Nutritional factors affecting length of hospital stay in patients undergoing cardiovascular surgery.

Cardiovascular surgery is a highly invasive intervention that is often performed in elderly patients at risks of complications because of malnutrition and reduced immunity. This study investigated nutritional factors that affected length of hospital stay in patients undergoing cardiovascular surgery. Among 68 patients who underwent surgery at the Department of Cardiovascular Surgery of Gifu Municipal Hospital between April 2013 and March 2015, 55 with complete data were included in the analysis. Data on serum albumin (ALB), transferrin (Tf), pre-albumin (PA) and retinol binding protein (RBP) levels were collected. The median length of hospital stay was 29 days (stays of ≥30 days were considered long-term hospitalization). Multivariate analysis (multiple logistic regression) included age (≥ 65 years), sex (female), and ALB (≤ 3.0 g/dL), Tf (≤ 150.0 mg/dL), PA (≤ 10.0 mg/dL) and RBP (≤ 1.5 mg/dL) levels. ALB [odds ratio (OR) 10.37, 95% CI (confidence interval): 1.185-90.80, P = 0.035] and Tf [OR 4.743, 95% CI: 1.375-16.36, P = 0.014] were significantly associated with length of hospital stay. Nutritional management of patients and careful monitoring of ALB and Tf levels can shorten length of hospital stay in patients undergoing cardiovascular surgery.

The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies.

Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats. Recent studies of diseases caused by several RNA viruses in people and other species indicate that antiviral therapy may be effective against FIP in cats. The small molecule nucleoside analog GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. We determined that GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. We determined the pharmacokinetics of GS-441524 in cats in vivo and established a dosage that would sustain effective blood levels for 24 h. In an experimental FIPV infection of cats, GS-441524 treatment caused a rapid reversal of disease signs and return to normality with as little as two weeks of treatment in 10/10 cats and with no apparent toxicity.

Ribavirin dose reduction during telaprevir/ribavirin/peg-interferon therapy overcomes the effect of the ITPA gene polymorphism.

Treatment success of chronic hepatitis C virus genotype 1 infection has improved with the advent of telaprevir plus peg-interferon/ribavirin triple combination therapy. However, the effect of inosine triphosphatase (ITPA) polymorphism on dose reduction during triple therapy, especially during the postmarketing phase, has not been sufficiently evaluated. We analysed 273 patients with genotype 1 infection who were treated with triple therapy and assessed the effect of the ITPA polymorphism on dose reduction. ITPA and IFNL4 SNP genotypes were determined by the Invader assay. A stepwise multivariate regression analysis was performed to identify factors associated with outcome of the therapy. The overall sustained viral response (SVR) rate 12 weeks after the end of therapy was 80.2% (219/273). Decline of haemoglobin was significantly faster, and ribavirin was more extensively reduced in patients with ITPA SNP rs1127354 genotype CC than CA/AA. Extensive reduction of ribavirin resulted in mild reduction of telaprevir and peg-interferon, but no significant increase in viral breakthrough. Although the amount of telaprevir given was slightly higher in CA/AA patients, the total dose of peg-interferon and the SVR rate did not differ between the two groups. Multivariate analysis showed that IFNL4 but not ITPA SNP genotype, platelet count and peg-interferon adherence were significantly associated with outcome of therapy. Postmarketing-phase triple therapy resulted in a high SVR rate in spite of extensive ribavirin dose reduction in a diverse patient population, indicating the importance of treatment continuation and appropriate management of adverse events.

Emergence of resistant variants detected by ultra-deep sequencing after asunaprevir and daclatasvir combination therapy in patients infected with hepatitis C virus genotype 1.

Daclatasvir (DCV) and asunaprevir (ASV) are NS5A and NS3 protease-targeted antivirals respectively, currently under development for the treatment of chronic hepatitis C virus (HCV) infection. We analysed the relationship between pre-existing drug-resistant variants and clinical outcome of the combination treatment with DCV and ASV. Ten patients with HCV genotype 1b were orally treated with a combination of ASV and DCV for 24 weeks. The frequencies of amino acid (aa) variants at NS3 aa positions 155, 156 and 168 and at NS5A aa31 and 93 before and after treatment were analysed by ultra-deep sequencing. We established a minimum variant frequency threshold of 0.3% based on plasmid sequencing. Sustained virological response (SVR) was achieved in 8 out of 10 patients (80%), and relapse of HCV RNA after cessation of the treatment and viral breakthrough occurred in the other two patients. Pre-existing DCV-resistant variants (L31V/M and/or Y93H; 0.9-99.4%) were detected in three out of eight patients who achieved SVR. Pre-existing DCV-resistant variants were detected in a relapsed patient (L31M, Y93H) and in a patient with viral breakthrough (Y93H); however, no ASV-resistant variants were detected. In these patients, HCV RNA rebounded with ASV- and DCV- double resistant variants (NS3 D168A/V plus NS5A L31M and Y93H). While pre-existing DCV-resistant variants might contribute to viral breakthrough in DCV and ASV combination therapy, the effectiveness of prediction of the outcome of therapy based on ultra-deep sequence analysis of pre-existing resistant variants appears limited.

Human microRNA hsa-miR-1231 suppresses hepatitis B virus replication by targeting core mRNA.

Pathogen-specific miRNA profiles might reveal potential new avenues for therapy. To identify miRNAs directly associated with hepatitis B virus (HBV) in hepatocytes, we performed a miRNA array analysis using urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice where the livers were highly repopulated with human hepatocytes and human immune cells are absent. Mice were inoculated with HBV-infected patient serum samples. Eight weeks after HBV infection, human hepatocytes were collected from liver tissues, and miRNAs were analysed using the Toray 3D array system. The effect of miRNAs on HBV replication was analysed using HBV-transfected HepG2 cells. Four miRNAs, hsa-miR-486-3p, hsa-miR-1908, hsa-miR-675 and hsa-miR-1231 were upregulated in mouse and human livers with HBV infection. These miRNAs were associated with immune response pathways such as inflammation mediated by chemokine and cytokine signalling. Of these miRNAs, hsa-miR-1231, which showed high homology with HBV core and HBx sequences, was most highly upregulated. In HBV-transfected HepG2 cells, overexpression of hsa-miR-1231 resulted in suppression of HBV replication with HBV core reduction. In conclusion, a novel interaction between hsa-miR-1231 and HBV replication was identified. This interaction might be useful in developing new therapeutic strategies against HBV.

Periphytic algae of the Garças Lake, Upper Paraná River floodplain: comparing the years 1994 and 2004.

The changes imposed by dams on hydrological regime, water transparence and nutrient concentrations downstream affect biodiversity in relation to species richness and specific composition of the community. The aim of this work was evaluate this effect on periphyton, comparing richness and composition of periphytic algae in the Garças Lake, Upper Paraná River floodplain, between the years 1994, before construction of the Porto Primavera Reservoir, and after its operation in 2004. This floodplain lake showed an increase in species, from 113 in 1994 to 159 in 2004. A few species, however, were common during the last year, dominated by Zygnemaphyceae and some Bacillariophyceae species. The increase in algal diversity in 2004 may be the result of the ability of the system to adapt to environmental changes. However, the large change in the periphyton species composition suggests further impacts on the food web, demanding continuity of long-term studies in order to determine their consequences on the biodiversity as a whole.

Effects of hydrological regime and connectivity on the interannual variation in taxonomic similarity of periphytic algae.

The aim of this study was to analyze the effects of flood pulses (intensity) on the richness and composition of periphytic algae in lentic environments of the Upper Paraná River floodplain, over a six-year period. Other factors, such as connectivity of the environments with the main channel of the river and the availability of substrate for the periphyton, were also evaluated. For qualitative analyses, periphyton community was sampled from adult petioles of Eichhornia azurea Kunth taken from the littoral regions of the lakes studied. A total of 457 taxa of periphytic algae, distributed within 141 genera and 10 classes, were registered in the four environments. The greatest richness of periphytic algae was observed in connected floodplain lakes, especially in 2007 and during high water periods. In both connected and disconnected lakes, richness correlated positively with water levels of the Paraná River. Richness was also positively correlated with the number of taxa of aquatic macrophytes. The specific composition of periphytic algae differed between high and low water periods, and between connected and disconnected lakes. Therefore, among the considered variables, it is evident that flood pulse constitutes the principal force acting on periphytic algae communities of the floodplain, followed by the degree of connectivity and the presence of aquatic macrophytes.

Periphytic algae of the Garças Lake, Upper Paraná River floodplain: comparing the years 1994 and 2004 / Algas perifíticas da Lagoa das Garças, planície de inundação do Alto Rio Paraná: comparação entre os anos de 1994 e 2004

The changes imposed by dams on hydrological regime, water transparence and nutrient concentrations downstream affect biodiversity in relation to species richness and specific composition of the community. The aim of this work was evaluate this effect on periphyton, comparing richness and composition of periphytic algae in the Garças Lake, Upper Paraná River floodplain, between the years 1994, before construction of the Porto Primavera Reservoir, and after its operation in 2004. This floodplain lake showed an increase in species, from 113 in 1994 to 159 in 2004. A few species, however, were common during the last year, dominated by Zygnemaphyceae and some Bacillariophyceae species. The increase in algal diversity in 2004 may be the result of the ability of the system to adapt to environmental changes. However, the large change in the periphyton species composition suggests further impacts on the food web, demanding continuity of long-term studies in order to determine their consequences on the biodiversity as a whole.

As mudanças impostas pela formação de reservatórios afetam a biodiversidade das algas perifíticas em relação à composição e riqueza de espécies. O objetivo deste trabalho foi comparar a riqueza e composição de espécies de algas perifíticas na Lagoa das Garças, planície de inundação do Alto Rio Paraná, entre os anos de 1994, antes da construção do reservatório de Porto Primavera, e em 2004, após seu funcionamento. Para a lagoa registrou-se um aumento na riqueza de 113 espécies em 1994, para 159 espécies em 2004. Contudo, poucas espécies foram comuns, sendo dominadas por Zygnemaphyceae e Bacillariophyceae. O aumento na riqueza de algas em 2004 pode estar indicando a capacidade do sistema em adaptar-se às alterações ambientais, com possíveis alterações na cadeia alimentar. Considera-se fundamental a continuidade de estudos de longo prazo para avaliar as conseqüências da alteração na riqueza e composição de espécies de algas perifíticas para a estrutura e o funcionamento da planície como um todo.

Effects of hydrological regime and connectivity on the interannual variation in taxonomic similarity of periphytic algae / Efeito do regime hidrológico e da conectividade na similaridade taxonômica de algas perifíticas: variação interanual

The aim of this study was to analyze the effects of flood pulses (intensity) on the richness and composition of periphytic algae in lentic environments of the Upper Paraná River floodplain, over a six-year period. Other factors, such as connectivity of the environments with the main channel of the river and the availability of substrate for the periphyton, were also evaluated. For qualitative analyses, periphyton community was sampled from adult petioles of Eichhornia azurea Kunth taken from the littoral regions of the lakes studied. A total of 457 taxa of periphytic algae, distributed within 141 genera and 10 classes, were registered in the four environments. The greatest richness of periphytic algae was observed in connected floodplain lakes, especially in 2007 and during high water periods. In both connected and disconnected lakes, richness correlated positively with water levels of the Paraná River. Richness was also positively correlated with the number of taxa of aquatic macrophytes. The specific composition of periphytic algae differed between high and low water periods, and between connected and disconnected lakes. Therefore, among the considered variables, it is evident that flood pulse constitutes the principal force acting on periphytic algae communities of the floodplain, followed by the degree of connectivity and the presence of aquatic macrophytes.

Este trabalho visou analisar o efeito do pulso de inundação (intensidade) sobre a riqueza e composição de algas perifíticas, ao longo de seis anos, em ambientes lênticos da planície de inundação do Alto Rio Paraná. A influência da conectividade dos ambientes com a calha principal do rio e disponibilidade de substratos para a comunidade de algas perifíticas também foi avaliada. Para análise, a comunidade perifítica foi amostrada de pecíolos adultos de Eichhornia azurea Kunth, retirados da região litorânea das lagoas estudadas. Considerando os quatro ambientes, foram registrados 457 táxons de algas, distribuídos em 141 gêneros e 10 classes. A maior riqueza de algas perifíticas foi observada em lagoas conectadas, com destaque para o ano de 2007 e para o período de águas altas. A riqueza apresentou correlação positiva, nas lagoas conectadas e não conectadas, com nível hidrométrico do Rio Paraná. Também esteve correlacionada positivamente com o número de táxons de macrófitas aquáticas. A composição de algas perifíticas diferiu entre os períodos de águas altas e águas baixas e entre lagoas conectadas e não conectadas. Ficou evidente que, dentre as variáveis consideradas, o pulso de inundação constitui a principal função de força atuando sobre a comunidade de algas perifíticas na planície, seguido pelo grau de conectividade e presença de macrófitas aquáticas.

In patients with ulcerative colitis, adsorptive depletion of granulocytes and monocytes impacts mucosal level of neutrophils and clinically is most effective in steroid naïve patients.

BACKGROUND: The aetiology of ulcerative colitis is inadequately understood, and drug therapy has been empirical rather than based on sound understanding of disease aetiology. This has been a major factor for refractoriness and adverse drug effects as additional complications. However, ulcerative colitis by its very nature is exacerbated and perpetuated by inflammatory cytokines, which are released by peripheral granulocytes and monocytes as well. Additionally, active ulcerative colitis is often associated with elevated peripheral granulocytes and monocytes with activation behaviour and are found in vast numbers within the colonic mucosa. Hence, from the clinicopathologic viewpoint, granulocytes and monocytes are appropriate targets for therapy in ulcerative colitis. Based on this thinking, an Adacolumn has been developed for depleting excess granulocytes and monocytes by adsorption. METHODS: By colonoscopy, biopsy and histology, we investigated the impact of granulocyte and monocyte adsorption (GMA) on the mucosal level of granulocytes and monocytes in patients with active ulcerative colitis. Forty-five patients (26 steroid naïve and 19 steroid-dependent), mean age 44.7 yr, were included. Twenty patients had total colitis and 25 had left-sided colitis. Each patient was given up to 11 GMA sessions over 12 weeks. No patient received additional medications within 4 weeks (steroid) to 8 weeks (other immunosuppressants) prior to entry or during the GMA course. Colonoscopy together with biopsy was done at entry and within 2 weeks after the last GMA session. RESULTS: At entry, the mean clinical activity index was 12.6; range 10-16. A total of 400 colonic biopsies were examined, which revealed massive infiltration of the colonic mucosa by granulocytes, and GMA was associated with striking reduction of granulocytes in the mucosa. At week 12, 33 of 45 patients (73.3%, P<0.01) had achieved clinical remission (the mean clinical activity index

Real-time monitoring of nitric oxide (NO) and pO2 levels under ischemic conditions associated with small bowel ischemia/reperfusion injury using selective electrodes for NO and oxygen molecules.

The present study demonstrated the feasibility of monitoring nitric oxide (NO) and pO2 levels under ischemic conditions associated with small bowel ischemia/reperfusion (I/R) injury through the use of selective electrodes for NO and oxygen molecules. NO levels gradually increased during ischemia. When reperfusion was started, the NO level decreased suddenly and returned to pre-ischemia values within 10 minutes. After clamping, pO2 decreased rapidly. When reperfusion was started, pO2 increased suddenly, returning to pre-ischemia values within 10 minutes. We concluded that it is feasible to monitor NO and pO2 levels under ischemic conditions of small bowel I/R injury through the use of electrodes selective for NO and oxygen molecules.

Protective effects of MnM2Py4P and Mn-salen against small bowel ischemia/reperfusion injury in rats using an in vivo and an ex vivo electron paramagnetic resonance technique with a spin probe.

BACKGROUND: Reperfusion of ischemic tissues results in the formation of toxic reactive oxygen species (ROS), such as superoxide anion, hydroxyl radicals, hydroperoxide, and peroxynitrite. ROS are potent oxidizing agents, capable of damaging cellular membranes by lipid peroxidation. In the present study, we applied an in vivo electron paramagnetic resonance (EPR)/spin probe and an ex vivo EPR technique to provide direct evidence of ROS following experimentally induced small bowel ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: We used a rat model of small bowel I/R injury to explore the possibility that MnM2Py4P or Mn-salen can prevent the accumulation of ROS species following experimentally induced I/R injury. We examined the ability of MnM2Py4P and Mn-salen to scavenge radicals in living Sprague-Dawley (SD) rats using an in vivo and an ex vivo EPR technique with a spin probe. RESULTS: The CP decay rates in the MnM2Py4P- and Mn-salen-treated rats were significantly higher than those in the untreated rats and almost equal to those in sham group rats. There were no significant differences between the MnM2Py4P-treated group and the Mn-salen-treated group. Superoxide scavenging activities (SSA) in the MnM2Py4P- and EUK-8-treated group were higher than those in the untreated group and almost equal to the sham group. CONCLUSION: The present study suggested that the protective effects of MnM2Py4P and Mn-salen against small bowel IR injury were mediated by the inhibition of O2, H2O2, and NO production.

[Determination of bisphenol A in foods using GC/MS].

An analytical method using GC/MS was developed for bisphenol A (BPA) in foods and BPA was determined in canned foods and fresh foods such as vegetables, fruit and meat. BPA was extracted with acetone from the samples and the extract was concentrated at under 40 degrees C in vacuo to afford an aqueous solution, which was washed with hexane after alkalization and extracted with 50% diethyl ether-hexane after acidification. Extracts were cleaned up on a PSA and/or a C18 cartridge column, and BPA was derivatized with heptafluorobutyric anhydride and determined by GC/MS (SIM). This method was applicable to the detection and determination of BPA residues in food samples at the level of 1 ng/g. Among canned foods, BPA was found in 6 corned beef, 1 chicken, 9 sweet corn and 3 bean samples at the levels of 17-602 ng/g, 212 ng/g, 2.3-75 ng/g and 3.5-26 ng/g, respectively. BPA was also detected in 1 retort soup and 1 retort pack product at the levels of 11 ng/g and 86 ng/g, respectively. As for dairy products, BPA was not detected in butter and milk. Among fresh foods, BPA was detected in 2 fish and 3 liver samples at the levels of trace (tr)-6.2 ng/g and tr-2.2 ng/g, respectively. In vegetables, fruits and chocolates, a trace level of BPA was detected in only 1 chocolate. Traces of BPA were also detected in 3 samples of 6 boxed lunches.

Characterization of the intramolecular electron transfer pathway from 2-hydroxyphenazine to the heterodisulfide reductase from Methanosarcina thermophila.

Heterodisulfide reductase (HDR) is a component of the energy-conserving electron transfer system in methanogens. HDR catalyzes the two-electron reduction of coenzyme B-S-S-coenzyme M (CoB-S-S-CoM), the heterodisulfide product of the methyl-CoM reductase reaction, to free thiols, HS-CoB and HS-CoM. HDR from Methanosarcina thermophila contains two b-hemes and two [Fe(4)S(4)] clusters. The physiological electron donor for HDR appears to be methanophenazine (MPhen), a membrane-bound cofactor, which can be replaced by a water-soluble analog, 2-hydroxyphenazine (HPhen). This report describes the electron transfer pathway from reduced HPhen (HPhenH(2)) to CoB-S-S-CoM. Steady-state kinetic studies indicate a ping-pong mechanism for heterodisulfide reduction by HPhenH(2) with the following values: k(cat) = 74 s(-1) at 25 degrees C, K(m) (HPhenH(2)) = 92 microm, K(m) (CoB-S-S-CoM) = 144 microm. Rapid freeze-quench EPR and stopped-flow kinetic studies and inhibition experiments using CO and diphenylene iodonium indicate that only the low spin heme and the high potential FeS cluster are involved in CoB-S-S-CoM reduction by HPhenH(2). Fe-S cluster disruption by mersalyl acid inhibits heme reduction by HPhenH(2), suggesting that a 4Fe cluster is the initial electron acceptor from HPhenH(2). We propose the following electron transfer pathway: HPhenH(2) to the high potential 4Fe cluster, to the low potential heme, and finally, to CoB-S-S-CoM.

Chromatographic and capillary electrophoretic methods for the analysis of nicotinic acid and its metabolites.

Methods for the assay of nicotinic acid (NiAc) and its metabolites in biological fluids using high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) are reviewed. Most of the references cited in this review concern HPLC methods. A few CE methods that have been recently reported are also included. As these compounds are relatively polar and have a wide range of physico-chemical properties, the sample pre-treatment or clean-up process prior to analysis is included. Most HPLC methods using an isocratic elution system allow determination of a single or few metabolites, but gradient HPLC methods enable simultaneous determination of five to eight compounds. Simultaneous determination of NiAc including many metabolites in a single run can be achieved by CE. We also discuss the pharmacokinetics of NiAc and some of its metabolites.

Treatment of established collagen induced arthritis with prostaglandin E1 incorporated in lipid microspheres.

OBJECTIVE: In view of evidence obtained from in vitro and in vivo experiments that prostaglandin E1 (PGE1) has regulatory effects on disordered immune responses and inflammation, we investigated whether lipo-PGE1, an efficient drug delivery system incorporating PGE1 into lipid microspheres, can ameliorate arthritis in the collagen induced arthritis (CIA) model of rheumatoid arthritis (RA). METHODS: DBA/1J male mice were immunized with bovine type II collagen in adjuvant, and treated daily from onset of clinical arthritis with intravenous administration of lipo-PGE1 (5-50 microg/kg) or lipid vehicle as a control. Arthritis was assessed over a 10 day treatment period by monitoring for paw swelling and clinical score. Histopathology of the arthritic hind paws was also evaluated. Lipo-PGE1 accumulation in arthritic joint tissues was measured using 3H labeled PGE1 incorporated in lipid microspheres. RESULTS: Arthritis was significantly suppressed in lipo-PGE1 treated mice compared with lipid vehicle treated controls (p < 0.05, p < 0.016, respectively) in a dose-dependent manner. Histopathological assessment showed a significant reduction of pannus formation and joint destruction in lipo-PGE1 treated mice compared with controls (p < 0.05). Lipo-PGE1 preferentially accumulated in arthritic joints for a longer period than free PGE1. CONCLUSION: Using an efficient drug delivery system, PGE1 can suppress CIA, and lipo-PGE1 may have a potential therapeutic role in RA.

[Changes in the antibacterial activity of chemotherapeutic agents (especially carbapenems) for 10 species of clinical isolates between 1994 and 1996. Surveillance group of the sensitivities of clinical isolates to antibacterial agents].

During October and December of each year of from 1994 to 1996, 3,849 strains of 10 species of bacteria were isolated from clinical materials in 21 institutions nationwide. The minimum inhibitory concentrations (MICs) for these bacteria of four carbapenems (imipenem [IPM], panipenem [PAPM], meropenem [MEPM], and biapenem [BIPM]) and other representative antibacterial agents were measured to investigate annual changes in antibacterial activity. Carbapenems showed potent activity against methicillin-sensitive S. aureus (MSSA), S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, S. marcescens, and the B. fragilis group, with the activity being stable. However, these drugs showed weak activity against methicillin-resistant S. aureus (MRSA) and P. aeruginosa. The antibacterial activity (MIC90) against the tested organisms generally remained stable. Particularly, there was annual improvement of the MIC90 values of IPM and BIPM for S. pneumoniae, as well as the values of IPM and PAPM for H. influenzae, and those of IPM, PAPM, and BIPM for S. marcescens. On the other hand, the activity of carbapenems (including IPM) against MRSA was not necessarily strong, but there was annual improvement of MIC90 values.

The effect of coronary vasospasm on the direction of ST-segment deviation in patients with both hypertrophic cardiomyopathy and vasospastic angina.

BACKGROUND: There has been no report of ECG changes during anginal attacks in patients with coexistent hypertrophic cardiomyopathy (HCM) and vasospastic angina. STUDY OBJECTIVES: To elucidate the change in ST-segment during anginal attacks in patients with coexistent HCM and vasospastic angina (the HCM group) in comparison with that of patients with vasospastic angina and no left ventricular hypertrophy (the non-HCM group). DESIGN: Retrospective study. PATIENTS: Twelve patients in the HCM group, and 28 patients in the non-HCM group. MEASUREMENTS: The direction of ST segment shift, either ST-segment elevation or depression, on the ECGs recorded during vasospastic anginal attacks with severe vasoconstriction in the epicardial coronary artery after intracoronary injection of acetylcholine. RESULTS: Age, male gender, and distribution of coronary arteries in which the vasospasm occurred were similar between the two groups. Collateral circulation to the affected arteries was absent in all the study patients. The prevalence of anginal attacks associated with ST-segment elevation was 2.7 times higher in the non-HCM group than in the HCM group (51. 5% [17 of 33 attacks] vs 18.8% [3 of 16 attacks], respectively; p = 0.03). CONCLUSIONS: In the HCM group, myocardial ischemia associated with a transmural injury pattern seen on the ECG, which is represented as ST-segment elevation, seldom develops during vasospastic anginal attacks because of marked left ventricular hypertrophy.

Evidence for intersubunit communication during acetyl-CoA cleavage by the multienzyme CO dehydrogenase/acetyl-CoA synthase complex from Methanosarcina thermophila. Evidence that the beta subunit catalyzes C-C and C-S bond cleavage.

The carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) from Methanosarcina thermophila is part of a five-subunit complex consisting of alpha, beta, gamma, delta, and epsilon subunits. The multienzyme complex catalyzes the reversible oxidation of CO to CO(2), transfer of the methyl group of acetyl-CoA to tetrahydromethanopterin (H(4)MPT), and acetyl-CoA synthesis from CO, CoA, and methyl-H(4)MPT. The alpha and epsilon subunits are required for CO oxidation. The gamma and delta subunits constitute a corrinoid iron-sulfur protein that is involved in the transmethylation reaction. This work focuses on the beta subunit. The isolated beta subunit contains significant amounts of nickel. When proteases truncate the beta subunit, causing the CODH/ACS complex to dissociate, the amount of intact beta subunit correlates directly with the EPR signal intensity of Cluster A and the activity of the CO/acetyl-CoA exchange reaction. Our results strongly indicate that the beta subunit harbors Cluster A, a NiFeS cluster, that is the active site of acetyl-CoA cleavage and assembly. Although the beta subunit is necessary, it is not sufficient for acetyl-CoA synthesis; interactions between the CODH and the ACS subunits are required for cleavage or synthesis of the C-C bond of acetyl-CoA. We propose that these interactions include intramolecular electron transfer reactions between the CODH and ACS subunits.