Efficacy and Safety of Warfarin for the Treatment of Venous Thromboembolism　- A Multicenter Prospective Observational Cohort Study in Japan (AKAFUJI Study).

BACKGROUND: A large-scale prospective study of the efficacy and safety of warfarin for the treatment of venous thromboembolism (VTE) has not been conducted in Japan. Therefore, we conducted a real-world prospective multicenter observational cohort study (AKAFUJI Study; UMIN000014132) to investigate the efficacy and safety of warfarin for VTE.Methods and Results: Between May 2014 and March 2017, 352 patients (mean [±SD] age 67.7±14.8 years; 57% female) with acute symptomatic/asymptomatic VTE were enrolled; 284 were treated with warfarin. The cumulative incidence of recurrent symptomatic VTE was higher in patients without warfarin than in those treated with warfarin (8.7 vs. 2.2 per 100 person-years, respectively; P=0.018). The cumulative incidence of bleeding complications was not significantly different between the 2 groups. The mean prothrombin time-international normalized ratio (PT-INR) during warfarin on-treatment was <1.5 in 180 patients, 1.5-2.5 in 97 patients, and >2.5 in 6 patients. The incidence of bleeding complications was significantly higher in patients with PT-INR >2.5, whereas the incidence of recurrent VTE was not significantly different between the 3 PT-INR groups. The cumulative incidence of recurrent VTE and bleeding complications did not differ significantly among those in whom VTE was provoked by a transient risk factor, was unprovoked, or was associated with cancer. CONCLUSIONS: Warfarin therapy with an appropriate PT-INR according to Japanese guidelines is effective without increasing bleeding complications, regardless of patient characteristics.

Mutagenicity of Tectona grandis Wood Extracts and Their Ability to Improve Carbohydrate Yield for Kraft Cooking Eucalyptus Wood.

Considering the toxicity of the impurities of synthesized anthraquinone, this study clarified new catalytic compounds for kraft cooking with improved carbohydrate yield and delignification and less mutagenicity, which are important for ensuring the safety of paper products in contact with food. The 2-methylanthraquinone contents of teak (Tectona grandis) woods were 0.18-0.21%. Acetone extracts containing 2-methylanthraquinone from Myanmar and Indonesia teak woods as additives improved lignin removal during kraft cooking of eucalyptus wood, which resulted in kappa numbers that were 2.2-6.0 points lower than the absence of additive. Myanmar extracts and 2-methylanthraquinone improved carbohydrate yield in pulps with 1.7-2.2% yield gains. Indonesia extracts contained more deoxylapachol and its isomer than 2-methylanthraquinone. The residual content of 2-methylanthraquinone in the kraft pulp was trace. Although Ames tests showed that the Indonesia and Myanmar extracts were mutagenic to Salmonella typhimurium, 2-methylanthraquinone was not. The kraft pulp obtained with the additives should be safe for food-packaging applications, and the addition of 0.03% 2-methylanthraquinone to kraft cooking saves forest resources and fossil energy in industries requiring increased pulp yield.

Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.

We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis. Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density. OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants. In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines. The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines. Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.

Composition of intake sugars and emission of gases from paper sludges by Coptotermes formosanus Shiraki.

Paper sludge is a by-product of the pulping process and is landfilled or incinerated for disposal. In this study, we evaluated ingestion and digestibility of carbohydrates, by the termite Coptotermes formosanus, in two kinds of sludges: sludge C from the chemical pulp mill and sludge M from the mechanical pulp mill. The no-choice tests using the termite for three weeks showed that the mass loss of sludge C was significantly higher than that of the control samples: a bleached pulp and red pine wood. It is considered that the higher inorganic content of sludge C resulted in the higher mass loss when the same amount of carbohydrates was taken by the pulp- or wood-fed termite. Although the inorganic content of sludge M was almost the same as that of sludge C, the higher lignin content in sludge M is thought to have resulted in the lower mass loss. Analysis of sugar composition in the faecal materials of the termite showed that about 73% of glucose and 81% of xylose in sludge C were digested. It was concluded that the digestibility of these sugars in sludge C was the same as that of the control samples despite containing high amounts of inorganic compounds. However, the hydrogen conversion rate by the termites that were fed sludge was lower than that of the termites that were fed pulp in the no-choice test for three days: one mole of glucose from the sludge and pulp was converted to 0.51 and 0.80 moles of hydrogen, respectively.

Preparation of an eco-friendly antibacterial agent for food packaging containing Houttuynia cordata Thunb. extract.

This study aims to develop an antibacterial agent that can be used for food packaging. Essential oils of Houttuynia cordata Thunb., a well-known medical herb, were extracted by two methods: multi-solvent consecutive extraction method and single ethanol extraction with a pre-heating method. Consequently, the extract obtained by the single ethanol extraction with a pre-heating method was more satisfactory from the operational and economic aspects. Afterwards, one of the encapsulation techniques: co-precipitation method using ß-cyclodextrins as wall materials, was applied to form capsules for the protection of the obtained extract. After the capsule synthesis, the results of scanning electron micrographs and X-ray diffraction showed ß-cyclodextrin crystallites in the form of thinner plates became oriented upon co-precipitation. Combining the results of Fourier transform-infrared spectra and an antibacterial assay using Bacillus subtilis as an object microorganism, the extract was confirmed to be successfully encapsulated within hollow cavities of ß-cyclodextrins. A significant inhibitory activity on the growth and breeding of Bacillus subtilis was observed after the addition of fabricated capsules, which suggests the capsules containing the Houttuynia cordata Thunb. extract can be used as eco-friendly antibacterial agents for food packaging.

Lignin degradation in wood-feeding insects.

The aromatic polymer lignin protects plants from most forms of microbial attack. Despite the fact that a significant fraction of all lignocellulose degraded passes through arthropod guts, the fate of lignin in these systems is not known. Using tetramethylammonium hydroxide thermochemolysis, we show lignin degradation by two insect species, the Asian longhorned beetle (Anoplophora glabripennis) and the Pacific dampwood termite (Zootermopsis angusticollis). In both the beetle and termite, significant levels of propyl side-chain oxidation (depolymerization) and demethylation of ring methoxyl groups is detected; for the termite, ring hydroxylation is also observed. In addition, culture-independent fungal gut community analysis of A. glabripennis identified a single species of fungus in the Fusarium solani/Nectria haematococca species complex. This is a soft-rot fungus that may be contributing to wood degradation. These results transform our understanding of lignin degradation by wood-feeding insects.

Long-term suicide mortality rates decrease in men and increase in women after the Niigata-Chuetsu earthquake in Japan.

A devastating earthquake causes psychological distress, and may increase suicide mortality thereafter, yet previous studies have made inconsistent conclusions regarding this issue. The purpose of the present study was to determine whether the 2004 Niigata-Chuetsu earthquake in Japan affected long-term mortality from suicide. We conducted a comparative study of suicide mortality rates during the 5-year period preceding and the 3-year period following the earthquake in the disaster area and a control area in Niigata Prefecture, by analyzing death certificate data from October 1, 1999, to September 30, 2007. In men, baseline suicide mortality rates (5 years preceding the earthquake) were 48.4 per 100,000 person-years in the disaster area and 46.1 in the control area, and suicide mortality rates during the 3-year period following the earthquake were 46.0 and 45.1, respectively. In women, baseline suicide mortality rates were 22.3 in the disaster area and 18.7 in the control area, and post-earthquake suicide mortality rates were 20.2 and 15.3, respectively. In consequence, the decrease in suicide mortality rate during the 3 years post-earthquake was significantly higher in the disaster area (2.5) than in the control area (1.0) (p = 0.0013) in men, whereas the decrease in suicide mortality rate was 2.1 in the disaster area and 3.0 in the control area (p = 0.1246) in women. We have concluded that the long-term mortality from suicide after the earthquake decreases in men and increases in women, suggesting that post-earthquake suicide mortality is sex-dependent. Post-earthquake suicide prevention strategies should more aggressively target women.

Early Helicobacter pylori eradication restores sonic hedgehog expression in the gastric mucosa of Mongolian gerbils.

BACKGROUND AND AIM: Sonic hedgehog (Shh) is a morphogen involved in the homeostasis of the gastric fundic glands. Alterations of gastric mucosal Shh expression after eradication of Helicobacter pylori were examined. METHOD: Mongolian gerbils were inoculated with H. pylori at the age of 5 weeks. H. pylori eradication was then carried out at 12, 24 or 48 weeks after the inoculation, and the gerbils were examined at 10 weeks after the eradication. Gastric inflammation was evaluated by the tissue myeloperoxidase activity and the histological scoring. Immunohistochemistry and in situ hybridization were performed for determining the Shh expression. RESULTS: Significant decrease of the myeloperoxidase activity and scores for acute and chronic inflammation as well as atrophy were observed in the H. pylori-eradicated gerbils as compared with the findings in the non-H. pylori-eradicated gerbils. Significant increase of the horizontal length of the area positive for Shh expression was noted in the H. pylori-eradicated gerbils as compared with that in the non-H. pylori-eradicated gerbils. Earlier eradication promoted better restoration of Shh expression. 50% of the animals of the 24-week eradication group and all animals in the 48-week eradication group exhibited heterotopic proliferative glands. In the animals showing heterotopic proliferative glands, the front line of Shh regeneration was cut off at the point of development of heterotopic proliferative glands. CONCLUSION: H. pylori-associated deregulation of Shh expression that could be linked to gastric atrophy and the associated preneoplastic transformation appears to be reversible with early H. pylori eradication.

Alpha-ketoglutarate oxidoreductase, an essential salvage enzyme of energy metabolism, in coccoid form of Helicobacter pylori.

In the Krebs cycle of Helicobacter pylori, the absence of alpha-ketoglutarate dehydrogenase and succinyl CoA synthetase are shown. Instead, alpha-ketoglutarate is converted to succinyl CoA and succinate by alpha-ketoglutarate oxidoreductase (KOR) and CoA transferase (CoAT). In the present study, when H. pylori transformed to the coccoid form, a viable but non-culturable form of H. pylori with reduced metabolic activity, the KOR activity was enhanced while the CoAT activity was reduced. Direct inactivation of KOR could potently kill the bacteria without allowing conversion to the coccoid form, suggesting a novel treatment strategy for the eradication of H. pylori, especially in cases infected with multiple antibiotic-resistant strains.

Additional small amounts of diuretics improve blood pressure control at low cost without disadvantages in blood sugar metabolism.

We evaluated our present treatment of hypertension and sought a way to improve it. We studied 164 of outpatients we treated in 2002. Mean systolic blood pressure (SBP)+/-SD was 142.0+/-11.3, and 56% of patients had SBP over 140 mmHg. We used more diuretics in patients with good control of SBP (19% vs. 7% of patients; p=0.012). After observing our hypertensive patients, we changed our treatment in a goal-oriented manner. Our goal was blood pressure below 140/90 mmHg. We used, in principle, additional small amounts of diuretics for inadequately treated patients. We followed 147 of the 164 patients from 2002 to 2006. During this period, mean SBP decreased to 134.7+/-9.1 mmHg (p<0.001), and the frequency of patients with SBP>140 mmHg decreased to 14% (p<0.001). We used more diuretics in 2006 than in 2002 (12% to 46% p<0.001). To estimate the risks and benefits of diuretics, in 2006 we analyzed 510 patients who had been followed for at least 2 years. Potassium supplementation was needed in 28% of diuretic-treated patients and 7% of patients without diuretics. We found a correlation between the use of diuretics and good SBP control in the entire patient group as well as in patients with diabetes. In the control of diabetes mellitus, we found no statistical difference between patients treated with diuretics and those not. We found diuretics had no adverse effects with respect to new-onset diabetes mellitus.

Gatifloxacin-based triple therapy as a third-line regimen for Helicobacter pylori eradication.

BACKGROUND AND AIM: This study was designed to investigate the efficacy of gatifloxacin (GAT)-based triple therapy as a third-line treatment for Helicobacter pylori (H. pylori) eradication, according to the assessment of the susceptibility to GAT and gyrA mutation. METHODS: Fourteen patients who had eradication failure following both clarithromycin-based triple therapy and metronidazole-based triple therapy, or who were infected with H. pylori isolates that were resistant to both clarithromycin and metronidazole after failure of clarithromycin-based triple therapy, were enrolled. These patients were randomly assigned to two groups: (i) rabeprazole and amoxicillin (RA) and (ii) rabeprazole, amoxicillin, and GAT for 7 days (RAG). The minimal inhibitory concentrations were determined by the agar dilution method. The gyrA gene was examined by sequencing. RESULTS: The eradication rate was 0% in the RA group and 75% in the RAG group. The eradication rate in the RAG group was 100% in patients infected with GAT-susceptible bacteria and/or bacteria without gyrA mutations, but was only 33.3% in those infected with GAT-resistant bacteria or bacteria with gyrA mutations. CONCLUSION: Although GAT may be a promising candidate for third-line therapy, its selection must be based on the results of drug susceptibility testing or gyrA analyses.

Enhanced activity of 3alpha-hydroxysteroid dehydrogenase by addition of the co-solvent 1-butyl-3-methylimidazolium (L)-lactate in aqueous phase of biphasic systems for reductive production of steroids.

The enzyme activity of 3alpha-hydrosteroid dehydrogenase (HSDH) was enhanced by the addition of the co-solvent 1-butyl-3-methylimidazolium (L)-lactate ([Bmim][lactate]) to 50 mM Tris-HCl buffer. When utilizing [Bmim][lactate], the reaction velocity of HSDH increased. Also, reductive production of androsterone was investigated in an aqueous-organic solvent biphasic system containing 5% [Bmim][lactate] as the co-solvent of aqueous phase. In a coupled-enzyme system comprising HSDH and formate dehydrogenase (FDH), a two-fold increase in production rate of androsterone was obtained when utilizing [Bmim][lactate] with NADH regeneration.

Deep vein thrombosis due to migrated graft bone after posterior lumbosacral interbody fusion. Case report.

The authors report the case of an 83-year-old woman with refractory sciatica attributable to isthmic spondylolisthesis at L-5. Her symptoms were successfully improved after posterior lumbar interbody fusion (PLIF) at L5-S1; however, notable swelling in her left leg suddenly developed 2 days postoperatively. Anterior migration of a fragment of bone graft was demonstrated on computed tomography scanning, and there was obvious occlusion of the left common iliac vein (CIV) on magnetic resonance venography. Ultrasonography revealed a thrombus in the left CIV at the site of compression. To prevent a pulmonary embolism during manipulation of the affected vein, an inferior vena cava filter was placed just before excision of the migrated bone fragment. The swelling in the patient's leg subsided quickly after the surgery, and she was treated with heparin and warfarin to prevent recurrent deep vein thrombosis (DVT). Six months after the second surgery, complete restoration of blood flow to the left CIV and no recurrence of DVT were demonstrated on magnetic resonance venography. Especially in elderly patients with degenerative disc disease, excessive curettage and impaction of disc materials during the PLIF procedure may cause migration of bone graft fragments. Surgeons should be aware of the possible vascular complications of PLIF.

Feeding Deterrence to Reticulitermes speratus (Kolbe) by Fibroporia radiculosa (Peck) Parmasto 1968.

Brown rot fungus Fibroporia radiculosa (Peck) Parmasto grown in decayed wood and non-wood material, potato dextrose agar (PDA) media, deterred Reticulitermes speratus (Kolbe) feeding. Decayed wood and PDA media were extracted and tests were performed to assess termite feeding behavior towards the extracts. We found that the extract from PDA media also suppressed termite feeding, although it did not induce mortality. Using gas chromatography and mass spectrometry analysis, two bioactive compounds were detected from the decayed wood extract, and one was detected from the PDA extract. Based on National Institute of Science and Technology (USA) Mass Spectral library match and compound fragmentation, both of the compounds belong to the sesquiterpenes family.

Use of a pneumatic tourniquet in total knee arthroplasty increases the risk of distal deep vein thrombosis: A prospective, randomized study.

BACKGROUND: There has been controversy regarding the incidence of deep vein thrombosis (DVT) after total knee arthroplasty (TKA) with or without the use of a tourniquet. The aim of this randomized, prospective study was to clarify the effects of tourniquet use on DVT in TKA. METHODS: The subjects were 109 patients scheduled to undergo TKA from April 2008 to March 2009 before the establishment of the American Association of Orthopedic Surgeons (AAOS) practice guidelines. They were randomized into two groups: 51 patients in the tourniquet group (group T) and 52 patients in the control group without a tourniquet (group C). We investigated the thrombotic presence using ultrasonography one week after surgery and compared both groups. RESULTS: There was no difference in the rate of proximal DVTs (P=0.63). However, the risk of distal DVT was significantly higher in group T than in group C (52.9% vs. 23.1%; P=0.002). CONCLUSIONS: Use of the tourniquet in TKA increased the risk of distal DVT.

Quality evaluation of dissolving pulp fabricated from banana plant stem and its potential for biorefinery.

The study was conducted to evaluate the quality of dissolving pulp of Musa sapientum L. (banana) plant stem and its potential for biorefinery. Introduction of pre-hydrolysis prior to any alkaline pulping process helps to reduce the content of hemicellulose and consequently produce acceptably high content of cellulose pulp. Water pre-hydrolysis was done at 150°C for 90min. The amount of lignin, xylan and glucan in the extracted pre-hydrolysis liquor (PHL) was 1.6, 4.9 and 1.6%, respectively. Pulping of pre-extracted chips was done following soda-AQ, alkaline sulfite and kraft process. The ratio of chip to liquor was 1:7 for both pre-hydrolysis and pulping. The kraft pulping process with 20% active alkali and 25% sulfidity at 150°C for 90min showed the best result. The lowest kappa number was 26.2 with a considerable pulp yield of 32.7%. The pulp was bleached by acidic NaClO2 and the consistency was 10% based on air-dried pulp. The lowest amount of 7% NaClO2 was used for the bleaching sequence of D0ED1ED2. After D0ED1ED2 bleaching, the pulp showed that α-cellulose, brightness and ash were 91.9, 77.9 and 1.6% respectively. The viscosity was 19.9cP. Hence, there is a possibility to use banana plant stem as a raw material for dissolving grade pulp and other bioproducts.

Toxicity and Feeding Deterrent Effect of 2-Methylanthraquinone from the Wood Extractives of Tectona grandis on the Subterranean Termites Coptotermes formosanus and Reticulitermes speratus.

No-choice feeding tests using ethanol, chloroform, and acetone extractives of teak (Tectona grandis) heartwood clearly showed feeding deterrent activity and toxicity to the subterranean termite Reticulitermes speratus. The amount of 2-methylanthraquinone (MAQ) in teak wood extractives was not related to the feeding deterrents or toxicity, as shown by the no-choice feeding tests conducted using crude extractives containing various amounts of MAQ, MAQ alone, and fractions of crude extractives. As a native pest, the subterranean termite Coptotermes formosanus was more tolerant to the fractions of crude extractives than Reticulitermes speratus, and the mortality observed in C. formosanus was not due to the presence of MAQ.

Evidence of Subterranean Termite Feeding Deterrent Produced by Brown Rot Fungus Fibroporia radiculosa (Peck) Parmasto 1968 (Polyporales, Fomitopsidaceae).

We found that decayed wood stakes with no termite damage collected from a termite-infested field exhibited a deterrent effect against the termite Reticulitermes speratus, Kolbe, 1885. The effect was observed to be lost or reduced by drying. After identification, it was found that the decayed stakes were infected by brown rot fungus Fibroporia radiculosa (Peck) Parmasto, 1968. In a no-choice feeding test, wood blocks decayed by this fungus under laboratory condition deterred R. speratus feeding and n-hexane extract from the decayed stake and blocks induced termite mortality. These data provided an insight into the interaction between wood-rot fungi and wood-feeding termites.

Tetramethylammonium hydroxide (TMAH) thermochemolysis of lignin: behavior of 4-O-etherified cinnamyl alcohols and aldehydes.

The thermochemolytic behavior of 4-O-etherified cinnamyl alcohols and aldehydes in lignin was investigated in the presence of tetramethylammonium hydroxide (TMAH) (315 degrees C/4 s), using veratrylglycol-beta-(coniferyl alcohol) ether (1a), veratrylglycol-beta-(sinapyl alcohol) ether (1b), and veratrylglycol-beta-(coniferyl aldehyde) ether (2). The methylated products were monitored with gas chromatography-mass spectrometry. Dimers 1a and 1b provided the coniferyl and sinapyl alcohol dimethyl ethers consisting of three isomers, respectively. Coniferyl alcohol dimethyl ether isomers were also observed in the TMAH thermochemolysis pyrolysates of a bulk dehydrogenation polymer of coniferyl alcohol and a Japanese cedar (Cryptomeria japonica) wood. Coniferyl aldehyde methyl ether was not provided from TMAH thermochemolyses of coniferyl aldehyde, 2, a dehydrogenation polymer of coniferyl aldehyde, and the cedar wood. The former three provided veratryl aldehyde in a large abundance, instead of coniferyl aldehyde methyl ether. Sinapyl aldehyde provided 3,4,5-trimethoxybenzaldehyde in a large abundance and sinapyl aldehyde methyl ether in a trace abundance. The results showed that TMAH thermochemolysis is an effective tool to obtain information on cinnamyl alcohol end groups, but is not applicable to analysis of cinnamyl aldehyde end groups.

Influences of saltwater immersion on properties of wood-cellulosic paper.

The saltwater immersion method was developed to inhibit mould growth on flood- or tsunami-damaged paper. Commercially available fine paper used for printing and writing showed decreased tensile indices after saltwater immersion. The salt remaining in the paper tended to increase the moisture content because of the salt deliquescence and moisture in the air. The tensile index was restored by removing salt from the paper. Crystallization and distribution of salt in interfibre pores were also considered to influence interfibre rebonding. The difference in the fibre responses to saltwater depended on the relationship between nano-scaled pores in the fibre walls, osmotic pressure, and the degree of sizing, which resulted in low water retention values. More of the starch applied as a surface sizing agent was dissolved or dispersed during distilled water immersion than saltwater immersion. This loosened the fibre network, which was a factor that decreased the sizing degree of the paper.