Alcohol consumption and persistent infection of high-risk human papillomavirus.

Alcohol consumption is a possible co-factor of high-risk human papillomavirus (HR-HPV) persistence, a major step in cervical carcinogenesis, but the association between alcohol and continuous HPV infection remains unclear. This prospective study identified the association between alcohol consumption and HR-HPV persistence. Overall, 9230 women who underwent screening during 2002-2011 at the National Cancer Center, Korea were analysed in multivariate logistic regression. Current drinkers [odds ratio (OR) 2·49, 95% confidence interval (CI) 1·32-4·71] and drinkers for ⩾5 years (OR 2·33, 95% CI 1·17-4·63) had a higher risk of 2-year HR-HPV persistence (HPV positivity for 3 consecutive years) than non-drinkers and drinkers for <5 years, respectively (vs. HPV negativity for 3 consecutive years). A high drinking frequency (⩾twice/week) and a high beer intake (⩾3 glasses/occasion) had higher risks of 1-year (OR 1·80, 95% CI 1·01-3·36) HPV positivity for 2 consecutive years) and 2-year HR-HPV persistence (OR 3·62, 95% CI 1·35-9·75) than non-drinkers. Of the HPV-positive subjects enrolled, drinking habit (OR 2·68, 95% CI 1·10-6·51) and high consumption of beer or soju (⩾2 glasses/occasion; OR 2·90, 95% CI 1·06-7·98) increased the risk of 2-year consecutive or alternate HR-HPV positivity (vs. consecutive HPV negativity). These findings suggest that alcohol consumption might increase the risk of cervical HR-HPV persistence in Korean women.

Proposed mechanism of inactivating Escherichia coli O157:H7 by ultra-high pressure in combination with tert-butylhydroquinone.

AIMS: Investigating mechanisms of lethality enhancement when Escherichia coli O157:H7, and selected E. coli mutants, were exposed to tert-butylhydroquinone (TBHQ) during ultra-high pressure (UHP) treatment. METHODS AND RESULTS: Escherichia coli O157:H7 EDL-933, and 14 E. coli K12 strains with mutations in selected genes, were treated with dimethyl sulfoxide solution of TBHQ (15-30 ppm), and processed with UHP (400 MPa, 23 +/- 2 degrees C for 5 min). Treatment of wild-type E. coli strains with UHP alone inactivated 2.4-3.7 log CFU ml(-1), whereas presence of TBHQ increased UHP lethality by 1.1-6.2 log CFU ml(-1); TBHQ without pressure was minimally lethal (0-0.6 log reduction). Response of E. coli K12 mutants to these treatments suggests that iron-sulfur cluster-containing proteins ([Fe-S]-proteins), particularly those related to the sulfur mobilization (SUF system), nitrate metabolism, and intracellular redox potential, are critical to the UHP-TBHQ synergy against E. coli. Mutations in genes maintaining redox homeostasis and anaerobic metabolism were associated with UHP-TBHQ resistance. CONCLUSIONS: The redox cycling activity of cellular [Fe-S]-proteins may oxidize TBHQ, potentially leading to the generation of bactericidal reactive oxygen species. SIGNIFICANCE AND IMPACT OF THE STUDY: A mechanism is proposed for the enhanced lethality of UHP by TBHQ against E. coli O157:H7. The results may benefit food processors using UHP-based preservation, and biologists interested in piezophilic micro-organisms.

Postoperative Doppler Ultrasonography in Liver Transplantation.

BACKGROUND: Doppler ultrasonography plays an important role in the postoperative management of liver transplantation. We present our initial experiences evaluating liver transplants with the use of postoperative Doppler sonography. METHODS: In our hospital, we performed 20 liver transplantations from July 2014 to October 2016. Among 20 patients, we performed 15 deceased-donor liver transplantations (DDLTs) and 5 living-donor liver transplantations (LDLTs). For deceased donors, inferior vena cava anastomoses were performed with the use of the piggyback technique, and for living donors, modified right grafts were used with middle hepatic vein reconstruction by Dacron graft. In the intensive care unit, we performed Doppler ultrasound at least once a day and at every clinical need. We checked hepatic blood flow by means of Doppler ultrasound. RESULTS: Eighteen patients underwent Doppler ultrasonography once a day up to postoperative day 6. Of the patients who received LDLT, 2 patients underwent Doppler ultrasonography twice a day because the operator was concerned about the hepatic artery anastomosis. Findings on Doppler ultrasound showed no abnormal wave form in hepatic artery, portal vein and hepatic veins. No patient had abnormal findings on angiographic computerized tomography. There was 1 graft failure in 20 recipients. The graft failure was primary nonfunction, and retransplantation was done. During the hospitalizations, there were no vascular complications. CONCLUSIONS: Doppler ultrasonography can be used to evaluate postoperative vascular complications in liver transplant patients. When the operator checks postoperative Doppler ultrasonography, it is possible to differentiate between patients, and it may help to detect the vascular complications earlier.

Apolipoprotein B: novel indicator of elevated intraocular pressure.

PURPOSE: Many studies have reported associations between elevated intraocular pressure (IOP) and systemic health parameters, which suggest a common mechanism links IOP elevation and various related cardiometabolic risk factors. Furthermore, according to a recent study, serum apolipoprotein B (APO B) level is a predictor of coronary artery disease. This study was undertaken to analyse the relationship between serum apolipoprotein levels and IOP. METHODS: Healthy people (28,852) who attended a community hospital for a health checkup between January 2011 and December 2013 were enroled in the study. We measured age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A1 (APO A1) and APO B, APO B/APO A1 ratios, and IOP. RESULTS: Univariate regression analysis showed IOP was positively correlated with BMI, SBP, DBP, TC, LDL-C, TG, APO B, and APO B/APO A1 (P<0.001), and negatively correlated with HDL-C (P<0.001). On the other hand, multivariate regression analysis adjusted for age, BMI, SBP, and DBP, revealed IOP was positive correlated with TC, TG, LDL-C, APO B, and APO B/APO A1, and negatively correlated with HDL-C (all <0.05). CONCLUSIONS: Among the various lipid profiles investigated, APO B was found to be most strongly correlated with IOP, regardless of sex. Additional studies are required to confirm the validity of apolipoprotein level as an index for predicting IOP.

Dicobalt octacarbonyl catalyzed carbonylated cycloaddition of triynes to functionalized tetracycles.

[reaction: see text]. We have demonstrated that a dicobalt octacarbonyl catalyzed double [2 + 2 + 1] carbonylative cycloaddition reaction of triyne can be carried out to yield a novel 5.5.5.6 tetracyclic di-enone system.

5-Hydroxytryptamine attenuates free radical injury in primary mouse cortical cultures.

The effects of 5-hydroxytryptamine (5-HT) on several types of neuronal injury in mouse cortical cell cultures were tested. Co-treatment with 5-HT prevented free radical-mediated neuronal necrosis induced by FeCl2 or buthionine sulfoximine (BSO) in a dose-dependent manner. Subtype antagonists did not reverse the protective effect and 5-HT showed direct free radical scavenging activity evidenced by its ability to reduce the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) in a cell-free system. Excitotoxic necrosis induced by NMDA or apoptosis induced by staurosporine was not sensitive to 5-HT treatment. These features raise the possibility that the endogenous neurotransmitter 5-HT may work as an innate antioxidant defense mechanism in the CNS.

Monitoring of dengue viruses in field-caught Aedes aegypti and Aedes albopictus mosquitoes by a type-specific polymerase chain reaction and cycle sequencing.

Virologic surveillance for dengue through the detection of the prevalent serotype(s) circulating in the human population during inter- and intra-epidemic periods constitutes a reliable sentinel system for dengue outbreaks. We have applied a rapid and sensitive, semi-nested, reverse transcription-polymerase chain reaction (RT-PCR) assay using nonstructural protein 3 gene primers for the type-specific-detection of dengue viruses in artificially infected and in field-caught adult Aedes mosquitoes. In laboratory experiments, the assay was sensitive enough to detect one virus-infected mosquito head in pools of up to 59 uninfected heads. In a prospective field study conducted from April 1995 to July 1996, female adult Ae. aegypti and Ae. albopictus mosquitoes were caught from selected dengue-sensitive areas in Singapore and assayed by RT-PCR. Approximately 20% of 309 mosquito pools were positive for dengue viruses. Of the 23 RT-PCR-positive Ae. aegypti pools (containing 1-17 mosquitoes each), 18 pools (78.3%) were positive for dengue 1 virus. There were 40 RT-PCR-positive Ae. albopictus pools (containing 1-33 mosquitoes each) of which 31 (77.5%) were positive for dengue 1 virus. The predominant virus type responsible for the current dengue epidemic since 1995 was also dengue 1. The geographic locations of the virus-infected mosquitoes correlated with the residences or workplaces of patients within dengue outbreak areas. A total of 43.5% of the positive Ae. aegypti pools and 25.0% of the positive Ae. albopictus pools contained only a single mosquito. Both Aedes species showed similar overall minimum infection rates of 57.6 and 50 per 1,000 mosquitoes. Infected Ae. aegypti were detected as early as six weeks before the start of the dengue outbreaks in 1995 and 1996. However, infected Ae. albopictus appeared later, when the number of cases was increasing. Virologic surveillance by RT-PCR for detecting dengue virus-infected Aedes mosquitoes in the field may serve as an early warning monitoring system for dengue outbreaks.

Inhibitory effect of ursolic acid purified from Origanum majorana L on the acetylcholinesterase.

We screened 139 herbal spices in search of the acetylcholinesterase (AChE) inhibitor from natural resources. AChE inhibitors, which enhance cholinergic transmission by reducing the enzymatic degradation of acetylcholine, are the only source of compound currently approved for the treatment of Alzheimer's Disease (AD). Among these herbs, edible plants and spices, the ethanol extract from Origanum majorana L. showed the highest inhibitory effect on AChE in vitro. By sequential fractionation of Origanum majorana L. the active component was finally identified as ursolic acid (3 beta-Hydroxyurs-12-en-28-oic acid). The ursolic acid of Origanum majorana L. inhibited AChE activity in a dose-dependent and competitive/non-competitive type. The Ki value (representing the affinity of the enzyme and inhibitor) of Origanum majorana L. ursolic acid was 6 pM, and that of tacrine was 0.4 nM. The concentration required for 50% enzyme inhibition of the active component (IC50 value) was 7.5 nM, and that of tacrine was 1 nM. This study demonstrated that the ursolic acid of Origanum majorana L. appeared to be a potent AChE inhibitor in Alzheimer's Disease.

DNA-mediated immunization of glycoprotein 350 of Epstein-Barr virus induces the effective humoral and cellular immune responses against the antigen.

Epstein-Barr virus (EBV) is a human pathogen that is involved in numerous diseases and tumors. Since the EBV infection occurs in the early ages of life, and most of the population is subsequently exposed to EBV, the conventional method of vaccination to induce the prophylactic immunity cannot be considered effective in coping with the virus infection. In this study, we tested whether the injection of a plasmid vector that contained the gene for glycoprotein 350 (gp350), which had been identified as a ligand for virus' adsorption and a target for virus neutralizing antibodies, could induce effective immune responses against the antigen. As a result, the injection of the constructed plasmid vector into mice induced the production of gp350-specific antibodies. A major isotype of the gp350-specific antibodies was IgG1. The antibodies efficiently mediated the antibody-dependent cellular cytotoxicity against the cells expressing the gp350 antigen. In addition, the injection of the constructed plasmid vector stimulated the precursor T cell population that was specific to the gp350 antigen. In addition, gp350-specific cytotoxic T lymphocytes were efficiently stimulated by the injection of the constructed plasmid vector. These results suggested that the injection of the plasmid vector, containing the gp350 gene of Epstein-Barr virus, could be one of the most effective ways to induce both prophylactic and therapeutic vaccinations against the virus infection.

The first Ru(II)-catalysed asymmetric hydrogen transfer reduction of aromatic ketones in aqueous media.

The first water-soluble asymmetric hydrogen-transfer ruthenium(II) catalyst system consisting of [Ru(p-cymene)Cl2]2, (S)-proline amide, and sodium formate, which gives high conversion rates with high ee values up to 95.3% and is reusable, has been developed.

Catalytic asymmetric synthesis of cyclopentenones from propargyl malonates and allylic acetate by successive action of homogeneous palladium(II) and cobalt on charcoal catalysts in a one-pot reaction.

The tandem action of a homogeneous chiral Pd(II) catalyst and a heterogeneous Co/C catalyst leads to a two-step one-pot highly enantioselective Pauson-Khand-type reaction.

Colloidal cobalt nanoparticles: a highly active and reusable Pauson-Khand catalyst.

A new Pauson-Khand catalyst based on colloidal cobalt nanoparticles has been developed; the catalyst is highly effective for many intra- and inter-molecular Pauson-Khand reactions and can be recycled and reused many times without losing catalytic activity.

Haloperidol and clozapine increase neural activity in the rat prefrontal cortex.

Haloperidol and clozapine have been widely used to alleviate schizophrenic symptoms, but their physiological effects in the prefrontal cortex (PFC) are not known. Effects of haloperidol and clozapine on single unit activity were investigated in the medial PFC of anesthetized rats. Injection (intraperitoneal) of haloperidol (1 mg/kg) or clozapine (20 mg/kg) significantly elevated discharge rates of PFC neurons. Considering that hypofrontality is one characteristic of schizophrenic symptoms, these results raise the possibility that enhancement of PFC neural activity contributes to therapeutic effects of haloperidol and clozapine.

Synthesis and antitumor activity of (diamine)platinum(II) complexes of benzylmalonate derivatives.

(Diamine)platinum(II) complexes of benzylmalonate derivatives as a leaving group designed in a wide range of lipophilicity and water-solubility were prepared and their antitumor activities were attempted to correlate to their lipophilicity or solubility. A good relationship was observed between their in vitro toxicity and solubility of the title complexes with the same carrier ligand, DACH (trans-(+/-)-1,2-diaminocyclohexane): The most soluble complexes are most cytotoxic whereas the least soluble complexes are least cytotoxic. However, no relationship could be established between their in vivo activity and their lipophilicity or solubility presumably due to other pharmacokinetic factors involved in vivo. The molecular structure of (IPA)2Pt(DBM).2CH3OH (IPA = isopropylamine; DBM = dibenzylmalonate) was determined by X-ray diffraction: space group P2(1)/n, a = 11.433 (3), b = 14.461 (4), c = 17.478 (4) A, beta = 97.25 (3) degrees, z = 4, R = 0.0437.

Biochemical and pharmacological characteristics of 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a new proton-pump inhibitor, in rabbit gastric microsomes and in rats.

We have investigated the properties of the newly synthesized proton-pump inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379-6), on gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+-ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approximately 14-times higher than that of omeprazole at pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg(-1)) but was less active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently protected the gastric mucosa from damage induced by water-immersion stress, indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by mepirizole. Repeated administration of YJA20379-6 also dose-dependently accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects which are exerted by suppression of H+/K+-ATPase activity in gastric parietal cells. YJA20379-6 might be useful for the clinical treatment of peptic ulcer diseases.

Biochemical and pharmacological characteristics of a newly synthesized H+/K+-ATPase inhibitor, YJA20379-8, 3-butyryl-4-[R-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, in pigs and rats.

We have investigated the effect of the newly synthesized proton-pump inhibitor YJA20379-8, 3-butyryl-4-[R-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, on gastric mucosal proton pump (H+/K+-ATPase) activity, gastric acid secretion and gastric lesions in experimental animals. In lyophilized pig gastric microsomes, YJA20379-8 was shown to inhibit H+/K+-ATPase activity; the inhibitory effect was not affected by pH, the IC50 (dose resulting in 50% inhibition) being 28.0 microM and 30.0 microM at pH 6.4 and pH 7.4, respectively. The effect was fully reversed by dilution and subsequent washing of the incubation mixtures of H+/K+-ATPase and YJA20379-8, suggesting the reversible nature of the enzyme inhibition. In pylorus-ligated rats, YJA20379-8 administered by different routes (intraduodenal, subcutaneous, intravenous or oral) resulted in dose-dependent suppression of basal gastric acid secretion. The duration of antisecretory action of 30 mg kg(-1) YJA20379-8 given intraduodenally was very brief (less than 7 h). Pretreatment with YJA20379-8 also dose-dependently prevented gastric lesions induced by absolute ethanol and water-immersion stress in rats. These results suggest that YJA20379-8 might exert its antiulcer activity partly by reversible suppression of acid secretion and partly by protecting the gastric mucosa against ulcerative stimuli.

Ipsilateral island fibula transfer for segmental tibial defects: antegrade and retrograde fashion.

Five patients with segmental tibial defects whose contralateral fibula could not be used as a donor were treated with ipsilateral island fibular transfer in an antegrade or retrograde fashion. Antegrade-flow pedicled flaps based on the peroneal vessel as in the conventional free flap were used for the proximal or middle one-third tibial defects, whereas retrograde-flow pedicled flaps based on the communicating branch between the peroneal and posterior tibial vessels were used for the middle or distal one-third of the tibia. All patients had one of the following problems: a previously failed free flap, below-knee amputation of the opposite leg because of open tibia fracture, refusal to use the contralateral sound leg, or poor general condition to endure a lengthy operation. Four of the patients also had an associated fibular fracture on the same leg, which was ultimately used as one of the osteotomy sites. The follow-up period was from 31 to 48 months. Time to bony union ranged from 4 to 7 months. Time to full weight bearing was from 5 to 9 months after operation. All of the transferred fibulas showed hypertrophy after weight bearing. Nonunion occurred in two cases, which were treated with a long leg cast and cancellous bone graft, respectively. The limb was shorter by an average of 0.5 cm in three cases, longer by 1.1 cm in one case, and in the last case, it was uncheckable because the opposite limb was previously amputated. Limited arc of rotation was not a problem. Other disabling complications were not seen. We believe that these methods can be a valuable alternative to the contralateral free fibula flap in certain cases.

Orbital floor and infraorbital rim reconstruction after total maxillectomy using a vascularized calvarial bone flap.

A number of techniques have been introduced to support the orbital floor after maxillectomy without orbital exenteration. These methods include skin graft or muscular sling, but they have resulted in severe complications, such as enophthalmos, global ptosis, diplopia, and facial deformity. Currently, advanced microvascular reconstruction using bone and soft tissue is performed by many surgeons. This usually results in the filling of the postmaxillectomy defect, but the lack of support for the orbital rim and floor by the bone flap may still cause the complications mentioned above. Vascularized calvarial bone flap was chosen in this study for reconstruction of the orbital floor and infraorbital rim to function as a buttress, to reconstruct recipient sites of poor vascular bed after radiation therapy, and to withstand further postoperative radiation. By providing a solid floor and rim, these complications can be prevented with satisfactory function and aesthetically acceptable results. From September of 1995 to July of 1998, we performed vascularized bone flap for the reconstruction of the orbital floor and infraorbital rim in four cases after total maxillectomy involving the orbital floor. With a follow-up period from 19 to 35 months (mean, 27 months), we obtained significant improvement of functional and aesthetically acceptable results without global ptosis, enophthalmos, diplopia, or severe facial contour deformity.

Simultaneous reconstruction of the Achilles tendon and soft-tissue defect using only a latissimus dorsi muscle free flap.

The combined loss of the Achilles tendon and the overlying soft tissue in the young ambulant patient with expectations of a normal life is a challenging problem. These patients need not only soft tissue but also dynamic and functional reconstruction. Four cases of major defects of the Achilles tendon and overlying soft tissue after trauma are presented. In each case, the tendon and the overlying soft tissues were reconstructed using only a latissimus dorsi muscle free flap and overlying split-thickness skin graft. In conventional methods, evolved in the reconstruction of the Achilles tendon and soft tissue, the size of the defect was a limit. However, this technique can be used to reconstruct an extensive defect, including distal calf muscle to the plantar metatarsal area. In one case, the flap was harvested in a myocutaneous unit, and the skin portion was deepithelialized for the coverage and enough padding on the bony exposure area in reverse position. The purpose of the present study was to reevaluate the potential of denervated muscle flap for a force-bearing conduit as an alternative reconstructive method of the Achilles tendon. The denervated latissimus dorsi muscle in this study eventually experienced the process of atrophy and fibrosis but maintained its original length. Although there remained some atrophic muscle fibers, a fibrosis of the muscle fibers formed a tendon-like fibrous band, and so the action of the posterior calf muscle could be transmitted through the tendon-like fibrotic change of the denervated latissimus dorsi muscle. The advantages of this technique are that (1) it is a single procedure, (2) it is adaptable to a wide range of defect sizes, (3) it allows faster wound healing supported by well-vascularized tissues, (4) it produces satisfactory function of the ankle joint and a padding effect, and (5) it produces good contour of the posterior calf to the sole and an acceptable donor-site morbidity.

Growth performance of weanling pigs fed corn-soybean meal diets with or without dried whey at various L-lysine.HCl levels.

A total of 490 crossbred weanling pigs were used to evaluate the responses to and the subsequent interaction between dietary dried whey and crystalline L-lysine.HCl on postweanling growth and feed efficiency at two periods postweaning. The experiment was conducted as a 2 x 5 factorial arrangement of treatments in a randomized complete block design to evaluate two levels of edible-grade dried whey (0 or 25%) and five dietary lysine levels ranging from 1.10 to 1.50% in .10% increments using a corn-soybean meal mixture as the basal feedstuff. Pigs were allotted by weight, litter, and sex to seven replicates at weaning (23 +/- 2 d) and fed their treatment diets for a 35-d period. Daily gain and feed intake were greater (P less than .01) for both the 0- to 21- and the 22- to 35-d periods when dried whey was fed; the relative magnitude of the response to dried whey was greatest during the initial 21-d period. Growth responses during the 0- to 21-d period were, however, independent of dietary lysine level, suggesting that dietary lysine at a level of 1.10% is not the limiting nutrient in a corn-soybean meal diet or a corn-soybean meal diet with dried whey. From 22 to 35 d postweaning a linear growth response to lysine level occurred when the dried whey diet was fed, but no response was detected when lysine was added to the corn-soybean diet, resulting in a diet x lysine level interaction (P less than .10).(ABSTRACT TRUNCATED AT 250 WORDS)