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1.
PLoS One ; 11(2): e0148666, 2016.
Article in English | MEDLINE | ID: mdl-26863419

ABSTRACT

BACKGROUND: Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB)-induced right heart failure model and investigated whether cardiac output (CO) is responsible for the progression of hepatic fibrosis. METHODS AND RESULTS: Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2±27.6 and 150.1±31.2 ml/min, P<0.01). Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8±1.7 and 1.0±0.2%, P<0.01, 76.2±27.5 and 32.7±7.5 ng/ml, P<0.01). Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1α positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-ß1, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2) were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1α was significantly increased in the PAB group than that in the control group (2.31±0.84 and 1.0±0.18 arbitrary units, P<0.05). CONCLUSIONS: Our study demonstrated that low CO and tissue hypoxia were responsible for hepatic fibrosis in right failure heart model rats.


Subject(s)
Cardiac Output, Low/complications , Heart Failure/complications , Liver Cirrhosis/etiology , Animals , Cardiac Output, Low/blood , Cell Hypoxia , Disease Models, Animal , Gene Expression , Heart Failure/blood , Hyaluronic Acid/blood , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Liver/pathology , Liver Cirrhosis/blood , Male , Myofibroblasts/pathology , Rats, Sprague-Dawley
2.
Pediatr Int ; 56(4): 644-6, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25252060

ABSTRACT

Questionnaires were sent to 14 maternity hospital staff members for qualitative assessment at the start of fetal telediagnosis and at the end of the study using a five-point Likert scale: 5, I strongly think so; 4, I think so; 3, I can't decide; 2, I don't think so; 1, I never think so. Ten questionnaires were returned to us (71%). The results showed that the staff reported a significant increase in confidence in performing fetal cardiac screening (score 2.3 at start, 3.4 at study completion; P = 0.034), the rate of score increase rose with the number of telediagnoses (r = 0.72, P < 0.05), feedback from a specialist was very useful (4.4 and 4.9, respectively), and real-time image transmission was preferred over recorded images (score 3.7 vs 2.4, respectively; P = 0.042). The excellent educational effect of telemedicine is useful for staff members to improve their skills while nurturing their motivation, leading to the promotion of fetal cardiac screening in regional areas.


Subject(s)
Fetal Diseases/diagnosis , Job Satisfaction , Personnel, Hospital , Prenatal Diagnosis/methods , Telemedicine , Female , Hospitals, Maternity , Humans , Male , Surveys and Questionnaires
3.
Pediatr Int ; 56(2): 289-91, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24730637

ABSTRACT

We verified the feasibility of telediagnosis of fetal disease by (i) grading telediagnosis by a pediatric cardiologist into five confidence levels; and (ii) comparison of fetal telediagnosis with hands-on fetal diagnosis or postnatal diagnosis. In 114 patients suspected of having heart disease (real time, n = 15; recorded image transmission, n = 99), 79 patients were in level 5 (excellent), 17 in level 4 (good), eight in level 3 (fair), 10 in level 2 (poor), and no patients in level 1 (bad). The average was 4.5, and in 96 patients (84% of all) telediagnosis was accurate (above 4), whereas in 18 patients it was inaccurate (level 2 or 3). In re-examination of 25 patients, telediagnosis was confirmed in patients in level 4 and 5, whereas heart disease was missed in patients in levels 2 or 3. The correct diagnosis matched the high confidence level of a specialist based on recognizable transmitted images.


Subject(s)
Fetal Diseases/diagnostic imaging , Heart Diseases/diagnostic imaging , Heart Diseases/embryology , Internet , Telemedicine , Ultrasonography, Prenatal , Feasibility Studies , Female , Humans , Pregnancy , Reproducibility of Results
4.
Pediatr Cardiol ; 35(4): 652-7, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24259010

ABSTRACT

Information and communication technology has been widely applied to various fields, including clinical medicine. We report here a telediagnosis system using ultrasound image transmission. The effect of telediagnosis, using a medical link between local maternity hospitals and our children's medical center, was verified. The number of fetal telediagnosis for cardiac disease, and cases referred to a perinatal care center and emergent transportation of neonates with congenital heart disease from maternity hospitals, were calculated based on the hospital records. The percentage of patients found to have heart disease was compared between out-patient clinic and telediagnosis cases. Telediagnosis increased, allowing maternity hospital staff to obtain support easily from a specialist when making a diagnosis. Many severe cases were transferred to tertiary centers with the correct diagnosis; consequently, the number of emergent transportations of neonates with severe cardiac anomalies continued to below. Telediagnosis was also useful as an educational tool for maternity hospital staff, who improved their skills during conversations with a specialist. Unlike in the outpatient clinic, consultation by telediagnosis was requested even for cases of mild abnormalities, and the number of false-positives increased, while many cardiac anomalies were found in the early stage. Furthermore, telediagnosis was helpful for pregnant women requiring bed rest, and also had the advantage of allowing a doctor to be able to talk with parents. Establishing a fetal telediagnosis system is a useful strategy to improve neonatal care through a medical link between local maternity hospitals and a tertiary center.


Subject(s)
Echocardiography/methods , Fetal Heart/diagnostic imaging , Heart Defects, Congenital/diagnostic imaging , Hospitals, Maternity/statistics & numerical data , Remote Consultation/methods , Tertiary Care Centers/statistics & numerical data , Ultrasonography, Prenatal/methods , Adolescent , Adult , Echocardiography/statistics & numerical data , Feasibility Studies , Female , Fetal Diseases/diagnostic imaging , Humans , Infant, Newborn , Japan , Middle Aged , Outpatients , Pregnancy , Remote Consultation/statistics & numerical data , Reproducibility of Results , Retrospective Studies , Ultrasonography, Prenatal/statistics & numerical data , Young Adult
5.
Cardiol Young ; 23(5): 759-62, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23083675

ABSTRACT

We describe the case of a 9-year-old girl demonstrating isolated absence of the coronary sinus with abnormal coronary venous drainage into the main pulmonary artery. Coronary angiography showed normal coronary arterial trees and contrast medium from both coronary arteries drained into the main pulmonary artery via an abnormal cardiac vein on the anterior wall of the right ventricle.


Subject(s)
Coronary Sinus/abnormalities , Coronary Vessel Anomalies/diagnostic imaging , Pulmonary Artery/abnormalities , Child , Coronary Angiography , Coronary Sinus/diagnostic imaging , Female , Humans , Pulmonary Artery/diagnostic imaging
6.
Anal Bioanal Chem ; 400(7): 1895-904, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21479793

ABSTRACT

Analyses of energy metabolism in human cancer have been difficult because of rapid turnover of the metabolites and difficulties in reducing time for collecting clinical samples under surgical procedures. Utilization of xenograft transplantation of human-derived colon cancer HCT116 cells in spleens of superimmunodeficient NOD/SCID/IL-2Rγ(null) (NOG) mice led us to establish an experimental model of hepatic micrometastasis of the solid tumor, whereby analyses of the tissue sections collected by snap-frozen procedures through newly developed microscopic imaging mass spectrometry (MIMS) revealed distinct spatial distribution of a variety of metabolites. To perform intergroup comparison of the signal intensities of metabolites among different tissue sections collected from mice in fed states, we combined matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry (MALDI-TOF-IMS) and capillary electrophoresis-mass spectrometry (CE-MS), to determine the apparent contents of individual metabolites in serial tissue sections. The results indicated significant elevation of ATP and energy charge in both metastases and the parenchyma of the tumor-bearing livers. To note were significant increases in UDP-N-acetyl hexosamines, and reduced and oxidized forms of glutathione in the metastatic foci versus the liver parenchyma. These findings thus provided a potentially important method for characterizing the properties of metabolic systems of human-derived cancer and the host tissues in vivo.


Subject(s)
Colonic Neoplasms/pathology , Liver Neoplasms/secondary , Transplantation, Heterologous , Animals , Colonic Neoplasms/metabolism , Disease Models, Animal , Electrophoresis, Capillary , Humans , Liver Neoplasms/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
7.
J Lipid Res ; 52(3): 463-70, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21149645

ABSTRACT

Salamander large cells facilitated identification and localization of lipids by MALDI imaging mass spectrometry. Salamander retina lipid extract showed similarity with rodent retina lipid extract in phospholipid content and composition. Like rodent retina section, distinct layer distributions of phospholipids were observed in the salamander retina section. Phosphatidylcholines (PCs) composing saturated and monounsaturated fatty acids (PC 32:0, PC 32:1, and PC 34:1) were detected mainly in the outer and inner plexiform layers (OPL and IPL), whereas PCs containing polyunsaturated fatty acids (PC 36:4, PC 38:6, and PC 40:6) composed the inner segment (IS) and outer segment (OS). The presence of PCs containing polyunsaturated fatty acids in the OS layer implied that these phospholipids form flexible lipid bilayers, which facilitate phototransduction process occurring in the rhodopsin rich OS layer. Distinct distributions and relative signal intensities of phospholipids also indicated their relative abundance in a particular cell or a cell part. Using salamander large cells, a single cell level localization and identification of biomolecules could be achieved by MALDI imaging mass spectrometry.


Subject(s)
Phospholipids/metabolism , Retina/cytology , Retina/metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Urodela/metabolism , Animals , Biological Transport , Phospholipids/chemistry , Retinal Photoreceptor Cell Inner Segment/metabolism , Retinal Photoreceptor Cell Outer Segment/metabolism
8.
Congenit Anom (Kyoto) ; 50(3): 197-9, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20584037

ABSTRACT

Peters Plus syndrome is a very rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor anomalies. Mutations in the B3GALTL gene encoding beta 1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome. We report on a female patient with unusually severe manifestations of Peters Plus syndrome, including anterior eye staphyloma, cleft lip and palate, and hypoplastic left heart syndrome (HLHS). Analysis of the B3GALTL gene revealed no mutation in the patient. To our knowledge, HLHS has not previously been reported in Peters Plus syndrome so far, and anterior staphyloma, a most severe defect of the anterior eye chamber, is also apparently rare in the syndrome. Our patient might represent a new syndrome of severe Peters Plus syndrome-like phenotype with anterior eye staphyloma and HLHS.


Subject(s)
Abnormalities, Multiple/diagnosis , Hypoplastic Left Heart Syndrome/diagnosis , Cleft Lip , Cornea/abnormalities , Fatal Outcome , Female , Galactosyltransferases/genetics , Glucosyltransferases/genetics , Growth Disorders/diagnosis , Humans , Infant, Newborn , Limb Deformities, Congenital/diagnosis
9.
Anal Chem ; 81(21): 9153-7, 2009 Nov 01.
Article in English | MEDLINE | ID: mdl-19788281

ABSTRACT

We have developed a mass microscope (mass spectrometry imager with spatial resolution higher than the naked eye) equipped with an atmospheric pressure ion-source chamber for laser desorption/ionization (AP-LDI) and a quadrupole ion trap time-of-flight (QIT-TOF) analyzer. The optical microscope combined with the mass spectrometer permitted us to precisely determine the relevant tissue region prior to performing imaging mass spectrometry (IMS). An ultraviolet laser tightly focused with a triplet lens was used to achieve high spatial resolution. An atmospheric pressure ion-source chamber enables us to analyze fresh samples with minimal loss of intrinsic water or volatile compounds. Mass-microscopic AP-LDI imaging of freshly cut ginger rhizome sections revealed that 6-gingerol ([M + K](+)at m/z 333.15, positive mode; [M - H](-) at m/z 293.17, negative mode) and the monoterpene ([M + K](+) at m/z 191.09), which are the compounds related to pungency and flavor, respectively, were localized in oil drop-containing organelles. AP-LDI-tandem MS/MS analyses were applied to compare authentic signals from freshly cut ginger directly with the standard reagent. Thus, our atmosphere-imaging mass spectrometer enabled us to monitor a quality of plants at the organelle level.


Subject(s)
Tandem Mass Spectrometry/instrumentation , Volatile Organic Compounds/analysis , Atmospheric Pressure , Catechols/analysis , Fatty Alcohols/analysis , Zingiber officinale/chemistry , Monoterpenes/analysis , Tandem Mass Spectrometry/methods , Volatile Organic Compounds/chemistry
10.
Circ J ; 73(11): 2169-72, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19352046

ABSTRACT

Isolated non-compaction of the ventricular myocardium (INCVM) is a relatively newly defined clinicopathologic entity. INCVM is clinically accompanied by depressed ventricular function, arrhythmias, and systemic embolization. We report two cases of INCVM with long QT syndrome (LQTS). In both cases the QT interval was over 0.55 s with episodes of torsades de pointes, and prominent ventricular trabeculations and deep intertrabecular recesses were detected by 2-dimensional echocardiography. Both cases had the KCNH2 mutation. To the best of our knowledge, this is the first report investigating INCVM with LQTS.


Subject(s)
Isolated Noncompaction of the Ventricular Myocardium/complications , Long QT Syndrome/complications , Child, Preschool , ERG1 Potassium Channel , Echocardiography , Electrocardiography , Ether-A-Go-Go Potassium Channels/genetics , Humans , Infant, Newborn , Isolated Noncompaction of the Ventricular Myocardium/diagnosis , Isolated Noncompaction of the Ventricular Myocardium/genetics , Long QT Syndrome/diagnosis , Long QT Syndrome/genetics , Male , Mutation , Torsades de Pointes/complications
11.
Pediatr Int ; 48(2): 112-7, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16635167

ABSTRACT

BACKGROUND: Administration of magnesium sulfate (MgSO4) is an effective and safe treatment for torsades de pointes (TdP) associated with acquired long QT syndrome (LQTS) in adults. As for children, there are few reports focusing on it. The authors discuss the efficacy of MgSO4 for TdP in children with congenital and acquired LQTS. The authors also discuss the optimal administration dosage and serum magnesium (SMg) concentration during MgSO4 therapy. METHODS: The authors studied seven consecutive LQTS children undergoing MgSO4 therapy for TdP. Of the seven children, five were congenital LQTS and two were acquired LQTS. A bolus injection of MgSO4 was given intravenously over 1-2 min followed by continuous infusion for the next 2-7 days. RESULTS: Of the seven patients, six responded completely to the initial bolus. The bolus dosage was 5.9 +/- 3.8 mg/kg (range, 2.3-12 mg/kg) in these six, and the other remaining one (neonate with congenital LQTS) required a total of 30 mg/kg until complete abolishment. The continuous infusion was given at rates of 0.3-1.0 mg/kg per h and patients did not show recurrence of TdP. The SMg concentration was 3.9 +/- 1.0 mg/dL (2.9-5.4 mg/dL) immediately after bolus injection. The mean corrected QT (QTc) interval before and after bolus injection did not show significant difference. CONCLUSION: Intravenous infusion of MgSO4 was effective for TdP in children with LQTS, and MgSO4 abolished TdP without shortening the QTc interval. The optimal bolus dosage, infusion rates and SMg concentration were 3-12 mg/kg, 0.5-1.0 mg/kg per h and 3-5 mg/dL, respectively.


Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Long QT Syndrome/epidemiology , Magnesium Sulfate/therapeutic use , Torsades de Pointes/drug therapy , Torsades de Pointes/epidemiology , Anti-Arrhythmia Agents/administration & dosage , Anti-Arrhythmia Agents/pharmacology , Child , Child, Preschool , Comorbidity , Electrocardiography , Humans , Infant , Infant, Newborn , Infusions, Intravenous , Long QT Syndrome/congenital , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacology , Male , Treatment Outcome
12.
J Pept Sci ; 12(1): 51-7, 2006 Jan.
Article in English | MEDLINE | ID: mdl-15948142

ABSTRACT

The solution conformation of human calcitonin in a mixture of 60% water and 40% trifluoroethanol has been determined by the combined use of 1H NMR spectroscopy and distance geometry calculations with a distributed computing technique. 1H NMR spectroscopy provided 195 distance constraints and 13 hydrogen bond constraints. The 20 best converged structures exhibit atomic rmsd of 0.43 A for the backbone atoms from the averaged coordinate position in the region of Asn3-Phe22. The conformation is characterized by a nearly amphiphilic alpha-helix domain that extends from Leu4 in the cyclic region to His20. There are no significant differences observed among the overall structures of a series of calcitonins obtained from ultimobranchial bodies, including those that possess 20- to 50-fold greater activity. Three aromatic amino acid residues, Tyr12, Phe16 and Phe19, form a hydrophobic surface of human calcitonin. Bulky side chains on the surface could interfere with the ligand-receptor interaction thereby causing its low activity, relative to those of other species.


Subject(s)
Calcitonin/chemistry , Animals , Eels , Humans , Magnetic Resonance Spectroscopy/methods , Magnetic Resonance Spectroscopy/standards , Models, Molecular , Protein Conformation , Protein Structure, Secondary , Reference Standards , Salmon , Solutions/chemistry
13.
J Am Coll Nutr ; 23(5): 497S-500S, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15466950

ABSTRACT

BACKGROUND: Intravenous administration of magnesium sulphate (MgSO(4)) is a very effective and safe treatment for torsades de pointes (TdP) associated with acquired long QT syndrome (LQTS) in adults. Discussed here is the efficacy of MgSO(4) for TdP in children with congenital and acquired LQTS. METHODS: The optimal MgSO(4) dosage and serum magnesium (SMg) was determined in six consecutive children with TdP; four had congenital LQTS and two had acquired LQTS. A bolus injection of MgSO(4) was given intravenously over 1 to 2 minutes followed by continuous infusion for the next 2 to 7 days. RESULTS: Of the six patients, five responded completely to the initial bolus of 6.1 +/- 4.2 mg/kg (range, 2.3-12 mg/kg). One (a neonate with congenital LQTS) required a total of 30 mg/kg until complete TdP elimination. Continuous infusion was given at rates of 0.3 to 1.0 mg/kg/hr with no recurrence of TdP. SMg concentration was 3.9 +/- 1.0 mg/dL (2.9-5.4 mg/dL) immediately after bolus injection. CONCLUSION: Intravenous MgSO(4) infusion effectively treated TdP in children with LQTS. Optimal bolus dosage, infusion rates and SMg concentration were 3 to 12 mg/kg, 0.5 to 1.0 mg/kg/hr and 3 to 5 mg/dL, respectively.


Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Magnesium Sulfate/therapeutic use , Magnesium/blood , Torsades de Pointes/drug therapy , Anti-Arrhythmia Agents/administration & dosage , Child , Child, Preschool , Dose-Response Relationship, Drug , Electrocardiography , Humans , Infant , Infant, Newborn , Infusions, Intravenous , Injections, Intravenous , Magnesium Sulfate/administration & dosage , Male , Torsades de Pointes/blood , Torsades de Pointes/congenital , Treatment Outcome
15.
Int J Oncol ; 23(1): 165-72, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12792790

ABSTRACT

Postoperative adjuvant chemotherapy reportedly improves advanced colorectal cancer patients' survival, however, it is necessary to assess what regimens are useful. Doxifluridine (5'-DFUR) is an intermediate of capecitabine approved in Europe and USA to treat metastatic colorectal cancer. 5'-DFUR is metabolized to 5-fluorouracil (5-FU) by thymidine phosphorylase existing in tumor at high concentrations, suggesting high 5-FU levels in tumor tissues and lesser complications. Present study compared usefulness of 5'-DFUR to that of oral 5-FU. Patients were enrolled at 38 centers from April 1993 to September 1996. They had diagnosed colorectal cancer of TNM stages II and III, and underwent macroscopic curative resection. Patients were prestratified into colon or rectum cancer and allocated into either 5'-DFUR (5'-DFUR 460 mg/m(2)/day + PSK 3 g/day) or 5-FU (5-FU 115 mg/m(2)/day + PSK 3 g/day) group by dynamic randomization (stratification factors such as depth of tumor, degree of lymph node metastasis, and location of tumor). Drugs were orally administered daily from postoperative week 2 to 54, with 6 mg/m(2) mitomycin C at operation and following days. Subjects for analysis were 277 in 5'-DFUR and 281 in 5-FU groups. Median follow-up was 6.5 years. Although no differences in overall survival curves were detected, multivariate analysis showed that 5'-DFUR + PSK regimen was a significantly better prognostic factor in patients with Dukes B or C (risk ratio, 1.451; p=0.048); with tumor depth of pT3 or pT4 (risk ratio, 1.568; p=0.020). For patients with advanced colorectal cancer, 5'-DFUR + PSK therapy may possibly be more useful than 5-FU + PSK, but further study is required.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Floxuridine/therapeutic use , Fluorouracil/therapeutic use , Administration, Oral , Adult , Aged , Antimetabolites, Antineoplastic/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Recurrence , Time Factors , Treatment Outcome
16.
Ann Thorac Surg ; 75(4): 1308-10, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12683583

ABSTRACT

A 1-month-old boy with tetralogy of Fallot, pulmonary atresia, right aortic arch, and right ductus arteriosus, exhibited progressive right upper lobar emphysema since his birth. The emphysema was caused by the right ductus arteriosus compressing the right upper bronchus. After division of the ductus arteriosus the emphysema completely regressed. We should explore the cause of lobar emphysema thoroughly before lobectomy especially when it is extrinsic. The emphysema may regress by eliminating the extrinsic factor.


Subject(s)
Bronchi , Ductus Arteriosus, Patent/complications , Heart Defects, Congenital/complications , Pulmonary Emphysema/etiology , Humans , Infant , Male , Pulmonary Emphysema/congenital
17.
Pediatr Int ; 45(1): 39-44, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12654067

ABSTRACT

BACKGROUND: There have been only a few investigations into the effects of cardiopulmonary bypass (CPB) on the magnesium (Mg) concentrations in pediatric patients. The purpose of the present study was to compare the postoperative Mg concentrations and their recovery time to pre-surgical values in pediatric patients undergoing CPB for surgical repair of congenital heart disease. The incidence of dysrhythmia was also determined. METHODS: Twenty-seven pediatric patients undergoing open-heart surgery with CPB were enrolled in this study. Controls were 23 pediatric patients undergoing palliative surgery without CPB. Serum Mg (SMg) concentrations and ionized Mg (iMg) concentrations were measured at four sample points: 24 h before the surgery, immediately after the surgery, 24 h after the surgery and 48 h after the surgery. RESULTS: Serum Mg and iMg concentrations were significantly decreased after open-heart surgery. Immediately after the surgery, the mean SMg concentration was 64.1% and the mean iMg concentration was 68.8% of the pre-surgical values. The concentration of iMg showed quicker recovery than that of SMg, and returned to normal range 48 h after surgery. However, SMg and iMg concentrations after palliative surgery did not show significant differences from the pre-surgical values. The incidence of dysrhythmia was almost the same between the two groups; dysrhythmia was observed in two patients in the open-heart surgery group and in three patients in the palliative surgery group. CONCLUSIONS: Mg concentrations showed significant decrease after CPB; however, they showed quick recovery and did not increase the incidence of dysrhythmia in pediatric patients.


Subject(s)
Heart Defects, Congenital/blood , Heart Defects, Congenital/surgery , Magnesium/blood , Cardiopulmonary Bypass , Child, Preschool , Female , Humans , Infant , Magnesium/urine , Male , Postoperative Period
19.
Chem Pharm Bull (Tokyo) ; 50(7): 966-8, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12130856

ABSTRACT

(1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (2b, PPDC), a new class of potent N-methyl-D-aspartic acid (NMDA) receptor antagonist, was designed based on a new method for restricting the conformation of compounds having a cyclopropane ring. The three-dimensional structures of PPDC obtained by the three different methods of X-ray crystallographic analysis, usual MM2-calculations in vacuum, and MM2 calculations based on the nuclear Overhauser effect (NOE) data in D2O are similar, which are in accord with that hypothesized. These results suggest that this conformational restriction method is particularly effective in designing novel biologically active molecules.


Subject(s)
Cyclopropanes/chemistry , Cyclopropanes/pharmacology , Excitatory Amino Acid Antagonists/chemistry , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Crystallography, X-Ray , Drug Design , Excitatory Amino Acid Antagonists/chemical synthesis , Excitatory Amino Acid Antagonists/pharmacology , Magnetic Resonance Spectroscopy , Milnacipran , Models, Molecular , Molecular Conformation , Structure-Activity Relationship
20.
Bioorg Med Chem ; 10(6): 1777-91, 2002 Jun.
Article in English | MEDLINE | ID: mdl-11937336

ABSTRACT

(1S,2R)-1-Phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC, ), which is a conformationally restricted analogue of the antidepressant milnacipran [(+/-)-1], represents a new class of potent NMDA receptor antagonists. A series of PPDC analogues modified at the carbamoyl moiety were synthesized. Among these, (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-dipropylcyclopropanecarboxamide (4d) was identified as the most potent NMDA receptor antagonist in this series and clearly reduced the MMDA receptor mediated potentiation of rat hippocampal slices, a model of long-term potentiation (LTP). The three-dimensional structure of 4d was also analyzed in detail to clarify the receptor-binding conformation.


Subject(s)
Cyclopropanes/chemical synthesis , Cyclopropanes/pharmacology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Animals , Biological Transport/drug effects , Cyclopropanes/chemistry , Cyclopropanes/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , In Vitro Techniques , Long-Term Potentiation , Magnetic Resonance Spectroscopy , Male , Models, Molecular , Molecular Conformation , Molecular Structure , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/metabolism , Serotonin/metabolism , Structure-Activity Relationship
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