Statins Show Anti-Atherosclerotic Effects by Improving Endothelial Cell Function in a Kawasaki Disease-like Vasculitis Mouse Model.

Kawasaki disease (KD) is an acute inflammatory syndrome of unknown etiology that is complicated by cardiovascular sequelae. Chronic inflammation (vasculitis) due to KD might cause vascular cellular senescence and vascular endothelial cell damage, and is a potential cause of atherosclerosis in young adults. This study examined the effect of KD and HMG-CoA inhibitors (statins) on vascular cellular senescence and vascular endothelial cells. Candida albicans water-soluble fraction (CAWS) was administered intraperitoneally to 5-week-old male apolipoprotein E-deficient (ApoE-) mice to induce KD-like vasculitis. The mice were then divided into three groups: control, CAWS, and CAWS+statin groups. Ten weeks after injection, the mice were sacrificed and whole aortic tissue specimens were collected. Endothelial nitric oxide synthase (eNOS) expression in the ascending aortic intima epithelium was evaluated using immunostaining. In addition, eNOS expression and levels of cellular senescence markers were measured in RNA and proteins extracted from whole aortic tissue. KD-like vasculitis impaired vascular endothelial cells that produce eNOS, which maintains vascular homeostasis, and promoted macrophage infiltration into the tissue. Statins also restored vascular endothelial cell function by promoting eNOS expression. Statins may be used to prevent secondary cardiovascular events during the chronic phase of KD.

Evidence for Spin-Triplet Electron Pairing in the Proximity-Induced Superconducting State of an Fe-Doped InAs Semiconductor.

We provide evidence for spin-triplet electron pairing in proximity-induced superconductivity in a ferromagnetic semiconductor (In,Fe)As. As discovered in half-metallic materials, an extraordinarily long proximity range is observed. More surprising is a very strong concentration of supercurrent to the edges of the superconducting region, which is deduced from the extremely persistent oscillation of the critical current vs magnetic field. The maxima of the critical current appear not at the zero magnetic flux but at around the maximum magnetic disorder, reflecting the connectivity between the spin-triplet and singlet pairings. These spin-triplet natures in proximity superconductivity also reveal ferromagnetic properties of (In,Fe)As.

[A Case of Primary Anal Fistula Cancer with Extensive Intrapelvic Spreading That Was Successfully Treated with Bevacizumab plus mFOLFOX6].

The patient was a 68-year-old man who had an anal fistula for>10 years. He was referred to our institution after visiting a local physician with left femoral pain as the main complaint and received a diagnosis of high inflammatory response. We then found discharge of pus in the perianal region during a medical examination. We also found an extensive intrapelvic tumor during a computed tomography(CT)/magnetic resonance imaging examination. In addition, the level ofa tumor marker and inflammatory response were high. To control the inflammation, we performed seton drainage and sigmoid colostomy. On the basis of the pathological findings from the mucus component, we confirmed a diagnosis of fistula cancer. Considering that the progressive lesion had extensively spread, we decided to initiate chemotherapy alone because ofthe absence ofan indication for radiotherapy. We administered bevacizumab plus mFOLFOX6, and partial response was observed on a CT scan. We could control the progression ofthe disease for>6 months. The present case suggests that bevacizumab plus mFOLFOX6 can be an effective regimen for unresectable advanced fistula cancers.

Multicenter prospective study to optimize the efficacy of triple therapy with telaprevir in patients with genotype 1b hepatitis C virus infection according to an algorithm based on the drug Adherence, IL-28B Gene Allele and Viral Response Trial (AG & RGT).

AIM: To optimize the therapeutic efficacy of NS3/4A protease inhibitors, a multicenter prospective study was performed according to an algorithm based on the Adherence, IL-28B Gene Allele and Viral Response Trial (AG & RGT). METHODS: A total of 340 patients with genotype 1b hepatitis C virus (HCV) showing serum RNA levels of >5 log were enrolled. The duration of ribavirin/pegylated interferon (PEG IFN)-α-2b therapy was prolonged to 48 weeks in patients with unfavorable IL28B alleles showing adherence rates of less than 80% for either drug during the first 12 weeks even if RVR had been achieved, and in those in whom cEVR, but not RVR, was achieved; furthermore, to 72 weeks in those showing partial early viral response. RESULTS: The therapeutic outcomes were assessed in 282 patients, and the therapy was set to complete at 24 weeks in 181 patients (64%) and to prolong to 48 weeks or 72 weeks in 71 patients (25%). The former group showed a SVR rate of 84%, while the latter group showed an SVR rate of 69% with a relapse rate of 7%. The SVR rate was 33% in the 30 patients (11%) in whom the therapy had to be discontinued in less than 12 weeks. Thus, the results of intention-to-treat analysis revealed an overall SVR rate of 75%. Multivariate analysis identified prolongation of the duration of therapy as a significant factor associated with SVR. CONCLUSION: Triple therapy yielded a high SVR rate in the AG & RGT trial via attenuation of viral relapse by prolonged ribavirin/PEG IFN-α-2b administration. © 2015 The Japan Society of Hepatology.

Randomized study comparing vitamin D3 and 1α-Hydroxyvitamin D3 in combination with pegylated interferon/ribavirin therapy for chronic hepatitis C.

BACKGROUND AND AIM: An intention-to-treat prospective randomized study was carried out to compare the potentiation of antiviral efficacies between cholecalciferol, non-activated vitamin D3 supplement, and alfacalcidol, activated 1α-Hydroxyvitamin D3 [1α (OH)-vitamin D3]. METHODS: Chronic hepatitis patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV-RNA levels greater than 5 Log IU/mL received oral administration of cholecalciferol (2000 IU/day) or alfacalcidol (0.5 µg/day) for 4 weeks, and then they were given pegylated interferon (Peg-IFN)-α2a plus ribavirin therapy in combination with either vitamin D3 for 48 or 72 weeks according to the response-guided manner. RESULTS: A total of 36 patients were evaluated. Serum 25-hydroxyvitamin D3 [25(OH)-D3] levels were increased only in patients in the cholecalciferol group during the lead-in vitamin D administration, and the levels at 4 weeks were higher in these patients than in those in the alfacalcidol group (P < 0.001), while serum 1α,25-dihydroxyvitamin D3 [1α,25(OH)2 -D3] levels were not different between both groups. Rapid virological response was obtained in six (33%) patients in the cholecalciferol group; the ratio was higher than that in the alfacalcidol group (one patient; 6%, P < 0.05). Serum HCV-RNA level decline at 4 weeks of combined Peg-IFN-α2a plus ribavirin therapy compared with the baseline levels were greater in the cholecalciferol group (4.6 Log IU/mL) than in the alfacalcidol group (3.5 Log IU/mL) (P < 0.05), when four patients showing null response to the therapy was excluded. However, both complete early virological response and sustained viral response rates were not different between both groups. CONCLUSION: Cholecalciferol produced superior potentiation of the antiviral activity than alfacalcidol only during the initial periods of combined Peg-IFN-α2a plus ribavirin therapy through upregulation of serum 25(OH)-D3 levels.

Candesartan Attenuates Vasculitis in a Mouse Model of Kawasaki Disease Induced by Candida albicans Water-Soluble Fraction.

BACKGROUND: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment. METHODS: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan. RESULTS: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFß receptors. Measurement of the inflammatory cytokines IL-1ß, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan. CONCLUSIONS: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.

Three cases of young children who underwent effective catheter treatment for severe coronary stenosis caused by Kawasaki disease.

Three patients, aged 2 years 0 months, 2 years 2 months, and 6 years 1 month at the time of plain old balloon angioplasty (POBA), developed an aneurysm in the left anterior descending coronary branch after suffering from Kawasaki disease. POBA was subsequently performed due to 99 % stenosis proximal to the aneurysm. There was no restenosis within a few years after percutaneous coronary intervention, and there was no evidence of ischemia, although 75 % restenosis occurred in two patients after 7 years.Although calcified lesions are more likely to occur 6 years after the onset of Kawasaki disease, none of the patients in this study had calcified lesions within 4 years of Kawasaki disease onset, and good results were obtained with POBA alone. POBA can be safely performed in children and is an effective treatment for improving myocardial ischemia if calcification has not progressed. Learning objective: Plain old balloon angioplasty (POBA) can be performed effectively and safely for Kawasaki disease coronary artery stenosis in early childhood if calcification is minimal, with little restenosis for at least several years. POBA is a useful tool in the treatment of coronary artery stenosis in early childhood.

Taxonomic study of Bornean species of Utivarachna Kishida, 1940 (Araneae: Trachelidae), with the description of a new species.

The genus Utivarachna Kishida, 1940 currently comprises 23 species, with eight described from Borneo. We examined the type materials of the Bornean species, except for U. fukasawana Kishida, 1940, as well as newly collected specimens. As a result, we describe a new species, Utivarachna itiokai sp. nov., which belongs to the dusun-group. We also provide the first description of the female of Utivarachna ichneumon and redescribe the known Utivarachna species of Borneo.

Simultaneous measurement of specific heat and thermal conductivity in pulsed magnetic fields.

We report an experimental setup for simultaneously measuring specific heat and thermal conductivity in feedback-controlled pulsed magnetic fields of 50 ms duration at cryogenic temperatures. A stabilized magnetic field pulse obtained by the feedback control, which dramatically improves the thermal stability of the setup and sample, is used in combination with the flash method to obtain absolute values of thermal properties up to 37.2 T in the 22-16 K temperature range. We describe the experimental setup and demonstrate the performance of the present method with measurements on single-crystal samples of the geometrically frustrated quantum spin-dimer system SrCu2(BO3)2. Our proof-of-principle results show excellent agreement with data taken using a standard steady-state method, confirming the validity and convenience of the present approach.

Effects of ethanol exposure on spatial learning in mice during synaptogenesis.

BACKGROUND: The effects of exposure to ethanol (EtOH) on spatial learning in mice during synaptogenesis and changes after maturation are not well understood. In this study, we used a water maze test to evaluate the effects of EtOH exposure on spatial learning during synaptogenesis period. METHODS: One-week-old pups from dams not exposed to EtOH during pregnancy were given 2 dorsal subcutaneous injections of 2.5 g/kg EtOH at a 2-h interval. At 8 h (n=6) and 24 h (n=5) after the first EtOH injection, the brains were perfused and fixed. The brain tissue sections were analyzed by TUNEL assay to detect DNA fragmentation and by immunohistochemistry to detect activated caspase-3. In addition, at 5 h (n=10), 8 h (n=5), and 24 h (n=7) after the first EtOH injection, blood and cerebral EtOH concentrations were measured by headspace gas chromatography. A water maze test was performed at age 7 weeks and 12 weeks. RESULTS: In neonatal EtOH exposure group, mice had a prolonged time to reach the platform compared to a control group. This trend was similar both trials of age 7 weeks and age 12 weeks. At 24 h after EtOH injection in the neonatal EtOH exposure group, the incidence of TUNEL and activated caspase-3 positive cells was 6.1 +/- 1.8% and 6.4 +/- 1.0%, respectively, in the cerebral cortex, 1.6 +/- 0.9% and 1.2 +/- 0.9%, respectively, in the hippocampus, and 11.0 +/- 4.4% and 16.3 +/- 7.8%, respectively, in the thalamus. In blood and cerebral tissue from mice treated with EtOH, as in the neonatal EtOH exposure group, EtOH remained at 0.93 +/- 0.79 mg/g and 0.96 +/- 0.78 mg/g, respectively, after 24 h. CONCLUSIONS: The impairment in spatial learning due to EtOH exposure during the neonatal periods did not tend to improve after reaching maturity. Impairment in spatial learning after maturity in mice exposed to EtOH during synaptogenesis is likely due to apoptosis of brain neurons caused by EtOH.

[Implications of nicotine detected in autopsy cases of newborn babies and infants from the perspective of social medicine].

Smoking by pregnant and parturient women is generally suspected to increase nicotine levels in fetal and infant blood. Supportive data of nicotine levels in infants is, however, inadequate. We investigated blood and muscle nicotine and cotinine levels in 14 autopsy cases of newborn babies and infants using gas chromatography. Among the 14 cases investigated, nicotine or cotinine was detected in six cases (42.9%). In each of these six cases, the mother was a smoker. Route of exposure to nicotine originating from smoking was transplacental in three cases, via breast milk in one case and secondhand smoke in two cases. Nicotine and cotinine levels in blood from the two cases with placental exposure were 10.6-84.4 ng/ml and 20.3-183 ng/ml, and levels in muscle from one case were 43.9 ng/g and 308 ng/g, respectively. Nicotine and cotinine levels in blood from exposure via breast milk were 19.1 ng/ml and 87.1 ng/ml, and from secondhand smoke were 0 ng/ml and 14.6-20.1 ng/ml. Mean concentrations of blood nicotine and cotinine in 68 autopsy cases of adult habitual smokers were 30.0 ng/ml and 247 ng/ml. Our data for nicotine and cotinine levels in infant blood seem to indicate that some infants who are born and develop under exposure to smoking by family members, particularly the mother, may show high nicotine levels in blood and experience possible health risks.

Constraints on the jumping and prey-capture abilities of ant-mimicking spiders (Salticidae, Salticinae, Myrmarachne).

Accurate morphological ant mimicry by Myrmarachne jumping spiders confers strong protective benefits against predators. However, it has been hypothesized that the slender and constricted ant-like appearance imposes costs on the hunting ability because their jumping power to capture prey is obtained from hydraulic pressure in their bodies. This hypothesis remains to be sufficiently investigated. We compared the jumping and prey-capture abilities of seven Myrmarachne species and non-myrmecomorphic salticids collected from tropical forests in Malaysian Borneo and northeastern Thailand. We found that the mimics had significantly reduced abilities compared with the non-mimics. The analysis using geometric morphometric techniques revealed that the reduced abilities were strongly associated with the morphological traits for ant mimicry and relatively lower abilities were found in Myrmarachne species with a more narrowed form. These results support the hypothesis that the jumping ability to capture prey is constrained by the morphological mimicry and provide a new insight into understanding the evolutionary costs of accurate mimicry.

Virtual histology intravascular ultrasound evaluation of coronary artery lesions within 1 year and more than 10 years after the onset of Kawasaki disease.

BACKGROUND: Coronary artery evaluation by virtual histological intravascular ultrasonography (VH-IVUS) late in Kawasaki disease (KD) shows intimal thickening, calcification, fatty components, and necrosis of regressed coronary artery lesions (CALs). However, it is not clear when these VH-IVUS findings start to occur. Therefore, we evaluated coronary arteries using VH-IVUS in patients with early-stage KD and tried to determine whether these atherosclerotic findings on VH-IVUS were different from that in patients with late-stage KD. METHODS: Eighteen patients with KD aged between 1 and 32 years who had CALs and underwent cardiac catheterization between January 1, 2008 and December 31, 2014 were included. They were divided into 2 groups-those with the disease for <1 year (group A) and those with it for >10 years (group B). VH-IVUS findings were compared between the groups. The coronary arteries were divided based on coronary angiography findings into normal, regressed (dilated CALs regressed to a normal size), and aneurysmal lesions. The Wilcoxon signed-rank test was used in the statistical analysis. RESULTS: In both regressed and aneurysmal lesions, marked intimal proliferation and atherosclerotic findings (fibro-fatty and necrotic core lesions) were observed. In addition, there was no difference in the area percentage of atherosclerosis between the groups. CONCLUSIONS: VH-IVUS revealed that atherosclerotic-like findings exist in CALs in patients with KD, even within a year of onset. The findings were almost the same in those with the disease for >10 years. Because there is no histological evidence of atherosclerosis in KD, these VH-IVUS findings may indicate complex histological findings of KD. Nevertheless, early interventions to help reduce the risk factors of atherosclerosis may be required in these patients.

[Practical research in morbid condition due to exogenous invasions for application in forensic diagnosis and preventive medical treatment].

We report research subjects on the morbid conditions due to various exogenous invasions, iatrogenic damages and suicide. The studies of morbid condition by exogenous invasions are as follows : 1) forensic significance of endocardial bleeding to diagnosing the causes of death, 2) forensic implication of intramuscular bleeding of the tongue of the fire victims, 3) stability of cyanide concentration in blood of the fire victims and the evaluation of the toxic potential, 4) histochemical detection of ABO blood type of the muscle of the fire victims by signal amplification method with biotinylated tyramide, 5) alcohol detection of purified brain tissue of the drowned victims and the estimation of the amount of drinking, and 6) investigation into unclosing a mechanism of postmortem production of endogenous gamma-hydroxybutyric acid(GHB). The researches for iatrogenic damages are as follows: 1) iatrogenic ribs fracture due to chest compression during cardiopulmonary resuscitation, 2) bone marrow embolism of the lung caused by iatrogenic ribs fracture, and 3) forensic application of lidocaine of blood and tissues, which is derived from xylocaine jelly, chemicals for surface anesthesia, frequently used with the purpose of lubricating effect when intubation tube is introduced into the trachea. The issues of suicide research aiming forensic and clinical application are as follows: 1) forensic significance of blood nicotine levels of the smokers who committed suicide, 2) forensic availability of muscle nicotine levels of the purified bodies who have suspected suicide, and 3) forensic value of analysis of chromogranin A mRNA in autopsy cases with various cause of death to diagnosing suicide.

Interleukin-1beta Inhibition Attenuates Vasculitis in a Mouse Model of Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD), a systemic vasculitis, is suspected to be related to abnormalities in innate immunity. Based on the important role of IL-1 signaling in innate immunity, we investigated the effects of an anti-IL-1ß antibody using a Candida albicans water-soluble fraction (CAWS)-induced mouse model of KD. METHODS: CAWS (0.5 mg/mouse) was injected intraperitoneally into 5-week-old DBA/2 mice on five consecutive days. An anti-Murine IL-1ß antibody (01BSUR) was administered at various doses (2.5, 5.0, and 10.0 mg/kg) and time points (2 days before, same day, and 2, 5, 7, and 14 days after CAWS administration). After 4 weeks, vasculitis in the aortic root was investigated histologically. Cytokines including IL-1ß, -6, -10, and TNF-α were also measured. RESULTS: Groups administered 01BSUR at all doses showed a significant reduction in the area of vasculitis. In addition, 01BSUR inhibited vasculitis until 7 days after CAWS administration. In the analysis of various time points, the level of IL-6 was lower in all groups compared to the CAWS only group, but the levels of IL-1ß, TNFα, and IL-10 were lower when 01BSUR was administered before CAWS. On the other hand, TNFα and IL-10 levels were restored when 01BSUR was administered after CAWS, suggesting that 01BSUR may have additional effects beyond blocking IL-1ß signaling. CONCLUSIONS: The anti-IL-1ß antibody significantly attenuated CAWS-induced vasculitis. The mechanism of inhibiting vasculitis is thought to include inhibition of the IL-1ß pathway and additional effects beyond blocking IL-1ß signaling.

New species of the ant-mimicking genus Myrmarachne MacLeay, 1839 (Araneae: Salticidae) from Sarawak, Borneo.

The genus Myrmarachne MacLeay, 1839 (Araneae: Salticidae) is one of the most diversified salticid groups in Southeast Asia, with 23 species previously recorded from Borneo. Based on the collections accumulated from 2004 to 2014 in the Lambir Hills National Park, we herein describe six new species: M. amabilis sp. nov., M. hashimotoi sp. nov., M. lagarosoma sp. nov., M. leptosoma sp. nov., M. salaputium sp. nov. and M. tintinnabulum sp. nov. In addition, we describe the female of M. endoi Yamasaki Ahmad, 2013 for the first time. The male-female combination in M. amabilis sp. nov., M. tintinnabulum sp. nov. and M. endoi were confirmed by DNA barcoding.

Forensic aspects of complications resulting from cardiopulmonary resuscitation.

While cardiopulmonary resuscitation (CPR) can save lives, it can also injure patients. As a result, forensic pathologists often see CPR-related injuries during autopsies that are unrelated to the patients' primary cause of death. Therefore, pathologists must be able to distinguish between CPR-related injuries and those caused by other factors, such as assaults or accidental violence. This distinction is complicated because even therapeutically unimportant injuries can have forensic significance. For example, resuscitative injuries are observed frequently in the neck and the chest. This article focuses mainly on complications due to ventilation and chest compression during CPR. The following iatrogenic complications are described: bruising and abrasions in the face and neck, fractures of the hyoid bone and thyroid cartilage, air way injuries, vomitus aspiration, positional error of the tube for intra-tracheal intubation, petechiae, retinal hemorrhages, subarachnoid hemorrhages, rib and sternum fractures, bone marrow embolism, cardiac injuries including myocardial hemorrhages and frothy heart blood, and injuries to the abdominal organs such as liver and spleen.

[Amounts of sweat and salt loss due to sweating during a three-hour badminton practice in summer].

In 7 men and 5 women, we measured the amounts of sweat and fluid intake, and the ionic composition of sweat during a 3-hour badminton practice in summer. The amount of sweat was calculated as follows; body weight before practice (g)--body weight after practice (g)--urine volume (ml) +fluid intake (ml). We collected sweat by covering the non-dominant forearm with a plastic bag. The amounts of sweat and fluid intake during the 3-hour practice were 1809 +/- 715ml (mean +/- SD) and 658 +/- 344ml, respectively. Weight loss after the practice was 2.0 +/- 0.9% of their weight before the practice. The Na(+) and Cl(-) levels of the sweat about 30 min after the start of practice were 66 +/- 34 mEq/l and 54 +/- 32mEq/l, respectively. There was no significant difference between those ionic levels of the sweat about 30 min after the start of practice and those about 30 min before the end of practice. The sum of Na(+) and Cl(-) loss into sweat during a 3-hour practice session was supposed to be 6.9 +/- 5.3g, and to be above 10 g in 4 of 7 men, assuming that there were no regional differences in the ionic composition of sweat. The findings suggested that most of the participants should take more fluid and some of them might need salt intake during the practice.

Conductance fluctuations in InAs quantum wells possibly driven by Zitterbewegung.

The highly successful Dirac equation predicts peculiar phenomena such as Klein tunnelling and Zitterbewegung (ZB) of electrons. From its conception by Erwin Schrödinger, ZB has been considered key in understanding relativistic quantum mechanics. However, observing the ZB of electrons has proved difficult, and instead various emulations of the phenomenon have been proposed producing several successes. Concerning charge transport in semiconductors and graphene, expectations were high but little has been reported. Here, we report a surprisingly large ZB effect on charge transport in a semiconductor nanostructure playing "flat pinball". The setup is a narrow strip of InAs two-dimensional electron gas with strong Rashba spin-orbit coupling. Six quantum point contacts act as pinball pockets. In transiting between two contacts, ZB appears as a large reproducible conductance fluctuation that depends on the in-plane magnetic field. Numerical simulations successfully reproduced our experimental observations confirming that ZB causes this conductance fluctuation.