupes et au sein des groupes. En conditions réelles, la température corporelle (37,6/36°C), la PAM (74,6/53,3) et la fréquence cardiaque (110/77) étaient statistiquement plus élevées (p<0,05) que dans le groupe contrôle. De la même manière, IL6, fibrinogène, cortisol et ACTH étaient plus élevées en conditions réelles, IL6 et fibrinogène restant élevés à h24. L'élévation de ces marqueurs cliniques et biologiques de risque cardio-vasculaire et de stress nécessitent une étude plus poussée avant leur utilisation éventuelle pour évaluer la prévention.

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.

Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain.

Survival and proliferation of cancer cells are often associated with hyperactivity of the serine/threonine kinase, Akt. Herein, we show that prosurvival activity of Akt can be converted into prodeath activity by embedding an Akt recognition sequence in the apoptogenic BH3 domain of human BIM. The recognition sequence was created by introducing two mutations, I155R and E158S, into the core region of the BIM BH3 domain. Although a 21-mer BIM BH3 peptide containing these two mutations bound weakly to BCL-XL and BCL-2, this peptide with phosphorylation of Ser158 bound to these proteins with a dissociation constant of <10 nM. The crystal structure of the phosphorylated peptide bound to BCL-XL revealed that the phospho-Ser158 makes favorable interactions with two BCL-XL residues, which cannot be formed with unphosphorylated Ser158. Remarkably, the designed peptide showed a cytotoxic effect on PTEN-null PC3 tumor cells whose Akt activity is aberrantly high. The cell-killing activity disappeared when the cellular Akt activity was lowered by ectopic PTEN expression. Thus, these results lay a foundation for developing a peptide or protein agent that is dormant in normal cells but is transformed into a potent apoptogenic molecule upon phosphorylation by hyperactivity of Akt in cancer cells.

Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension.

We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as add-ons to metformin in patients with type 2 diabetes. Patients who were inadequately controlled by metformin were randomized and treated once daily with either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24 weeks, with a 28-week extension trial of lobeglitazone treatment in patients who consented. The primary endpoint was the change in glycated haemoglobin (HbA1c) concentration from baseline to week 24. At week 24, the mean change from baseline in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone group, with a mean difference of 0.01% [95% confidence interval (CI) of difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to metformin in terms of their efficacy and safety.

Efficacy and safety of teneligliptin, a dipeptidyl peptidase-4 inhibitor, combined with metformin in Korean patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled phase III trial.

The aim of the present study was to assess the efficacy and safety of teneligliptin in combination with metformin in Korean patients with type 2 diabetes mellitus who were inadequately controlled with metformin monotherapy. Patients [glycated haemoglobin (HbA1c) 7.0-10.0%, on stable metformin ≥1000 mg/day] were randomized 2 : 1 to receive 20 mg teneligliptin plus metformin (n = 136) or placebo plus metformin (n = 68). The primary endpoint was the change in HbA1c levels from baseline to week 16. The mean baseline HbA1c was 7.9% in the teneligliptin group and 7.8% in the placebo group. The differences between the teneligliptin and placebo groups regarding changes in HbA1c and fasting plasma glucose levels were -0.78 % and -1.24 mmol/l (22.42 mg/dl), respectively, at week 16. The incidence of adverse events was similar between the groups. The addition of teneligliptin once daily to metformin was effective and generally well tolerated in Korean patients with type 2 diabetes.

Production of secoisolariciresinol from defatted flaxseed by bacterial biotransformation.

AIMS: Secoisolariciresinol (SECO) is increasingly recognized for potential clinical application because of its preventive effects against breast and colon cancers, atherosclerosis and diabetes, and its production through biotransformation has been attempted. However, previously reported bacteria all required stringent anaerobic culture conditions, precluding large-scale production. Here, we report the isolation and characterization of bacteria that produce SECO under less stringent anaerobic culture conditions. METHODS AND RESULTS: Using defatted flaxseed as raw material, we isolated a facultative anaerobic bacterium from human faeces that hydrolysed secoisolariciresinol diglucoside-3-hydroxy-3-methyl glutaric acid (SDG-HMGA) oligomers in flaxseed to produce SECO. Both conventional assays and 16S rRNA gene sequence analysis demonstrated its close relatedness with Bacteroides uniformis. The transformation efficiency of SDG in defatted flaxseed to SECO was more than 80% by this bacterial strain. We investigated factors that might influence fermentation, such as redox potential and pH, for large-scale fermentation of defatted flaxseed to produce SECO. CONCLUSIONS: The method to produce SECO through biotransformation of defatted flaxseed with this bacterial strain is highly efficient and economic. SIGNIFICANCE AND IMPACT OF THE STUDY: This bacterial strain can transform SDG to SECO under less stringent anaerobic culture conditions, which will greatly facilitate industry-scale production of SECO.

Dark green discoloration of the urine after prolonged propofol infusion: a case report.

WHAT IS KNOWN AND OBJECTIVE: Propofol, a commonly used sedative, has on rare occasions, been reported to discolour urine green. However, in previous reports, it is uncertain that whether this colour change is dose dependent. We report on a patient who produced dark green discoloration of urine from prolonged propofol infusion, administered for intractable epilepsy. CASE SUMMARY: The colour intensity of the patient's urine was dependent on propofol infusion rate. Reducing propofol infusion rate lightened the colour of the urine, eventually back to normal. WHAT IS NEW AND CONCLUSION: Green discoloration of the urine from propofol infusion is dose dependent. It is usually benign and reversible, as was the case for our patient.

Downregulation of autophagy by Bcl-2 promotes MCF7 breast cancer cell growth independent of its inhibition of apoptosis.

The anti-apoptotic Bcl-2 protein, which confers oncogenic transformation and drug resistance in most human cancers, including breast cancer, has recently been shown to effectively counteract autophagy by directly targeting Beclin1, an essential autophagy mediator and tumor suppressor. However, it remains unknown whether autophagy inhibition contributes to Bcl-2-mediated oncogenesis. Here, by using a loss-of-function mutagenesis study, we show that Bcl-2-mediated antagonism of autophagy has a critical role in enhancing the tumorigenic properties of MCF7 breast cancer cells independent of its anti-apoptosis activity. A Bcl-2 mutant defective in apoptosis inhibition but competent for autophagy suppression promotes MCF7 breast cancer cell growth in vitro and in vivo as efficiently as wild-type Bcl-2. The growth-promoting activity of this Bcl-2 mutant is strongly correlated with its suppression of Beclin1-dependent autophagy, leading to sustained p62 expression and increased DNA damage in xenograft tumors, which may directly contribute to tumorigenesis. Thus, the anti-autophagic property of Bcl-2 is a key feature of Bcl-2-mediated oncogenesis and may in some contexts, serve as an attractive target for breast and other cancer therapies.

Transcortical sensory aphasia following a left frontal lobe infarction probably due to anomalously represented language areas.

A 57-year-old right-handed man presented with speech disturbance 1 day prior to his admission. The standardized aphasia test batteries showed transcortical sensory aphasia. MRI revealed a left frontal and insular infarct. Positron emission tomography scans also revealed a glucose hypometabolism in the same region as the infarcted area on MRI. Repeated aphasia testing showed that his aphasia only partially improved.

GP3 is a structural component of the PRRSV type II (US) virion.

Glycoprotein 3 (GP3) is a highly glycosylated PRRSV envelope protein which has been reported as being present in the virions of PRRSV type I, while missing in the type II PRRSV (US) virions. We herein present evidence that GP3 is indeed incorporated in the virus particles of a North American strain of PRRSV (FL12), at a density that is consistent with the minor structural role assigned to GP3 in members of the Arterivirus genus. Two 15aa peptides corresponding to two different immunodominant linear epitopes of GP3 derived from the North American strain of PRRSV (FL12) were used as antigen to generate a rabbit monospecific antiserum to this protein. The specificity of this anti-GP3 antiserum was confirmed by radioimmunoprecipitation (RIP) assay using BHK-21 cells transfected with GP3 expressing plasmid, MARC-145 cells infected with FL12 PRRSV, as well as by confocal microscopy on PRRSV-infected MARC-145 cells. To test if GP3 is a structural component of the virion, (35)S-labelled PRRSV virions were pelleted through a 30% sucrose cushion, followed by a second round of purification on a sucrose gradient (20-60%). Virions were detected in specific gradient fractions by radioactive counts and further confirmed by viral infectivity assay in MARC 145 cells. The GP3 was detected in gradient fractions containing purified virions by RIP using anti-GP3 antiserum. Predictably, the GP3 was less abundant in purified virions than other major structural envelope proteins such as GP5 and M. Further evidence of the presence of GP3 at the level of PRRSV FL12 envelope was obtained by immunogold staining of purified virions from the supernatant of infected cells with anti-GP3 antiserum. Taken together, these results indicate that GP3 is a minor structural component of the PRRSV type II (FL12 strain) virion, as had been previously described for PRRSV type I.

African swine fever virus.

African swine fever virus (ASFV) is a large, intracytoplasmically-replicating DNA arbovirus and the sole member of the family Asfarviridae. It is the etiologic agent of a highly lethal hemorrhagic disease of domestic swine and therefore extensively studied to elucidate the structures, genes, and mechanisms affecting viral replication in the host, virus-host interactions, and viral virulence. Increasingly apparent is the complexity with which ASFV replicates and interacts with the host cell during infection. ASFV encodes novel genes involved in host immune response modulation, viral virulence for domestic swine, and in the ability of ASFV to replicate and spread in its tick vector. The unique nature of ASFV has contributed to a broader understanding of DNA virus/host interactions.

Development of an advanced water treatment system for wastewater reuse.

The aim of this research was to develop an optimal reuse system applying various types of advanced oxidation processes such as titanium dioxide (TiO2), ozone (O3) and electro-coagulation/oxidation methods. This system is suitable for improving the treatment efficiency of difficult wastewaters, and for the efficient reuse of wastewater. The connecting systems were divided into various types to investigate the stability and treatment efficiency according to the kinds of waste load. Different treatment sequences were examined taking into consideration the characteristics and economical efficiency. In the case of electro-coagulation/oxidation + ozone system, the mean treatment efficiency in terms of BOD5, CODCr and SS removal was 98.7%. The effluent concentration was 50.2 mg l(-1), 38.3 mg l(-1), 30.4 mg l(-1), respectively. In considering the economical efficiency and commercial use, around an eighth of the treatment expenses and around a fifth of the maintenance expenses could be saved compared with existing water treatment systems. The initial construction expenses could be reduced by a third to a fifth. Therefore, if a proper implementation of this research is carried out in relation to site conditions and the purpose of the water reuse, the water reuse rate will be higher and water resources can be protected.

Potentiating effects of L-type Ca(2+) channel blockers on pentobarbital-induced hypnosis are influenced by serotonergic system.

In order to elucidate the mechanism(s) behind the interactions between barbiturates and Ca(2+) antagonists, the effects of three structurally diverse types of Ca(2+) antagonists combined or not with 5-HT on pentobarbital-induced hypnosis in mice were investigated. The results showed that dihydropyridine derivative nifedipine (10.0 and 20.0 mg/kg, p.o.) and other types of Ca(2+) antagonist, verapamil (5.0 and 10.0 mg/kg, p.o.) and diltiazem (2.5, 5.0 and 10.0 mg/kg, p.o.) increased both the sleeping time in hypnotic dosage of pentobarbital (45 mg/kg, i.p.) treated mice and the rate of sleep onset in the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.) treated mice in a dose-dependent manner, respectively, and these effects were significantly augmented by 5-hydroxytryptophan (5-HTP), the immediate precursor of 5-hydroxytryptamine (5-HT). Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleeping time and nifedipine (10.0 mg/kg, p.o.), verapamil (5.0 mg/kg, p.o.) and diltiazem (2.5 mg/kg, p.o.) abolished this effect. From these results, it should be presumed that the augmentative effect of L-type Ca(2+) channel blockers on pentobarbital-induced sleep may be influenced by serotonergic system.

Fangchinoline inhibited the antinociceptive effect of morphine in mice.

Fangchinoline (FAN), a non-specific calcium antagonist, is a major alkaloidal component of the creeper Stephania tetrandra S. Moore (or fenfangji). It has been shown to possess antagonistic activity on morphine-induced antinociception in mice. This study was undertaken to assess the antagonistic mechanism. The results demonstrated that FAN (IP) attenuated morphine (SC)-induced antinociception in a dose-dependent manner with significant effect at doses of 30 and 60mg/kg body wt. (IP) in the tail-flick test but not the tail-pinch tests, carried out in mice. This antagonism was abolished by pretreatment with a serotonin precursor, 5-hydroxytryptophan (5-HTP, IP), but not by pretreatment with a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA, IP) in the tail-flick test. On the other hand, the development of morphine-induced analgesic tolerance was not prevented by FAN. These results suggest that the serotonergic pathway may be involved in the antagonism of morphine-induced antinociception by FAN and, in agreement with other reports, also indicates the possible dissociation of the morphine analgesic effect from its tolerance-development mechanism.

Undiagnosed glucose intolerance encountered in clinical practice: reappraisal of the use of the oral glucose tolerance test.

BACKGROUND: In 1997, the Expert Committee of the American Diabetes Association (ADA) revised the diabetes mellitus (DM) diagnostic criteria to facilitate the diagnosis of DM on the basis of fasting plasma glucose (PG). The major purpose of the study is to evaluate if oral glucose tolerance test (OGTT) is still needed after the revision of criteria. METHODS: From September 1994 to March 1995, 247 ambulatory subjects referred by clinicians for 75-g OGTT were recruited for the study. Fasting and 2-h PG and serum insulin concentrations were determined. Additional fasting blood samples were collected for the measurement of HbA1c. We used the receiver operating characteristic (ROC) curve to locate a cut-point of fasting PG corresponding to 2-h PG of 200 mg/dl. RESULTS: The optimal fasting PG level depicted by ROC curve was more than 105 mg/dl, giving 80.6% sensitivity and 85.6% specificity for the diagnosis of DM in clinical setting. If fasting PG > or = 126 mg/dl was employed, the specificity was 98.3% but the sensitivity went down to 42.6%. High rates of glucose intolerance would remain undiagnosed in subjects with fasting PG less than 126 mg/dl (41.6% of them being IGT and 38.6% DM), if the OGTT was exempted from clinical practice. HbA1c more than 6.2% could be a clue to recognize undiagnosed DM, but was unable to separate impaired glucose tolerance (IGT) from non-DM. CONCLUSIONS: In the population studied, undiagnosed glucose intolerance can still be encountered in a large number of subjects with fasting PG less than 126 mg/dl. OGTT is still indispensable in clinical setting for the diagnosis of DM and IGT after the revision of diagnostic criteria.

Detection of epidermal growth factor receptor in the serum of patients with cervical carcinoma.

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignancies, including breast, lung, gastric, and cervical carcinoma. Its overexpression has been associated with disease progression or poor prognosis in patients with cervical carcinoma. In the present study, the levels of EGFR were determined in serum from 38 patients with cervical carcinoma [invasive or recurrent carcinoma (n = 26) and carcinoma in situ (CIS; n = 12)] and 38 healthy female controls using ELISA. The mean serum level for EGFR in patients with invasive or recurrent carcinoma (165 +/- 60 fmol/ml) was significantly elevated (P < 0.0001) compared with that of healthy controls (66 +/- 17 fmol/ml) and also higher (P = 0.015) than that of patients with CIS (126 +/- 25 fmol/ml). In addition, there was a significant difference in the mean serum levels of EGFR between patients with CIS and healthy controls (P < 0.0001). Thirty-five patients (92%) with cervical carcinoma [invasive or recurrent (n = 24) and CIS (n = 11)] had elevated serum, EGFR levels above the cutoff value of 100 fmol/ml (defined as 2 SD above the mean of the controls). In conclusion, the serum EGFR level was elevated in a significant proportion of patients with cervical carcinoma, and it demonstrated an increasing tendency according to disease progression from normal tissue through CIS to invasive cervical carcinoma. Therefore, it may have a potential usefulness as a biological marker of cervical carcinoma.