Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.

We estimated the total number of undiagnosed HBV and HCV carriers and patients with hepatitis virus-related disease in Japan according to 6 different groups classified by their natural histories during 2011. In 2011, the total number of carriers and patients infected with HBV or HCV was estimated according to 6 groups using government reports and reports from the hepatitis epidemiology research group of The Ministry of Health, Labor and Welfare in Japan. In 2011, the total number of hepatitis virus carriers was estimated to be 2 090 128-2 840 128 in which the estimated number of undiagnosed HCV and HBV carriers was 776 826 (HBV: 481 470; HCV: 295 356). The total number of treated patients, as either inpatients or outpatients, was estimated to be 811588 (HBV: 303 366; HCV: 520 600) in 2011. It is presumed that many carriers shirk consultation for many reasons, such as patients' misunderstanding, lack of awareness and forgetfulness of their positive status. The numbers of infected patients who did not seek treatment increased gradually to 501 714-1 251 714 (HBV: 333 791-483 791; HCV: 167 923-767 923) in 2011. Compared to 2000, the number of undiagnosed carriers was significantly reduced in 2011 probably because of the well-organized, effective national hepatitis virus screening system that has been launched by the Japanese government since 2002. Moreover, the increase in the number of untreated persons who are aware of their positive status shows that more effort should be invested in improving the referral system from screening centres to core hospitals.

A clustering approach to identify and characterize the asthma and chronic obstructive pulmonary disease overlap phenotype.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. The phenotypes that have clinical features of both asthma and COPD are still incompletely understood. OBJECTIVE: To clarify the best discriminators of the asthma-COPD overlap phenotype from asthma and COPD subgroups using a clustering approach. METHODS: This study assessed pathophysiological parameters, including mRNA expression levels of T helper cell-related transcription factors, namely TBX21 (Th1), GATA3 (Th2), RORC (Th17) and FOXP3 (Treg), in peripheral blood mononuclear cells in asthma patients (n=152) and in COPD patients (n=50). Clusters were determined using k-means clustering. Exacerbations of asthma and COPD were recorded during the 1-year follow-up period. RESULTS: The cluster analysis revealed four biological clusters: cluster 1, predominantly patients with COPD; cluster 2, patients with an asthma-COPD overlap phenotype; cluster 3, patients with non-atopic and late-onset asthma; and cluster 4, patients with early-onset atopic asthma. Hazard ratios for exacerbation were 2.5 (95% confidence interval [CI], 1.1-5.6) in cluster 1 and 2.3 (95% CI, 1.0-5.0) in cluster 2 compared with patients in other clusters. Cluster 2 was discriminated from other clusters by total serum IgE level ≥310 IU/mL, blood eosinophil counts ≥280 cells/µL, a higher ratio of TBX21/GATA3, FEV1 /FVC ratio <0.67 and smoking ≥10 pack-years with an area under the curve of 0.94 (95% CI, 0.90-0.98) in the receiver operating characteristic analysis. CONCLUSIONS AND CLINICAL RELEVANCE: The asthma-COPD overlap phenotype was characterized by peripheral blood eosinophilia and higher levels of IgE despite the Th2-low endotype.

Systematic review and meta-analysis of hepatitis C virus infection in the Democratic Republic of Congo.

OBJECTIVES: Hepatitis C virus (HCV) infection is endemic in the Democratic Republic of the Congo (DRC), where the prevalence of HCV antibodies (anti-HCV) is reported to range from 0.2% to 13.7%. However, the reported prevalence rates have been inconsistent. Therefore, a meta-analysis of observational studies was conducted to provide updates on the prevalence of HCV infection in the DRC. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Medline, EMBASE and Google Scholar were searched for publications reporting on HCV infection in the DRC up to autumn 2015. In addition, a manual search was undertaken to detect relevant papers. Studies performed in groups at low risk of HCV (blood donors and pregnant women) were used for the meta-analysis. The random effects model was used to estimate the pooled prevalence of anti-HCV. RESULTS: Sixteen studies with 13,799 participants (aged 6 months-71 years) met the inclusion criteria. The studies were performed in blood donors, pregnant women, military personnel, individuals with human immunodeficiency virus, children, commercial sex workers, Congolese patients living in Canada, patients with sickle cell disease and hospitalized patients. The reviewed studies revealed the presence of anti-HCV in almost all studied age groups and did not differ between sexes. The pooled prevalence of anti-HCV was 2.9% [95% confidence interval 1.5-4.3%]. Subgroup analyses revealed that the prevalence rates of anti-HCV in blood donors and pregnant women were 2.7% (95% confidence interval: 1.1-4.4%) and 3.3% (1.4-5.1%), respectively. CONCLUSIONS: HCV infection remains an issue of public concern in the DRC, demonstrating a need for adequate hepatitis control programmes. Efforts must be made to virtually eliminate transfusion-transmitted HCV throughout the country.

Respiratory mechanics and peripheral airway inflammation and dysfunction in asthma.

BACKGROUND: Clinical application of the forced oscillation technique (FOT) has progressed with the spread of commercially available FOT devices. The correlation between respiratory impedance and spirometry has been reported; however, the association with airway inflammation and pulmonary function, in the lung periphery in particular, is unclear. OBJECTIVE: To assess whether respiratory impedance is associated with peripheral airway inflammation and dysfunction in asthma. METHODS: Subjects included 78 patients with overall controlled asthma. We measured whole-breath or within-breath respiratory system resistance (Rrs) and reactance (Xrs) using a commercially available multi-frequency FOT device (MostGraph-01), and assessed the correlation with the fraction of exhaled nitric oxide (FeNO), alveolar nitric oxide concentration (CANO), maximal NO flux in the conductive airways (J'awNO), and the N2 phase III slope of single breath N2 washout (delta N2 ). RESULTS: The differences between inspiratory and expiratory phases of Xrs at 5 Hz (X5), resonant frequency (Fres), and a low-frequency reactance area (ALX) were significantly correlated with CANO; however, there was no correlation between respiratory impedance and FeNO or J'awNO. The delta N2 values were significantly correlated with whole-breath, inspiratory, and expiratory Rrs and Xrs, except for R20. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that respiratory impedance reflects peripheral airway inflammation and ventilation inhomogeneity.

Prognosis of chronic spontaneous urticaria in 117 patients not controlled by a standard dose of antihistamine.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disorder, but its clinical course reported so far is largely variable, probably due to the heterogeneity of the clinical background of patients and pathogenesis of this disease. METHODS: To reveal the prognosis of refractory CSU, we retrospectively studied the patients who suffered from spontaneous urticaria for six weeks or longer at their first visit to our outpatient clinic, who were insufficiently controlled by a standard dose of antihistamine, and revisited from 2003 to 2009. RESULTS: Among 223 patients with CSU, 117 patients fulfilled the criteria mentioned above. Mean disease duration at first visit and mean duration of follow-up at our hospital were 27.4 ± 4.2 months and 18.7 ± 1.9 months, respectively. By using Kaplan-Meier methods, the estimated improved rates at 12 months, 24 months, and 60 months were 36.6%, 51.2%, and 66.1%, respectively. The overall improvement rate of childhood cases (<19 years) was significantly higher than that of adult cases (P = 0.007, log-rank test). Moreover, the improvement rate of patients with short disease durations (<1 year at the first visit) was significantly (P = 0.003, log-rank test) higher than that of patients with long disease durations (one year or more). CONCLUSION: Our data indicate that the condition of patients with CSU can be gradually improved even in intractable cases. Information about the clinical course and prognostic factors of CSU in this study could help physicians predict the prognosis of patients and ensure medication adherence of patients with CSU.

Pig cloning by microinjection of fetal fibroblast nuclei.

Pig cloning will have a marked impact on the optimization of meat production and xenotransplantation. To clone pigs from differentiated cells, we microinjected the nuclei of porcine (Sus scrofa) fetal fibroblasts into enucleated oocytes, and development was induced by electroactivation. The transfer of 110 cloned embryos to four surrogate mothers produced an apparently normal female piglet. The clonal provenance of the piglet was indicated by her coat color and confirmed by DNA microsatellite analysis.

Propane reacts with O2 and H2 on gold supported TS-1 to form oxygenates with high selectivity.

Gold nanoparticles supported on a microporous titanosilicate (TS-1) were found to be highly selective (95%) towards the formation of acetone and isopropanol from propane, O(2), and H(2) at moderate temperatures (443 K).

[Aortic valve replacement for the small aortic annulus].

Aortic valve surgery for the small aortic annulus is still challenging for surgeons. Recently, the new types of high performance prosthesis have been developed and the chance of an aortic root enlargement (ARE) is decreasing. In this study, we propose the ideal strategy of the aortic surgery for the small aortic annulus. We analyzed the clinical records of 158 patients who underwent aortic valve replacement from August 1999 to October 2005 in our institution. The small aortic annulus was observed in 38 patients (24%). Fourteen patients of this group underwent ARE. Patient-prosthesis mismatch (PPM) was less frequently observed in patients with ARE compared to those without ARE. The additional time required for ARE was not considerable, and neither ischemic time nor cardiopulmonary bypass time was significantly prolonged by ARE. In conclusion, we have to select a prosthesis with sufficient orifice area to avoid PPM, otherwise we should choose an option of ARE. For this consideration, we definitely need the chart that demonstrates the relationship between the nominal size of various types of prostheses and the size of a patient's annulus that those prostheses actually fit.

Functional triads consisting of ryanodine receptors, Ca(2+) channels, and Ca(2+)-activated K(+) channels in bullfrog sympathetic neurons. Plastic modulation of action potential.

Fluorescent ryanodine revealed the distribution of ryanodine receptors in the submembrane cytoplasm (less than a few micrometers) of cultured bullfrog sympathetic ganglion cells. Rises in cytosolic Ca(2+) ([Ca(2+)](i)) elicited by single or repetitive action potentials (APs) propagated at a high speed (150 microm/s) in constant amplitude and rate of rise in the cytoplasm bearing ryanodine receptors, and then in the slower, waning manner in the deeper region. Ryanodine (10 microM), a ryanodine receptor blocker (and/or a half opener), or thapsigargin (1-2 microM), a Ca(2+)-pump blocker, or omega-conotoxin GVIA (omega-CgTx, 1 microM), a N-type Ca(2+) channel blocker, blocked the fast propagation, but did not affect the slower spread. Ca(2+) entry thus triggered the regenerative activation of Ca(2+)-induced Ca(2+) release (CICR) in the submembrane region, followed by buffered Ca(2+) diffusion in the deeper cytoplasm. Computer simulation assuming Ca(2+) release in the submembrane region reproduced the Ca(2+) dynamics. Ryanodine or thapsigargin decreased the rate of spike repolarization of an AP to 80%, but not in the presence of iberiotoxin (IbTx, 100 nM), a BK-type Ca(2+)-activated K(+) channel blocker, or omega-CgTx, both of which decreased the rate to 50%. The spike repolarization rate and the amplitude of a single AP-induced rise in [Ca(2+)](i) gradually decreased to a plateau during repetition of APs at 50 Hz, but reduced less in the presence of ryanodine or thapsigargin. The amplitude of each of the [Ca(2+)](i) rise correlated well with the reduction in the IbTx-sensitive component of spike repolarization. The apamin-sensitive SK-type Ca(2+)-activated K(+) current, underlying the afterhyperpolarization of APs, increased during repetitive APs, decayed faster than the accompanying rise in [Ca(2+)](i), and was suppressed by CICR blockers. Thus, ryanodine receptors form a functional triad with N-type Ca(2+) channels and BK channels, and a loose coupling with SK channels in bullfrog sympathetic neurons, plastically modulating AP.

Functional coupling of Ca(2+) channels to ryanodine receptors at presynaptic terminals. Amplification of exocytosis and plasticity.

Ca(2+)-induced Ca(2+) release (CICR) enhances a variety of cellular Ca(2+) signaling and functions. How CICR affects impulse-evoked transmitter release is unknown. At frog motor nerve terminals, repetitive Ca(2+) entries slowly prime and subsequently activate the mechanism of CICR via ryanodine receptors and asynchronous exocytosis of transmitters. Further Ca(2+) entry inactivates the CICR mechanism and the absence of Ca(2+) entry for >1 min results in its slow depriming. We now report here that the activation of this unique CICR markedly enhances impulse-evoked exocytosis of transmitter. The conditioning nerve stimulation (10-20 Hz, 2-10 min) that primes the CICR mechanism produced the marked enhancement of the amplitude and quantal content of end-plate potentials (EPPs) that decayed double exponentially with time constants of 1.85 and 10 min. The enhancement was blocked by inhibitors of ryanodine receptors and was accompanied by a slight prolongation of the peak times of EPP and the end-plate currents estimated from deconvolution of EPP. The conditioning nerve stimulation also enhanced single impulse- and tetanus-induced rises in intracellular Ca(2+) in the terminals with little change in time course. There was no change in the rate of growth of the amplitudes of EPPs in a short train after the conditioning stimulation. On the other hand, the augmentation and potentiation of EPP were enhanced, and then decreased in parallel with changes in intraterminal Ca(2+) during repetition of tetani. The results suggest that ryanodine receptors exist close to voltage-gated Ca(2+) channels in the presynaptic terminals and amplify the impulse-evoked exocytosis and its plasticity via CICR after Ca(2+)-dependent priming.

A Ca2+-induced Ca2+ release mechanism involved in asynchronous exocytosis at frog motor nerve terminals.

The extent to which Ca2+-induced Ca2+ release (CICR) affects transmitter release is unknown. Continuous nerve stimulation (20-50 Hz) caused slow transient increases in miniature end-plate potential (MEPP) frequency (MEPP-hump) and intracellular free Ca2+ ([Ca2+]i) in presynaptic terminals (Ca2+-hump) in frog skeletal muscles over a period of minutes in a low Ca2+, high Mg2+ solution. Mn2+ quenched Indo-1 and Fura-2 fluorescence, thus indicating that stimulation was accompanied by opening of voltage-dependent Ca2+ channels. MEPP-hump depended on extracellular Ca2+ (0.05-0.2 mM) and stimulation frequency. Both the Ca2+- and MEPP-humps were blocked by 8-(N, N-diethylamino)octyl3,4,5-trimethoxybenzoate hydrochloride (TMB-8), ryanodine, and thapsigargin, but enhanced by CN-. Thus, Ca2+-hump is generated by the activation of CICR via ryanodine receptors by Ca2+ entry, producing MEPP-hump. A short interruption of tetanus (<1 min) during MEPP-hump quickly reduced MEPP frequency to a level attained under the effect of TMB-8 or thapsigargin, while resuming tetanus swiftly raised MEPP frequency to the previous or higher level. Thus, the steady/equilibrium condition balancing CICR and Ca2+ clearance occurs in nerve terminals with slow changes toward a greater activation of CICR (priming) during the rising phase of MEPP-hump and toward a smaller activation during the decay phase. A short pause applied after the end of MEPP- or Ca2+-hump affected little MEPP frequency or [Ca2+]i, but caused a quick increase (faster than MEPP- or Ca2+-hump) after the pause, whose magnitude increased with an increase in pause duration (<1 min), suggesting that Ca2+ entry-dependent inactivation, but not depriming process, explains the decay of the humps. The depriming process was seen by giving a much longer pause (>1 min). Thus, ryanodine receptors in frog motor nerve terminals are endowed with Ca2+ entry-dependent slow priming and fast inactivation mechanisms, as well as Ca2+ entry-dependent activation, and involved in asynchronous exocytosis. Physiological significance of CICR in presynaptic terminals was discussed.

Three-dimensional mesoporous titanosilicates prepared by modified sol-gel method: Ideal gold catalyst supports for enhanced propene epoxidation.

Mesoporous titanosilicates with 1-12 mol % Ti content and with three-dimensional wormhole-like mesoporosity are prepared by a modified sol-gel technique. Sorption analysis shows that there is little change in the surface properties with increasing Ti concentration in the samples, implying that Ti atoms either are well-dispersed on the walls of the silica matrix or are present inside the framework with no pore blocking effect. Spectroscopic analysis shows that the Ti atoms are atomically dispersed in the silica matrix even at very high Ti concentration and there is no observable Ti aggregate (anatase) present in the samples. These titanosilicate samples after Au deposition followed by trimethylsilylation (for enhanced hydrophobicity) are highly efficient catalysts for vapor-phase propene epoxidation using O2 and H2. It was possible to achieve commercially desirable performance with about 7% propene conversion, >90% propene oxide selectivity, and about 40% hydrogen efficiency.

Hyperhomocysteinemia impairs angiogenesis in response to hindlimb ischemia.

Hyperhomocysteinemia (HH) is an independent risk factor for atherosclerosis, including peripheral arterial occlusive disease (PAOD). Because angiogenesis and collateral vessel formation are important self-salvage mechanisms for ischemic PAOD, we examined whether HH modulates angiogenesis in vivo in a rat model of hindlimb ischemia. Rats were divided into 3 groups: the control group was given tap water, the HH group was given water containing L-methionine (1 g x kg(-1) x d(-1)), and the HH+L-arg group was given water containing methionine (1 g x kg(-1) x d(-1)) and l-arginine (2.25 vol%). At day 14 of the dietary modifications, the left femoral artery and vein were excised, and the extent of angiogenesis and collateral vessels in the ischemic limb were examined for 4 weeks. Plasma homocysteine levels significantly increased (P:<0.001), and plasma and tissue contents of nitrite+nitrate as well as tissue cGMP levels significantly decreased in the HH group compared with the control group (P:<0.01). Laser Doppler blood flowmetry (LDBF) revealed a significant decrease in the ischemic/normal limb LDBF ratio in the HH group at days 7, 14, 21, and 28 (P:<0.01 versus control). Angiography revealed a significant decrease in the angiographic score in the HH group at day 14 (P:<0.001 versus control). Immunohistochemistry of ischemic tissue sections showed a significant reduction in the capillary density in the HH group (P:<0. 001 versus control). Oral l-arginine supplementation in rats with HH (HH+L-arg) restored the decreased plasma and tissue nitrite+nitrate and cGMP contents (P:<0.05) as well as angiogenesis, as assessed by LDBF (P:<0.05 versus HH), angiographic score (P:<0.01 versus HH), and capillary density (P:<0.001 versus HH). In summary, HH impaired ischemia-induced angiogenesis and collateral vessel formation in a rat model of hindlimb ischemia in vivo. The mechanism of the HH-induced impairment of angiogenesis might be mediated in part by a reduced bioactivity of endogenous NO in the HH state.

[Short-term results of the Fontan operation in patients with Down syndrome].

Despite an extensive experience with Fontan operation, there is a paucity of information to guide the indication of the procedure in patients with Down syndrome. Of 79 patients who had undergone a Fontan operation in our hospital between 1995 and 2003, 3 had Down syndrome. All 3 patients had complete atrioventricular septal defect with single ventricular physiology. Two patients survived, and 1 died of chylothorax and respiratory infection. The 2 survivors have done well in the short-term without complications. We consider that in appropriately selected patients with Down syndrome in whom biventricular repair is precluded, the Fontan operation is the choice of the procedures.

[Repair of tetralogy of Fallot with obstruction of right pulmonary artery; report of a case].

Patients with tetralogy of Fallot showing unilateral obstruction of a pulmonary artery, especially the right pulmonary artery, are a high-risk group for pulmonary hypertension after repair. This case of tetralogy of Fallot with the obstruction of the right pulmonary artery received a Blalock-Taussig shunt at 7 months old, and the occluded right pulmonary artery caused empyema after surgery. At 2 years old, a cardiac catheter study showed a pulmonary artery index of 193.6 mm2/m2, so we undertook intracardiac repair. After the repair, she showed a relativery favorable clinical course. Systolic pulmonary artery pressure and right ventricular pressure were about 30 and 50 mmHg, respectively. We considered that tetralogy of Fallot with obstruction of right pulmonary artery could be repaired, as long as the pulmonary artery index was within the limits of indication and the left ventricle was well-developed.

Neo-kyotorphin (Thr-Ser-Lys-Tyr-Arg), a new analgesic peptide.

The amino acid sequence of a newly isolated pentapeptide, neo-kyotorphin from bovine brain was synthetically verified to be Thr-Ser-Lys-Tyr-Arg corresponding to the C-terminal portion of hemoglobin alpha-chain. The synthetic neo-kyotorphin showed the dose-dependent analgesia in mice which was approximately equal to that of Leu-enkephalin.

Protective effects of diltiazem and ryanodine against ischemia-reperfusion injury in neonatal rabbit hearts.

The effects of diltiazem, a sarcolemmal Ca2+ channel blocker, and ryanodine, an inhibitor of sarcoplasmic reticulum function, were investigated in isolated newborn rabbit hearts (2 to 5 days old) subjected to ischemia and reperfusion. After cardioplegic arrest with St. Thomas' Hospital solution, global ischemia was induced at 37 degrees C (normothermia) for 45 minutes or at 20 degrees C (hypothermia) for 180 minutes. The hearts were then reperfused at 37 degrees C for 30 minutes. Diltiazem or ryanodine, at concentrations that have minimal to moderately negative inotropic effects under nonischemic conditions, was added to the cardioplegic solution. After normothermic ischemia, reperfusion of untreated hearts resulted in recovery of left ventricular developed pressure to 52.9% +/- 2.5% of the preischemic level. In hearts treated with diltiazem, recovery of left ventricular developed pressure was significantly improved (84.2% +/- 2.9% at 3 x 10(-8) mol/L; p < 0.01). Comparable improvement was achieved with ryanodine (90.5% +/- 4.1% at 10(-9) mol/L; p < 0.01). Creatine kinase leakage and structural derangement of mitochondria were also reduced by both agents. With hypothermic ischemia, left ventricular developed pressure recovered in untreated hearts to 72.7% +/- 3.3% of preischemic values. Treatment with diltiazem improved the recovery of left ventricular developed pressure to 96.9% +/- 3.5% at 3 x 10(-8) mol/L and reduced creatine kinase leakage and mitochondrial damage. Ryanodine also improved the recovery of left ventricular developed pressure and attenuated ultrastructural damage. These findings suggest that Ca2+ handling by the sarcoplasmic reticulum, like transsarcolemmal Ca2+ influx, plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury in the neonatal heart despite the morphologic and functional immaturity of the sarcoplasmic reticulum in the neonate.

Protective effects of dimethyl amiloride against postischemic myocardial dysfunction in rabbit hearts: phosphorus 31-nuclear magnetic resonance measurements of intracellular pH and cellular energy.

The effects of 5-(N,N-dimethyl)amiloride, a potent and specific Na(+)-H+ exchange inhibitor, were investigated in isolated perfused rabbit hearts subjected to ischemia and reperfusion. Phosphorus 31-nuclear magnetic resonance spectroscopy was used to monitor intracellular pH, creatine phosphate, beta-adenosine triphosphate, and inorganic phosphate. After cardioplegic arrest with St. Thomas' Hospital solution, normothermic (37 degrees C) global ischemia was induced for 45 minutes, and the hearts were reperfused for 50 minutes. Dimethyl amiloride at 10 mumol/L, which has minimal inotropic and chronotropic effects on the nonischemic heart, was added to the cardioplegic solution. Treatment with dimethyl amiloride reduced the elevation of left ventricular end-diastolic pressure during and after the ischemia and improved the postischemic recovery of developed pressure from 76% +/- 3.2% at 30 minutes of reperfusion in control hearts (n = 6) up to 99% +/- 1.9% in hearts treated with dimethyl amiloride (n = 8). Dimethyl amiloride did not affect the decline in intracellular pH during ischemia for up to 30 minutes but enhanced the intracellular acidosis thereafter. The intracellular pH at the end of ischemia was 6.21 +/- 0.05 in control hearts compared with 5.24 +/- 0.17 in hearts treated with dimethyl amiloride (p < 0.05). During reperfusion, intracellular pH of hearts treated with dimethyl amiloride was less than control for 5 minutes, but subsequent recovery of intracellular pH was similar to control. Treatment with dimethyl amiloride did not affect creatine phosphate breakdown, inorganic phosphate accumulation, and beta-adenosine triphosphate depletion during 45 minutes of ischemia. The creatine phosphate resynthesis and inorganic phosphate reduction during reperfusion were also unaffected. These findings suggest that Na(+)-H+ exchange plays an important role not only during reperfusion but also during ischemia for the development of postischemic cardiac dysfunction most likely by inducing primary Na+ and secondary Ca2+ overload. Specific Na(+)-H+ exchange inhibitors like dimethyl amiloride would have a potential therapeutic profile in cardiac surgery, especially if added before ischemia.

Biochemical studies of pigments from a pathogenic fungus Microsporum cookei. III. Comparison of the effects of xanthomegnin and O-methylxanthomegnin on the oxidative phosphorylation of rat liver mitochondria.

The effects of xanthomegnin and O-methylxanthomegnin on the oxidative phosphorylation of rat liver mitochondria were compared. The n-octanol/water partition coefficient of xanthomegnin was markedly enhanced by O-methylation, but O-methylation of xanthomegnin reduced the uncoupling effect on the respiratory system of mitochondria. Analogous results were obtained in the uncoupling action of 5-hydroxy-1, 4-naphthoquinone (juglone) and 5-methoxy-1, 4-naphthoquinone (O-methyljuglone) on the oxidative phosphorylation of rat liver mitochondria. These data indicate that the phenolic hydroxyl groups of xanthomegnin might contribute to its uncoupling action on the oxidative phosphorylation of mitochondria. Bovine serum albumin (BSA) improved the efficiency of oxidative phosphorylation of mitochondria which were uncoupled by xanthomegnin. Spectroscopic observations revealed that xanthomegnin interacted with BSA by means of hydrophobic and ionic forces but O-methylxanthomegnin showed only hydrophobic interaction. Analogous interactions between mitochondria and xanthomegnin or O-methylxanthomegnin were observed. These results indicate that the uncoupling action of xanthomegnin on the respiratory system in mitochondria might involve ionic interaction of xanthomegnin with cationic residues in the hydrophobic region of mitochondrial membrane proteins.

Long-term use-dependent enhancement of impulse-induced exocytosis by adrenaline at frog motor nerve terminals.

Adrenaline (5-20 microM) use-dependently increased end-plate potentials (EPPs) in normal Ringer solution (containing d-tubocurarine to partially block acetylcholine receptors) and a low Ca2+, high Mg2+ solution for more than several hours and decreased the coefficient of variation of EPP amplitude in the latter solution in frog neuromuscular junctions. The amplitude and frequency of miniature EPPs and impulse-induced increases in intraterminal Ca2+ concentration were unaffected. Adrenaline thus causes sustained enhancement of impulse-induced exocytosis by acting at a mechanism of exocytosis downstream to Ca2+ entry.