Decrescent intensity training concurrently improves maximal anaerobic power, maximal accumulated oxygen deficit, and maximal oxygen uptake.

This study aimed to investigate the effects of a gradually decreasing intensity training from that corresponding to maximal anaerobic power (MAnP) to that of near maximal oxygen uptake ([Formula: see text]) (decrescent intensity training) on MAnP, maximal accumulated oxygen deficit (MAOD), and [Formula: see text] in untrained young men. Seventeen untrained young men were randomly divided into either a training (TR; n = 9) group or a control (CON; n = 8) group. The TR group performed the decrescent intensity training, whereas the CON group did not perform any exercises. The mean training time per session throughout the training period was 275 ± 135 s. There was a Group × Time interaction for both absolute and relative (p < 0.01) values of [Formula: see text], MAOD, and MAnP. The TR group had significantly increased values for all variables after the 8-week training program, and the relative values of all variables were significantly higher in the TR group than in the CON group. Muscle thicknesses in the anterior and posterior aspects of the thigh and maximal isokinetic knee extension and flexion strengths improved only in the TR group (p < 0.05). A single-exercise training with gradually decreasing intensity from that corresponding to the MAnP to that of approximately 100% [Formula: see text] improves MAnP, MAOD, and [Formula: see text] concurrently, despite the short training time per session.

Validation of claims data to identify death among aged persons utilizing enrollment data from health insurance unions.

The identification of death is critical for epidemiological research. Despite recent developments in health insurance claims databases, the quality of death information in claims is not guaranteed because health insurance claims are collected primarily for reimbursement. We aimed to examine the usefulness and limitations of death information in claims data and to examine methods for improving the quality of death information for aged persons.We used health insurance claims data and enrollment data (as the gold standard) from September 2012 through August 2015 for nondependent persons aged 65-74 years enrolled in Japanese workplace health insurance. Overall, 3,710,538 insured persons were registered in the database during the study period. We analyzed 45,441 eligible persons. Inpatient and outpatient deaths were identified from the discharge/disease status in the claims, with sensitivities of 94.3% and 47.4%, specificities of 98.5% and 99.9%, and PPVs of 96.3% and 95.7%, respectively, using enrollment data as the gold standard. For outpatients, death defined as a combination of disease status and charge data for terminal care still indicated low sensitivity (54.7%).The validity of death information in inpatient claims was high, suggesting its potential usefulness for identifying death. However, given the low sensitivity for outpatient deaths, the use of death information obtained solely from records in outpatient claims is not recommended.

Susceptibility of isogeneic ginbuna Carassius auratus langsdorfii Temminck et Schlegel to cyprinid herpesvirus-2 (CyHV-2) as a model species.

Herpesviral haematopoietic necrosis (HVHN), caused by cyprinid herpesvirus-2 (CyHV-2), has affected the commercial production of the goldfish Carassius auratus and gibelio carp Carassius auratus gibelio. High water temperature treatments are reported to reduce the mortality rate of infected goldfish and elicit immunity in the survivors. To define the mechanism by which this intervention induces resistance, clonal ginbuna Carassius auratus langsdorfii, which is closely related to both species and has been used in fish immunology, may represent a promising model species. In this study, we investigated the susceptibility of clonal ginbuna strains to CyHV-2 and the effect of high water temperature treatment on infected ginbuna and goldfish. Experimental intraperitoneal infection with CyHV-2 at 25 °C caused 100% mortality in ginbuna strains, which was accompanied by histopathological changes typical of HVHN. Both infected ginbuna S3n strain and goldfish, exposed to high temperature for 6 days [shifting from 25 °C (permissive) to 34 °C (non-permissive)], showed reduced mortalities after the 1st inoculation, and subsequent 2nd virus challenge to 0%, indicating induction of immunity. It was concluded that ginbuna showed a similar susceptibility and disease development in CyHV-2 infection compared to goldfish, suggesting that ginbuna can be a useful fish model for the study of CyHV-2 infection and immunity.

Liver injury is associated with mortality in sickle cell disease.

BACKGROUND: Increased life expectancy in sickle cell disease (SCD) has resulted in greater recognition of the consequences of repeated intravascular vaso-occlusion and chronic haemolysis to multiple organ systems. AIM: To report the long-term consequences of liver dysfunction in SCD. METHODS: A cohort of SCD patients was prospectively evaluated at the National Institutes of Health (NIH) Clinical Center. The association of mortality with liver enzymes, parameters of liver synthetic function and iron overload was evaluated using Cox regression. RESULTS: Exactly, 247 SCD patients were followed up for 30 months of whom 22 (9%) died. After controlling for predictors, increased direct bilirubin (DB), ferritin, alkaline phosphatase and decreased albumin were independently associated with mortality. In a multivariable model, only high DB and ferritin remained significant. Ferritin correlated with hepatic iron content and total blood transfusions but not haemolysis markers. Forty patients underwent liver biopsies and 11 (28%) had fibrosis. Twelve of 26 patients (48%) had portal hypertension by hepatic venous pressure gradient (HVPG) measurements. All patients with advanced liver fibrosis had iron overload; however, most patients (69%) with iron overload were without significant hepatic fibrosis. Ferritin did not correlate with left ventricular dysfunction by echocardiography. DB correlated with bile acid levels suggesting liver pathology. Platelet count and soluble CD14 correlated with HVPG indicating portal hypertension. CONCLUSIONS: Ferritin and direct bilirubin are independently associated with mortality in sickle cell disease. Ferritin likely relates to transfusional iron overload, while direct bilirubin suggests impairment of hepatic function, possibly impairing patients' ability to tolerate systemic insults.

Mechanisms of hemolysis-associated platelet activation.

BACKGROUND: Intravascular hemolysis occurs after blood transfusion, in hemolytic anemias, and in other conditions, and is associated with hypercoagulable states. Hemolysis has been shown to potently activate platelets in vitro and in vivo, and several mechanisms have been suggested to account for this, including: (i) direct activation by hemoglobin (Hb); (ii) increase in reactive oxygen species (ROS); (iii) scavenging of nitric oxide (NO) by released Hb; and (iv) release of intraerythrocytic ADP. OBJECTIVE: To elucidate the mechanism of hemolysis-mediated platelet activation. METHODS: We used flow cytometry to detect PAC-1 binding to activated platelets for in vitro experiments, and a Siemens' Advia 120 hematology system to assess platelet aggregation by using platelet counts from in vivo experiments in a rodent model. RESULTS: We found that Hb did not directly activate platelets. However, ADP bound to Hb could cause platelet activation. Furthermore, platelet activation caused by shearing of red blood cells (RBCs) was reduced in the presence of apyrase, which metabolizes ADP to AMP. The use of ROS scavengers did not affect platelet activation. We also found that cell-free Hb enhanced platelet activation by abrogating the inhibitory effect of NO on platelet activation. In vivo infusions of ADP and purified (ADP-free) Hb, as well as hemolysate, resulted in platelet aggregation, as shown by decreased platelet counts. CONCLUSION: Two primary mechanisms account for RBC hemolysis-associated platelet activation: ADP release, which activates platelets; and cell-free Hb release, which enhances platelet activation by lowering NO bioavailability.

Cytokine profile during the clinical course of toxic shock syndrome.

Toxic shock syndrome (TSS) is an acute febrile disease with multiple organ involvement caused by massive and rapid release of cytokines induced by staphylococcal exotoxins. However, the precise cytokine profile is still undefined in clinical cases. We measured serum cytokine concentrations in a patient who developed TSS after a caesarean section. Measurements were taken on admission and several times during the course of the disease. Methicillin-resistant Staphylococcus aureus producing TSS toxin-1 and staphylococcal enterotoxin C was detected in the lochia and venous blood. Serum interleukin (IL)-6 level was markedly increased on admission, and IL-10, tumour necrosis factor-alpha, and interferon-gamma levels were also raised. These cytokine levels rapidly returned to normal levels. In contrast, IL-1beta and IL-2 were below the analytical sensitivity threshold throughout the course. Our data and other previous case reports indicate that a marked increase in IL-6 concentration could be a clinical marker of TSS onset.

Thoracodorsal artery as a collateral source to the artery of Adamkiewicz after endovascular aneurysm repair for descending thoracic aortic aneurysm.

Paraplegia is one of the most tragic complications following endovascular aneurysm repair (EVAR) for descending thoracic aortic aneurysm (DTAA). Collateral circulation to the artery of Adamkiewicz (AA) is important to avoid spinal cord ischaemia. We report a case in which the thoracodorsal artery had become a collateral source to the AA. A 71-year-old man had undergone EVAR for DTAA. Three years after EVAR, an angiography demonstrated that the thoracodorsal artery had joined the 11th intercostal artery and had become a collateral source to the AA. The collateral circulation of thoracic wall arteries may play an important role in the postoperative spinal perfusion.

Responses to 5-HT in morphologically identified neurons in the rat substantia gelatinosa in vitro.

Bath application of 5-HT (1-1000 muM) induced a tetrodotoxin (TTX)-resistant outward current at the holding membrane potential (V(H)) of -50 mV in 104/162 (64.2%) of substantia gelatinosa (SG) neurons from the rat spinal cord in vitro. The 5-HT-induced outward current was suppressed by an external solution containing Ba(2+), or a pipette solution containing Cs(2)SO(4) and tetraethylammonium. It was reversed near the equilibrium potential of the K(+) channel. The response to 5-HT was abolished 30 min after patch formation with a pipette solution containing guanosine-5-O-(2-thiodiphosphate)-S. The 5-HT-induced outward current was mimicked by a 5-HT(1A) agonist, (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide, and suppressed by a 5-HT(1A) antagonist, WAY100635, suggesting the 5HT(1A) receptor-mediated activation of K(+) channels in the outward current. In 11/162 (6.8%) SG neurons, 5-HT produced an inward current, which was mimicked by a 5-HT(3) agonist, 1-(m-chlorophenyl)-biguanide (mCPBG). The 5-HT-induced outward currents were observed in vertical cells (21/34) and small islet cells (11/34), while inward currents were induced in islet cells (1/5) and small islet (4/5) cells, but not in vertical cells. It is known that most vertical cells and islet cells in the SG are excitatory (glutamatergic) and inhibitory interneurons, respectively, while small islet cells consist of both excitatory and inhibitory neurons. Bath application of 5-HT or mCPBG increased the amplitude and the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), but no neurons showed a decrease in sIPSC. Furthermore, frequency, but not amplitude, of miniature IPSCs increased with perfusion with 5-HT in the presence of TTX. These findings, taken together, suggest that 5-HT induces outward currents through 5-HT(1A) receptors in excitatory SG neurons. These findings also suggest that the inward currents are post- and presynaptically evoked through 5-HT(3) receptors, probably in inhibitory neurons.

Near-infrared spectra absorbance of blood from sickle cell patients and normal individuals.

Limited data are available regarding the physicochemical dynamics of tissue hypoxia in sickle cell disease. Studies using near-infrared spectroscopy (NIRS) have reported that patients with sickle cell disease (SCD) have lower cerebral oxygen saturation values (rSO2) than normal individuals. The reason SCD patients have subnormal rSO2 values is not known. It may be related to the degree of anaemia, sickle haemoglobin, disease complications and the possibility of SCD different NIRS absorbance spectra than normal. This study compared NIRS absorbance spectra of blood with adult haemoglobin AA, sickle haemoglobin SS, and AS. Venous blood was collected from SCD (SS and AS) and non-SCD patients (AA). Whole blood, cell free haemoglobin samples were scanned through the wavelength range of 600-1000 nm. The results showed no different NIRS spectra absorbance between the haemoglobin's AA, SS. It thus appears that lower brain oxygen saturation in sickle cell anaemia patients is related to impaired oxygen carrying capacity or delivery by sickle haemoglobin.

Pulmonary hypertension in children and adolescents with sickle cell disease.

The prevalence of pulmonary hypertension (PHTN) in the pediatric sickle cell disease (SCD) population is not known despite its high prevalence in adult patients. Our hypothesis was that increased pulmonary artery pressures (PAPs) would be found in SCD children and adolescents, especially those with a history of pulmonary complications: acute chest syndrome, obstructive sleep apnea, asthma, and reactive airway disease. Fifty-two SCD children, 23 of whom had underlying pulmonary disease, were screened for PHTN, which was defined as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/s. Twenty-four (46.15%) SCD patients had increased PAP (i.e., TRV > or =2.5 m/s), and 6 (11.5%) had significant PHTN (i.e., TRV > or =3.0 m/s). Pulmonary disease was marginally associated with PHTN (odds ratio 2.80 and confidence interval 0.88 to 8.86; p = 0.0795). As in adult SCD patients with PHTN, this complication was correlated with the degree of hemolysis as manifested by significantly higher lactate dehydrogenase and bilirubin, lower hemoglobin and hematocrit levels, and a strong association with Hb-SS phenotype. However, after statistical adjustment for age and sex, increased serum LDH was not associated with the development of PHTN. Further studies are needed to clarify the prevalence and mechanisms of PHTN in pediatric and adolescent patients with SCD.

Action of neuropeptide Y on nociceptive transmission in substantia gelatinosa of the adult rat spinal dorsal horn.

Effects of neuropeptide Y (NPY) on substantia gelatinosa neurons were investigated in adult rat spinal cord slices using blind whole-cell patch-clamp technique. Bath application of NPY (1 microM) induced a membrane hyperpolarization, resulting in a suppression of the dorsal root stimulation-induced action potentials in 24% of the substantia gelatinosa neurons tested. In voltage clamp mode, NPY produced an outward current dose-dependently in about one third of substantia gelatinosa neurons at the holding potential of -60 mV, which was not affected by tetrodotoxin (1 microM). The NPY-induced current was suppressed by perfusion with a Ba2+-containing external solution and a Cs2SO4 or tetraethylammonium-containing pipette solution. In addition, The NPY-induced outward currents reversed its polarity near the equilibrium potential of K+ ions (-93 mV). The response to NPY recorded with guanosine-5'-O-(2-thiodiphosphate)-beta-S (GDP-beta-S) containing pipette solution was abolished 30 min after patch formation, suggesting that the response was mediated by the G-protein-coupled receptors. Application of an NPY-Y1 selective agonist, [Leu(31), Pro(-34)]-NPY (1 microM), for 30 s also induced an outward current with a similar time course and amplitude to that induced by NPY. On the other hand, the NPY response was blocked by a simultaneous application of NPY-Y1 selective antagonist, BIBP 3226 (1 microM). No significant changes were found in amplitude and frequency of miniature excitatory postsynaptic currents and dorsal root evoked excitatory postsynaptic currents by NPY. In addition, NPY did not affect both of the miniature inhibitory postsynaptic currents and evoked inhibitory postsynaptic currents, mediated by either the GABA or glycine receptor. These findings, taken together, suggest that NPY produces an outward current in substantia gelatinosa neurons through G-protein coupled, and NPY-Y1 receptor-mediated activation of K+ channels without affecting presynaptic components. The inhibition of the synaptic transmission from the primary fibers to the substantia gelatinosa neurons is considered to contribute to the antinociceptive effects of NPY.

Neuroprotective properties of tianeptine: interactions with cytokines.

Tianeptine is an antidepressant with proven clinical efficacy and effects on hippocampal plasticity. Hypoxia increased lactate dehydrogenase (LDH) release from cortical neuronal cultures, and tianeptine (1, 10 and 100 microM) inhibited LDH release as efficiently as the N-methyl-D-aspartate (NMDA) antagonist, MK-801. However, tianeptine did not block apoptosis in cultured cortical neurones caused by NMDA, but reduced apoptosis when interleukin-1beta (IL-1beta) was included with NMDA. In 5-day old mice, intracerebral injection of ibotenate induced reproducible lesions in cortex and white matter. Lesion size was markedly reduced by co-administration of MK-801 (1 mg/kg i.p.) but neither by tianeptine or its enantiomers administered acutely (1, 3 or 10 mg/kg i.p.) nor by tianeptine administered chronically (10 mg/kg i.p. for 5 days). Chronic administration of IL-1beta (10 ng/kg i.p. for 5 days) prior to ibotenate injection exacerbated lesion size in cortex and white matter, and this exacerbation was prevented by chronic pre-treatment with tianeptine (10 mg/kg i.p.) or by acute administration of tianeptine (10 mg/kg i.p.) concomitantly with ibotenate. Thus tianeptine has neuroprotective effects against hypoxia in tissue culture and against the deleterious effects of cytokines in cortex and white matter, but not against NMDA receptor-mediated excitotoxicity.

[Bilateral coronary ostial stenoses with aortic regurgitation in a patient with syphilitic aortitis].

Syphilitic aortitis is now rare in developed countries and is sometimes overlooked. A 61-year-old man with bilateral coronary ostial stenoses (#5:90%, #1:99%) and Sellers III/IV aortic regugitatioin (AR) induced by syphilitic aortitis presented with chest pain. Preoperative rapid plasma reagin titer and Treponema pallidum hemagglutination test were strongly positive, 256 fold and 191.25 C.O.I., respectively. Aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) with bilateral internal thoracic arteries (ITA) was performed successfully. The angiographic features as follows: 1) coronary artery stenosis is generally limited to the ostia, 2) the grade of stenosis is almost always more than 90%, 3) AR is frequently associated with coronary ostial stenosis. CABG should be performed with ITA, not saphenous vein grafts, to avoid occlusion of the ostium of the saphenous vein graft by syphilitic aortitis. Retrograde cardioplegia should be performed if ostial stenosis is severe.

Antisense-mediated reduction in thrombospondin-1 expression reduces cell motility in malignant glioma cells.

Thrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-beta. The involvement of TSP-1 in the motility of malignant glioma cells was investigated by transfection of TSP-1 complementary deoxyribonucleic acid (cDNA) sense and antisense expression vectors into the glioblastoma cell line T98G-G7 that secretes high amounts of TSP-1. TSP-1 production in the 3 antisense cDNA-transfected clones was significantly reduced to 51%, 43% and 47% compared to the host T98G-G7 cells. Motility of the 3 clones was evaluated by invasion assay and compared to the motility of host T98G-G7 cells and 2 sense-transfected clones. Migration of cells was significantly reduced in the 3 antisense-transfected clones with reduced TSP-1 production to 56%, 61% and 43% compared to the host T98G-G7 cells. The host T98G-G7 and another TSP-1-secreting A172 and YMG5 glioblastoma cells were also treated with a synthetic peptide, WSHWSPWSSCSVTCG, which includes 3 consecutive sequences of the adhesion sites in the TSP-1 molecule and with a control peptide. The synthetic peptide significantly inhibited the migration of T98G-G7 and A172 cells in a dose-related manner. Maximum inhibition of migration was achieved by 100 microg/ml of the peptide and the reduction of cell motility compared to untreated cells was 34.6 % and 53.9 %, respectively. On the other hand, the inhibition of migration by the peptide was minimal in YMG5 cells, which secretes a smaller amount of TSP-1 than T98G-G7 and A172 cells. These results suggest that TSP-1 secreted by malignant glioma cells is involved in the motility of glioma cells.

Risk factors reducing blood transfusion requirements in pediatric open heart surgery after introduction of vacuum assisted circuits.

OBJECTIVES: Open heart surgery without homologous blood transfusion remains difficult in children. The introduction of vacuum-assisted cardiopulmonary bypass circuits to reduce priming volume for pediatric patients has improved the percentage of transfusion-free operations. We retrospectively analyzed blood transfusion risk factors to further reduce blood transfusion requirements after vacuum-assisted circuit introduction. METHODS: From March 1995 to June 1996, 49 patients weighing between 5 and 20 kg underwent cardiac surgery with cardiopulmonary bypass at our institution, excluding hospital deaths. We retrospectively analyzed risk factors influencing blood use in 37 patients with no blood priming in cardiopulmonary bypass after introducing a vacuum-assisted system. Factors selected for univariate analysis were age, body weight, cyanosis, preoperative Hb, operation time, cardiopulmonary bypass time, aortic cross-clamping time, and intraoperative and postoperative bleeding volume. Correlation between total bleeding volume/body weight and cardiopulmonary bypass time was studied by regression analysis. RESULTS: As risk factors, univariate analysis identified cyanotic disease, longer operation time (> 210 minutes), longer cardiopulmonary bypass time (> 90 minutes), longer aortic cross-clamping time (> 45 minutes), greater intraoperative bleeding volume/body weight (> 4 ml/kg), and greater postoperative bleeding volume/body weight (> 15 ml/kg). Regression analysis showed a significant positive correlation between total bleeding volume/body weight and cardiopulmonary bypass time. CONCLUSIONS: Cyanotic disease and long bypass time are risk factors in reducing blood transfusion requirements in pediatric open heart surgery after introduction of vacuum-assisted circuits. Further efforts are needed, however, to reduce blood transfusion requirements, particularly in these children.

[Isolated cerebral and myocardial perfusion during aortic arch repair in neonates].

OBJECTIVES: To prevent possible neurologic injury after hypothermic circulatory arrest, aortic arch obstruction with cardiac defects is repaired in one stage using isolated cerebral and myocardial perfusion (ICMP). This study investigated serum S-100 protein(S-100) levels in neonates undergoing ICMP. METHODS: Between February 2000 and January 2001, 19 neonate patients underwent repair of critical congenital heart defects. Seven of these patients with aortic coarctation(n = 3) or interrupted aortic arch (n = 4) with ventricular septal defect(ICMP group) underwent primary total repair. An arterial cannula was inserted either into the ascending aorta or into a polytetrafluoroethylene graft which was anastomosed to the innominate artery. During arch repair, a cross-clamp was placed between the innominate and left carotid arteries, and an end-to-end arch anastomosis was performed with cerebral perfusion and heart beating. During ICMP the flow was reduced to maintain a radial artery pressure of 30-45 mmHg. The remaining 12 patients underwent complete transposition of great arteries(n = 9) or total anomalous pulmonary venous connection(n = 3) using a cardiopulmonary bypass(CPB) with flow of 150-180 ml/kg/min(control group). Sequential blood samples for S-100 determinations were taken after induction of anesthesia, 30 min after aortic declamping(post-ACC), 30 min after CPB, and 24 hr after CPB. RESULTS: There were no early and late deaths. Neurologic symptoms were not observed in any patients. Mean ICMP time in ICMP group was 17 +/- 4 min. In all patients, S-100 showed the highest value post-ACC and then declined with time. There were no differences in S-100 between the groups at any other time point. CONCLUSIONS: Selective cerebral perfusion through the innominate artery may be able to maintain brain circulation.

[Relationship between periodontitis and lifestyle and health status].

The purpose of this study is to clarify the relationship between periodontitis and lifestyle and health status. The subjects were 349 male workers aged on 40s and 50s, who had been working on the development and manufacture of computers. Multiple logistic regression analysis showed that the existence of periodontitis was associated positively with age, the Brinkman index, systolic blood pressure, number of white blood cells, feeling of irritation, and negatively with the use of interdental cleaners. It is therefore important to practice more active oral health promotion in cooperation with the medical staff concerned, as a part of THP (Total Health Promotion) in the workplace.