Clinical implication of persistent ischemic chest pain on admission in patients with late reperfused acute myocardial infarction

OBJECT: Although previous studies reported that late reperfusion might prevent left ventricular dilation after acute myocardial infarction (AMI), implication of persistent ischemic chest pain on admission remains to be investigated. This study was undertaken to assess the implication of persistent ischemic chest pain on in-hospital outcome and left ventricular function after late reperfused AMI. METHODS AND PATIENTS: We studied 63 patients with a first anterior AMI who underwent percutaneous coronary intervention 6 to 24 hours (11.2+/-4.5 hours) after the onset. Of 63 patients, 48 (76%) had persistent ischemic chest pain on admission. RESULTS: Incidence of in-hospital death, reinfarction or congestive heart failure was similar between the 2 groups. Pretreatment left ventricular ejection fraction and end-diastolic volume were similar between the 2 groups. Predischarge angiography was performed at 17+/-5 days after the onset. Late reperfusion prevented the dilation of left ventricular end-diastolic volume in patients with chest pain (78+/-12 to 75+/-17 ml/m2, p=0.15), but did not in those without (75+/-20 to 93+/-28 ml/m2, p=0.03). A multivariate analysis revealed that absence of persistent ischemic chest pain was an independent predictor of predischarge left ventricular end-diastolic volume >100 ml/m2 (odds ratio 0.10, p=0.04). CONCLUSIONS: Our data demonstrated that absence of persistent ischemic chest pain appears to be a simple and reliable marker which predicts left ventricular dilation after late reperfused AMI.     

Rapid bactericidal activities of carbapenems against Pseudomonas aeruginosa in simulating human plasma concentrations

The rapid bactericidal activities of panipenem (PAPM), imipenem (IPM), and meropenem (MEPM) against Pseudomonas aeruginosa were investigated by using in vitro pharmacodynamic model simulating the human plasma concentrations after intravenous drip infusion at 500 mg for 0.5 hours. Against P. aeruginosa PAO1, PAPM and IPM showed rapider reduction in viable cell counts than MEPM at 0.5 hours after exposure. All drugs showed more than 3 log10 reduction in viable cell counts at 2 hours after exposure and bacterial regrowth was not observed throughout 6 hours. The initial bactericidal activities of the drugs against 4 clinical isolates within 1 hour after exposure were also investigated by the same method. Against P. aeruginosa strain 12,475, the 3 drugs showed similar initial bactericidal activity but PAPM and IPM showed stronger initial bactericidal activity than MEPM against the other strains as did against P. aeruginosa PAO1. The morphological change of a strain 12,489, for which the initial bactericidal activities were different largely, after 0.5 hours exposure to simulated drug-concentrations was investigated by scanning electron microscope. PAPM and IPM induced morphological changes in most of the cells and cell lysis and bulge formation. On the other hand, MEPM induced changes of the surface structure of cells and slightly elongated cells, but not cell lysis.     

Dimerumic acid as an antioxidant from the mold, Monascus anka: the inhibition mechanisms against lipid peroxidation and hemeprotein-mediated oxidation

This study aimed to investigate the antioxidant mechanism of dimerumic acid isolated as the active component with a radical scavenging action from the mold Monascus anka, traditionally used for the fermentation of foods. Dimerumic acid inhibited NADPH- and iron(II)-dependent lipid peroxidation (LPO) of rat liver microsomes at 20 and 200 microM, respectively. When ferrylmyoglobin was incubated with dimerumic acid, the myoglobin was scavenged and an electron spin resonance (ESR) signal with nine peaks was observed. The spin adduct was identified as a nitroxide radical by analysis of hyperfine structure. Similar ESR signal was also detected by incubation of dimerumic acid with peroxyl radicals. Thus, it was clarified that the antioxidant action of dimerumic acid is due to one electron donation of the hydroxamic acid group in the dimerumic acid molecule toward oxidants resulting in formation of nitroxide radical.     

Effect of protease-activated receptor-2 deficiency on allergic dermatitis in the mouse ear

To investigate the involvement of protease-activated receptor-2 (PAR-2) in allergic dermatitis, we generated PAR-2-deficient (PAR-2(-/-)) mice. Ear thickness, contact hypersensitivity (CH) induced by topical application of picryl chloride (PC) or oxazolone (Ox) after sensitization, and vascular permeability after ear passive cutaneous anaphylaxis (PCA) were compared between wild-type (WT) and PAR-2(-/-) mice. Ear thickness was almost the same in untreated WT and PAR-2(-/-) mice. Topical application of PC or Ox thickened the ears at 6, 24 and 48 h after challenge with a peak at 24 h in WT mice. In PAR-2(-/-) mice, the ear swelling induced by both PC and Ox was suppressed at every time point, and significant inhibition was found at 24 h in PC-induced CH and at 24 and 48 h in Ox-induced CH. Histopathological observation of the ears at 24 h after challenge revealed that PC- or Ox-induced ear edema and infiltration of inflammatory cells in WT mice were greatly attenuated in PAR-2(-/-) mice. The vascular permeability in the ears after PCA was not different between WT and PAR-2(-/-) mice. These results strongly suggest that PAR-2 plays a crucial role in type IV allergic dermatitis but not in type I allergic dermatitis.     

2a-[4-(Tetrahydropyridoindol-2-yl)butyl]tetrahydrobenzindole derivatives: new selective antagonists of the 5-hydroxytryptamine7 receptor

A series of tetrahydrobenzindoles was prepared, and the affinity of these compounds for the 5-hydroxytryptamine7 (5-HT7) receptor and other receptors was evaluated. Most of the compounds showed high affinity for the 5-HT7 receptor, and 2a-[4-(tetrahydropyridoindol-2-yl)butyl]tetrahydrobenzindole derivatives (26a-j) exhibited high selectivity for this receptor. The nature of the substituent at the 9-position of the tetrahydropyridindole ring affected the affinity for the 5-HT7 receptor, and the 9-carbamoyl moiety afforded increased selectivity. Compound 26j exhibited high affinity for the 5-HT7 receptor, with at least 280-fold selectivity over the 5-HT2 receptor. In a functional model of 5-HT7 receptor activation, this compound was confirmed to have 5-HT7 receptor antagonist activity. It should be a useful tool for clarifying the biological role of the 5-HT7 receptor.     

Antineoplastic agents. 489. Isolation and structures of meliastatins 1-5 and related euphane triterpenes from the tree Melia dubia

The bark of the giant neem tree Melia dubia was found to contain 11 euphane-type triterpenes. Five new compounds, meliastatins 1-5 (1-5), proved to inhibit growth of the P388 lymphocytic leukemia cell line (ED(50) 1.7-5.6 microg/mL). Four of the others, the previously known methyl kulonate (8), kulinone (9), 16-hydroxybutyrospermol (10), and kulactone (11), were also found to inhibit (ED(50) 2.5-6.2 microg/mL) the P388 cancer cell line. In addition, two new euphane triterpenes were isolated and named dubione A (6) and dubione B (7). Structures for each of the 11 euphane triterpenes were established by spectral techniques that included HRMS and 2D NMR.     

Experience of Aozora Medical Clinic in EMInet

We present here the EMInet (Electronic Medical Information network), a closed information network established by the City government and the Medical Association in Matsudo City, Chiba, Japan. In this network, medical information is shared by multiple certified medical facilities under the informed consent of the patients. The medical record is written only by the physician in charge of the patient and reserved in the server computer. The medical record cannot be rewritten or modified by anyone except the physician in charge of the patient. Other medical professionals can only have access to the record. In the emergency room of certified hospitals, a physician can open the patient's record by using the IC card carried by the patient.     

Role of heparan sulfate proteoglycan (syndecan-1) on the renal epithelial cells during calcium oxalate monohydrate crystal attachment

We have reported that heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG, syndecan-1) expression significantly increased in the rat kidney during calcium oxalate (CaOx) nephrolithiasis. Although the exact role of syndecan still remains unclear, HS/syndecan-1 is thought to have some important role in the CaOx crystal formation. Mardin-Darby canine kidney (MDCK) cells are most commonly used in kidney stone research. It was reported that MDCK cells do not express syndecan-1. In the present study, we established a novel MDCK cell line (KIC-synd-1) that expressed the human syndecan-1 gene. In this cell line, we confirmed stable expression of both sndecan-1 gene and core protein. Immunohistochemical study revealed positive staining of syndecan-1 monoclonal antibody in the basolateral and cytosolic area of the KIC-synd-1 cells. We also investigated the composition of glycosaminoglycans (GAGs) side chains in MDCK cells and KIC-synd-1 cells by using high-performance liquid chromatography (HPLC). Four types of HS chains were identified in both cells as follows; delta diHS-NS, delta diHS-6S, delta diHS-diS1, delta diHS-diS2. Increased production of delta diHS-NS and delta diHS-diS2 were shown in KIC-synd-1 cells compared with production in MDCK cells (p < 0.05). In contrast, only a small amount of delta diHS-6S and delta diHS-diS1 was contained in both cell lines. Total amount of HS was significantly increased in the KIC-synd-1 cells compare with that in the wild type MDCK cells (p < 0.05). Scanning electron microscopy revealed no significant difference between cell surface of wild type MDCK cells and that of KIC-synd-1 cells in normal conditions. However, calcium oxalate crystal attachment was apparently decreased in the KIC-synd-1 cells. These results suggested that cell surface HS/syndecan-1 has preventive role for calcium oxalate nephrolithiasis via creation of a charge barrier against COM crystal attachment.     

Activation of the hypothalamic-pituitary-adrenal axis with repetitive umbilical cord occlusion in the preterm ovine fetus

OBJECTIVE:To determine whether repeated hypoxic insults with umbilical cord occlusion over 4 days will lead to activation of the hypothalamic-pituitary-adrenal (HPA) axis altered adrenocortical responsiveness in the preterm ovine fetus. METHODS: Umbilical cord occlusions of 90 seconds duration were performed every 30 minutes for 3 to 5 hours each day (experimental group n = 7, control group n = 7; at 112-116 days' gestation, term = 147 days). Arterial blood was sampled at predetermined times for blood gases and pH, plasma ACTH, and cortisol. Pituitary proopiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA also were localized and quantified by in situ hybridization. RESULTS: During umbilical cord occlusions fetal arterial oxygen pressure (approximately 17 mmHg) and pH (approximately 0.05) decreased, and carbon dioxide pressure increased (approximately 8 mmHg) as measured on days 1 and 4, but with no cumulative blood gas or pH change over successive occlusions for any of the 4 study days. Plasma ACTH increased, as measured after cord occlusion and over the course of successive cord occlusions on days 1 and 4, and returned to control values by the next day. The cumulative increase in ACTH was much less on day 4 than day 1 (15 +/- 3 compared with 101 +/- 25 pg/mL, P <.05). Plasma cortisol increased, as measured after cord occlusion and over the course of successive cord occlusions on day 4 only (2.7 +/- 0.4 to 4. 7 +/- 0.3 ng/mL, P <.05). POMC mRNA increased 2.5-fold in the pars distalis of the pituitaries from cord occlusion compared to control fetuses, but was unchanged in the pars intermedia. GR mRNA, which was detected in the pars distalis only, was unaltered. CONCLUSION: Repetitive umbilical cord occlusion in the preterm ovine fetus resulted in the activation of the HPA axis, with increased adrenocortical responsiveness over time, and involved differential regulation of POMC mRNA expression in the pars distalis and pars intermedia of the pituitary, but with no change in GR.