bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of glycemic control on periodontitis in type 2 diabetic patients with periodontal disease
Authors: Katagiri Sayaka , Nitta Hiroshi , Nagasawa Toshiyuki , Izumi Yuichi , Kanazawa Masao , Matsuo Akira , Chiba Hiroshige , Fukui Michiaki , Nakamura Naoto , Oseko Fumishige , Kanamura Narisato , Inagaki Koji , Noguchi Toshihide , Naruse Keiko , Matsubara Tatsuaki , Miyazaki Shigeru , Miyauchi Takashi , Ando Yuichi , Hanada Nobuhiro , Inoue Shuji
Published: February 2013

Aims/Introduction

Diabetes mellitus and periodontitis are closely related. A huge number of reports has addressed the effect of periodontal intervention therapy on glycemic control, but no reports have addressed the effect of glycemic intervention therapy on periodontal disease in type 2 diabetic patients. The aim of this study was to examine the effect of improved glycemic control by glycemic intervention therapy on periodontitis in type 2 diabetic patients.

Materials and Methods

A total of 35 patients underwent intervention therapy to improve glycemic control without periodontal treatment. Glycohemoglobin (HbA1c), high‐sensitivity C‐reactive protein (hs‐CRP), bleeding on probing (BOP), probing pocket depth (PPD) and intraoral community periodontal index (CPI) codes of the World health Organization (WHO) were examined at baseline, and 2 and 6 months after the intervention therapy to improve glycemic control.

Results

After the improvement of glycemic control, BOP lesions improved, but deep PPD lesions and WHO CPI codes did not improve. Subanalyses showed that effective glycemic control (average HbA1c reduction 1.8%) improved BOP lesions, but did not affect deep PPD lesions and WHO CPI codes. In addition, high BOP lesions at baseline responded more effectively to glycemic intervention. Further analysis of CPI codes in all individual periodontal sites independent of WHO CPI codes in 35 patients showed that only gingival inflammation without a deep periodontal pocket improved after glycemic intervention.

Conclusions

Effective glycemic control improves BOP lesions in type 2 diabetic patients with periodontitis through ameliorating inflammation at the gingival sites of periodontal tissue. This trial was registered with the University Hospital Medical Information Network (no. UMIN000007670).
Distribution of Androgen and Oestrogen Receptors‐α in the Seminal Vesicle‐Related Spinal Neurones in Male Rats
Authors: Sun X. Q. , Xu C. , Leclerc P. , Giuliano F. , Benoît G. , Droupy S.
Published: February 2013

The seminal vesicles are male accessory sex glands that contribute much of the seminal fluid volume. Previous studies have suggested that the majority of autonomic innervations to the rat seminal vesicles originate from the bilateral major pelvic ganglia. Many preganglionic autonomic neurones innervating the pelvic ganglion were expressed androgen receptors (AR) or oestrogen receptor (ER)‐α immunoreactivity. However, direct neuroanatomic data regarding the distribution of AR and ER‐α in seminal vesicle related‐spinal neurones are lacking. In the present study, a nonvirulent pseudorabies virus (PRV‐152 strain) was used in a retrograde tracing experiment. Four days after PRV injection into the seminal vesicles of male rats, spinal cord sections were prepared. Double‐ and triple‐fluorescence techniques using AR and ER‐α with choline acetyltransferase (ChAT) and PRV were used to investigate the AR and ER‐α distribution in the seminal vesicles related spinal neurones in male rats. In lamina X, 14% of the PRV‐labelled neurones in the L1–L4 segments and 43% in the L5–S1 segments were double‐labelled with AR. In the L1–L4 segments, 6% of PRV‐labelled neurones and 26% in the L5–S1 segments were double‐labelled with ER‐α. In the intermedial cell column area, 10% of PRV‐labelled neurones in the L1–L4 segments and 47% of PRV‐labelled neurones in the L5–S1 segments were double‐labelled with AR. Up to 16% of PRV‐labelled neurones in the L5–S1 segments were double‐labelled with ER‐α. No PRV‐labelled neurones in the L1–L4 segments were double‐labelled with ER‐α. However, for the AR and ER‐α/PRV/ChAT triple‐fluorescence experiments, very few seminal vesicle preganglionic neurones expressed AR or ER‐α. Our data suggests that many spinal interneurones but not preganglionic neurones involved in the seminal vesicle control in male rats were double‐labelled with AR or ER‐α, and they were mainly located at the parasympathetic level in the spinal cord.
Pricing Model Performance and the Two‐Pass Cross‐Sectional Regression Methodology
Authors: KAN RAYMOND , ROBOTTI CESARE , SHANKEN JAY
Published: February 2013

Over the years, many asset pricing studies have employed the sample cross‐sectional regression (CSR) R2 as a measure of model performance. We derive the asymptotic distribution of this statistic and develop associated model comparison tests, taking into account the impact of model misspecification on the variability of the CSR estimates. We encounter several examples of large R2 differences that are not statistically significant. A version of the intertemporal capital asset pricing model (CAPM) exhibits the best overall performance, followed by the Fama–French three‐factor model. Interestingly, the performance of prominent consumption CAPMs is sensitive to variations in experimental design.
Pantoea stewartii Causing Stewart's Wilt on Dracaena sanderiana in Korea
Authors: Choi Okhee , Kim Jinwoo
Published: February 2013

In April 2010, a severe occurrence of Stewart's wilt on Dracaena sanderiana plants was observed in greenhouses in Seongnam, Gyeonggi Province, South Korea, with an incidence of 35‐50%. Being imported plants, little was known about the pathogens associated with D. sanderiana. Symptoms included chlorosis, wilting and leaf blight on the leaf surfaces. Physiological analysis, pathogenicity tests, sequencing and phylogenetic analysis of the 16S rRNA gene revealed that the pathogen was the bacterium Pantoea stewartii. To the best of our knowledge, this is the first report on bacterial wilt caused by P. stewartii on D. sanderiana.
Outing Courtesy: The Role of Rude Dissent in Rule of Law Systems
Authors: Burgess Susan
Published: February 2013

This essay critically examines Keith Bybee's All Judges Are Political, Except When They Are Not. Although Bybee's creative use of the cultural form of courtesy helps us better understand the consensus-building and legitimating features of rule-of-law systems, it overlooks the role that rude dissent can play in exposing the violent, exclusionary, and materially disadvantaging aspects of such systems. Using examples of outing closeted public figures and the rude AIDS activism of the 1990s, this essay explores the rule of law from the perspective of those who are subject to it.
Principles, Passions, and the Paradox of Modern Law: A Comment on Bybee
Authors: Ewick Patricia
Published: February 2013

In All Judges Are Political—Except When They Are Not: Acceptable Hypocrisies and the Rule of Law (2010), Keith Bybee considers the hypocrisy of modern law—that is, the widespread view that judges are both principled and partisan—by drawing an analogy with courtesy. Both law and courtesy contain and manage the diverse and potentially divisive interests that would, were they not contained, disrupt social life. In this essay I extend this argument by considering whether the relationship between law and courtesy is more than merely analogical. I suggest that both systems are aspects of larger historical developments out of which emerged the modern subject and the modern state, creating a social world made up of apparently bounded individuals and institutions. As such, law and courtesy do more than conceal and contain interests and subjectivity; they produce the unruly, partisan subjects they are designed to manage.
Calcium supply effects on wheat cultivars differing in salt resistance with special reference to leaf cytosol ion homeostasis
Authors: Morgan Sherif H. , Lindberg Sylvia , Mühling Karl H.
Published: February 2013

Salinity causes changes in cytosolic Ca2+, [Ca2+]cyt, Na+, [Na+]cyt and pH, pHcyt, which induce specific reactions and signals. Reactions causing a rebalancing of the physiological homeostasis of the cytosol could result in plant resistance and growth. Two wheat cultivars, Triticum aestivum, Seds1 and Vinjett, were grown in nutrient solution for 7 days under moderate salinity (0 and 50 mM NaCl) with and without extra addition of 5 mM CaSO4 to investigate the seedling‐ion homeostasis under salinity. In the leaf protoplasts [Ca2+]cyt, [Na+]cyt and pHcyt were detected using acetoxymethyl esters of the ion‐specific dyes, Fura 2, SBFI and BCECF, respectively, and fluorescence microscopy. In addition, both cultivars were grown for 3 weeks at 0, 50 and 125 mM NaCl with, or without, extra addition of 5 mM CaSO4 to detect overall Na+ and Ca2+ concentrations in leaves and salinity effects on dry weights. In both cultivars, salinity decreased [Ca2+]cyt, while at extra Ca2+ supplied, [Ca2+]cyt increased. The [Ca2+]cyt increase was accompanied by increase in the overall Ca2+ concentrations in leaves and decrease in the overall Na+ concentration. Moreover, irrespective of Ca2+ treatment under salinity, the cultivars reacted in different ways; [Na+]cyt significantly increased only in cv. Vinjett, while pHcyt increased only in cv. Seds1. Even at rather high total Na+ concentrations, the cytosolic concentrations were kept low in both cultivars. It is discussed whether the increase of [Ca2+]cyt and pHcyt can contribute to salt tolerance and if the cytosolic changes are due to changes in overall Ca2+ and Na+ concentrations.
The Deinstitutionalization of Children in Bulgaria – The Role of the EU
Authors: Ivanova Vyara , Bogdanov George
Published: February 2013

In this article, the role of the EU as a key factor for the development of the deinstitutionalization of children is explored. A series of hypotheses concerning EU funding, policies and politics are addressed with regards to how the EU as a whole has affected the deinstitutionalization of children. The article explains the presence of association between instigation of public interest and civil mobilization and the launch of a nationwide reform – in particular how advocacy both at national and EU level led to the adoption of a national reform strategy in Bulgaria. Further, the association between the availability of an innovative approach to spending the EU funds and the decision generally to reform the system for institutional care for children is presented. The article explains the difference that €107.6 million will make for Bulgaria's abandoned children if the European structural funds are realized with their full potential. On the other hand, it reveals the challenges that the process is facing. A great deal of non‐governmental organization (NGO) experience concerning EU involvement in the process has been generalized and construed in order to achieve the best possible understanding of the whole process, the key players and the fundamental issues.
Radio Frequency Identification as a Testbed for Integration of Low Frequency Radio Frequency Sensors Into Orthopedic Implants
Authors: Korduba Laryssa A. , Grabowsky Mary Beth M. , Uhl Richard L. , Hella Mona M. , Ledet Eric H.
Published: February 2013

Recent advances in radio frequency (RF) sensor systems provide new opportunities to wirelessly collect data from inside the body. “Smart implants” instrumented with sensors have been used as research tools for decades, but only recently have implantable sensors become small enough and robust enough to be used in daily clinical practice. In orthopedic surgery, implants provide a vehicle onto which small RF sensors can be mounted to gather data for diagnostics. However, the sensors must function in a challenging environment which requires long term functionality under demanding physical and mechanical conditions. The purpose of this study was to parametrically test low frequency RF systems under simulated in vivo conditions to determine feasibility of sensor integration into orthopedic applications. Three low frequency RF systems were tested in several clinically relevant scenarios in vitro to characterize (1) strategies for maximizing communication range, (2) physical robustness, and (3) mechanical performance. Systems were tested in air, saline, soft tissue, bone, and in proximity to metal. Hermeticity was assessed during a 208 week period. Effects of γ-irradiation and repeated steam sterilized were measured. Strain at failure was measured by mechanical testing of various packaging configurations. All systems were capable of greater than 20 cm read range under ideal conditions. Saline, soft tissue, and bone had minimal effect on signal transmission, but read range was sensitive to the proximity of stainless steel. The electronics were tolerant of steam sterilization but not of γ-irradiation. Polymer encapsulation is robust enough for many orthopedic applications, but ceramic encapsulated sensors need to be optimized for weight-bearing applications to avoid brittle failure. Although sensor packaging remains a challenge, the technology exists to incorporate passive wireless implantable sensors into orthopedic daily practice.
On the change of preferential growth orientation in chemical vapor deposition of titanium carbide by aromatic hydrocarbon precursors
Authors: Pedersen Henrik , Lin Ching-Chi , Ojamäe Lars
Published: February 2013

Thin films of titanium carbide grown by chemical vapor deposition exhibit a strong preferential (111) growth direction if aromatic hydrocarbons, such as benzene, are used as a carbon precursor. If aliphatic hydrocarbons such as methane are used, growth on the (100) surface is preferred. In this study, quantum chemical computations are used to study the adsorption of benzene and methane on the (100) and (111) surfaces to provide an explanation for the changed growth behavior. The adsorption energy of benzene is found to be approximately twice as high on the (111) surface as compared to the (100) surface, and adsorption studies further suggest that benzene chemisorbs on the (111) surface, while it physisorbs on the (100) surface. The studies reveal no significant differences in adsorption energy or behavior for methane on the two surfaces. The authors propose that the higher benzene adsorption energy and different adsorption behavior on the (111) surface are the explanations for the preferential growth orientation.
RNA Helicase DDX3 Is a Regulatory Subunit of Casein Kinase 1 in Wnt–β-Catenin Signaling
Authors: Cruciat Cristina-Maria , Dolde Christine , de Groot Reinoud E. A. , Ohkawara Bisei , Reinhard Carmen , Korswagen Hendrik C. , Niehrs Christof
Published: February 2013

Three Tales of Wnt Signaling

The Wnt signaling pathway has important roles in regulating many biological processes during development and is also implicated in the behavior of some cancer cells (see the Perspective by

Berndt and Moon

).

Cruciat
et al.

(p.
1436
, published online 14 February) describe the mechanism of action of a protein found in a screen for proteins that influence Wnt signaling. DDX3, a DEAD-box RNA helicase, is required for proper Wnt signaling in
Xenopus
and
Caenorhabditis elegans
. It appears to act not through its action as an RNA helicase or through adenosine triphosphate binding, but rather by interacting with the protein kinase, casein kinase 1, and promoting its activation.

Huang
et al.

(p.
1441
, published online 31 January) investigated the function of receptor-interacting protein kinase 4 (RIPK4), the product a gene whose mutation causes severe developmental defects in mice and humans. Over-expression of the protein in cultured human cells activated transcription of genes regulated by the Wnt signaling pathway, and loss of RIPK4 function inhibited Wnt signaling in
Xenopus
embryos. At the molecular level, RIPK4 interacted with the Wnt co-receptor LRP6 and the Wnt signaling adaptor protein DVL2 and promoted phosphorylation of DVL2.

Habib
et al.

(p.
1445
) used Wnt-immobilized beads to understand how external cues direct asymmetrical stem cell divisions. Spatially restricted Wnt signals oriented the plane of mitotic division and lead to pluripotency gene expression in the Wnt-proximal daughter cell while the more distal daughter cell acquired hallmarks of differentiation. Thus, asymmetric gene expression patterns can arise as a consequence of orientation by a short-range signal.
Simultaneous Femtosecond X-ray Spectroscopy and Diffraction of Photosystem II at Room Temperature
Authors: Kern Jan , Alonso-Mori Roberto , Tran Rosalie , Hattne Johan , Gildea Richard J. , Echols Nathaniel , Glöckner Carina , Hellmich Julia , Laksmono Hartawan , Sierra Raymond G. , Lassalle-Kaiser Benedikt , Koroidov Sergey , Lampe Alyssa , Han Guangye , Gul Sheraz , DiFiore Dörte , Milathianaki Despina , Fry Alan R. , Miahnahri Alan , Schafer Donald W. , Messerschmidt Marc , Seibert M. Marvin , Koglin Jason E. , Sokaras Dimosthenis , Weng Tsu-Chien , Sellberg Jonas , Latimer Matthew J. , Grosse-Kunstleve Ralf W. , Zwart Petrus H. , White William E. , Glatzel Pieter , Adams Paul D. , Bogan Michael J. , Williams Garth J. , Boutet Sébastien , Messinger Johannes , Zouni Athina , Sauter Nicholas K. , Yachandra Vittal K. , Bergmann Uwe , Yano Junko
Published: February 2013

One Protein, Two Probes

A central challenge in the use of x-ray diffraction to characterize macromolecular structure is the propensity of the high-energy radiation to damage the sample during data collection. Recently, a powerful accelerator-based, ultrafast x-ray laser source has been used to determine the geometric structures of small protein crystals too fragile for conventional diffraction techniques.

Kern
et al.

(p.
491
, published online 14 February) now pair this method with concurrent x-ray emission spectroscopy to probe electronic structure, as well as geometry, and were able to characterize the metal oxidation states in the oxygen-evolving complex within photosystem II crystals, while simultaneously verifying the surrounding protein structure.
Draft Genome Sequence of Rhodococcus opacus Strain M213 Shows a Diverse Catabolic Potential
Authors: Pathak Ashish , Green Stefan J. , Ogram Andrew , Chauhan Ashvini
Published: February 2013

Soil-borne Gram-positive bacteria from the genus
Rhodococcus
metabolize a range of aromatic hydrocarbons and also produce a variety of value-added products, such as triacylglycerols and steroids. We report the draft genome sequence of
Rhodococcus opacus
strain M213 (9,193,504 bp with a G+C content of 66.99%), providing a comprehensive understanding of the repertoire of metabolic genes of this strain.
Draft Genome Sequences of the Enterococcus faecium Strain LCT-EF258
Authors: Chang De , Zhu Yuanfang , Fang Xiangqun , Li Tianzhi , Wang Junfeng , Guo Yinghua , Su Longxiang , Liu Yan , Jiang Xuege , Wang Li , Guo Na , Liu Changting
Published: February 2013

The space environment has been shown to affect microbes by altering various features, including morphology, growth rate, metabolism, virulence, drug resistance, and gene expression and mutation. Here we present the draft genome sequence of the
Enterococcus faecium
strain LCT-EF258, derived from the
E. faecium
strain CGMCC 1.1736, which was exposed to 17-day space flight.
Draft Genome Sequence of a Humic Substance-Degrading
Paenibacillus
sp. Isolated from the Subarctic Grasslands at Low Temperature
Authors: Park Ha Ju , Kim Dockyu
Published: February 2013

The
Paenibacillus
sp. strain PAMC 26794 was isolated from the tundra grasslands in Alaska for its high ability to degrade humic acids. We sequenced the PAMC 26794 genome to discover the degradative genes for natural humic substances and we propose the degradation pathway(s) of an abundant bacterial group (genus
Paenibacillus
) that inhabits cold environments.
Genome Sequence of Weissella ceti NC36, an Emerging Pathogen of Farmed Rainbow Trout in the United States
Authors: Ladner Jason T. , Welch Timothy J. , Whitehouse Chris A. , Palacios Gustavo F.
Published: February 2013

Novel
Weissella
sp. bacteria have recently been reported to be associated with disease outbreaks in cultured rainbow trout (
Oncorhynchus mykiss
) at commercial farms in China, Brazil, and the United States. Here we present the first genome sequence of this novel
Weissella
species, isolated from the southeastern United States.
Rare case of orofaciodigital syndrome type I
Authors: Singh Abhishek Bahadur , Girhotra Manish , Goel Medha , Bhatia Shilpee
Published: February 2013

Orofaciodigital syndrome (OFDS) is a group of congenital anomalies which affects the face, oral structures and digits. There are nine subtypes with different modes of inheritance. OFDS type I is an X-linked dominant trait with lethality in the vast majority of affected males. We report a case of OFDS type I in an Indian girl at the age of seven who had most of the typical features of OFDS type I and nephrocalcinosis.
MRI findings in chronic relapsing inflammatory optic neuropathy
Authors: Sharma Ankush , Khurana Dheeraj , Kesav Praveen
Published: February 2013

Chronic relapsing inflammatory optic neuropathy is a steroid responsive recurrent optic neuropathy. We describe a patient who presented with recurrent episodes of painful visual loss over a period of 19 years and atypical findings on cranial MRI.
An ACE diagnosis
Authors: Nasher Omar , Gupta Anindya
Published: February 2013

Gaucher's disease is not commonly considered in the differential diagnosis of adult patients with hepatosplenomegaly and increased serum ACE. A 19-year-old girl presented with recurrent epigastric and left hypochondrial pain over a period of 9 years, associated with episodes of nausea and diarrhoea. She was extensively investigated and found to have splenomegaly and raised serum ACE. A screen for haematological disorders was negative. She reported an insect bite during an overseas holiday preceding her symptoms. She was therefore also screened for infectious causes of hepatosplenomegaly but without success. Later on in life, she reported joint pain and discomfort. Sarcoidosis was thought to be the putative cause on more than one occasion. However, the presence of splenomegaly and her relatively young age, led the rheumatologist to the correct diagnosis.
Myasthenia gravis and pure red cell aplasia: a rare association
Authors: Balikar Riya , Redkar Neelam Narendra , Patil Meenakshi Amit , Pawar Sunil
Published: February 2013

This is a case of a patient who presented with generalised weakness, dysphagia and ptosis. Upon evaluating the patient, she was found to have myasthenia gravis (MG) with anaemia and hypothyroidism. Further evaluation for the cause of anaemia revealed that the patient had pure red cell aplasia (PRCA). CT thorax revealed a thymoma. The patient was given packed cell transfusions, steroids and pyridostigmine. The patient improved symptomatically. Her haemoglobin level at follow-up was 9.5 gm/dl. The patient has been posted for thymectomy. This is a rare case of PRCA seen in a patient with MG, with thymoma associated with hypothyroidism.
Solving the puzzle of strong French coffee, palpitation and dizziness
Authors: Park John Jungpa , Grubb Neil
Published: February 2013

A 38-year-old gentleman presented to the emergency department at the University Hospital in Geneva with nausea, rapid palpitation and presyncope. This was followed by a poor night's sleep, a day of strenuous walking in the city and drinking a large quantity of strong French coffee. 12-lead ECG revealed tachycardia with slightly increased QRS duration of right bundle branch block pattern and left axis deviation. Without the electrophysiological (EP) study, the patient was diagnosed with supraventricular tachycardia. On return to Edinburgh, he was investigated under the EP study, which confirmed fascicular tachycardia, a rare and uncommon presentation of ventricular tachycardia. The patient was successfully treated with radiofrequency catheter ablation therapy, which is curative in over 80% of the cases. This case highlights the importance of referring patients with repeatedly presenting arrhythmic episodes to undergo EP study. This will avoid putting them at unnecessary future risk, while offering the opportunity to definitely diagnose and provide curative therapy.
Polyorchidism: a torted right-sided supernumerary testis
Authors: Thyoka Mandela , Lall Anupam , Godse Alok
Published: February 2013

Polyorchidism is a rare congenital anomaly defined by the presence of more than two histologically proven testes. The commonest variant is triorchidism, the supernumerary testis being commonly reported on the left side. Most cases of polyorchidism are found incidentally in association with undescended testis, hydrocele, hernia or torsion. We report a right-sided triorchidism in a 15-year-old boy found at time of groin exploration for an irreducible right inguinal hernia.
Synthesis and studies of covalently linked BF2-oxasmaragdyrin-BODIPY and BF2-oxasmaragdyrin-ferrocene dyads
Authors: Pareek Yogita , Ravikanth Mangalampalli
Published: February 2013

Covalently linked BF2 -oxasmaragdyrin-BODIPY and BF2 -oxasmaragdyrin-ferrocene dyads were synthesized by coupling of meso-triaryl oxasmaragdyrin containing meso-iodophenyl group with meso-(p-ethynylphenyl) borondipyrromethene and α-ethynyl ferrocene respectively under mild Pd(0) coupling conditions. NMR, absorption and electrochemical studies indicated that the two moieties in the dyads retain their individual characteristic features. The fluorescence studies indicated a possibility of photoinduced singlet-singlet energy transfer from BODIPY unit to BF2 -oxasmaragdyrin unit in BF2 -oxasmaragdyrin-BODIPY dyad and photoinduced electron transfer from ferrocene unit to excited state of BF2 -oxasmaragdyrin unit in BF2 -oxasmaragdyrin-ferrocene dyad.
Structural Biology of the Proteasome
Authors: Kish-Trier Erik , Hill Christopher P.
Published: February 2013

The proteasome refers to a collection of complexes centered on the 20S proteasome core particle (20S CP), a complex of 28 subunits that houses proteolytic sites in its hollow interior. Proteasomes are found in eukaryotes, archaea, and some eubacteria, and their activity is critical for many cellular pathways. Important recent advances include inhibitor binding studies and the structure of the immunoproteasome, whose specificity is altered by the incorporation of inducible catalytic subunits. The inherent repression of the 20S CP is relieved by the ATP-independent activators 11S and Blm10/PA200, whose structures reveal principles of proteasome mechanism. The structure of the ATP-dependent 19S regulatory particle, which mediates degradation of polyubiquitylated proteins, is being revealed by a combination of crystal or NMR structures of individual subunits and electron microscopy reconstruction of the intact complex. Other recent structural advances inform us about mechanisms of assembly and the role of conformational changes in the functional cycle.
Lymphatic diamine oxidase secretion stimulated by fat absorption is linked with histamine release
Authors: Ji Yong , Sakata Yasuhisa , Li Xiaoming , Zhang Chao , Yang Qing , Xu Min , Wollin Armin , Langhans Wolfgang , Tso Patrick
Published: February 2013

Diamine oxidase (DAO) is abundantly expressed in mammalian small intestine catalyzing the oxidative breakdown of polyamines and histamine. The aim of this study was to determine the relationship between stimulation of intestinal diamine oxidase secretion with intestinal fat absorption and histamine release. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated and intraduodenal tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic DAO activity and protein secretion were analyzed by radiometric assay and Western blot, respectively. Lymphatic histamine concentration was measured by ELISA. Infusion of Liposyn II (4.43 kcal/3 ml) resulted in a ∼3.5-fold increase in lymphatic DAO protein secretion and DAO activity, peaking at 1 h and lasting for 3 h. Liposyn II infusion also increased the lymphatic histamine release, a substrate for DAO. To determine the relationship of DAO release with histamine release, histamine was administered intraperitoneally (10 mg/kg) in fasting rats and resulted in a significant doubling in lymphatic DAO activity, supporting a link between histamine and DAO. In addition, ip administration of the histamine H4receptor antagonist JNJ7777120 significantly reduced the Liposyn II-induced DAO output by 65.9%, whereas H1(pyrilamine maleate), H2(ranitidine), and H3(thioperamide maleate) receptor antagonists had little effect. We conclude that DAO secretion may contribute to the catabolism of histamine released during fat absorption and this is probably mediated through the histamine H4receptor.
Role of PKC and RhoA/ROCK pathways in the spontaneous phasic activity in the rectal smooth muscle
Authors: Singh Jagmohan , Rattan Satish
Published: February 2013

The role of PKC and RhoA/ROCK pathways in the phasic activities in the rectal smooth muscles (RSM) in the basal state is not known. We examined this issue by determining the effects of PKC inhibitors (calphostin C and Gö-6850) and a ROCK inhibitor (Y-27632) on the slow-rate (∼3/min) and fast-rate (∼25/min) phasic activities. We also examined the corresponding signal transduction cascades and the PKC and ROCK enzymatic activities in the RSM in the basal state. PKC inhibition with calphostin C and Gö-6850 (10−5M) caused a significant decrease (∼25%) in slow-rate (but not fast-rate) phasic activity (monitored by frequency and amplitude of contractions) of the RSM. Conversely, ROCK inhibition with Y-27632 (10−5M) caused a significant decrease not only in slow-rate, but also fast-rate, phasic activity caused by ROCK inhibition in the RSM. Western blot analysis revealed that the PKC inhibition-induced decrease in RSM phasic activity was associated with decreases in PKCα translocation, phosphorylated (Thr38) PKC-potentiated inhibitor (CPI-17), and phosphorylated (Thr18/Ser19) 20-kDa myosin regulatory light chain. Conversely, decreases in the phasic activity in the RSM by ROCK inhibition were accompanied by the additional decrease in phosphorylated (Thr696) myosin phosphatase target subunit 1. Data show that while PKC and RhoA/ROCK pathways play a significant role in slow-rate high-amplitude spontaneous phasic activity, only the RhoA/ROCK pathway primarily mediates fast-rate low-amplitude phasic activity, in the RSM. Such knowledge is important in the understanding of the pathophysiology of large intestinal motility disorders. Relative contributions of the PKC vs. the RhoA/ROCK pathway in the phasic activity remain to be determined.
Self-Concept Deficits in Massively Multiplayer Online Role-Playing Games Addiction
Authors: Leménager Tagrid , Gwodz Alexander , Richter Anne , Reinhard Iris , Kämmerer Nina , Sell Madlen , Mann Karl
Published: February 2013

Background: Previous studies on Internet addiction point towards a particular constellation of personality traits and deficits in social competence of players addicted to massively multiplayer online role-playing games (MMORPGs), which are hypothesized to result from impairments in self-concept. The aim of this study was to examine differences in self-concept and degree of avatar identification in World of Warcraft addicted, non-addicted and naive (nonexperienced) participants. Methods: Participants (n = 45) completed interviews and self-report questionnaires on social, emotional and physical aspects of self-concept. Attributes of participants’ ‘actual self’, ‘ideal self’ and their avatar were assessed using the Giessen test. The extent of avatar identification was examined by assessing differences between ‘ideal self’ and avatar evaluations. Results: In contrast to nonaddicted and naive participants, addicted players showed a more negative body appraisal and lower self-esteem as well as lower permeability, social response, general mood and social potency on the Giessen test subscales. They further showed significantly lower discrepancies between ‘ideal self’ and avatar ratings on nearly all Giessen test subscales. Discussion: The results point towards impairments in self-concept and a higher degree in avatar identification in addicted MMORPG players compared to the remaining participants. These results could have important implications for the treatment of addicted MMORPG players.
Antibiotic Use in Newborns with Transient Tachypnea of the Newborn
Authors: Weintraub Andrea S. , Cadet Claudia T. , Perez Roxane , DeLorenzo Elissa , Holzman Ian R. , Stroustrup Annemarie
Published: February 2013

Background: Initiation of empiric antibiotic treatment for possible early-onset sepsis is recommended for late preterm and term neonates with respiratory distress. There is no evidence base to this approach. Objectives: To determine the incidence of adverse infectious events in neonates with transient tachypnea of the newborn (TTN) managed with a risk-factor-based restrictive antibiotic use policy. Methods: This is a single institution retrospective cohort study of neonates with primary diagnosis of TTN between 2004 and 2010. The relationship between antibiotic exposure and infectious outcomes during the neonatal hospitalization was evaluated. An infectious outcome was defined as pneumonia, bacteremia, clinical sepsis, or death. Analysis included t test, χ2 test, and analysis of variance as appropriate. Results: 745 neonates with TTN met inclusion criteria. None of the 494 antibiotic-naive infants, and 212 of the 251 antibiotic-exposed infants had identifiable risk factors for sepsis. No infectious outcomes occurred in infants who did not receive antibiotics. Eight neonates with TTN received full antibiotic treatment for early-onset sepsis. Each was appropriately identified for early receipt of antibiotics based on historical or clinical risk factors for early-onset sepsis. Conclusions: This study suggests that empiric postnatal antibiotic treatment may not be warranted for late preterm and term infants with TTN in the absence of specific infectious risk factors.
Model Calculations to Quantify Clinical and Economic Effects of Pathogen Inactivation in Platelet Concentrates
Authors: Berger Karin , Bauer Matthaeus , Schopohl Dorothee , Henschler Reinhard , Ostermann Helmut
Published: February 2013

Background: Future shortages in platelet supply are expected in Germany due to demographic changes. A rising cancer incidence will lead to an increasing demand for platelet concentrates (PCs) while the number of potential donors will decrease. Pathogen inactivation (PI) aims to inactivate various infectious agents including emerging pathogens to extend the shelf-life of PCs and reduce the frequency of acute transfusion reactions (ATRs). In this context, the clinical and economic impact of PI on platelet transfusion was evaluated. Material and Methods: Model calculations were conducted for 2 scenarios considering different production settings. Frequencies of ATRs were based on literature analyses, platelet and ATR costs on cost analyses. Results: The estimated average costs for ATRs of grade 1 and 2, irrespective of origin, and grade 3 (allergic) were € 104, € 238, and € 1,200, respectively. Approximately 400 PC-related ATRs per 105 transfusions can be avoided, with estimated savings amounting to € 77,000. The total cost increase was calculated to approximately € 30-50 per PI-treated PC. Conclusion: PI potentially saves plasma, prolongs shelf-life, decreases donor deferral, and reduces ATRs. Model calculations considering clinical and safety benefits of PI show a rational cost increase. The impact of PI should be further evaluated from a societal perspective regarding future blood supply and infectious disease globalization.
Impact of Severe Sepsis on Serum and Urinary Biomarkers of Acute Kidney Injury in Critically Ill Children: An Observational Study
Authors: Di Nardo Matteo , Ficarella Alessio , Ricci Zaccaria , Luciano Rosa , Stoppa Francesca , Picardo Sergio , Picca Stefano , Muraca Maurizio , Cogo Paola
Published: February 2013

Background/Aims: We hypothesized that sepsis could have an impact on the sensitivity of serum and urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) for acute kidney injury (AKI) diagnosis in critically ill children. Methods: Serum NGAL (sNGAL) and urinary NGAL (uNGAL) and CysC were measured daily in the first 48 h from pediatric intensive care unit admission in 11 consecutive critically ill children with severe sepsis; a single measurement was made in a population of 10 healthy controls undergoing minor ambulatory surgery to exclude possible biases in the laboratory methods. Results: uNGAL, serum CysC (sCysC), and urinary CysC (uCysC) levels were significantly increased in patients with septic AKI compared with septic patients without AKI, while sNGAL levels were not significantly different between septic patients with and without AKI. Median serum creatinine levels did not show significant differences between AKI and non-AKI patients. Conclusions: uNGAL, sCysC and uCysC were not altered by sepsis and were good predictors of AKI. In a septic state, sNGAL alone did not discriminate patients with AKI from those without AKI.
Relationship of CYP2C19*2 and CYP2C19*3 Gene Polymorphism with Clopidogrel Response Variability and Recurrent Cardiovascular Events in Chinese Patients Undergoing Percutaneous Coronary Intervention
Authors: Liu Yamin , Liu Naifeng , Li Weilan , Shao Hua , Zhi Hong , Li Jie
Published: February 2013

Background/Aims: The study was conducted to assess the influence of CYP2C19 polymorphisms on clopidogrel response variability and recurrent cardiovascular (CV) events in Chinese patients undergoing percutaneous coronary intervention (PCI). Methods: Platelet aggregation induced by 5 and 20 µmol/l adenosine diphosphate was measured in 109 patients at baseline, 12 h and 36 h after loading with 300 mg of clopidogrel. The primary end point was recurrent CV events, and the follow-up was scheduled at 1, 3, 6 and 12 months after PCI. The polymorphisms of CYP2C19*2 and CYP2C19*3 were genotyped by DNA sequencing analysis. Results: The maximal aggregation rates and inhibition of platelet aggregation among CYP2C19*1/*1, CYP2C19*1/*2 or *3 and CYP2C19*2/*2 or *3 genotypes were significantly different at 12 and 36 h after clopidogrel loading dose administration. Multiple linear regression analysis demonstrated that CYP2C19*2 and CYP2C19*3 might be predictors of clopidogrel response variability. During the 12-month follow-up, recurrent CV events occurred in 21 (19.63%) patients, and there were 5 (6.47%) deaths, 3 (2.80%) cases of ischemic stroke and 14 (13.1%) cases of acute coronary syndrome. Carriers of at least one CYP2C19 loss-of-function allele (*1/*2 or *3, *2/*2 or *3) incurred a 3.65-fold increase (95% CI 1.07–12.38; p = 0.038) in the risk of recurrent CV events 1 year after PCI compared to noncarriers (*1/*1). Conclusion: Polymorphisms in CYP2C19*2 and CYP2C19*3 contribute to variabilities in clopidogrel responsiveness. Patients carrying at least one CYP2C19 loss-of-function allele (CYP2C19*2, *3) are associated with an increased risk of recurrent CV events undergoing PCI.
Multidrug Therapy for Polycystic Kidney Disease: A Review and Perspective
Authors: Aguiari Gianluca , Catizone Luigi , del Senno Laura
Published: February 2013

Autosomal dominant polycystic kidney disease (ADPKD) is a renal disorder characterized by the development of cysts in both kidneys leading to end-stage renal disease (ESRD) by the fifth decade of life. Cysts also occur in other organs, and phenotypic alterations also involve the cardiovascular system. Mutations in the PKD1 and PKD2 genes codifying for polycystin-1 (PC1) and polycystin-2 (PC2) are responsible for the 85 and 15% of ADPKD cases, respectively. PC1 and PC2 defects cause similar symptoms; however, lesions of PKD1 gene are associated with earlier disease onset and faster ESRD progression. The development of kidney cysts requires a somatic ‘second hit’ to promote focal cyst formation, but also acute renal injury may affect cyst expansion, constituting a ‘third hit’. PC1 and PC2 interact forming a complex that regulates calcium homeostasis. Mutations of polycystins induce alteration of Ca2+ levels likely through the elevation of cAMP. Furthermore, PC1 loss of function also induces activation of mTOR and EGFR signaling. Impaired cAMP, mTOR and EGFR signals lead to activation of a number of processes stimulating both cell proliferation and fluid secretion, contributing to cyst formation and enlargement. Consistently, the inhibition of mTOR, EGFR activity and cAMP accumulation ameliorates renal function in ADPKD animal models, but in ADPKD patients mild results have been shown. Here we briefly review major ADPKD-related pathways, their inhibition and effects on disease progression. Finally, we suggest to reduce abnormal cell proliferation with possible clinical amelioration of ADPKD patients by combined inhibition of cAMP-, EGFR- and mTOR-related pathways.
Molecular Magnetic Resonance Imaging for the Detection of Vulnerable Plaques
Authors: den Adel Brigit , Daemen Mat J. , Poelmann Robert E. , van der Weerd Louise
Published: February 2013

Recent advances in molecular resonance imaging of atherosclerosis enable to visualize atherosclerotic plaques in vivo using molecular targeted contrast agents. This offers opportunities to study atherosclerosis development and plaque vulnerability noninvasively. In this review, we discuss MRI contrast agents targeted toward atherosclerotic plaques and illustrate how these new imaging platforms could assist in our understanding of atherogenesis and atheroprogression. In particular, we highlight the challenges and limitations of the different contrast agents and hurdles for clinical application. We describe the most promising existing compounds to detect atherosclerosis and plaque vulnerability. Of particular interest are the fibrin-targeted compounds that detect thrombi and, furthermore, the contrast agents targeted to integrins that allow to visualize plaque neovascularization. Moreover, vascular cell adhesion molecule 1–targeted iron oxides seem promising for early detection of atherosclerosis. These targeted MRI contrast agents, however promising and well characterized in (pre)clinical models, lack specificity for plaque vulnerability.
Deletion of FHL2 Gene Impaired Ischemia-Induced Blood Flow Recovery by Modulating Circulating Proangiogenic Cells
Authors: Huang Po-Hsun , Chen Chi-Yu , Lin Chih-Pei , Wang Chao-Hung , Tsai Hsiao-Ya , Lo Wei-Yuh , Leu Hsin-Bang , Chen Jaw-Wen , Lin Shing-Jong , Chu Pao-Hsien
Published: February 2013

Objective—

The four and a half Lin11, Isl-1 and Mec-3 (LIM) domain protein 2 (FHL2) is a member of the four and a half LIM domain-only (FHL) gene family, and has been shown to play an important role in inhibiting inflammatory angiogenesis. Here, we tested the hypothesis that impaired ischemia-induced neovascularization in mice lacking FHL2 is related to a defect in proangiogenic cell mobilization and functions in vasculogenesis.

Approach and Results—

Unilateral hindlimb ischemia surgery was conducted in FHL2
−/−
mice and wild-type (FHL2
+/+
) mice. After hindlimb ischemia surgery, expression of FHL2 protein was noted in ischemic tissues of wild-type mice. All FHL2-null mice (100%) suffered from spontaneous foot amputation, but only 20% of wild-type mice had ischemia-induced foot amputation after ischemic surgery. Blood flow recovery was significantly impaired in FHL2
−/−
mice when compared with that in wild-type mice as determined by laser Doppler imaging. Histological analysis revealed that the capillary density in the ischemic limb was increased in wild-type mice, whereas no such increase was noted in FHL2
−/−
mice. Flow cytometry demonstrated that the number of CD34
+
or CD34
+
/Sca-1
+
/Flk-1
+
in peripheral blood after ischemic surgery significantly decreased in FHL2-null mice than those in wild-type mice after hindlimb ischemia surgery. FHL2 deficiency impaired ex vivo angiogenesis in mouse aortic-ring culture assay, which revealed that the mean density of the microvessels was significantly higher in the wild-type aorta than in the FHL2
−/−
aorta. Western blot analysis showed that vascular endothelial growth factor (VEGF), interleukin-6, matrix metalloproteinase-2, matrix metalloproteinase-9, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 levels were significantly downregulated in ischemic muscles in FHL2-null mice compared with wild-type mice. Deletion of FHL2 protein by FHL2 small interfering RNA impaired VEGF production under hypoxia conditions, and also suppressed endothelial progenitor cell angiogenic functions, but these effects could be recovered by administration of VEGF.

Conclusions—

Deficiency of FHL2 impairs ischemia-induced neovascularization, and these suppressive effects may occur through a reduction in proangiogenic cell mobilization, migration, and vasculogenesis functions.
Redox-Sensitive Transcription Factor Nrf2 Regulates Vascular Smooth Muscle Cell Migration and Neointimal Hyperplasia
Authors: Ashino Takashi , Yamamoto Masayuki , Yoshida Takemi , Numazawa Satoshi
Published: February 2013

Objective—

Reactive oxygen species are important mediators for platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells, whereas excess reactive oxygen species–induced oxidative stress contributes to the development and progression of vascular diseases, such as atherosclerosis. Activation of the redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), is pivotal in cellular defense against oxidative stress by transcriptional upregulation of antioxidant proteins. This study aimed to elucidate the role of Nrf2 in PDGF-mediated vascular smooth muscle cell migration and neointimal hyperplasia.

Approach and Results—

PDGF promoted nuclear translocation of Nrf2, followed by the induction of target genes, including NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, and thioredoxin-1. Nrf2 depletion by small interfering RNA enhanced PDGF-promoted Rac1 activation and reactive oxygen species production and persistently phosphorylated downstream extracellular signal–regulated kinase-1/2. Nrf2 depletion enhanced vascular smooth muscle cell migration in response to PDGF and wound scratch. In vivo, Nrf2-deficient mice showed enhanced neointimal hyperplasia in a wire injury model.

Conclusion—

These findings suggest that the Nrf2 system is important for PDGF-stimulated vascular smooth muscle cell migration by regulating reactive oxygen species elimination, which may contribute to neointimal hyperplasia after vascular injury. Our findings provide insight into the Nrf2 system as a novel therapeutic target for vascular remodeling and atherosclerosis.