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Biomedical subjects

M K Chung

Publications and source records attributed to M K Chung.

At least 19 recordsLinked to original sources

Pollutants in Hong Kong soils: polycyclic aromatic hydrocarbons.

An extensive soil survey was carried out to study the polycyclic aromatic hydrocarbon (PAH) contaminations in 138 soil samples collected throughout Hong Kong. Results demonstrated that there were low levels of PAH contaminations (median of summation operator 16US EPA PAHs=140 microg kg(-1)) for all land uses (urban park, greening area, country park, rural area, restored landfill, agricultural farmland, orchard farm, crematorium, industrial and near highway area). However, localized hotspots were identified with summation operator 16PAH concentrations as high as 19,500 microg kg(-1) in one urban park. These findings were also confirmed by multivariate analysis. Comparison of PAH profiles showed a widespread domination of its 4-ring member. The major contribution was vehicular emissions from petroleum, and however at the hotspots, the improper disposal of used motor oils. In general, the pollution levels for all the land uses were below the recommended values for residential and general purposes stated in soil quality guidelines such as Netherlands and Denmark except certain identified hotspots. The potential health hazards imposed by these hotspots were alarming, and their existence (3 out of 138 samples) suggested that sole monitoring of atmospheric PAHs may not adequately address the hidden risks to human in urban city.

Hong Kong↗

Evaluation of developmental toxicity of amitraz in Sprague-Dawley rats.

This study investigated the potential adverse effects of amitraz on the initiation and maintenance of pregnancy in Sprague-Dawley rats as well as its effects on embryo-fetal development after maternal exposure during the entire pregnancy period. Amitraz was administered to pregnant rats by gavage from days 1 to 19 of gestation at dose levels of 0, 3, 10, and 30 mg/kg/day. All dams underwent a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 30 mg/kg, maternal toxicity manifested as an increase in the incidence of abnormal clinical signs and a lower body weight gain and food intake. Developmental toxicity included an increase in the fetal death rate, a decrease in the litter size, and a reduction in the fetal body weight. In addition, there was an increase in the incidence of fetal external, visceral, and skeletal abnormalities. At 10 mg/kg, maternal toxicity observed included a decrease in the body weight gain and a decrease in food intake. In addition, minimal developmental toxicity, including a decrease in the fetal body weight, an increase in the visceral and skeletal aberrations, and a delay in fetal ossification. There were no signs of either maternal toxicity or developmental toxicity at 3 mg/kg. These results show that amitraz administered during the entire pregnancy period in rats is embryotoxic and teratogenic at the maternally toxic dose (i.e., 30 mg/kg/day) and is minimally embryotoxic at a minimally maternally toxic dose (i.e., 10 mg/kg/day). Under these experimental conditions, the no-observed-adverse-effect level of amitraz for both dams and embryo-fetal development is estimated to be 3 mg/kg/day.

Abnormalities, Drug-Induced↗

Diagnostic yield of advanced colorectal neoplasia at colonoscopy, according to indications: an investigation from the Korean Association for the Study of Intestinal Diseases (KASID).

BACKGROUND AND STUDY AIMS: The factors that more accurately predict the detection of colorectal cancers and adenomas at colonoscopy are different. We conducted a prospective multicenter study to evaluate which indications were most closely associated with advanced colorectal neoplasm (CRN), including colorectal cancer, in a group of patients undergoing colonoscopy. PATIENTS AND METHODS: The 17 468 patients were enrolled in this study between July 2003 and March 2004, from 11 tertiary medical centers in Korea. They were recruited according to 11 itemized colonoscopic indications. The term "advanced adenoma" refers here to tubular adenomas of diameter of 11 mm or more, or to tubulovillous, villous, or severely dysplastic adenomas, irrespective of their size. Cancer was defined as the invasion of malignant cells beyond the muscularis mucosa. Advanced CRN was defined as advanced adenoma or invasive cancer. RESULTS: Advanced CRN was found in 1227/17 307 patients (1176 advanced adenomas plus 51 carcinomas, 7.1 %). According to univariate and multivariate analysis, the factors associated with advanced CRN included age >60 years (odds ratio (OR) 2.1, 95 % confidence interval (CI) 1.8 - 2.4, P < 0.0001), male gender (OR 2.1, 95 %CI 1.7 - 2.7, P < 0.0001), referral for colonoscopy from primary care physician (OR 3.1, 95 %CI 2.5 - 3.7, P < 0.0001), and several other indications (OR 1.8, 95 %CI 1.5 - 2.3, P < 0.001). The yield of colonoscopy for advanced CRN was lower (2.2 %) than expected in patients with iron-deficiency anemia (OR 0.5, 95 %CI 0.2 - 0.9, P = 0.03). CONCLUSIONS: Age, gender, and referral for colonoscopy from primary care physician constituted important independent predictors of advanced CRN in patients undergoing colonoscopy.

Adenoma↗

Preimplantation B-type natriuretic peptide concentration is an independent predictor of future appropriate implantable defibrillator therapies.

OBJECTIVE: To assess prospectively whether preimplantation B-type natriuretic peptide (BNP) and C reactive protein (CRP) concentrations predict future appropriate therapies from an implantable cardioverter-defibrillator (ICD). DESIGN AND SETTING: Prospective cohort study conducted in a tertiary cardiac care centre. METHODS: 345 consecutive patients undergoing first time ICD implantation were prospectively studied. Serum BNP and CRP concentrations were obtained the day before ICD implantation. Patients were followed up with device interrogation to assess for appropriate shocks or antitachycardia pacing. Inappropriate therapies were excluded. Mean (SD) follow up was 13 (5) months. RESULTS: Patients had ischaemic (71%), primary dilated (17%), and valvar or other cardiomyopathies (12%). About half (52%) had ICDs implanted for primary prevention. Sixty three (18%) received appropriate ICD therapies. Serum creatinine, beta blocker, statin, and angiotensin converting enzyme inhibitor usage did not differ between therapy and no therapy groups. By univariate comparison, ejection fraction (p = 0.048), not taking amiodarone (p = 0.033), and BNP concentration (p = 0.0003) were risk factors for ICD therapy. However, by Cox regression multivariate analysis, only BNP above the 50th centile was a significant predictor (hazard ratio 2.19, 95% confidence interval 1.07 to 4.71, p = 0.040). Median BNP was 573 ng/l versus 243 ng/l in therapy and no therapy patients, respectively (p = 0.0003). More patients with BNP above the 50th centile (27% v 10%, p = 0.006) received ICD therapies. CONCLUSIONS: A single preimplantation BNP concentration determination is independently predictive of ICD therapies in patients with cardiomyopathies undergoing first time ICD implantation. CRP was not independently predictive of ICD therapies when compared with BNP.

Biomarkers↗

C reactive protein concentration and recurrence of atrial fibrillation after electrical cardioversion.

BACKGROUND: To test the hypothesis that a high C reactive protein (CRP) concentration would predict recurrence of atrial fibrillation (AF) after cardioversion in patients taking antiarrhythmic drugs. METHODS: 111 patients who underwent direct current cardioversion for symptomatic AF were enrolled. Blood was drawn for CRP determination before cardioversion on the same day. All patients were taking antiarrhythmic drugs before and after electrical cardioversion. RESULTS: After a mean follow up of 76 days, 75 patients had recurrence of AF. In univariate analysis, the median CRP concentration was significantly higher in patients with AF recurrence (3.95 mg/l v 1.81 mg/l, p = 0.002). Among the 55 patients with CRP in the upper 50th centile, 44 (80%) experienced recurrence of AF over a total follow up of 8.98 patient years, whereas among the 56 patients with CRP in the lower 50th centile, 31 (55%) experienced recurrence of AF over a total follow up of 14.3 patient years (p < 0.001). The adjusted hazard ratio comparing the upper 50th centile of CRP with the lower 50th centile of CRP was 2.0 (95% confidence interval 1.2 to 3.2, p = 0.007). CONCLUSIONS: CRP is independently associated with recurrence of AF after electrical cardioversion among patients taking antiarrhythmic drugs. These results suggest that inflammation may have a role in the pathogenesis of AF resistant to antiarrhythmic drugs.

Aged↗

Evaluation of spermatogenesis and fertility in F1 male rats after in utero and neonatal exposure to extremely low frequency electromagnetic fields.

AIM: To determine whether in utero and neonatal exposure to a 60 Hz extremely low frequency electromagnetic field (EMF) results in spermatotoxicity and reproductive dysfunction in the F1 offspring of rats. METHODS: Age-matched, pregnant Sprague-Dawley rats were exposed continuously (21 h/day) to a 60 Hz EMF at field strengths of 0 (sham control), 5, 83.3 or 500 microT from day 6 of gestation through to day 21 of lactation. The experimentally generated magnetic field was monitored continuously (uninterrupted monitoring over the period of the study) throughout the study. RESULTS: No exposure-related changes were found in exposed or sham-exposed animals with respect to the anogenital distance, preputial separation, testis weight, testicular histology, sperm count, daily sperm production, sperm motility, sperm morphology and reproductive capacity of F1 offspring. CONCLUSION: Exposure of Sprague-Dawley rats to a 60 Hz EMF at field strengths of up to 500 microT from day 6 of gestation to day 21 of lactation did not produce any detectable alterations in offspring spermatogenesis and fertility.

Animals↗

The three-dimensional microstructure of the trabecular bone in the mandible.

This study investigated the three dimensional (3D) trabecular microstructure of the alveolar and basal bone in the mandible using micro-CT and compared the morphometric values of the different sites. Ten specimens were prepared and scanned using a micro-CT system. Both the alveolar and basal trabecular bone of the premolar region in the mandible were measured for the structural analysis. Cross-sectional 1024x1024 pixel images were created. From the two-dimensional (2D) images produced, 3D structural images were reconstructed. After scanning the specimen, the volumes of interest (VOI) of the alveolar and basal bone regions were selected from the 3D reconstruction images, and the structural parameters such as bone volume fraction, bone surface density, trabecular thickness, trabecular separation, trabecular number and structural model index were analyzed. The trabecular structure showed a marked variation within the sites of the specimen, especially in the basal trabecular bone inferior to the mandibular canal. In both the alveolar and basal bone regions, a mixture of both plate-like and rod-like structures was observed. The alveolar region showed a more compact, plate-type trabecular structure than the basal regions. In parametric comparison with the basal bone, the alveolar bone generally had a higher bone volume fraction, bone trabecular thickness and trabecular number, and lower bone surface density, trabecular separation and structural model index. The alveolar bone consisted of a compact bone structure with a large amount of thick plate-type trabecular bone, which was effectively resistant to the masticatory forces. As the measurements were made closer to the basal bone, a loose structure was observed with lower bone volume and fewer, thin, rod-like trabeculae.

Adult↗

Subacute toxicity evaluation of a new camptothecin anticancer agent CKD-602 administered by intravenous injection to rats.

The subacute toxicity of a new camptothecin anticancer agent, CKD-602, was investigated after 4-week repeated intravenous administration of the chemical in Sprague-Dawley rats. The test chemical was administered intravenously to rats at dose levels of 0, 0.003, 0.013, or 0.067 mg/kg/day for males and 0, 0.004, 0.018, or 0.089 mg/kg/day for females. At the end of the treatment period, 10 rats/sex/group were sacrificed. The remaining 5 rats/sex in the vehicle control and high dose groups continued the study without treatment for 2 weeks (recovery period). During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. In both sexes of the high dose group, an increase in the incidence of abnormal clinical signs and paleness of the eyes, a reduction in the body weight gain, food consumption and urine protein, and an increase in the water consumption were observed. Hematological investigations revealed a decrease in the red blood cells, hemoglobin and hematocrit and an increase in the mean corpuscular volume, mean corpuscular hemoglobin, platelets, and reticulocytes in a dose-dependent manner. Serum total cholesterol and total protein values were lower in females than those of controls, but not in males. An increase in the heart and liver weights and a decrease in the thymus weight were also found. Histopathological alterations included an increase in the incidence of atrophy of the sternal marrow, atrophy, fibrosis and mast cell hyperplasia of the femoral marrow, atrophy of the white pulp and extramedullary hematopoiesis of the spleen, atrophy of the thymus, auricular hypertrophy of the heart, extramedullary hematopoiesis and centriacinar telangiectasis of the liver, follicular degeneration of the ovary, and inflammation of the tail. The major treatment-related effects were not recovered at the end of 2-week recovery period. There were no adverse effects in the low and middle dose groups of both genders. In the present experimental conditions, the target organs were determined to be bone marrow, blood cells, spleen, liver, thymus, and heart. The no-observed-adverse-effect level was considered to be 0.013 mg/kg/day for males and 0.018 mg/kg/day for females.

Animals↗

Functional but not structural subgenual prefrontal cortex abnormalities in melancholia.

Major depression is a heterogeneous condition, and the search for neural correlates specific to clinically defined subtypes has been inconclusive. Theoretical considerations implicate frontostriatal, particularly subgenual prefrontal cortex (PFC), dysfunction in the pathophysiology of melancholia--a subtype of depression characterized by anhedonia--but no empirical evidence has been found yet for such a link. To test the hypothesis that melancholic, but not nonmelancholic depression, is associated with the subgenual PFC impairment, concurrent measurement of brain electrical (electroencephalogram, EEG) and metabolic (positron emission tomography, PET) activity were obtained in 38 unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18 nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with a tomographic source localization method that computed the cortical three-dimensional distribution of current density for standard frequency bands, allowing voxelwise correlations between the EEG and PET data. Voxel-based morphometry analyses of structural magnetic resonance imaging (MRI) data were performed to assess potential structural abnormalities in melancholia. Melancholia was associated with reduced activity in the subgenual PFC (Brodmann area 25), manifested by increased inhibitory delta activity (1.5-6.0 Hz) and decreased glucose metabolism, which themselves were inversely correlated. Following antidepressant treatment, depressed subjects with the largest reductions in depression severity showed the lowest post-treatment subgenual PFC delta activity. Analyses of structural MRI revealed no group differences in the subgenual PFC, but in melancholic subjects, a negative correlation between gray matter density and age emerged. Based on preclinical evidence, we suggest that subgenual PFC dysfunction in melancholia may be associated with blunted hedonic response and exaggerated stress responsiveness.

Adult↗

KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death.

Long QT syndrome (LQTS) is the prototype of the cardiac ion channelopathies which cause syncope and sudden death. LQT1, due to mutations of KCNQ1 (KVLQT1), is the most common form. This study describes the genotype-phenotype characteristics in 10 families with mutations of KCNQ1, including 5 novel mutations. One hundred and two families with a history of lethal cardiac events, 55 LQTS, 9 Brugada syndrome, 18 idiopathic ventricular fibrillation (IVF), and 20 acquired LQTS, were studied by single-strand conformational polymorphism (SSCP) and DNA sequence analyzes. Families found to have KCNQ1 mutations were phenotyped using ECG parameters and cardiac event history, and genotype-phenotype correlation was performed. No mutations were found in Brugada syndrome, IVF, or acquired LQTS families. Ten out of 55 LQTS families had KCNQ1 mutations and 62 carriers were identified. Mutations included G269S in domain S5; W305X, G314C, Y315C, and D317N in the pore region; A341E and Q357R in domain S6; and 1338insC, G568A and T587M mutations in the C-terminus. W305X, G314C, Q357R, 1338insC, and G568A, appeared to be novel mutations. Gene carriers were 26 +/- 19 years (32 females). Baseline QTc was 0.47 +/- 0.03 s (range 0.40-0.57 s) and 40% had normal to borderline QTc (< or = 0.46 s). Typical LQT1 T wave patterns were present in at least one affected member of each family, and in 73% of all affected members. A history of cardiac events was present in 19/62 (31%), 18 with syncope, 2 with aborted cardiac arrest (ACA) and six with sudden death (SD). Two out of 6 SDs (33%) occurred as the first symptom. No difference in phenotype was evident in pore vs. non-pore mutations. KCNQ1 mutations were limited to LQTS families. All five novel mutations produced a typical LQT1 phenotype. Findings emphasize (1) reduced penetrance of QTc and symptoms, resulting in diagnostic challenges, (2) the problem of sudden death as the first symptom (33% of those who died), and (3) genetic testing is important for identification of gene carriers with reduced penetrance, in order to provide treatment and to prevent lethal cardiac arrhythmias and sudden death.

Arrhythmias, Cardiac↗

SNP S1103Y in the cardiac sodium channel gene SCN5A is associated with cardiac arrhythmias and sudden death in a white family.

Cardiac arrhythmias cause 400 000 sudden deaths annually in the United States alone. Mutations in the cardiac sodium channel gene SCN5A on chromosome 3p21 cause cardiac arrhythmias and sudden death. In this study, we define an SCN5A mutation, S1103Y, in a white family associated with syncope, ventricular fibrillation, and sudden death. A very recent study reported the same mutation in 13.2% of African Americans, but not in the white population. Our study shows that mutation S1103Y does exist in the white population, and it is associated with a considerable risk of syncope, ventricular arrhythmia, ventricular fibrillation, and sudden death in this population.

Adult↗

Volume-activated chloride currents from human fibroblasts: blockade by nimodipine.

The whole-cell patch clamp technique was used to identify and to characterize volume-activated Cl- current (ICl(vol)) in fibroblasts derived from human periodontal ligament. During osmotic cell swelling, the cells exhibited an outwardly rectifying current, which was dependent upon the concentration of external Cl-. The anion permeability sequence of the chloride channel for anions was as follows: SCN- > I- > Br- > Cl- > F- > methanesulphonate > gluconate. Being an inhibitor of Cl- channels and Cl-/HCO exchanger, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) inhibited the currents with a voltage-dependence (EC50 57 micromol/l at +80 mV), and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), a carboxylate analogue Cl- channel blocker, showed the reversible suppression of the currents in a dose-dependent manner (EC50 = 59 micromol/l). Nimodipine, a selective dihydropyridine Ca2+ channel blocker suppressed ICl(vol) (EC50 = 66 micromol/l) and the effects were quite similar to those of NPPB. Nifedipine, another DHP blocker also inhibited the currents but with lesser efficacy (EC50 = 139 micromol/l). The removal of external Ca2+ or the addition of Cd2+ in the bath solution did not affect the blocking effects of nimodipine on ICl(vol). These findings demonstrate that the human fibroblasts ICl(Vol) was suppressed by nimodipine in an extracellular Ca2+-independent way. These results may provide, at least in part, an explanation for the Ca2+-independent decrease in Cl-/organic osmolytes efflux and RVD responses by nimodipine in some cell types.

Calcium↗

C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) may persist due to structural changes in the atria that are promoted by inflammation. C-reactive protein (CRP), a marker of systemic inflammation, predicts cardiovascular events and stroke, a common sequela of AF. We hypothesized that CRP is elevated in patients with atrial arrhythmias. METHODS AND RESULTS: Using a case-control study design, CRP in 131 patients with atrial arrhythmias was compared with CRP in 71 control patients. Among arrhythmia patients, 6 had frequent atrial ectopy or tachycardia, 86 had paroxysmal AF, 39 had persistent AF lasting >30 days, and 70 had lone arrhythmias. CRP was higher in arrhythmia than in control patients (median, 0.21 versus 0.096 mg/dL; P<0.001). Arrhythmia patients in AF within 24 hours before sampling had higher CRP than those in sinus rhythm (0.30 versus 0.15 mg/dL; P<0.001). CRP in controls was not different than in patients with atrial ectopy or tachycardia. Lone arrhythmia patients had a CRP of 0.21 mg/dL, which was not significantly lower than arrhythmia patients with structural heart disease (CRP, 0.23 mg/dL) but higher than controls (P=0.002). Persistent AF patients had a higher CRP (0.34 mg/dL) than paroxysmal AF patients (0.18 mg/dL; P=0.008); both groups had higher CRP levels than controls (P</=0.005). CONCLUSIONS: CRP is elevated in AF patients. This study is the first to document elevated CRP in non-postoperative arrhythmia patients. These findings are reinforced by stepwise CRP elevation with higher AF burden. Although the cause of elevated CRP levels in AF patients remains unknown, elevated CRP may reflect an inflammatory state that promotes the persistence of AF.

Analysis of Variance↗

Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy.

Bisphenol A (BPA) is an essential component of epoxy resins used in the lacquer lining of metal food cans, as a component of polycarbonates, and in dental sealants. The present study was conducted in an attempt to evaluate the adverse effects of the environmental estrogen BPA on initiation and maintenance of pregnancy and embryofetal development after maternal exposure during the entire period of pregnancy in Sprague-Dawley rats. The test chemical was administered by gavage to mated females from days 1 to 20 of gestation (sperm in varginal lavage = day 0) at dose levels of 0, 100, 300, and 1000 mg/kg. All females were subjected to caesarean section on day 21 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1000 mg/kg group, significant toxic effects including abnormal clinical signs, decreased maternal body weight and body weight gain, and reduced food consumption were observed in pregnant rats. An increase in pregnancy failure was also found in the successfully mated females. In addition, increased number of embryonal deaths, increased postimplantation loss, reduced litter size and fetal body weight, and decreased number of fetal ossification centers of several skeletal districts were seen. On the contrary, no significant changes induced by BPA were detected in the number of corpora lutea and implantation sites and by fetal morphological examinations. In the 300 mg/kg group, suppressed maternal body weight and body weight gain, decreased food intake and reduced body weight of male fetuses were seen. There were no adverse signs of either maternal toxicity or developmental toxicity in the 100 mg/kg group. It was concluded that BPA administration during the entire period of pregnancy in rats produced pregnancy failure, pre- and postimplantation loss, fetal developmental delay and severe maternal toxicity, but no embryo-fetal dysmorphogenesis at an oral exposure level of 1000 mg/kg.

Air Pollutants↗

Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation.

Atrial fibrillation (AF), the most common chronic arrhythmia, increases the risk of stroke and is an independent predictor of mortality. Available pharmacological treatments have limited efficacy. Once initiated, AF tends to self-perpetuate, owing in part to electrophysiological remodeling in the atria; however, the fundamental mechanisms underlying this process are still unclear. We have recently demonstrated that chronic human AF is associated with increased atrial oxidative stress and peroxynitrite formation; we have now tested the hypothesis that these events participate in both pacing-induced atrial electrophysiological remodeling and in the occurrence of AF following cardiac surgery. In chronically instrumented dogs, we found that rapid (400 min(-1)) atrial pacing was associated with attenuation of the atrial effective refractory period (ERP). Treatment with ascorbate, an antioxidant and peroxynitrite decomposition catalyst, did not directly modify the ERP, but attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing. Biochemical studies revealed that pacing was associated with decreased tissue ascorbate levels and increased protein nitration (a biomarker of peroxynitrite formation). Oral ascorbate supplementation attenuated both of these changes. To evaluate the clinical significance of these observations, supplemental ascorbate was given to 43 patients before, and for 5 days following, cardiac bypass graft surgery. Patients receiving ascorbate had a 16.3% incidence of postoperative AF, compared with 34.9% in control subjects. In combination, these studies suggest that oxidative stress underlies early atrial electrophysiological remodeling and offer novel insight into the etiology and potential treatment of an enigmatic and difficult to control arrhythmia. The full text of this article is available at http://www.circresaha.org.

Aged↗

A unified statistical approach to deformation-based morphometry.

We present a unified statistical framework for analyzing temporally varying brain morphology using the 3D displacement vector field from a nonlinear deformation required to register a subject's brain to an atlas brain. The unification comes from a single model for structural change, rather than two separate models, one for displacement and one for volume changes. The displacement velocity field rather than the displacement itself is used to set up a linear model to account for temporal variations. By introducing the rate of the Jacobian change of the deformation, the local volume change at each voxel can be computed and used to measure possible brain tissue growth or loss. We have applied this method to detecting regions of a morphological change in a group of children and adolescents. Using structural magnetic resonance images for 28 children and adolescents taken at different time intervals, we demonstrate how this method works.

Adolescent↗

NQ-Y15 inhibits the calcium mobilization by elevation of cyclic AMP in rat platelets.

2-1(4-Cyanophenyl)aminol-3-chloro-1,4-naphthalenedione (NQ-Y15) is a dual action drug which acts as a thromboxane A2 (TXA2) synthase inhibitor and TXA2/PGH2 receptor antagonist. In the present study, we examined the effects of NQ-Y15 on Ca2+ mobilization, which is the common event in various types of platelet activation, in arachidonic acid (AA)-stimulated rat platelets. The elevation of cytosolic Ca2+ concentration ([Ca2+]i) induced by AA was inhibited by NQ-Y15 in a concentration-dependent manner. This inhibition-effect of NQ-Y15 was found to be based on the suppression of the rise in [Ca2+]i by the inhibition of both Ca2+ release from internal stores and Ca2+ influx from the extracellular space. Our successive trial was focused on the role of cyclic AMP (cAMP) in the action of NQ-Y15, because cAMP was reported to be increased by dual action drugs such as picotamide and to inhibit the increase in [Ca2+]i. NQ-Y15 was confirmed to increase cAMP in AA-stimulated rat platelets. These results suggested that NQ-Y15 might inhibit the rise in [Ca2+]i in AA-treated rat platelets by increasing cAMP, which is involved in the inhibition of platelet activation.

Animals↗