bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANTI‐OXIDANT EFFECTS OF ATORVASTATIN IN DEXAMETHASONE‐INDUCED HYPERTENSION IN THE RAT
Authors: Mondo Charles K , Yang Wan‐Song , Zhang Nan , Huang Ti‐Gang 
Published: October 2006

SUMMARY

Dexamethasone (Dex)‐induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide () production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in in Sprague‐Dawley (SD) rats, thereby reducing blood pressure.
Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 µg/kg per day, s.c.) or saline was started after 4 days in Ato‐treated and non‐treated rats and continued for 11–13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail‐cuff method. Endothelial function was assessed by acetylcholine‐induced vasorelaxation and phenylephrine‐induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi‐quantitative reverse transcription–polymerase chain reaction.
In rats treated with Dex alone, SBP was increased from 109 ± 2 to 133 ± 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 ± 2 to 119 ± 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial‐dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001).
Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex‐treated SD rats.
d‐DOPA IS UNIDIRECTIONALLY CONVERTED TOl‐DOPA BYd‐AMINO ACID OXIDASE, FOLLOWED BY DOPA TRANSAMINASE
Authors: Wu Mei , Zhou Xiang‐Jun , Konno Ryuichi , Wang Yong‐Xiang 
Published: October 2006

SUMMARYMany studies have shown that administration ofd‐3, 4‐dihydroxyphenylalanine (d‐dopa) produces contralateral rotation in hemi‐parkinsonian animals comparable tol‐dopa, with less potency and slower onset. It was postulated thatd‐dopa was converted tol‐dopa to produce these effects.To investigate the postulated chiral inversion ofd‐dopa tol‐dopa and the related mechanism, an enantiomeric separation method ford‐ andl‐dopa using HPLC was first established. Then, rat kidney homogenates containingd‐dopa orl‐dopa were incubated and subjected to HPLC to detect traces of respective enantiomer generation. The mechanism of the chiral inversion ofd‐dopa was explored by direct measurement of the production ofl‐dopa in kidney homogenates.d‐Dopa incubations containing different concentrations of an inhibitor ofd‐amino acid oxidase (DAAO) and an inhibitor of dopa transaminase were measured forl‐dopa generation using HPLC. The role of DAAO in the chiral inversion ofd‐dopa tol‐dopa was further investigated by using purified DAAO and mutant ddY/DAAO−mouse kidney lacking DAAO activity.In rat kidney homogenate,d‐dopa was, indeed, converted tol‐dopa, whereasl‐dopa was not converted tod‐dopa. Sodium benzoate, a selective inhibitor of DAAO, blockedl‐dopa generation in a concentration‐dependant manner. In contrast with kidney homogenates of wild‐type ddY/DAAO+mice, those of mutant ddY/DAAO−mice lacking DAAO activity did not convertd‐dopa tol‐dopa unless exogenous DAAO protein was added. Conversely, when carbidopa, an inhibitor of dopa transaminase, was added to the homogenates, significant inhibition ofl‐dopa production was noted.These results prove the proposal thatd‐dopa undergoes unidirectional chiral inversion and further suggest thatd‐dopa is first oxidatively deaminated by DAAO to its α‐keto acid and then transaminated by dopa transaminase tol‐dopa.
EFFECTS OF GENETIC POLYMORPHISMS OFCYP3A4,CYP3A5ANDMDR1ON CYCLOSPORINE PHARMACOKINETICS AFTER RENAL TRANSPLANTATION
Authors: Hu Yong‐Fang , Qiu Wen , Liu Zhao‐Qian , Zhu Li‐Jun , Liu Zhong‐Qi , Tu Jiang‐Hua , Wang Dan , Li Zhi , He Jun , Zhong Gan‐Ping , Zhou Gan , Zhou Hong‐Hao 
Published: October 2006

SUMMARYThe calcineurin inhibitor cyclosporine is widely used to prevent allograft rejection after solid organ transplantation. It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics. Interindividual differences in the activity and expression of the metabolising enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P‐glycoprotein (P‐gp) contribute considerably to cyclosporine pharmacokinetics. Variability in the activity of CYP3A4, CYP3A5 and P‐gp could be considered to result from genetic polymorphisms encoding their genes.The aim of the present study was to evaluate retrospectively the effects of genetic polymorphisms ofCYP3A4,CYP3A5andMDR1on cyclosporine dose adjusted trough blood concentration during the early period after renal transplantation in Chinese patients.One hundred and six renal transplant recipients in China were genotyped by polymerase chain reaction–restriction fragment length polymorphism forCYP3A4*18A,CYP3A5*3andMDR1 C3435T.Cyclosporine whole blood levels were measured by fluorescence polarization immunoassay. Dose‐adjusted trough blood concentrations (C0) were determined and compared among the different genotype groups.The frequency of theCYP3A4*18A, CYP3A5*3andMDR1 C3435Tvariant alleles were 0.005 (95% confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528 (95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete linkage disequilibrium. The median cyclosporine dose‐adjusted C0inCYP3A5*1/*1genotype subjects (n = 6) was 14.8 ng/mL per mg per kg (range 11.1–26.8 ng/mL per mg per kg), inCYP3A5*1/*3patients (n = 34) it was 23.7 ng/mL per mg per kg (range 9.0–61.0 ng/mL per mg per kg) and forCYP3A5*3/*3patients (n = 66) it was 26.4 ng/mL per mg per kg (range 9.8–85.8 ng/mL per mg per kg;P = 0.012, Kruskal–Wallis test). Accordingly, cyclosporine dose‐adjusted C0was larger in CYP3A5 non‐expressors than expressors in the first week after renal transplantation. In addition, wild‐type homozygotes (n = 21) forMDR1 C3435Thad a slight but significantly lower dose‐adjusted C0compared with heterozygotes (n = 58): 17.7 (10.3–60.8) versus 26.4 (9.0–67.3) ng/mL per mg per kg, respectively (P = 0.014, Mann–WhitneyU‐test).In conclusion, the present study shows that genetic polymorphisms inCYP3A5may be responsible, in part, for the large interindividual variability of cyclosporine pharmacokinetics during the early phase after renal transplantation in Chinese patients. Patients with theCYP3A5*3variant genotype require a low dose of cyclosporine to reach target levels compared with those with theCYP3A5*1allele.
ANTIHYPERGLYCAEMIC AND ANTIPEROXIDATIVE ROLES OF ACARBOSE IN TYPE 2 DIABETES MELLITUS ARE POSSIBLY MEDIATED THROUGH CHANGES IN THYROID FUNCTION
Authors: Rameshwar Jatwa , Anand Kar 
Published: October 2006

SUMMARY

The aim of the present study was to reveal the possible involvement of thyroid hormones in the antihyperglycaemic and antiperoxidative effects of acarbose.
The effects of acarbose on changes in serum concentration of thyroid hormones, insulin and glucose in dexamethasone‐induced type 2 diabetic mice were investigated. Simultaneously, changes in lipid peroxidation (LPO), reduced glutathione (GSH) content and the activity of associated endogenous anti‐oxidant enzymes, such as superoxide dismuatase (SOD) and catalase (CAT), were investigated in renal and cardiac tissues, which are commonly affected in diabetes mellitus.
Although administration of dexamethasone (1.0 mg/kg, i.m., for 22 days) caused hyperglycaemia with a parallel increase in serum insulin and tissue LPO, it decreased thyroid hormone concentrations and the activity of SOD and CAT.
When dexamethasone‐induced hyperglycaemic mice were treated with acarbose (10 mg/kg per day, p.o., for 15 days), levels of thyroid hormones were increased and most of the abnormalities, including serum insulin and glucose levels, tissue LPO, SOD and CAT activity and GSH content, were reversed.
These findings suggest the involvement of thyroid hormones in the mode of action of acarbose in amelioration of type 2 diabetes mellitus.
ClC‐1 CHLORIDE CHANNEL: MATCHING ITS PROPERTIES TO A ROLE IN SKELETAL MUSCLE
Authors: Aromataris Edoardo C , Rychkov Grigori Y 
Published: October 2006

SUMMARY

ClC‐1 is a Cl− channel in mammalian skeletal muscle that plays an important role in membrane repolarization following muscular contraction. Reduction of ClC‐1 conductance results in myotonia, a state characterized by muscle hyperexcitability.
As is the case for other members of the ClC family, ClC‐1 exists as a dimer that forms a double‐barrelled channel. Each barrel, or pore, of ClC‐1 is gated by its own gate (‘fast’ or ‘single pore’ gate), whereas both pores are gated simultaneously by another mechanism (‘slow’ or ‘common’ gate).
Comparison of the biophysical and pharmacological properties of heterologously expressed ClC‐1 with the properties of the Cl− conductance measured in skeletal muscle strongly suggests that ClC‐1 is the major Cl− channel responsible for muscle repolarization. However, not all results obtained in experiments on whole muscle or muscle fibres support this notion.
In the present review we attempt to bring together the current knowledge of ClC‐1 with the physiology of skeletal muscle.
Treatment of functional dyspepsia with serotonin agonists: A meta‐analysis of randomized controlled trials
Authors: Hiyama Toru , Yoshihara Masaharu , Matsuo Keitaro , Kusunoki Hiroaki , Kamada Tomoari , Ito Masanori , Tanaka Shinji , Chayama Kazuaki , Haruma Ken 
Published: October 2006

AbstractBackground:  Functional dyspepsia (FD) is often treated with serotonin agonists; however, the efficacy of such agents has recently been questioned. The aim of this study was to perform a meta‐analysis of randomized controlled trials (RCTs) comparing serotonin agonists with other types of prokinetics in patients with FD.Methods:  Included studies were RCTs that compared serotonin agonists, including cisapride and mosapride, with dopamine antagonists, including metoclopramide and domperidone, and an opiate agonist, trimebutine, in patients with FD. Studies were identified by searching the Medline database (January 1951 – January 2005) and Cochrane Library (Issue 4, 2004), and by manual searches. The difference in the probability of patients' responses between the serotonin agonists and control agents was used as a summary statistic for the treatment effect. Meta‐regression analysis was used to detect sources of heterogeneity.Results:  Five studies were identified. In total, 467 subjects were assigned to a serotonin agonist arm, and 322 subjects were assigned to a control arm. In the overall analysis, the summary statistic was 0.019 (95% confidence interval [CI]: −0.055 to 0.093; P = 0.612), indicating that the patients' responses to serotonin agonists were similar to those to control agents. However, in the stratified meta‐analysis of cisapride and mosapride, mosapride had a 6.7% greater probability of producing a response compared with control agents (summary statistic: 0.067; 95% CI: 0.010–0.124; P = 0.021), whereas no significant effect was observed with cisapride.Conclusion:  The data suggest that mosapride may be more effective than cisapride for the treatment of FD. Although FD is a chronic condition, efficacy was assessed over short periods in the studies used for the present meta‐analysis. Long‐term RCTs are needed to confirm the effect.
Serology of Chlamydia pneumoniae in patients with chronic cough
Authors: KIM Woo Jin , LEE Hui Young , LEE Mi Eun , LEE Seung‐Joon 
Published: October 2006

Objective and background:  Chronic cough is one of the more common respiratory symptoms. Controversy exists as to whether Chlamydia infection is associated with chronic cough. As such, the association of chronic cough with serological evidence of Chlamydia pneumoniae (C. P) infection and a systemic inflammatory marker was assessed.Methods:  Thirty‐seven patients who visited Kangwon National University Hospital for chronic cough between September 2003 and August 2004 and 37 age‐matched healthy controls were evaluated for C. P. antibodies and C‐reactive protein. Chronic infection was defined as an IgG or IgA titre between 1:64 and 1:512, and acute infection was defined as IgM = 1:16 or IgG titre of = 1:512 or IgA = 1:512. A nasopharyngeal swab was evaluated for C. P. DNA using the polymerase chain reaction.Results:  The median duration of cough was 3 months (1–240). Nineteen patients (49%) and 19 controls had titres consistent with chronic infection, and the titre difference was not significant (P = 0.592). Nine patients and two controls had titres consistent with acute infection (24.3% vs. 5.4%). Acute infection was significantly more prevalent in the patients with chronic cough (P = 0.023). There was no difference in the C‐reactive protein value (0.13 vs. 0.14, P = 0.84). Three patients were positive for C. P. DNA.Conclusion:  Acute Chlamydia infection was more prevalent in patients with chronic cough, whereas chronic Chlamydia infection was not. There was no elevation of a systemic inflammatory marker in patients with chronic cough.
Clinical analysis of chronic obstructive pulmonary disease phenotypes classified using high‐resolution computed tomography
Authors: FUJIMOTO Keisaku , KITAGUCHI Yoshiaki , KUBO Keishi , HONDA Takayuki 
Published: October 2006

Objective and background:  The present study was performed to clarify the clinical characteristics of patients with COPD classified into phenotypes according to the dominancy of emphysema and the presence of bronchial wall thickening (BWT) evaluated by chest high‐resolution CT.Methods  A total of 172 patients with stable COPD (FEV1 < 80%) were examined by chest high‐resolution CT. Emphysematous changes and BWT were evaluated visually, and COPD patients were classified into three phenotypes: absence of emphysema, with little emphysema with or without BWT (A phenotype), emphysema without BWT (E phenotype) and emphysema with BWT phenotype (M phenotype). The clinical characteristics were compared among the three phenotypes.Results  The A phenotype showed a higher prevalence of those who had never smoked and patients with wheezing both on exertion and at rest, higher values of BMI and diffusing capacity for carbon mononide (DLCO), milder lung hyperinflation, and greater reversibility of airflow limitation responsive to β2‐agonist as compared with the E phenotype. The M phenotype showed a higher prevalence of patients complaining of a large amount of sputum, productive cough and wheezing, higher rate of exacerbation or hospitalization and greater reversibility of airflow limitation responsive to β2‐agonist as compared with the E phenotype.Conclusions  These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different responsiveness to bronchodilators.
Effectiveness of early budesonide intervention in Caucasian versus Asian patients with asthma: 3‐year results of the START study
Authors: TAN Wan C. , LAMM Carl J. , CHEN Yu‐Zhi , O’BYRNE Paul M. , PEDERSEN Søren , BUSSE William W. , OHLSSON Stefan V. , ULLMAN Anders , ANDERSSON Bertil , PAUWELS Romain A. 
Published: October 2006

Objective and background:  Few studies have assessed the effectiveness of inhaled corticosteroid therapy exclusively in Asian patients with asthma. The present analysis compared the efficacy of early intervention with inhaled budesonide in Caucasian and Asian patients over the first 3 years of the inhaled Steroid Treatment As Regular Therapy in early asthma study.Methods:  Patients aged 5–66 years with mild persistent asthma of ≤2 years’ duration were randomized to 3 years of double‐blind treatment with once‐daily budesonide 200 µg (for patients aged <11 years) or 400 µg administered via Turbuhaler or placebo, plus usual asthma therapy.Results:  Budesonide significantly improved asthma outcomes in both Caucasian (n = 4661) and Asian (n = 1995) patients compared with reference therapy (placebo plus usual asthma therapy). Budesonide reduced the risk of a first severe asthma‐related event by 42% and 49% in Caucasian and Asian patients, respectively, over the 3‐year treatment period (P < 0.001 for both). Moreover, budesonide significantly increased symptom‐free days, decreased nights with sleeping problems, improved pre‐ and postbronchodilator FEV1 and reduced the need for additional asthma medications of particular drug classes compared with reference therapy. Except for differences in the patterns of use of additional asthma medications, outcomes with budesonide and overall adverse events were similar in the Caucasian and Asian patient populations.Conclusion:  Inhaled budesonide administered once daily in Asian patients with recent‐onset, mild persistent asthma significantly improved asthma control and pulmonary function compared with reference therapy. Moreover, this effectiveness paralleled that observed in Caucasian patients.
Cost of treatment for multidrug‐resistant tuberculosis in South Korea
Authors: KANG Young Ae , CHOI Yong‐Jun , CHO Young‐Jae , LEE Sang Min , YOO Chul‐Gyu , KIM Young Whan , HAN Sung Koo , SHIM Young‐Soo , YIM Jae‐Joon 
Published: October 2006

Objective and background:  Costs associated with multidrug‐resistant tuberculosis (MDR‐TB) are higher than those associated with drug‐susceptible TB because of the higher prices of second‐line anti‐TB drugs, the prolonged duration of treatment, greater productivity loss and higher mortality. The aim of this study was to estimate the cost of treatment for MDR‐TB according to the treatment strategy and prognosis in South Korea.Methods:  We estimated the direct (medical and non‐medical) and indirect cost for the treatment of MDR‐TB according to the treatment strategies and prognosis: in medically treated, surgically treated and deceased patients groups. The same analyses were undertaken for drug‐susceptible TB for comparison. The patients with MDR‐TB or drug‐susceptible TB were randomly selected from the TB cohort of Seoul National University Hospital, Seoul, South Korea.Results:  Direct costs per person were US$4000 (US$2527–4841) in the medically treated group, US$17 457 (US$10 133–26 418) in the surgically treated group and US$33 362 (US$25 386–40 338) in the deceased group. Total costs per person were US$15 856 (US$10 752–38 421), US$47 159 (US$20 587–77 622) and US$478 357 (US$257 377–777 778), respectively. For the patients with drug‐susceptible TB, the total cost ranged from US$1680 to US$7637 (median US$2166).Conclusions:  The cost for the treatment of MDR‐TB is seven to 22 times that of managing the drug‐susceptible TB in South Korea. Considering the high cost, transmissibility and considerable fatality of MDR‐TB, there is a need to provide specific separate funding for multidrug‐resistant tuberculosis.
Effect of indomethacin on Bfl‐1, WISP‐1 and proliferating cell nuclear antigen in colon cancer cell line HCT116 cells
Authors: WANG Juan , ZHANG Gui Ying , LI Xin Hua 
Published: October 2006

BACKGROUND:  Non‐steroidal anti‐inflammatory drugs such as indomethacin can inhibit the growth of tumors through both the cyclooxygenase‐2 (COX‐2) dependant and COX‐2 independent pathways, but the exact mechanism has not yet been shown. In our previous study, COX‐2 independent proteins (Bfl‐1, WISP‐1 and proliferating cell nuclear antigens [PCNA]) in indomethacin‐treated colorectal cancer cells with the use of proteomics technology had been identified.OBJECTIVES:  To study and confirm the effect of indomethacin on the expression of Bfl‐1, WISP‐1 and PCNA in human colon cancer line HCT116 cells and the COX‐2 independent tumor inhibiting pathway.METHODS:  Human colon cancer cell line HCT116 cells were divided into a treatment with indomethacin (IC 50) group, and a treatment with dimethyl sulfoxide (DMSO) as a control group for 48 h. The expression of Bfl‐1, WISP‐1 and PCNA, mRNA and protein were determined by a real‐time quantitative PCR and Western blot, respectively.RESULTS:  Indomethacin down‐regulated the expression of Bfl‐1, WISP‐1 and PCNA mRNA in vitro (9.53 ± 0.15 vs 27.87 ± 0.12, 7.37 ± 0.58 vs 20.17 ± 0.58, 5.17 ± 0.06 vs 0.87 ± 0.06). Indomethacin also down‐regulated the expression of Bfl‐1, WISP‐1 and PCNA protein (40.01 ± 1.61 vs 43.76 ± 1.63, 22.50 ± 1.17 vs 30.30 ± 1.55, 17.69 ± 1.18 vs 20.80 ± 1.08).CONCLUSIONS:  Inducing apoptosis and inhibiting proliferation contribute to the anticancer activity of indomethacin via COX‐2 independent pathway of Bfl‐1, WISP‐1 and PCNA. This further confirms the results of our previous study.
Alternation of substance P‐containing neural pathways in a rat model of irritable bowel syndrome with rectal distension
Authors: WANG Wei Feng , YANG Yun Sheng , PENG Li Hua , SUN Gang 
Published: October 2006

OBJECTIVE:  Irritable bowel syndrome (IBS) is a common disorder in clinical practice, but the pathophysiology of IBS has not been completely elucidated yet. Experiments have revealed that the concentrations of some kinds of brain–gut peptides, such as substance P, were abnormal in the plasma and/or the intestinal mucosa. In order to explore further the possible role of substance P containing nerve fibers in the enteric nervous system and central nervous system, the expression of c‐fos, a well‐established marker of activated neural pathway, was induced to show substance P containing a neural pathway in the rat model of constipation‐predominant IBS by rectal distention.METHODS:  The rat model was set up by intragastric instillation of 2.0 mL water at 0–4°C in 20 male Wistar rats for two weeks. Both the model group and the controls underwent rectal distention under deep anesthesia. Sections containing the anatomical areas of interest were obtained and processed for c‐fos protein and substance P immunohistochemistry using the strept avidin‐biotin complex (SABC) method. The staining results were analyzed semi‐quantitatively, using a computerized color image analyzer with two parameters: opacity density and immunoreactive areas. The statistical difference of the opacity density and immunoreactive areas between the two groups was analyzed by a t‐test. Correlation analysis was used to investigate the relationship between the expression of substance P and c‐fos protein of the same region in the model group.RESULTS:  The opacity density of substance P immunoreactive tissues in the ileocecal junction, colon, the posterior horn of the spinal cord and the hypothalamus of the model group were all significantly higher compared with those in the control group (176.6 vs 155.5, 172.3 vs 152.0, 182.1 vs 160.2, 128.3 vs 117.9; P < 0.05, respectively). Meanwhile in the ileocecal junction, colon, the posterior horn of the spinal cord and the hypothalamus of the model group, the opacity density of c‐fos protein‐positive tissue were all significantly higher than those of the same region in the controls (120.9 vs 109.0, 101.3 vs 92.2, 125.4 vs 88.7, 115.5 vs 88.6; P < 0.05, respectively). The distribution of c‐fos protein‐positive tissue is similar to that of the substance P and the analysis shows that there is close correlation between the expression of substance P and c‐fos protein of the same region in the model group (r = 0.594–0.721, P < 0.05).CONCLUSIONS:  The expression of substance P and c‐fos protein in both the enteric nervous system and the central nervous system of the constipation‐predominant IBS rat model is abnormal, which suggests that an abnormal change in substance P may be involved in the pathogenesis of IBS and the substance P‐containing neural pathway may be one of the neural pathways that play important role in the regulation of the gastrointestinal function.