Purpose: Colistin heteroresistance mediates the failure of antibiotic treatments, is prone to lead to colistin resistance, and has been frequently reported in Klebsiella pneumoniae. This study investigated origins of the increase in colistin resistance following colistin exposure to colistin-heteroresistant K. pneumoniae. Methods: A modeled colistin-heteroresistant K. pneumoniae strain (i.e., mimicking colistin- heteroresistant [m-CLHR]) was generated using a susceptible K. pneumoniae strain ATCC 10031 and its resistance-induced mutant. Heteroresistance patterns were investigated through population analysis profiling (PAP), competition assays, and fluctuation and stability tests. An in vitro time-killing assay for colistin was performed for the m-CLHR to identify the change in susceptible and resistant populations before and after colistin exposure. Results: The generated m-CLHR strain showed a typical heteroresistance pattern for colistin in PAP, and its competition assay did not show fitness costs for any population. The ratio of resistant cells to susceptible cells did not deviate significantly from the range of heteroresistance in the fluctuation test, while the ratios of resistant cells preserved their stability. The in vitro time-killing assay thus showed that the resistant cells increased upon colistin exposure; sequencing analyses confirmed that the surviving resistant cells did not originate from susceptible cells by mutation. This study successfully modeled a colistin-heteroresistant K. pneumoniae strain, i.e., m-CLHR. Conclusion In this modeled heteroresistant strain, only the colistin-resistant population survived the colistin treatment—this suggests that the development of colistin resistance from heteroresistant strain is because of the selection of a resistant population and not by the induction of resistance through mutations in susceptible populations.

The central dopaminergic receptor is believed to suppress the cardiovascular system So it may be involved in the blood pressure regulation But, it's action is still controversial. Furthermore, the mechanisms involved in the central dopaminergic receptor-induced blood pressure regulation is unclear. So, present study was performed in order to clarify the effects of central dopaminergic receptor and to investigate the mechamisms involved in it. Lisuride a D2-receptor agonist, and clonidine, a alpha2-receptor agonist, were administered into lateral ventricle in rat and the changes of blood pressure were compared The results were as follows; 1. Intracerebroventricular administration of lisuride amd clonidine from 0.3 ug to 10 ug elicited dose related decrease of blood pressure and heart rate. The potencies were similar in both drugs. 2. Centrally administered sulpiride, a D2-antagonist, blocked only the lisuride-induced hypotension while the clonidine induced hypotension was blocked only by centrally adrninistered tolazoline, a alpha2-antagonist. Intravenous administration of both antagonists elicited no or minimal attenuabon of agonists effects. 3. After desipramine pretreatment, which increases the norepinephrine concentration lisuride elicited somewhat further decrease of blood pressure than normal, while clonidine administration caused rather increase in blood pressure. 4. After chemical sympathectomy by 6-hydroxydopamine, lisuride administration still elicited strong suppression of blood pressure. From thses above results, it is concluded that central dopaminergic receptor activation decrease the blood pressure. Suppression of the norepinephrine release at the sympathetic nerve terminal is not related with central dopaminergic receptor induced hypotension.
Administration, Intravenous ; Animals ; Blood Pressure ; Cardiovascular System* ; Clonidine ; Desipramine ; Heart Rate ; Hypotension ; Lateral Ventricles ; Lisuride ; Norepinephrine ; Oxidopamine ; Rats ; Sulpiride ; Sympathectomy, Chemical ; Tolazoline

Although trimethoprim-sulfamethoxazole (TMP-SXT) is considered the first-line therapy for Stenotrophomonas maltophilia infections, there is debate on the use of the bacteriostatic drug in serious infections, and recently, there has been an increasing occurrence of acquired resistance to TMP-SXT. In the present study, the effect of efflux pump inhibitors on the susceptibility of TMP-SXT and other antibiotics were investigated in S. maltophilia complex. The sul and/or dfrA genes were identified in only up to 27.8% of all 36 TMP-SXT-resistant S. maltophilia complex isolates. Thus, TMP-SXT resistance in S. maltophilia was not explained completely by the presence of sul and dfrA genes. Carbonyl cyanide-m-chlorophenylhydrazone (CCCP) decreased the minimum inhibitory concentration (MIC) of TMP-SXT by eight to 128 folds in all 14 isolates. In contrast, 2,4-dinitrophenol (DNP), phenyl-arginine-β-naphthylamide (PAβN), and reserpine did not reduce the MIC of TMP-SXT. In addition to TMP-SXT, slight decrease in MICs was observed for tigecycline and piperacillin/tazobactam by CCCP (by two folds) in one isolate. Although efflux pump may play a role in TMP-SXT resistance in S. maltophilia, inhibition of the efflux pump could be done by active proton pore.
2,4-Dinitrophenol ; Anti-Bacterial Agents ; Carbonyl Cyanide m-Chlorophenyl Hydrazone ; Korea* ; Microbial Sensitivity Tests ; Protons ; Reserpine ; Stenotrophomonas maltophilia* ; Stenotrophomonas* ; Thiram* ; Trimethoprim, Sulfamethoxazole Drug Combination*

Nine athletes and ten nonathletes were selected randomly to study the changes of cardiac function during exercise by impedance cardiography. The speed of the treadmill was maintained at 3.4 mph, and its grade was increased by 1% (Balke protocol). The exercise was continued until the target heart rate (THR), 85% of maximum oxygen uptake (VO2max). The measured parameters for pre- and post-exercise were stroke volume (SV), heart rate (HR), and cardiac output (CO). Average stroke volume of athletes at pre-exercise, 71.1 ml, was higher than that of nonathletes, 64.6 ml, and stroke volume of the former at post-exercise, 97.0 ml, was also higher than that of the latter, 85.2 ml. Therefore, despite the lower heart rate, cardiac outputs of athletes at pre- and post-exercise, 4.98 and 16.3 L/min, were higher than those of nonathletes, 4.87 and 14.2 L/min. For the second phase of the study, cardiac outputs of three subjects were measured during the continuous treadmill exercise with newly developed electrodes and shoes for minimizing motion artifact. Though there were several studies measuring cardiac output during continuous bicycle exercise, this is thought to be the first study in the world measuring cardiac output during continuous treadmill exercise without aid of ensemble averaging.
Adult ; *Cardiac Output ; *Cardiography, Impedance ; *Exertion ; Heart Rate ; Human ; Sports Medicine ; Stroke Volume ; Support, Non-U.S. Gov't

Clonorchiasis is known to be closely related with the development of recurrent pyogenic cholangitis and carcinoma of the bile ducts. In order to ascertain the cholangiographic signs for recurrent pyogenic cholangitis or carcinoma of the bile ducts arising in patients with clonorchiasis. we reviewed cholangiograms in 42 patients with proven clonorchiasis. The population consisted of 29 patients with clonorchiasis alone, six patients with clonorchiasis and recurrent pyogenic cholangitis, and seven patients with clonorchiasis and carcinoma of the bile ducts. Cholangiographic abnormalities in 29 patients with clonorchiasis alone, six patients with clonorchiasis and recurrent pyogenic cholangitis, and seven patients with clonorchiasis and carcinoma of the bile ducts. Cholangiographic abnormalities in 29 patients with clonorchiasis alone were intrahepatic multiple, oval, or elliptic filling defects measuring 2-10 mm in size, representing adult flukes (n=24). The peripheral bile duct were obstructed (n=18), and the margins were ragged (n=20) and hazy (n=12) the intrahepatic bile ducts were dilated diffusely (n=27), and the dilated peripheral small tributaries gave the impression of "too many ducts appearance" (n=7) and dilatation was mid (n=17) In six patients with clonorchiasis and recurrent pyogenic cholangitis, there were filling defects of stones, and the extrahepatic ducts and larger intrahepatic ducts were predominantly dilated. In seven patients with clonorchiasis and cholangiocarcinoma all the biliary tree proximal to the tumor was markedly and diffusely dilated In the latter two groups, filling defects of flukes and associated findings were less prominent, but there was disproportionately severe dilatation of too many intrahepatic ducts. In patients with recurrent pyogenic cholangitis or cholangiocarcinoma, clonorchiasis should be considered as a underlying cause when cholangiogram shows "disproportionately" severe dilatation of too many intrahepatic ducts. intrahepatic ducts.
Adult ; Bile Ducts ; Bile Ducts, Intrahepatic ; Biliary Tract ; Cholangiocarcinoma ; Cholangitis ; Clonorchiasis* ; Dilatation ; Humans ; Trematoda

BACKGROUND: Stenotrophomonas maltophilia is one of several opportunistic pathogens of growing significance. Several studies on the molecular epidemiology of S. maltophilia have shown clinical isolates to be genetically diverse. MATERIALS AND METHODS: A total of 121 clinical isolates tentatively identified as S. malophilia from seven tertiary-care hospitals in Korea from 2007 to 2011 were included. Species and groups were identified using partial gyrB gene sequences and antimicrobial susceptibility testing was performed using a broth microdilution method. Multi locus variable number of tandem repeat analysis (MLVA) surveys are used for subtyping. RESULTS: Based on partial gyrB gene sequences, 118 isolates were identified as belonging to the S. maltophilia complex. For all S. maltophilia isolates, the resistance rates to trimethoprime-sulfamethoxazole (TMP/SMX) and levofloxacin were the highest (both, 30.5%). Resistance rate to ceftazidime was 28.0%. 11.0% and 11.9% of 118 S. maltophilia isolates displayed resistance to piperacillin/tazobactam and tigecycline, respectively. Clade 1 and Clade 2 were definitely distinguished from the data of MLVA with amplification of loci. All 118 isolates were classified into several clusters as its identification. CONCLUSION: Because of high resistance rates to TMP/SMX and levofloxacin, the clinical laboratory department should consider providing the data about other antimicrobial agents and treatment of S. maltophilia infections with a combination of antimicrobials can be considered in the current practice. The MLVA evaluated in this study provides a fast, portable, relatively low cost genotyping method that can be employed in genotypic linkage or transmission networks comparing to analysis of the gyrB gene.
Anti-Infective Agents ; Ceftazidime ; Korea ; Levofloxacin ; Methods ; Molecular Epidemiology ; Stenotrophomonas maltophilia* ; Stenotrophomonas* ; Tandem Repeat Sequences*

TGF-p receptor mutation is now considered as one of the carcinogenic process of many tumors. To evaluate whether there is an abnormality in TGF-p type II receptor in osteosarcoma cell lines, we performed Northern analysis, cross-linking assay, luciferase activity and TGF-p growth inhibition assay in four osteosarcoma cell lines: G292, U202, HOS and SaOS. We also transfected the tumor cells with normal TGF-p type II receptor sequence to find if there is a possibility of gene therapy in osteosarcoma. In Northern analysis, Type II receptor expressions were decreased at SaOS, U202 and HOS cell lines. In cross-linking assay, all four cell lines didnt show type II receptor at their cell surface. The growth of these tumor cells were not suppressed by TGF-p. From these findings, we concluded that the normal production of TGF-p type II receptor was impaired in osteosarcoma. The transfection of these tumor cells with normal type II receptor sequence restored growth inhibition by TGF-p. This means even though TGF-p type II receptor is abnormal in osteosarcoma, we can restore its function by transfection of normal sequence. We think that the TGF-p type Il receptor gene therapy can be one of the treatment method for osteosarcoma in the future.
Cell Line* ; Genetic Therapy ; Luciferases ; Osteosarcoma* ; Transfection

BACKGROUND: Irbersatan, an orally active antihypertensive agent, effectively reduce blood pressure by directly blocking angiotensin II receptors without any significant adverse effects. The purpose of this study is to evaluate the efficacy and safety of irbesartan in patients with mild to moderate hypertension. METHODS: This study enrolled 83 patients who had diastolic pressure above 95 mmHg and below 110 mmHg on two measurements. Sixty eight patients were administered 150mg of irbesartan, an angiotensin II receptor blocker, daily for four weeks as an initial dosage. If the sitting diastolic pressure was equal to or greater than 90 mmHg after a 4 week treatment period, the dosage was doubled until the end of 8 weeks. Baseline pressures, antihypertensive effect, side effects, laboratory findings were compared before and after treatment. RESULTS: Fourty two patients out of 53 patients having completed this study showed decreased blood pressure equal to or more than 5 mmHg of the sitting diastolic pressure (response rate=79%). Twenty one patients out of 53 patients showed normalized blood pressure below 90 mmHg of the sitting diastolic pressure (normalization rate=40%). The extent of decrease in diastolic and systolic blood pressure after eight week treatment was an average 11.7+/-10.1 mmHg and 16.3+/-18.9 mmHg, respectively (p<0.05). Nineteen ontoward side effects was observed in 17 patients out of 68 patients with medication (frequency of ontoward effects=25%). Only one case with headache was considered to be related to the medication. Abnormal laboratory findings were observed in eight patients, and only one case with elevation of bilirubin and ALT levels was considered to be related to the medication. CONCLUSION: In conclusion, irbesartan is a safe and effective antihypertensive drug in patients with mild to moderate hypertension with tolerable side effects.
Bilirubin ; Blood Pressure ; Headache ; Humans ; Hypertension* ; Receptors, Angiotensin

Hypoglycemia due to non-islet cell tumor is usually associated with hypersecretion of big insulin-like growth factor II (IGF-II). This big IGF-II cannot form ternary IGF complex, and is biologically more active in peripheral tissue, inducing increased glucose utilization and hypoglycemia. A 57-year-old man developed severe hypoglycemia due to hepatocellular carcinoma. To control hypoglycemia, the patient required continuous glucose infusion. The circulating levels of cortisol and free T4 were in the normal range. The plasma levels of insulin, C-peptide, IGF-I, IGF binding protein-3 (IGFBP-3), and total IGF-II levels were decreased. Radioimmunoassay of IGF-II revealed that big IGF-II immunoreactivity markedly increased compared to that of normal control. In this patient, it was strongly suggested that big IGF-II might be a cause of severe intractable hypoglycemia.
C-Peptide ; Carcinoma, Hepatocellular ; Glucose ; Humans ; Hydrocortisone ; Hypoglycemia* ; Insulin ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II* ; Middle Aged ; Plasma ; Radioimmunoassay ; Reference Values

No abstract available.
Diabetes Mellitus, Type 2