bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota is associated with obesity and cardiometabolic disease in a population in the midst of Westernization
Authors: de la Cuesta-Zuluaga Jacobo , Corrales-Agudelo Vanessa , Velásquez-Mejía Eliana P. , Carmona Jenny A. , Abad José M. , Escobar Juan S.
Published: July 2018

Westernization and its accompanying epidemiological transitions are associated with changes in gut microbiota. While the extremes of this lifestyle spectrum have been compared (hunter-gatherers, industrialized countries), populations undergoing such shifts have received little attention. To fill the gap of knowledge about the microbiome evolution following broad lifestyle changes and the emergence of disease-associated dysbiosis, we performed a cross-sectional study in which we characterized the microbiota of 441 Colombian adults through 16S rRNA gene sequencing and determined its relationship with demographic, health-related and dietary parameters. We showed that in the gut microbiota of this cohort thrive taxa proper of both hunter-gatherers (Prevotella, Treponema) and citizens of industrialized countries (Bacteroides, Bifidobacterium, Barnesiella); the relative abundances of these taxa differed from those in Western and non-Western populations. We also showed that the Colombian gut microbiota is composed of five consortia of co-abundant microorganisms that are differentially associated with lifestyle, obesity and cardiometabolic disease, and highlighted metabolic pathways that might explain associations between microbiota and host health. Our results give insights into the evolution of the gut microbiota, and underscore the importance of this community to human health. Promoting the growth of specific microbial consortia could help ameliorating physiological conditions associated with Western lifestyles.
Inflammatory response of microglia to prions is controlled by sialylation of PrPSc
Authors: Srivastava Saurabh , Katorcha Elizaveta , Makarava Natallia , Barrett James P. , Loane David J. , Baskakov Ilia V.
Published: July 2018

Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer’s, Parkinson’s or prion diseases. In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPScand microglial-mediated neuroinflammation has been established. Yet, it remains unclear whether activation of microglia is triggered directly by a contact with PrPSc, and what molecular features of PrPScmicroglia sense and respond to that drive microglia to inflammatory states. The current study asked the questions whether PrPSccan directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPScparticles. PrPScwas purified from brains of mice infected with mouse-adapted prion strain 22L or neuroblastoma N2a cells stably infected with 22L. BV2 microglial cells or primary microglia were cultured in the presence of purified 22L. We found that exposure of BV2 cells or primary microglia to purified PrPSctriggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS). Very similar patterns of inflammatory response were induced by PrPScpurified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc. To test whether the microglial response is mediated by carbohydrate epitopes on PrPScsurface, the levels of sialylation of PrPScN-linked glycans was altered by treatment of purified PrPScwith neuraminidase. Partial cleavage of sialic acid residues was found to boost the inflammatory response of microglia to PrPSc. Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPScsuggests that canonical NFκB activation pathway is involved in inflammatory response. The current study is the first to demonstrate that PrPSccan directly trigger inflammatory response in microglia. In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPScsurface is important for microglial activation.
Types of tobacco consumption and the oral microbiome in the United Arab Emirates Healthy Future (UAEHFS) Pilot Study
Authors: Vallès Yvonne , Inman Claire K. , Peters Brandilyn A. , Ali Raghib , Wareth Laila Abdel , Abdulle Abdishakur , Alsafar Habiba , Anouti Fatme Al , Dhaheri Ayesha Al , Galani Divya , Haji Muna , Hamiz Aisha Al , Hosani Ayesha Al , Houqani Mohammed Al , Junaibi Abdulla Al , Kazim Marina , Kirchhoff Tomas , Mahmeed Wael Al , Maskari Fatma Al , Alnaeemi Abdullah , Oumeziane Naima , Ramasamy Ravichandran , Schmidt Ann Marie , Weitzman Michael , Zaabi Eiman Al , Sherman Scott , Hayes Richard B. , Ahn Jiyoung
Published: July 2018

Cigarette smoking alters the oral microbiome; however, the effect of alternative tobacco products remains unclear. Middle Eastern tobacco products like dokha and shisha, are becoming globally widespread. We tested for the first time in a Middle Eastern population the hypothesis that different tobacco products impact the oral microbiome. The oral microbiome of 330 subjects from the United Arab Emirates Healthy Future Study was assessed by amplifying the bacterial16S rRNAgene from mouthwash samples. Tobacco consumption was assessed using a structured questionnaire and further validated by urine cotinine levels. Oral microbiome overall structure and specific taxon abundances were compared, using PERMANOVA and DESeq analyses respectively. Our results show that overall microbial composition differs between smokers and nonsmokers (p = 0.0001). Use of cigarettes (p = 0.001) and dokha (p = 0.042) were associated with overall microbiome structure, while shisha use was not (p = 0.62). The abundance of multiple genera were significantly altered (enriched/depleted) in cigarette smokers; however, onlyActinobacillus,Porphyromonas,LautropiaandBifidobacteriumabundances were significantly changed in dokha users whereas no genera were significantly altered in shisha smokers. For the first time, we show that smoking dokha is associated to oral microbiome dysbiosis, suggesting that it could have similar effects as smoking cigarettes on oral health.
Gut microbiota modulation accounts for the neuroprotective properties of anthocyanins
Authors: Marques Cláudia , Fernandes Iva , Meireles Manuela , Faria Ana , Spencer Jeremy P. E. , Mateus Nuno , Calhau Conceição
Published: July 2018

High-fat (HF) diets are thought to disrupt the profile of the gut microbiota in a manner that may contribute to the neuroinflammation and neurobehavioral changes observed in obesity. Accordingly, we hypothesize that by preventing HF-diet induced dysbiosis it is possible to prevent neuroinflammation and the consequent neurological disorders. Anthocyanins are flavonoids found in berries that exhibit anti-neuroinflammatory properties in the context of obesity. Here, we demonstrate that the blackberry anthocyanin-rich extract (BE) can modulate gut microbiota composition and counteract some of the features of HF-diet induced dysbiosis. In addition, we show that the modifications in gut microbial environment are partially linked with the anti-neuroinflammatory properties of BE. Through fecal metabolome analysis, we unravel the mechanism by which BE participates in the bilateral communication between the gut and the brain. BE alters host tryptophan metabolism, increasing the production of the neuroprotective metabolite kynurenic acid. These findings strongly suggest that dietary manipulation of the gut microbiota with anthocyanins can attenuate the neurologic complications of obesity, thus expanding the classification of psychobiotics to anthocyanins.
ClpB mutants of Francisella tularensis subspecies holarctica and tularensis are defective for type VI secretion and intracellular replication
Authors: Alam Athar , Golovliov Igor , Javed Eram , Sjöstedt Anders
Published: July 2018

Francisella tularensis, a highly infectious, intracellular bacterium possesses an atypical type VI secretion system (T6SS), which is essential for the virulence of the bacterium. Recent data suggest that the HSP100 family member, ClpB, is involved in T6SS disassembly in the subspecies Francisella novicida. Here, we investigated the role of ClpB for the function of the T6SS and for phenotypic characteristics of the human pathogenic subspecies holarctica and tularensis. The ∆clpB mutants of the human live vaccine strain, LVS, belonging to subspecies holarctica, and the highly virulent SCHU S4 strain, belonging to subspecies tularensis, both showed extreme susceptibility to heat shock and low pH, severely impaired type VI secretion (T6S), and significant, but impaired intracellular replication compared to the wild-type strains. Moreover, they showed essentially intact phagosomal escape. Infection of mice demonstrated that both ΔclpB mutants were highly attenuated, but the SCHU S4 mutant showed more effective replication than the LVS strain. Collectively, our data demonstrate that ClpB performs multiple functions in the F. tularensis subspecies holarctica and tularensis and its function is important for T6S, intracellular replication, and virulence.
Mechanical Metrics of the Proximal Tibia are Precise and Differentiate Osteoarthritic and Normal Knees: A Finite Element Study
Authors: Arjmand Hanieh , Nazemi Majid , Kontulainen Saija A. , McLennan Christine E. , Hunter David J. , Wilson David R. , Johnston James D.
Published: July 2018

Our objective was to identify precise mechanical metrics of the proximal tibia which differentiated OA and normal knees. We developed subject-specific FE models for 14 participants (7 OA, 7 normal) who were imaged three times each for assessing precision (repeatability). We assessed various mechanical metrics (minimum principal and von Mises stress and strain as well as structural stiffness) across the proximal tibia for each subject. In vivo precision of these mechanical metrics was assessed using CV%RMS. We performed parametric and non-parametric statistical analyses and determined Cohen’s d effect sizes to explore differences between OA and normal knees. For all FE-based mechanical metrics, average CV%RMS was less than 6%. Minimum principal stress was, on average, 75% higher in OA versus normal knees while minimum principal strain values did not differ. No difference was observed in structural stiffness. FE modeling could precisely quantify and differentiate mechanical metrics variations in normal and OA knees, in vivo. This study suggests that bone stress patterns may be important for understanding OA pathogenesis at the knee.
Silicon quantum dot involved luminol chemiluminescence and its sensitive detection of dopamine
Authors: Zhang Lei , Tang ZhaoRong , Dong YongPing
Published: July 2018

Water dispersible silicon quantum dots (SiQDs) were synthesized by in situ growth under microwave irradiation.
Dinuclear tethered pyridine, diimine complexes
Authors: Dammann Wiebke , Buban Tabea , Schiller Carl , Burger Peter
Published: July 2018

Synthesis and structures of aryl tethered pyridine, diimine complexes.
Curcumin attenuates doxorubicin-induced cardiotoxicity via suppressing oxidative stress and preventing mitochondrial dysfunction mediated by 14-3-3γ
Authors: He Huan , Luo Yong , Qiao Yang , Zhang Zeyu , Yin Dong , Yao Jianguo , You Jiegen , He Ming
Published: July 2018

Doxorubicin (Dox) induces cardiotoxicity, thereby limiting its clinical application for chemotherapy of cancer.
Directional sensing based on flexible aligned carbon nanotube film nanocomposites
Authors: Sui Chao , Yang Yingchao , Headrick Robert J. , Pan Zixuan , Wu Jianyang , Zhang Jing , Jia Shuai , Li Xinwei , Gao Weilu , Dewey Oliver S. , Wang Chao , He Xiaodong , Kono Junichiro , Pasquali Matteo , Lou Jun
Published: July 2018

An aligned SWCNT-film with anisotropic mechanical and electrical properties was utilized to prepare directional sensor.
Strain engineering of photo-induced phase transformations in Prussian blue analogue heterostructures
Authors: Adam Adeline , Poggi Mélanie , Larquet Eric , Cortès Robert , Martinelli Lucio , Coulon Pierre-Eugène , Lahera Eric , Proux Olivier , Chernyshov Dmitry , Boukheddaden Kamel , Gacoin Thierry , Maurin Isabelle
Published: July 2018

The lattice mismatch acts as an efficient leveller to control the coupling in magnetostrictive/photostrictive heterostructures.
Atomic-engineered gold@silvergold alloy nanoflowers for in vivo inhibition of bacteria
Authors: Yan Wenjing , Yang Longping , Wang Hongxia , Zhang Jianhao , Shen Wenbiao
Published: July 2018

Au@AgAu ANFs with safe, stable and potent antibacterial activity are promising candidate antibacterial agents for infection therapy.
An electron-transfer induced conformational transformation: from non-cofacial “sofa” to cofacial “boat” in cyclotetraveratrylene (CTTV) and formation of charge transfer complexes
Authors: Wang Denan , Ivanov Maxim V. , Mirzaei Saber , Lindeman Sergey V. , Rathore Rajendra
Published: July 2018

Cyclotetraveratrylene (CTTV) undergoes oxidation-induced folding, consistent with interconversion from a non-cofacial “sofa” conformation to a cofacial “boat” conformer.
Metal-free synthesis of imidazo[1,5-a]pyridines via elemental sulfur mediated sequential dual oxidative Csp3–H amination
Authors: Sheng Jie , Liu Jidan , Zhao He , Zheng Liyao , Wei Xingchuan
Published: July 2018

An efficient procedure for imidazo[1,5-a]pyridine formation via dual oxidative Csp3–H amination using elemental sulfur is described.
Structural diversities and gas adsorption properties of a family of rod-packing lanthanide–organic frameworks based on cyclotriphosphazene-functionalized hexacarboxylate derivatives
Authors: Bai Dongjie , Wang Yao , He Minghui , Gao Xiaoxia , He Yabing
Published: July 2018

A family of Ln-MOFs constructed from flexible hexacarboxylate derivatives exhibit substituent-driven structural diversity, and the methoxy-modified one displays the potential for natural gas purification.
An alternative method to enhance w/o emulsion stability using modified dimer acid and its application in oil based drilling fluids
Authors: Huang Xianbin , Sun Jinsheng , Lv Kaihe , Liu Jingping , Shen Haokun
Published: July 2018

Modified dimer acid (MDA) can improve the stability of water-in-oil emulsions by establishing a network structure.
Facile tailoring of the electrical transport in representative hole transport materials by molecular doping
Authors: Li Bixin , Zhao Chenyang , Zhang Shiyang , Zhen Min
Published: July 2018

Hole transport can be facilely tailored by dopants with different HOMO levels as well as distinct mechanisms.
Synthesis of Zn-based metal–organic frameworks in ionic liquid microemulsions at room temperature
Authors: Ye Ranfeng , Ni Min , Xu Yuanyuan , Chen Hao , Li Shengqing
Published: July 2018

For the first time, Zn-metal–organic frameworks (Zn-MOFs) were prepared using Zn2+ and the aromatic ligand 1,3,5-benzenetricarboxylic acid (BTC) in ionic liquid microemulsions stabilized by the surfactant TX-100.
Fluorescence enhancement of carbon dots by graphene for highly sensitive detection of tetracycline hydrochloride
Authors: He Wei , Sun Xiangying , Weng Wenting , Liu Bin
Published: July 2018

The fluorescence of carbon dots self-assembled multilayers (CDs SAMs) can be enhanced by graphene, the sensing sensitivity for tetracycline hydrochloride of CDs SAMs with graphene is two orders higher than that of SAMs without graphene.
OH formation and H2adsorption at the liquid water–Pt(111) interface
Authors: Kristoffersen Henrik H. , Vegge Tejs , Hansen Heine Anton
Published: July 2018

The liquid water–Pt(111) interface is studied with constant temperatureab initiomolecular dynamics to explore the importance of liquid water dynamics on catalytic reactions such as the oxygen reduction reaction in PEM fuel cells.
Treatment of hyperphosphatemia based on specific interactions between phosphorus and Zr(iv) active centers of nano-MOFs
Authors: Zhang Wei , Xu Jiheng , Li Ping , Gao Xiaonan , Zhang Wen , Wang Hui , Tang Bo
Published: July 2018

We describe a kind of Zr(iv)-based nano-MOF that is well suited for specific adsorption and selective fluorescence sensing of phosphate based on specific interactions between Zr(iv) and phosphate which provides a new approach for treatment of hyperphosphatemia.
Stimulation of the ATPase activity of Hsp90 by zerumbone modification of its cysteine residues destabilizes its clients and causes cytotoxicity
Authors: Nakamoto Hitoshi , Amaya Yosuke , Komatsu Taiwa , Suzuki Takehiro , Dohmae Naoshi , Nakamura Yusuke , Jantan Ibrahim , Miyata Yoshihiko
Published: July 2018

Hsp90 is an ATP-dependent molecular chaperone that assists folding and conformational maturation/maintenance of many proteins. It is a potential cancer drug target because it chaperones oncoproteins. A prokaryotic homolog of Hsp90 (HtpG) is essential for thermo-tolerance in some bacteria and virulence of zoonotic pathogens. To identify a new class of small molecules which target prokaryotic and eukaryotic Hsp90s, we studied the effects of a naturally occurring cyclic sesquiterpene, zerumbone, which inhibits proliferation of a wide variety of tumor cells, on the activity of Hsp90. Zerumbone enhanced the ATPase activity of cyanobacterial Hsp90 (Hsp90SE), yeast Hsp90, and human Hsp90α. It also enhanced the catalytic efficiency of Hsp90SE by greatly increasing kcat. Mass analysis showed that zerumbone binds to cysteine side chains of Hsp90SE covalently. Mutational studies identified 3 cysteine residues (one per each domain of Hsp90SE) that are involved in the enhancement, suggesting the presence of allosteric sites in the middle and C-terminal domains of Hsp90SE. Treatment of cyanobacterial cells with zerumbone caused them to become very temperature-sensitive, a phenotype reminiscent of cyanobacterial Hsp90 mutants, and also decreased the cellular level of linker polypeptides that are clients for Hsp90SE. Zerumbone showed cellular toxicity on cancer-derived mammalian cells by inducing apoptosis. In addition, zerumbone inhibited the binding of Hsp90/Cdc37 to client kinases. Altogether, we conclude that modification of cysteine residues of Hsp90 by zerumbone enhances its ATPase activity and inhibits physiological Hsp90 function. The activation of Hsp90 may provide new strategies to inhibit its chaperone function in cells.
‘Blow my mind(in)’ – mindin neutralization for the prevention of atherosclerosis?
Authors: MacRitchie Neil , Maffia Pasquale
Published: July 2018

The hallmark features of atherosclerosis include accumulation of low-density lipoprotein (LDL) carrying cholesterol in the vessel wall, formation of lipid-laden foam cells, and the creation of a pro-inflammatory microenvironment. To date, no effective treatments are clinically available for increasing cholesterol efflux from vascular macrophages and inducing reverse cholesterol transport (RCT). In an article published recently in Clinical Science (vol 132, issue 6, 1199-1213), Zhang and colleagues identified the extracellular matrix protein mindin/spondin 2 as a positive regulator of atherosclerosis. Genetic knockout of mindin in apolipoprotein-E (apoE)−/− mice attenuated atherosclerosis, foam cell formation, and inflammation within the vessel wall. Conversely, selective overexpression of mindin in macrophages in apoE−/− mice was sufficient to promote the greater severity of atherosclerosis. Interestingly, foam cell formation was closely associated with the expression of cholesterol transporters (ABCA1 and ACBG1) that facilitate cholesterol efflux. Liver X receptor (LXR)-β is a key modulator of cholesterol transporter expression and formed direct interactions with mindin. Furthermore, the protective effects of mindin deficiency on foam cell formation were blocked by inhibition of LXR-β. This article highlights a novel role of mindin in modulating foam cell formation and atherosclerosis development in mice through direct regulation of LXR-β. Thus far, direct targetting of LXR-β via pharmacological agonists has proven to be problematic due to the lack of subtype selective inhibitors and associated adverse effects. Indirect targetting of LXR-β, therefore, via mindin inhibition offers a new therapeutic strategy for increasing LXR-β induced cholesterol efflux, reducing foam cell formation, and preventing or treating atherosclerosis.
Alles nur Import? Thailändische Phytotherapie und ihre Einbettung in die Traditionelle Thailändische Medizin (TTM)
Authors: Burri Josef
Published: July 2018

Traditionelle Thailändische Medizin ist mehr als eine Mixtur aus Ayurveda und Traditioneller Chinesischer Medizin. Sie nahm zwar zahlreiche Einflüsse aus dem asiatischen Raum auf, verarbeitete sie aber im Verlauf einer rund 2000-jährigen Geschichte zu einem eigenständigen und höchst originellen Medizinsystem mit präventiven und therapeutischen Einsatzbereichen. Massage und Meditation sind die meist verbreiteten Disziplinen. Weit weniger bekannt außerhalb Thailands sind hingegen die Phytotherapie, die Geburtshilfe und die Ernährungslehre. Seit den 1990er-Jahren werden große Anstrengungen unternommen, um das traditionelle Heilwissen zu dokumentieren, zu lehren und weiterzuentwickeln.
Der ärztliche Sachverständige im Arzthaftungsprozess: Was hat sich seit Inkrafttreten des Patientenrechtegesetzes geändert?
Authors: Hofmann Werner , Zobel Astrid
Published: July 2018

Mit dem Gesetz zur Verbesserung der Rechte von Patientinnen und Patienten (Patientenrechtegesetz) wurden im Februar 2013 eine ganze Reihe gesetzlicher Neuregelungen für unterschiedliche Geltungsbereiche des Gesundheitswesens in Kraft gesetzt. Für die Arzthaftung brachte das Patientenrechtegesetz mit der Einführung der Paragraphen 630a–h in das Bürgerliche Gesetzbuch (BGB) eine auf Transparenz ausgerichtete Darstellung allgemeiner vertragstypischer Aspekte, eine zusammenfassende gesetzliche Regelung der Patientenaufklärung und -einwilligung, die Normierung der Behandlungsdokumentation und eine neue Grundlage für die Einsichtsrechte in die Behandlungsakte. Dabei wurden die im Rahmen höchstrichterlicher Rechtsprechung entwickelten Besonderheiten des Behandlungsvertrags in Gesetzesform überführt und die aus der gefestigten Rechtsprechung bekannten, unter bestimmten Voraussetzungen für den Patienten als günstig anzunehmenden Tatsachenvermutungen als Ausnahmen vom Prinzip der objektiven Beweislast abschließend zusammengefasst. In der vorliegenden Arbeit werden die Regelungen der neuen Paragraphen 630a–h im BGB vorgestellt und im Hinblick auf die vom ärztlichen Sachverständigen im Arzthaftungsprozess zu berücksichtigenden Konsequenzen untersucht.
The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis
Authors: Tóth Barbara , Hegyi Péter , Lantos Tamás , Szakács Zsolt , Kerémi Beáta , Varga Gábor , Tenk Judit , Pétervári Erika , Balaskó Márta , Rumbus Zoltán , Rakonczay Zoltán , Bálint Emese , Kiss Tivadar , Csupor Dezső
Published: July 2018

Herbal products, especially Hypericum perforatum extracts, have been widely used as first-line treatments for mild to moderate depression. Recently, several randomized, controlled clinical trials have been conducted to evaluate the efficacy of another plant, saffron (Crocus sativus), in mild to moderate depression. We have carried out a literature review of currently available published randomized, controlled clinical trials to give an up-to-date evaluation of the efficacy of saffron in mild to moderate depression, compared to placebo or routinely used antidepressants. The meta-analysis is reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using the PICO (patients, intervention, comparison, outcome) format and was conducted using the statistical programs Comprehensive Meta-analysis and RevMan. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for relevant studies. Only placebo or active controlled, randomized clinical studies involving patients suffering from mild to moderate depression and using pharmacological doses of saffron per os were included. Hedgesʼ g was used to calculate effect sizes. Risk of bias was assessed using the Cochrane Collaboration tool, and heterogeneity was tested by both performing the Cochranʼs Q test and calculating Higginsʼ I2
indicator. Eleven randomized trials were included in the qualitative analysis, and nine were pooled for statistical analysis. According to the present meta-analysis, saffron has a significant effect on the severity of depression. Available data from randomized, controlled clinical trials support that saffron is significantly more effective than placebo (g = 0.891; 95% CI: 0.369 – 1.412, p = 0.001), and non-inferior to tested antidepressant drugs (g = − 0.246; 95% CI: − 0.495 – 0.004, p = 0.053).
Metal-Free One-Pot Chemoselective Thiocyanation of Imidazothiazoles and 2-Aminothiazoles with in situ Generated N-Thiocyanatosuccinimide
Authors: Dawane Bhaskar , Kadam Shuddhodan , Ambhore Ajay , Hebade Madhav , Kamble Rahul , Hese Shrikant , Gaikwad Milind , Gavhane Priya
Published: July 2018

A chemoselective thiocyanation of imidazothiazoles and 2-aminothiazoles with use of in situ generated N-thiocyanatosuccinimide (NTS) at room temperature is described. The protocol offers mild reaction conditions and high chemoselectivity for electrophilic substitution in imidazothiazoles over nucleophilic substitution. This method provides metal-free and easy conversion of imidazothiazoles and 2-aminothiazoles into their corresponding C-3 and C-5 thiocyanates, respectively, in good to excellent yield. The present protocol also offers the effective thiocyanation of bifunctional imidazothiazoles containing ­aliphatic –OH and C(sp2)–H bond functionalities.
Facile, Stereocontrolled Synthetic Route towards Bis-functionalised Pyrrolizidines
Authors: Jurczak Janusz , Lindner Marcin , Krasiński Antoni
Published: July 2018

A simple and convenient method for the synthesis of bis-functionalised pyrrolizidines starting from readily available N-Cbz-l-prolinal is described. This aldehyde was converted within two concise steps to the corresponding aminoepoxides, which were separately subjected to regioselective cyclisation induced by a reductive cleavage of the Cbz protecting group. The versatile and concise strategy holds great potential for practical application in the straightforward preparation of pyrrolizidine-based drugs and natural products.
Long-term Results for the BacJac Interspinous Device in Lumbar Spine Degenerative Disease
Authors: Spallone Aldo , Lavorato Luigi , Belvisi Daniele
Published: July 2018

Objective To evaluate the long-term results of using the BacJac interspinous device (Pioneer Surgical Technology Inc.) in a series of patients with degenerative lumbar spine disease.

Methods Forty-one patients undergoing lumbar surgery with implantation of a BacJac device from 2009 to 2012 were enrolled in the present study. Patients were evaluated using the Oswestry Disability Scale (ODI).

Results Although all patients showed a significant improvement of the ODI score immediately after surgery, only 41% of patients showed a satisfactory outcome. We observed worse results in the patients operated on at the L3–L4 level and in whom the device was implanted in a segment different from the one where surgical decompression had been performed. Weight gain in the months after surgery was also a poor outcome-influencing factor.

Conclusions This study confirms what is already suggested in the relevant literature regarding the long-term inefficacy of the so-called dynamic stabilization devices.
Antithrombotic and Bleeding Effects of a New Synthetic Direct Thrombin Inhibitor and of Standard Heparin in the Rabbit
Authors: Cadroy Y , Caranobe C , Bernat A , Maffrand J P , Sié P , Boneu B
Published: July 2018

This study reports on (he anticoagulant, antithrombotic and bleeding effects of a new synthetic direct thrombin inhibitor (SDTI) in comparison with standard heparin (SH). The anticoagulant effect was determined with the thrombin clotting time (TCI) and the activated partial thromboplastin time (APTT). SDTI was more potent than SII in prolonging the TCT, but as potent as SH in prolonging the APTT. The antithrombotic effect was determined using a modified Wessler model in the rabbit, either 30 min after a continuous IV infusion of increasing doses or at various times after a single SC injection (20 mg/kg). After continuous IV infusion of 187 μg/kg/h of SDTI and of 60 μg/kg/h of SH, significant thrombus prevention effects were obtained (59 and 57% respectively). Increasing the dose of SDTI up to 3000 μg/kg/h did not significantly impiove the antithrombotic effect. After SC injection, a significant antihrombotic effect was observed for 12 h with SDTI but for more than 24 h with SH. The bleeding effect was studied using the rabbit ear model 15 min after a continuous infusion of 7.5 and 15 mg/kg/h: the amounts of blood loss were dose-dependent and comparable for SDTI and SH. These studies also indicated that SDTI possesses a considerable shorter half-life in comparison with SH. Accordingly, the ex vivoconcentrations generated after continuous IV infusion or SC injection of the same dose were higher for SH than for the SDTI.
Standardization of Factor IX: Standards for "Purified" Factor IX Concentrates
Authors: Lamb M A , Fricke W A , Rastogi S C
Published: July 2018

An international collaborative study was carried out to determine the suitability of the current WHO II-IX-X concentrate standard, 84/681, for assigning potency to the more highly purified factor IX concentrates. Three Coagulation Factor IX (Human) preparations and one Factor IX Complex preparation were assayed by the one stage method against WHO 84/681 following predilution to 1.0 u/ml in buffer, 1% albumin, or factor IX deficient plasma.

There were no cases of non-parallelism between any of the preparations and the current WHO standard. Predilution of the Coagulation Factor IX (Human) preparations in 1% albumin or factor IX deficient plasma gave similar potency values. Predilution in buffer gave significantly lower (p <0.01) potency values. For the Factor IX Complex preparation, potency estimates were significantly different (p <0.01) with each prediluent. The overall precision was similar within each predilution for all preparations with predilution in buffer being less precise than predilution in albumin or in deficient plasma.

WHO standard 84/681 appears to be a suitable standard for the potency determination of the more highly purified factor IX preparations. Predilution in 1% albumin or factor IX deficient plasma is recommended as they give equivalent results with the least variability.
Two Mutations of the Factor IX Gene Including a Donor Splice Consensus Deletion and a Point Mutation in a Dutch Patient with Severe Hemophilia B
Authors: Poort S R , Briët E , Bertina R M , Reitsma P H
Published: July 2018

The abnormal factor IX gene of a patient with severe hemophilia B (hemophilia B Ursem) was selected for study. All of the coding and their flanking regions and parts of the 5′- and 3′-untranslated regions of the factor IX gene were amplified from the patient’s genomic DNA by using the polymerase chain reaction (PCR). By analyzing the nucleotide sequence of the PCR products we have identified two mutations in the patient’s factor IX gene, viz. a tetranucleotide deletion (GAGT, nt 6492 to 6495) or (TGAG, nt 6491 to 6494) in the 5′-donor splice site consensus at the exon 2-intron B boundary, and a point mutation at nucleotide 31103 in the catalytic domain (exon 8) of factor IXa, which changes the codon for valine 328 (GTT) to one for isoleucine (ATT). PCR-amplified exon 8 from 45 normal males and 55 normal females had the codon for valine-328. We propose that the deletion within the donor splice-site consensus is the cause of the disease in this individual, whereas the substitution of valine-328 by isoleucine may be a neutral variant which is, at least, very rare in the normal population. In a family study the DNA sequence of the patient’s mother shows both the G to A transition in exon 8 and the 5′-donor splice consensus deletion in intron B in one allele.
Warfarin Effect on Rat Liver Ultrastructure, RNA Content and Polysome Distribution
Authors: Noonan Sharon M. , Lorusso David J. , Barnhart Marion I. , Suttie John W.
Published: July 2018

Hepatic RNA content and distribution, polysome piofiles, and ultrastructure were studied in normal and vitamin K deficient rats following warfarin and/or vitamin Kx stimulation. Cellular RNA content was not influenced by warfarin treatment. The percentage of free ribosomes decreased slightly after warfarin but remained at normal values in vitamin K deficient rats. Polysome profiles from warfarin treated and vitamin K deficient rats were similar to control patterns.

The hepatic ultrastructural appearance in normal rats following warfarin treatment revealed the rough endoplasmic reticulum (RER) as the most responsive intracellular organelle. With increasing warfarin concentration, the RER demonstrated increasing dilatation and morphologic ribosome loss. These changes were reversed by vitamin Kx administration. Nutritional vitamin K deficiency did not significantly alter the ultrastructural picture from normal. These morphologic studies are in agreement with previous studies of hepatic structure in coumarin treated dogs. They also suggest the control of prothrombin synthesis at the intracellular site of the rough endoplasmic reticulum.
Liquid Posterior Fossa Epidural Hematoma in Pediatric Trauma: A Single-Center Case Series
Authors: Han Kun , Yin Hongwei , Yao Weicheng , Lan Xiaolei , Bo Yongli , Li Zhaojian
Published: July 2018

Background Liquid posterior fossa epidural hematoma (LPFEH) following head trauma is uncommon, and very few such cases have been described in the literature. Eight patients with this entity and their treatments are presented here.

Methods We performed a single-institution retrospective analysis of all patients with diagnosed LPFEH over a 3-year period. Collected data included clinical history, laboratory results, treatment, and review of all imaging studies performed.

Results Eight pediatric cases were identified with imaging findings consistent with LPFEH; no adult case was identified. Enlargement of ventricles appeared on computed tomography (CT) in six cases, and secondary epilepsy onset occurred in three cases with severe dilated ventricles. Routine hematologic and coagulation tests failed to disclose anemia or abnormal coagulation in each case. Five patients underwent burr-hole drainage of the hematoma and recovered completely. Conservative therapy was adopted in three patients for small hematomas, and hematoma enlargement was not observed in the follow-up CT scans.

Conclusions LPFEH is a rare subtype of traumatic epidural hematoma specifically recognized in the pediatric population. Minimally invasive burr-hole drainage is a feasible procedure for the patient with evident space-occupying effect. Coagulation dysfunction or low hemoglobin as a possible contributing factor and its role in formation of LPFEH was excluded.
Plasma Heparin And Antithrombin III Response Following Endotracheal Administration Of Heparin
Authors: OBrien P F , Clemenson J , Browse N L
Published: July 2018

Plasma heparin and antithrombin III (AT III) concentrations were determined using chromogenic peptide substrates in patients undergoing various forms of minor surgery. After anaesthesia, patients were given small volumes of concentrated heparin (25,000 IU/ml) at various doses based on body weight. Administration was by the endotracheal route via a fine cannula by either instillation or insufflation.

Calibration curves for low-dose heparin (in the range 0.02 to 0.20 IU/ml) were constructed for each patient using pretreatment platelet free plasma. The total amount of heparin neutralizing activity in each plasma was determined and the observed heparin concentration was adjusted to compensate for the interference caused by heparin neutralizing activity released in vivo.

Heparin administered by endotracheal insufflation was more effective than heparin given by instillation in producing satisfactory levels of heparin in the plasma. Peak levels were attained 6 to 24 hours after administration and the effect lasted for several days. By altering the dose, the peak level of heparin could be adjusted in order to achieve a low concentration without affecting the duration of the anticoagulant action.

A parallel moderate decrease in the AT III level was observed within 6 to 24 hours of administration, with recovery toward the pre-treatment level beginning by 48 hours.

Endotracheal insufflation of heparin provides a convenient method of obtaining a prolonged effect at levels low enough to avoid bleeding, yet sufficient to prevent thromboembolic complications following various surgical procedures. Since the anticoagulant effect lasts for at least several days, this method provides an attractive alternative to 8 or 12 hourly subcutaneous injections of heparin.
Experimental DIC Developed In Dogs With Pulmonary And Renal Involvement Induced By Oleic Acid And Anti-Lung Antibody
Authors: Abe T , Nakamura K , Kazama M , Kinoshita T , Matsuda J , Kobayashi K
Published: July 2018

In order to have pathogenetic comprehension on the causal relationship between shock state and development of DIC, the following experiments were carried out and compared with the clinical and laboratory findings in human cases with pulmonary and/or renal diseases. An ordinary shock state was invited in dogs by means of exsanguination, depressing mean blood pressure down to 70mmHg and sustaining it for one hour, but almost no changes were realized in coagulation and fibrinolysis parameters including platelet count and functions of blood as well as the heart rate and cardiac index of animals.

The additional injection of a rather small amount of thromboplastin, however, caused typical hematological changes of DIC and demonstrable disturbance of pulmonary-cardiac (p-c) functions which were restored spontaneously. Repeated injections of oleic acid introduced significant histological changes in the lung and kidney of dogs, but only slight shifts were proved in hematological findings and p-c functions and not so much modification of them was noticed even under the exsanguination shock state. The additional injection of thromboplastin, however, showed exaggerated histological and functional changes.

The long term injections of anti-lung antibody to dogs introduced a certain kind of histological changes, similar to those of so-called “Goodpasture’s syndrome” in the lung and kidney as well as blood findings like DIC and p-c disturbance, and the simultaneous manipulation of exsanguination and thromboplastin injection promoted those changes more gravely.

The same kind of exaggerated reactions in blood findings and p-c functions was encountered in clinical cases with lung and/or kidney disorders and suggested that these damages might play much role in the development of DIC.
Coagulant And Procoagulant Factors In Ascitic Fluid.-About Etiology Of Dic Induced By Ascitic Fluid Infusion
Authors: Ojiro M , Takenoshita M , Nishi M
Published: July 2018

We have experienced two cases of DIC following infusion of ascitic fluid from the peritoneal cavity to the vascular system. We have studied the etiology of this DIC. So, FDP, endotoxin, coagulant factors and procoagulant activity were investigated in ascitic fluid of 11 hepatic cirrhosis cases and 15 cancer cases.

Method and Result; FDP in ascites were more included than in plasma. Endotoxin were positive in about 60% of ascitic fluid. The coagulant factors were recognized a littile except VUI-factor. Only ascitic fluid ded not clott the fibrinogen and did not affect the platlate aggregation. The procoagulant activities were measured by clotting times which the normal plasma (0.lcc) was added with the ascitic fluid or buffer (0.1cc), after 3 minutes incubation, and then added with 1/40 M Cacl2 (0.1cc).

The clotting time was shortened in the ascitic fluid than buffer (buffer 120.7 ± 7.9 sec, Cancer 82 ± 23.8 sec., cirrhosis 91.4 ± 16.5 sec), and both VII and VIII deficient plasma was shortened too, but X dificient plasma was not coagulated. Also FDP and endotoxin did not shorten the clotting time of normal plasma. Experimentally, the ascitic fluid in dog by binding vena cava in ferior and the ascitic fluid in rat by transplantation of tumor cells shortened the clotting time. Conclusion; Coagulant, fibrinolytic and procoagulant factors were existed in ascitic fluid. We think that DIC induced by ascitic fluid are due to this procoagulant factor and this procoagulant factor may be not tissue - thromboplastin only.
The Absolute Requirement Of Platelets During The Induction Phase Of Intravascular Coagulation
Authors: Nelson Wm R
Published: July 2018

This study was conducted to ascertain the role of platelets during the induction phase of intravascular coagulation.

E. Coli endotoxin(1mg/kg) (Difo Laboratories, Detroit) was infused into a 10 control and 6 treated dogs. The treated animals had received 4 to 6 daily intramuscular injections of 6 cc. of a goat anti-dog platelet serum until their peripheral platelet counts were less than 10,000 mm3 at which time the experiment was conducted.

Control animals had a pre-infusion fibrinogen concentration of 237 mg/100 ml whereas the treated animals had 312 mg/100 ml. The fibrinogen concentration changed in response to the endotoxin according to the following table (numbers are percentage of pre-infusion, asterisks note ps≤0.05).

It has been suggested that platelets are not important in the etiology for intravascular coagulation. These investigators have focused upon the accumulation of emboli in the microcirculation and few have monitored the early alterations in coagulation factor concentrations. However in the canine model, the platelet is definitely a pivotal mediator of the coagulopathy experienced during early endotoxemia.
Un nouveau Cas d’Anomalie constitutionnelle et familiale du Fibrinogène sans Diathese hémorragique
Authors: Streiff F , Alexandre P , Vigneron C , Soria J , Soria C , Mester L
Published: July 2018

A new family with congenital dysfibrinogenemia without bleeding tendency has been discovered in Nancy. Identical laboratory abnormalities were found in the mother and son plasma: prolongation of thrombin and reptilase clotting time.

The abnormal fibrinogen affects, only a little, the normal plasma fibrinoformation.

The functional characterization of the defect is localized in fibrin monomer aggregation. The release of fibrinopeptides is normal.

The abnormal fibrinogen shows

a) an alteration in glucidic moiety of the molecule with a high level of sialic acid,

b) an disturbance of chromatography on D. E. A. E. cellulose and

c) of the electrophoretic mobility.
Spontaneous Consumption Coagulopathy in a Dog with Thyroid Cancer
Authors: Slappendel R. J , de Maat C.E.M , Rijnberk A , van Arkel Miss C
Published: July 2018

A case of metastasized anaplastic thyroid carcinoma associated with severe hemorrhagic diathesis in a boxer dog is described. The bleeding tendency was apparently due to consumption coagulopathy, since there was simultaneous occurrence of thrombocytopenia, hypofibrinogenemia and depletion of clotting factors II, V, VIII and X. Fibrinogen breakdown products were demonstrated by three different immunochemical techniques.
Blood Coagulation, in Normal and Hypercholesterolemic Dogs, Unmodified by Chylomicrons*
Authors: Kelly L. A , Newman H. A. I
Published: July 2018

Investigations were performed on the effects of chylomicrons on blood coagulation. No clotting occurred when dog thoracic duct chylomicrons were substituted for the platelets used in the measurement of thromboplastin generation time.

Hypercholesterolemic or normal dog serum was incubated for 3 hours with chylomicrons to transfer 40% of the chylomicron phospholipids to serum lipoproteins. These sera also did not decrease thromboplastin generation time.

Thromboplastin generation of plasma and whole blood clotting times of dogs on high fat diets were not different than normal controls.
Effects of Thorium Dioxide upon Blood Clotting and Platelets. I. In Vitro Studies
Authors: Hjort P. F , McGehee W. G , Rapaport S. I
Published: July 2018

Thorium dioxide was found to damage clotting factors and to interfere with platelet functions in vitro:

1. Fibrinogen and factor V were progressively inactivated. Citrate did not prevent damage to these factors. Thorium dioxide was concentrated in the clot, which suggests that it binds to fibrinogen.

2. Factors II, VII, IX, and X were also inactivated. Inactivation of these factors could be prevented or reversed by citrate.

3. Factors VIII, XI, and XII were not altered.

4. Platelets became less adhesive and less subject to aggregation.

These effects were more marked with unfiltered suspensions of thorium dioxide (TDS) than with filtered suspensions (Thorotrast). They were also increased by increasing the concentration of thorium dioxide, and the time and temperature of incubation. Thorium dioxide probably forms complexes with the clotting proteins, thereby making them less reactive.
The Plasmin Inhibitors of Plasma
Authors: Shamash Y , Rimon A
Published: July 2018

A new method for the assay of plasmin inhibitors in human plasma is described. The method consists of determination of the caseinolytic activity of a standard plasmin solution before and after incubation with the inhibitor, with lysine added to the mixture as a stabilizer of plasmin. Using this method, it was found that plasma contains enough inhibitors to inactivate 30 caseinolytic units of plasmin, or 10 times the normal amount of plasminogen in human plasma.
Hemifacial Trigeminal Pain Referred from Occipital Neuralgia Due to Compression of the Greater Occipital Nerve by the Occipital Artery
Authors: Ko Hak-cheol , Choi Jin-gyu , Son Byung-chul
Published: July 2018

Although pathologic vascular contact between the occipital artery and the greater occipital nerve (GON) at the crossing point in the nuchal subcutaneous layer can cause occipital neuralgia, referred hemifacial trigeminal pain from chronic occipital neuralgia owing to this cause is extremely rare.

A 61-year-old female patient with left-sided occipital neuralgia for 4 years presented with a new onset of left-sided hemifacial pain. Decompression of the left GON from pathologic contacts with the occipital artery resulted in immediate relief for hemifacial pain and chronic occipital neuralgia. The present case implies that sensitization and hyperactivity of the trigeminocervical complex that receives the convergent input from trigeminal and high cervical occipital nociceptive pathways can be a pathogenic mechanism in referred hemifacial pain from occipital neuralgia. In the present case, a branching tributary of the occipital artery at the crossing point forming a constricting loop above the course of the GON was found to be the cause of entrapment. Because the occipital artery is reported to be consistently located superficial to the GON at the crossing point, a spatial relationship between the occipital artery and the GON rather than a mere adhesion or contact might have pathologic significance in the development of occipital neuralgia.
Faktor XIII, Thrombin und Fibronectin als Regulatoren der Fibroblastenproliferation bei der Wundheilung Untersuchungen an Fibroblastenkulturen. Vergleichende Analysen an Gefäßwand- und Malignomzellen
Authors: Bruhn H. D.
Published: July 2018

Thrombin und Faktor XIII stimulieren die Fibroblastenproliferation unter gleichzeitiger intrazellulärer Zunahme von cGMP. Fibronectin hemmt dagegen die relative 3H-Thymidin-Aufnahme von Fibroblasten, so daß Thrombin, Faktor XIII und Fibronectin bei der Wundheilung regulatorische Einflüsse ausüben. Vergleichende Untersuchungen an Gefäßwand-und Malignomzellen zeigen vergleichbare Wirkungen.