Effect of carvacrol essential oils on immune response and inflammation-related genes expression in broilers challenged by lipopolysaccharide.

This experiment was conducted to study the effects of orally administered carvacrol essential oils on immune response and inflammation-related genes expression in broilers challenged by lipopolysaccharide (LPS). Eighty 28-day-old (1.28 ± 0.15 kg) ROSS 308 broilers were assigned to a 2 × 2 factorial arrangement of treatments (20 pens of 1 chick/trt). Factors were carvacrol essential oil (orally administered or non-orally administered) and LPS (challenged or non-challenged). Individually housed broilers were randomly assigned (n = 20 broilers per treatment: 10 males and 10 females) to four treatments: (1) basic diet (CTR), (2) basic diet + carvacrol (CAR), (3) basic diet + LPS-challenge (LPS), (4) basic diet + carvacrol + LPS-challenge (CAR+LPS). All were fed with the same diet. The experimental period was for 15 d, after which injecting LPS significantly up-regulated the gene expression levels of TNF-α (P < 0.05), IL-1ß (P < 0.05), IL-6 (P < 0.05), IL-8 (P < 0.05), TLR2 (P < 0.05), TLR4 (P < 0.05), NF-κB p65 (P < 0.05), AVBD-9 (P < 0.05), and SIgA(P < 0.05) compared with the CTR group; the broilers were challenged by LPS after oral administration of carvacrol, they had significant lower on the gene expression levels of TNF-α (P < 0.05), IL-1ß (P < 0.05), IL-6 (P < 0.05), TLR4 (P < 0.05), NF-κB p65 (P < 0.05), and AVBD-9 (P < 0.05) than the LPS group. In conclusion, the broilers orally administrated carvacrol essential oils inhibited the secretion of inflammatory cytokines caused by LPS, affected the pathway of TLRs/NF-κB, and showed an anti-inflammatory function.

[On the epidemic of cholera and its prevention and control by the railway authorities in 1932].

In 1932, the epidemic of cholera in China was serious, spreading to all provinces nationwide, causing heavy casualties. In order to prevent cholera epidemics spread along the railway line, the National Government Ministry of Railways and the local railway administration had taken all countermeasures, including the promulgation of epidemic prevention laws and regulations, quarantine, isolated check-up, disinfection, vaccination and even interruption of traffic. The measures of railway authorities had achieved a certain success. In August 1932, cholera epidemic began to subside gradually.

Tetrafluoroethane (R134a) hydrate formation within variable volume reactor accompanied by evaporation and condensation.

Vast size hydrate formation reactors with fast conversion rate are required for the economic implementation of seawater desalination utilizing gas hydrate technology. The commercial target production rate is order of thousand tons of potable water per day per train. Various heat and mass transfer enhancement schemes including agitation, spraying, and bubbling have been examined to maximize the production capacities in scaled up design of hydrate formation reactors. The present experimental study focused on acquiring basic knowledge needed to design variable volume reactors to produce tetrafluoroethane hydrate slurry. Test vessel was composed of main cavity with fixed volume of 140 ml and auxiliary cavity with variable volume of 0 ∼ 64 ml. Temperatures at multiple locations within vessel and pressure were monitored while visual access was made through front window. Alternating evaporation and condensation induced by cyclic volume change provided agitation due to density differences among water and vapor, liquid and hydrate R134a as well as extended interface area, which improved hydrate formation kinetics coupled with latent heat release and absorption. Influences of coolant temperature, piston stroke/speed, and volume change period on hydrate formation kinetics were investigated. Suggestions of reactor design improvement for future experimental study are also made.

Geographical distribution of indoor radon and related geological characteristics in Bonghwa County, a provisional radon-prone area in Korea.

The detailed indoor radon survey was conducted during a year (from September 2012 to August 2013) quarterly in Bonghwa county, one of the provisional radon-prone areas in Korea. The surveyed area was selected on the basis of previously conducted nationwide radon survey results. In order to minimise statistical and environmental uncertainties, ∼3 % of the entire dwellings were carefully selected based on the statistical annual report of Bonghwa county. The measurement is carried out by using solid-state nuclear track detector. The range of indoor radon concentration in each dwelling was 4.36-858 Bq m(-3) and that of annual effective dose due to inhaled radon of the resident in each dwelling was 0.19-23.5 mSv y(-1). Each dwelling was determined for geology criterion using one-way Analysis of Variance for the purpose of comparing indoor radon distribution with geology. Geographical distribution of indoor radon is closely related to the geological characteristics of basement rocks. In addition, the comparison between geographical distribution of indoor radon and terrestrial gamma radiation was done.

Comparative analysis of bilirubin in correlation to albumin between nephrotic syndrome patients and postoperative gastroparesis syndrome patients.

This study aimed to disclose the potential causality of low bilirubin in patients with nephrotic syndrome (NS). Correlation analysis was carried out on total bilirubin (TBIL) to serum albumin (ALB), urine protein (Upr), and urinary microalbumin/creatinine (Umalb/cr) for three groups in a case-control study. P < 0.001 was observed for TBIL, ALB, Umalb/cr, and Upr between the NS and chronic nephritis (CN) groups, and P values of 0.0001, 1.000, 0.0001, and 0.0001 were observed for TBIL, ALB, Umalb/cr, and Upr, respectively, between the postoperative gastroparesis (PGS) and CN groups. The values of r and P in correlation to TBIL were 0.549 and 0.000 for ALB, -0.405 and 0.000 for Umalb/cr, and -0.448 and 0.000 for Upr in the NS group; -0.007 and 0.959 for ALB, 0.213 and 0.091 for Umalb/cr, and -0.082 and 0.519 for Upr in the PGS group; and 0.509 and 0.000 for ALB, -0.431 and 0.000 for Umalb/cr, and -0.362 and 0.002 for Upr in the CN group. A probable causality is implied between the low level of blood bilirubin and its loss in urine in NS patients. This conclusion may provide a theoretical basis for the feasibility of therapies against oxidative stress in NS patients.

Correlation between genotype and phenotype in patients with bi-allelic SLC26A4 mutations.

Mutation of SLC26A4 is the most common cause of prelingual hearing loss in East Asia. Patients with SLC26A4 mutations have variable phenotypes ranging from non-syndromic hearing loss to Pendred syndrome. Here, we analyzed the correlation between genotype and various inner ear phenotypes and found a possible underlying mechanism. This study included 111 patients with bi-allelic SLC26A4 mutations who had bilateral enlarged vestibular aqueduct (EVA) and hearing loss. p.H723R (61%), c.919-2A>G (24%), and p.T410M (4%) were the most common mutations in Korean patients with EVAs. Residual hearing in patients with c.919-2A>G or p.T410M mutations was better than that of patients with p.H723R homozygous mutations. Interestingly, quantitative polymerase chain reaction showed normal pendrin transcript (6-17% of normal levels) was produced from patients with c.919-2A>G homozygous mutations. Surface expression ratio of pendrin and residual anion exchange activity were higher in cells transfected with p.T410M in comparison to cells transfected with p.H723R. These results suggest that there is a correlation between degree of residual hearing and the SLC26A4 genotype commonly found in the East Asian population.

The population pharmacokinetics of fentanyl in patients undergoing living-donor liver transplantation.

Fentanyl, an opioid analgesic with a high hepatic extraction ratio, is frequently used to supplement general anesthesia during liver transplantation and is also continuously infused to provide postoperative analgesia. However, because fentanyl is metabolized mainly in the liver, the pharmacokinetics of fentanyl may vary widely during the different phases of the surgery, potentially leading to adverse events. Using nonlinear mixed-effects modeling, we characterized the pharmacokinetics of fentanyl in 15 patients (American Society of Anesthesiologists Physical Status Classification 2 or 3) undergoing living-donor liver transplantation (LDLT). Fentanyl was continuously infused at the rate of 200-400 µg/h throughout the operation. The time course of the fentanyl plasma concentration levels was best described in terms of a two-compartment model. Estimates were made of the pharmacokinetic parameters during the preanhepatic, anhepatic, and neohepatic phases: central volume of distribution (V(1)) (l): 59.0 + hourly volume infused by rapid infusion system (RIS) × 42.5, 113.0, and 189.0, respectively, × (body weight/69)(1.3); peripheral volume of distribution (V(2)) (l): 94.3, 412.0, and 427.0, respectively; intercompartmental clearance (Q) (l/h): 96.4 × (cardiac output (CO)/6.7)(2.5), 22.6, and 28.2, respectively; metabolic clearance (Cl) (l/h): 21.7 during the preanhepatic and neohepatic phases, and 0 during the anhepatic phase. The preanhepatic central volume of distribution was found to be markedly influenced by the massive infusion of fluids and blood products. The more hyperdynamic the circulation was during the preanhepatic phase, the higher the distributional clearance.

A retrospective case-control study of intraoperative cardiac dysfunction in elderly patients (≥60 years) undergoing live donor liver transplantation.

BACKGROUND: The age range of patients accepted for the orthotopic liver transplantation (OLT) has widened. Concerns have arisen, therefore, about the ability of the hearts of elderly patients to manage these stressful conditions. The aim of this study was to investigate the preoperative echocardiographic findings and the intraoperative cardiac dysfunction among elderly cirrhotic recipients undergoing live donor OLT. METHODS: In this retrospective case-control study we evaluated clinical data, echocardiography, and intraoperative right-sided heart hemodynamic measurements from 2007 and 2009 among 56 recipients aged at least 60 years who were matched for gender and the severity of cirrhosis. Intraoperative cardiac dysfunction was defined as a decreased left ventricular stroke work index despite an increase in right ventricular end diastolic volume index (RVEDVI) or pulmonary artery occlusion pressure (PAOP). We compared measurements at predetermined times during the anhepatic and neohepatic periods with those at baseline. RESULTS: Older recipients (mean, 63 years; range, 60-69) showed significantly reduced early diastolic annular velocity (E'), early maximal ventricular filling velocity (E)/late filling velocity (A) ratio, and increased A on echocardiography versus younger recipients (mean 48 years; range, 31-56). We observed negative correlation between age and E' (r = -0.44; P < .001) and a positive correlation between age and E/E' (r = 0.31; P < .01). The incidence of intraoperative cardiac dysfunction did not differ between case and control groups with an increase of RVEDVI (11.4% vs 10.6%) or PAOP (27.2% vs 25.0%) during the anhepatic and neohepatic periods. A higher proportion of older recipients needed inotropic agents during OLT (60.7% vs 39.3%; P = .04). CONCLUSIONS: OLT patients of ar least 60 years of age may not show a greater incidence of cardiac dysfunction during OLT versus younger ones, although older recipients showed reduced diastolic function and more frequently required inotropic support.

Clinical evaluation of DFN3 patients with deletions in the POU3F4 locus and detection of carrier female using MLPA.

X-linked deafness type 3 (DFN3), the most prevalent X-linked form of hereditary deafness, is caused by mutations of the POU3F4 locus in the Xq21 region. We evaluated two Korean families showing typical characteristics of DFN3, such as congenital hearing loss and pathognomonic inner ear anomalies. Genetic analysis of these families did not reveal any mutations in the POU3F4 coding sequence. Instead, one family carried a genomic deletion upstream of POU3F4 gene, where the regulatory element is predicted to reside, and the other family possessed a deletion of almost the entire Xq21 region. The lack of mutation in the POU3F4 coding sequence makes the detection of carrier females using conventional sequencing methods difficult. By applying the multiplex ligation-dependent probe amplification (MLPA) method, we successfully determined the carrier status of female members in these families, demonstrating that MLPA is a rapid and accurate way to detect POU3F4 deletions in sporadic undiagnosed carriers of DNF3.

Pharmacokinetics and pharmacodynamics of a new reformulated microemulsion and the long-chain triglyceride emulsion of propofol in beagle dogs.

BACKGROUND AND PURPOSE: Microemulsion propofol was developed to eliminate lipid solvent-related adverse events of long-chain triglyceride emulsion (LCT) propofol. We compared dose proportionality, pharmacokinetic and pharmacodynamic characteristics of both formulations. EXPERIMENTAL APPROACH: The study was a randomized, two-period and crossover design with 7-day wash-out period. Microemulsion and LCT propofol were administered by zero-order infusion (0.75, 1.00 and 1.25 mg kg(-1) min(-1)) for 20 min in 30 beagle dogs (male/female = 5/5 for each rate). Arterial samples were collected at preset intervals. The electroencephalographic approximate entropy (ApEn) was used as a measure of propofol effect. Dose proportionality, pharmacokinetic and pharmacodynamic bioequivalence were evaluated by non-compartmental analyses. Population analysis was performed using nonlinear mixed effects modelling. KEY RESULTS: Both formulations showed dose proportionality at the applied dose range. The ratios of geometric means of AUC(last) and AUC(inf) between both formulations were acceptable for bioequivalence, whereas that of C(max) was not. The pharmacodynamic bioequivalence was indicated by the arithmetic means of AAC (areas above the ApEn time curves) and E(0) (baseline ApEn)-E(max) (maximally decreased ApEn) between both formulations. The pharmacokinetics of both formulations were best described by three compartment models. Body weight was a significant covariate for V(1) of both formulations and sex for k(21) of microemulsion propofol. The blood-brain equilibration rate constants (k(e0), min(-1)) were 0.476 and 0.696 for microemulsion and LCT propofol respectively. CONCLUSIONS AND IMPLICATIONS: Microemulsion propofol was pharmacodynamically bioequivalent to LCT propofol although pharmacokinetic bioequivalence was incomplete, and demonstrated linear pharmacokinetics at the applied dose ranges.

Classification of temporal bone pneumatization based on sigmoid sinus using computed tomography.

AIM: To analyse several reference structures using axial computed tomography (CT) imaging of the temporal bone, which may reflect pneumatization of the entire temporal bone by statistical correlation to the actual volume of the temporal bone measured using three-dimensional reconstruction. MATERIALS AND METHODS: One hundred and sixteen temporal bones were studied, comprising 48 with normal findings and 68 sides showing chronic otitis media or temporal bone fracture. After measuring the volume of temporal bone air cells by the volume rendering technique using three-dimensional reconstruction images, classification of temporal bone pneumatization was performed using various reference structures on axial images to determine whether significant differences in the volume of temporal bone air cells could be found between the groups. RESULTS: When the sigmoid sinus at the level of the malleoincudal complex was used in the classification, there were statistically significant differences between the groups that correlated with the entire volume of the temporal bone. Grouping based on the labyrinth and the ascending carotid artery showed insignificant differences in volume. Furthermore, there was no significant correlation between the cross-sectional area of the antrum and the entire volume of the temporal bone. CONCLUSION: The degree of pneumatization of temporal bone can be estimated easily by the evaluation of the air cells around the sigmoid sinus on axial CT images.

Accuracy of magnetic resonance cholangiopancreatography for locating hepatolithiasis and detecting accompanying biliary strictures.

BACKGROUND AND STUDY AIMS: Magnetic resonance cholangiopancreatography (MRCP) is rapidly replacing diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in various pancreaticobiliary diseases. This study was designed to evaluate the accuracy of MRCP in detection of hepatolithiasis and accompanying biliary strictures. PATIENTS AND METHODS: A prospective study over 2 years was conducted in 66 patients with primary intrahepatic stones. All patients with hepatolithiasis underwent percutaneous transhepatic cholangioscopy (PTC) within 2 weeks of the MRCP examination. The MRCP findings were compared with those of PTC as the reference standard for assessing the location of intrahepatic stones and the presence or absence of accompanying biliary strictures. RESULTS: The sensitivity, specificity, and accuracy of MRCP for detecting and locating intrahepatic stones were 97 %, 99 %, and 98 %, respectively. The sensitivity, specificity, and accuracy of MRCP for detecting and locating intrahepatic bile duct strictures were 93 %, 97 %, and 97 %, respectively. During PTC, six of the 66 patients (9 %) were found on histology to have intraductal cholangiocarcinoma in stone-bearing ducts, which had not been suspected on MRCP. CONCLUSIONS: In this study, MRCP allowed intrahepatic stones and accompanying biliary strictures to be located accurately. MRCP may therefore be able to replace diagnostic ERCP in patients with primary intrahepatic stones. However, MRCP had a limited ability to reveal concurrent intraductal cholangiocarcinoma associated with hepatolithiasis.

Comparison of the acute pharmacodynamic responses after single doses of ephedrine or sibutramine in healthy, overweight volunteers.

OBJECTIVE: With an increase in the incidence of obesity, tremendous effort has been devoted to the development of weight loss agents and the prospective surrogate markers of both a product's efficacy and safety. The objective of the present study was to compare the pharmacodynamic responses of ephedrine and sibutramine using surrogate markers of weight loss potential and potential adverse events. DESIGN AND SUBJECTS: The study was designed as a 5-way, randomized, double-blinded, placebo-controlled trial with 3 single doses of ephedrine sulfate (0.25, 0.5 and 1 mg x kg(-1)) followed by an open-labeled sibutramine (10 mg) treatment. Healthy, mildly overweight (BMI = 25) subjects were administered the respective treatment and pharmacokinetic and pharmacodynamic measurements (body surface temperature, resting metabolic rate, blood pressure, heart rate, glucose, glycerol, nonesterified fatty acids, triglycerides) were obtained for 8 hours post dose and for an additional 4 measurements during the sibutramine treatment period. RESULTS: Sibutramine treatment significantly increased resting metabolic rate compared to the placebo condition. Ephedrine significantly increased heart rate, systolic blood pressure and glucose but did not significantly affect other measurements. CONCLUSION: Both sibutramine and ephedrine have been shown to have weight loss potential, however, they elicit different metabolic and biochemical responses after a single dose. The nontherapeutic responses from these types of compounds may serve as a screening tool for the development of agents in the treatment of obesity.

Three-dimensional simulation of the Blalock-Taussig shunt using computational fluid dynamics.

To examine blood flow after the placement of a Blalock-Taussig shunt, three complex T-figure models were developed according to shunt size and the degree of pulmonary artery hypoplasia. With the use of computational fluid dynamics, the net energy loss and wall shear stress were calculated under pulsatile conditions. We calculated that the 5-mm shunt carried the least energy loss, but the most wall shear stress. In this simulation, the 5-mm shunt was thought to be superior to the 4-mm and 3-mm shunts in terms of energy loss and smooth flow, but it produced high wall shear stress.

Giant vegetation mimicking cardiac tumor in tricuspid valve endocarditis after catheter ablation.

A 33-year-old man suffered from fever of unknown origin and developed right-sided heart failure. A transeshophageal echocardiogram revealed an progressive enlarging mass in the right atrium mainly attached to the tricuspid valve and a previous ablation site, which mimicked a cardiogenic tumor. He was operated on to remove the mass and intraoperative pathology showed it was large vegetation and secondary granulation due to tricuspid endocarditis. Tricuspid valve replacement was performed combined with reconstruction of the right atrial wall.

Three-dimensional simulation of coronary artery bypass grafting with the use of computational fluid dynamics.

In search of an optimal anastomosis conformation in coronary artery bypass grafting surgery and flow visualization, three-dimensional simulation of the anastomosis has been developed with the use of computational fluid dynamics. To simulate the surgery, a Y-figure model with proximal stenosis was developed in three cases according to angles ranging from 10 degrees to 30 degrees. The boundary condition of velocity and flow of the model were given based on the average velocity and flow of coronary artery measured intraoperatively. Using this information, the fluid dynamics of three models were calculated by commercial computation fluid dynamics code. The convergent results showed the least recirculating jet in the 10 degrees anastomosis without back flow into the graft. The total energy loss in the field was most affected in 30 degrees anastomosis. The wall shear stress profile showed maximum values at the heel region where recirculating jet takes place. This simulation suggests that the more acute is the angle of anastomosis, the smaller is the energy loss. Based on this phenomenon, surgery should therefore be designed to obtain as acute an angle as possible in light of the fluid dynamics.

Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products.

Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are recessive genetic disorders with susceptibility to cancer and similar cellular phenotypes. The protein product of the gene responsible for A-T, designated ATM, is a member of a family of kinases characterized by a carboxy-terminal phosphatidylinositol 3-kinase-like domain. The NBS1 protein is specifically mutated in patients with Nijmegen breakage syndrome and forms a complex with the DNA repair proteins Rad50 and Mrel1. Here we show that phosphorylation of NBS1, induced by ionizing radiation, requires catalytically active ATM. Complexes containing ATM and NBS1 exist in vivo in both untreated cells and cells treated with ionizing radiation. We have identified two residues of NBS1, Ser 278 and Ser 343 that are phosphorylated in vitro by ATM and whose modification in vivo is essential for the cellular response to DNA damage. This response includes S-phase checkpoint activation, formation of the NBS1/Mrel1/Rad50 nuclear foci and rescue of hypersensitivity to ionizing radiation. Together, these results demonstrate a biochemical link between cell-cycle checkpoints activated by DNA damage and DNA repair in two genetic diseases with overlapping phenotypes.