bluuebunny/crossref_metadata_2025 huggingface dataset:
Bauhinia variegataLeaf Extracts Exhibit Considerable Antibacterial, Antioxidant, and Anticancer Activities
Authors: Mishra Amita , Sharma Amit Kumar , Kumar Shashank , Saxena Ajit K. , Pandey Abhay K.
Published: September 2013

The present study reports the phytochemical profiling, antimicrobial, antioxidant, and anticancer activities ofBauhinia variegataleaf extracts. The reducing sugar, anthraquinone, and saponins were observed in polar extracts, while terpenoids and alkaloids were present in nonpolar and ethanol extracts. Total flavonoid contents in various extracts were found in the range of 11–222.67 mg QE/g. In disc diffusion assays, petroleum ether and chloroform fractions exhibited considerable inhibition againstKlebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains ofE. coli,Proteusspp. andPseudomonasspp. Minimum bactericidal concentration (MBC) values of potential extracts were found between 3.5 and 28.40 mg/mL. The lowest MBC (3.5 mg/mL) was recorded for ethanol extract againstPseudomonasspp. The antioxidant activity of the extracts was compared with standard antioxidants. Dose dependent response was observed in reducing power of extracts. Polar extracts demonstrated appreciable metal ion chelating activity at lower concentrations (10–40 μg/mL). Many extracts showed significant antioxidant response in beta carotene bleaching assay. AQ fraction ofB. variegatashowed pronounced cytotoxic effect against DU-145, HOP-62, IGR-OV-1, MCF-7, and THP-1 human cancer cell lines with 90–99% cell growth inhibitory activity. Ethyl acetate fraction also produced considerable cytotoxicity against MCF-7 and THP-1 cell lines. The study demonstrates notable antibacterial, antioxidant, and anticancer activities inB. variegataleaf extracts.
Reliability and Validity of the Persian Version of the Fatigue Severity Scale in Idiopathic Parkinson’s Disease Patients
Authors: Fereshtehnejad Seyed-Mohammad , Hadizadeh Hasti , Farhadi Farzaneh , Shahidi Gholam Ali , Delbari Ahmad , Lökk Johan
Published: September 2013

As one of the most frequent symptoms, measurement of fatigue is an issue of interest in Parkinson’s disease (PD). The fatigue severity scale (FSS) is one of the recommended questionnaires for this purpose. The aim of our study was to evaluate psychometric properties of the Persian version of the FSS (FSS-Per) to assess fatigue in PD patients. Ninety nondemented idiopathic Parkinson’s disease (IPD) patients were consecutively recruited from an outpatient referral movement disorder clinic. In addition to the disease severity scales, the FSS-Per was used for fatigue measurement. The internal consistency coefficient was larger than 0.8 for all of the items with a total Cronbach’s alpha of 0.96 (95% CI: 0.95–0.97). The FSS-Per score correlated with the UPDRS score (, ) and the “Hoehn and Yahr” (HY) stage (, ). The total score of the FSS-Per significantly discriminated IPD patients with more severe disability (HY stage > 2) versus those with less severe disease (HY stage ) (AUC = 0.81 (95% CI: 0.72–0.90)). The FSS-Per fulfilled a high internal consistency and construct validity to measure the severity of fatigue in Iranian IPD patients. These acceptable psychometric properties were reproducible in subgroups of IPD patients regarding different levels of education, disease severity, sex and age groups.
Early Stakeholder Involvement in the Project Definition Phase: Case Renovation
Authors: Aapaoja Aki , Haapasalo Harri , Söderström Pia
Published: September 2013

Relational project delivery methods (RPDMs) have been widely offered as a solution to increasing holistic project value creation. Furthermore, early stakeholder involvement has been emphasized as one of the cornerstones of RPDM. The purpose of this paper is to examine who the stakeholders are that should be involved early in the project definition phase. This paper discusses the process and nature of the project definition phase in RPDM, with the main focus on early stakeholder involvement. The results are derived from the analysis of the literature and an empirical study (interviews). The stakeholders, their roles in the renovation project, and at which stage they should each be involved in the project definition process are determined. The findings show that projects cover different levels of stakeholders, whose requirements and purposes must be considered and managed. Early involvement allows room for creative solutions and the intensive exchange of ideas. Thus, it leads to procedures that run in phases, which in turn change the project’s value creation to holistic value cocreation. This article facilitates and contributes to early stakeholder involvement and the creation of integrated teams by identifying and consolidating the different levels, roles, responsibilities, and objectives of the stakeholders.
Accessory Cells of the Microenvironment Protect Multiple Myeloma from T-Cell Cytotoxicity through Cell Adhesion-Mediated Immune Resistance
Authors: de Haart Sanne J. , van de Donk Niels W.C.J. , Minnema Monique C. , Huang Julie H. , Aarts-Riemens Tineke , Bovenschen Niels , Yuan Huipin , Groen Richard W.J. , McMillin Douglas W. , Jakubikova Jana , Lokhorst Henk M. , Martens Anton C. , Mitsiades Constantine S. , Mutis Tuna
Published: September 2013

Purpose: Cellular immunotherapy frequently fails to induce sustained remissions in patients with multiple myeloma, indicating the ability of multiple myeloma cells to evade cellular immunity. Toward a better understanding and effective therapeutic modulation of multiple myeloma immune evasion mechanisms, we here investigated the role of the tumor microenvironment in rendering multiple myeloma cells resistant to the cytotoxic machinery of T cells.

Experimental Design: Using a compartment-specific, bioluminescence imaging-based assay system, we measured the lysis of luciferase-transduced multiple myeloma cells by CD4+ or CD8+ CTLs in the presence versus absence of adherent accessory cells of the bone marrow microenvironment. We simultaneously determined the level of CTL activation by measuring the granzyme B release in culture supernatants.

Results: Bone marrow stromal cells from patients with multiple myeloma and healthy individuals, as well as vascular endothelial cells, significantly inhibited the lysis of multiple myeloma cells in a cell–cell contact-dependent manner and without substantial T-cell suppression, thus showing the induction of a cell adhesion-mediated immune resistance (CAM-IR) against CTL lysis. Further analyses revealed that adhesion to accessory cells downregulated Fas and upregulated the caspase-3 inhibitor survivin in multiple myeloma cells. Reconstitution of Fas expression with bortezomib enhanced the CTL-mediated lysis of multiple myeloma cells. Repressing survivin with the small-molecule YM155 synergized with CTLs and abrogated CAM-IR in vitro and in vivo.

Conclusion: These results reveal the cell adhesion-mediated induction of apoptosis resistance as a novel immune escape mechanism and provide a rationale to improve the efficacy of cellular therapies by pharmacologic modulation of CAM-IR. Clin Cancer Res; 19(20); 5591–601. ©2013 AACR.
Molecular Pathways: Targeting MALT1 Paracaspase Activity in Lymphoma
Authors: Fontán Lorena , Melnick Ari
Published: September 2013

MALT1 mediates the activation of NF-κB in response to antigen receptor signaling. MALT1, in association with BCL10 and CARD11, functions as a scaffolding protein to activate the inhibitor of IκB kinase (IKK) complex. In addition, MALT1 is a paracaspase that targets key proteins in a feedback loop mediating termination of the NF-κB response, thus promoting activation of NF-κB signaling. Activated B-cell subtype of diffuse large B-cell lymphomas (ABC-DLBCL), which tend to be more resistant to chemotherapy, are often biologically dependent on MALT1 activity. Newly developed MALT1 small-molecule inhibitors suppress the growth of ABC-DLBCLs in vitro and in vivo. This review highlights the recent advances in the normal and disease-related functions of MALT1. Furthermore, recent progress targeting MALT1 proteolytic activity raises the possibility of deploying MALT1 inhibitors for the treatment of B-cell lymphomas and perhaps autoimmune diseases that involve increased B- or T-cell receptor signaling. Clin Cancer Res; 19(24); 6662–8. ©2013 AACR.
Allopurinol Reverses Liver Damage Induced by Chronic Carbon Tetrachloride Treatment by Decreasing Oxidative Stress, TGF-ß Production and NF-κB Nuclear Translocation
Authors: Aldaba-Muruato Liseth R. , Moreno Mario G. , Shibayama Mineko , Tsutsumi Víctor , Muriel Pablo
Published: September 2013

Allopurinol is an inhibitor of xanthine oxidase. The aim of this work was to evaluate the efficacy of allopurinol to reverse the experimental cirrhosis induced by CCl4. Rats received CCl4 for 8 weeks, and immediately after allopurinol was administered for 4 weeks more. Allopurinol reversed all markers of liver damage and oxidative stress to normal values, restoring the metabolic capacity of the liver. Chronic injury by CCl4 induced significant overexpression of profibrogenic cytokine TGF-ß, while allopurinol decreased this production and consequently decreased the collagen content. Moreover, allopurinol is capable of partially inhibiting NF-κB. These findings suggest that allopurinol is capable of reversing the cirrhosis induced by CCl4, modulating oxidative stress, TGF-ß expression and NF-κB nuclear translocation.
Does Neutrophil Gelatinase-Asociated Lipocalin Have Prognostic Value in Patients with Stable Angina Undergoing Elective PCI? A 3-Year Follow-Up Study
Authors: Bachorzewska-Gajewska Hanna , Tomaszuk-Kazberuk Anna , Jarocka Iwona , Mlodawska Elzbieta , Lopatowska Paulina , Zalewska-Adamiec Malgorzata , Dobrzycki Slawomir , Musial Wlodzimierz J. , Malyszko Jolanta
Published: September 2013

Background: Neutrophil gelatinase-associated lipocalin (NGAL), a widely accepted diagnostic marker of acute renal injury (AKI) may be involved in the development of atherosclerosis. Purpose: To assess the prognostic significance of serum and urinary NGAL and serum cystatin C in patients with stable angina undergoing percutaneous coronary intervention (PCI) on a 3-year follow-up. Methods: We included patients with stable angina undergoing PCI. Serum NGAL and cystatin C were evaluated before and 4h, 8h after PCI. Urinary NGAL was evaluated before and 12h and 24h after the procedure. The primary end-point was all-cause mortality on a 3-year follow-up. Results: Among 132 patients there were 63% of males (mean age 64,5±9,8 years). Mean eGFR was 86.2±28.5 ml/min. During follow-up 8% of the patients died. All-cause mortality was significantly higher in patients with increased urinary NGAL concentration 12h after PCI (p=0.04). Urinary NGAL 12h after PCI correlated with eGFR (p<0.05), with serum NGAL evaluated before and 4h and 8h after PCI (p<0.05) and with increased serum cystatin C evaluated 4 hours after PCI (p<0.05). Conclusions: Increased urinary NGAL concentration is a strong predictor of mortality in patients with stable angina who undergo PCI and may be used for the risk stratification in this population.
The Anticipatory Proportion as an Indicator of Language Impairment in Early-Stage Cognitive Disorder in the Elderly
Authors: Wutzler Alexander , Becker Regine , Lämmler Gernot , Haverkamp Wilhelm , Steinhagen-Thiessen Elisabeth
Published: September 2013

Background: The anticipatory proportion (AP), the ratio between perseverative and anticipatory speech errors, is reduced in patients with brain injury. However, it is unknown whether the AP is also reduced in elderly speakers with cognitive impairment. Methods: 20 elderly speakers with a Mini Mental State Examination (MMSE) score of 25-27 and 20 elderly speakers with an MMSE score of 28-30 were assessed using a tongue-twister-based speech test, the Regensburg Word Fluency Test (RWT) and an object naming test. Results: The AP in the group of speakers with an MMSE score of 25-27 was significantly lower. Accordingly, the AP and scores in the RWT and the object naming test were higher in persons with an MMSE score of 28-30. Conclusion: Language alterations in mild cognitive dysfunction are detectable with the AP. Further longitudinal studies are needed to evaluate the predictive value of the AP.
Human Papillomavirus 16/18 Infections in Lung Cancer Patients in Mexico
Authors: Badillo-Almaraz Isaías , Zapata-Benavides Pablo , Saavedra-Alonso Santiago , Zamora-Avila Diana , Reséndez-Pérez Diana , Tamez-Guerra Reyes , Herrera-Esparza Rafael , Rodríguez-Padilla Cristina
Published: September 2013

Background/Aims: Human papillomavirus (HPV) is an epitheliotropic, double-stranded DNA virus, and its high-risk genotypes are associated with human cancer. HPV genome has been detected in lung carcinomas in certain places around the world, including Mexico; however, the prevalence of this is unclear. In this study, we examine the frequency of high-risk HPV 16/18 in lung cancer tissues from a Mexican population. Methods: 39 lung cancer specimens were analyzed by polymerase chain reaction (PCR) using HPV GP5+/GP6+ primers and then were genotyped using specific primers to HPV 16/18. Additionally, in situ hybridization (ISH) was performed using BIO-labeled oligonucleotide probes. Results: Our results identified 15 positive cases (38.46%) for HPV 16 and 1 positive case (2.56%) for HPV 18 by PCR. ISH showed the presence of HPV DNA in 13 of 16 (81%) samples, in agreement with the PCR results. Conclusions: In this study, we detected HPV 16/18 gene sequences in lung cancer samples obtained from Mexican patients by PCR and ISH. We found the highest prevalence of HPV 16 infection in lung adenocarcinomas, suggesting that HPV infection may be associated with lung cancer. However, further studies are needed to elucidate the role of HPV in lung carcinogenesis.
Architectural Organization of the African Elephant Diencephalon and Brainstem
Authors: Maseko Busisiwe C. , Patzke Nina , Fuxe Kjell , Manger Paul R.
Published: September 2013

The current study examined the organization of the diencephalon and brainstem of the African elephant (Loxodonta africana) - a region of the elephant brain that has not been examined for at least 50 years. The current description, employing material amenable for use with modern neuroanatomical methods, shows that, for the most part, the elephant diencephalon and brainstem are what could be considered typically mammalian, with subtle differences in proportions and topology. The variations from these previous descriptions, where they occurred, were related to four specific aspects of neural information processing: (1) the motor systems, (2) the auditory and vocalization systems, (3) the orexinergic satiety/wakefulness centre of the hypothalamus and the locus coeruleus, and (4) the potential neurogenic lining of the brainstem. For the motor systems, three specific structures exhibited interesting differences in organization - the pars compacta of the substantia nigra, the facial motor nerve nucleus, and the inferior olivary nuclear complex, all related to the timing and learning of movements and likely related to the control of the trunk. The dopaminergic neurons of the substantia nigra appear to form distinct islands separated from each other by large fibre pathways, an appearance unique to the elephant. Each island may send topologically organized projections to the striatum forming a dopaminergic innervation mosaic that may relate to trunk movements. At least five regions of the combined vocalization production and auditory/seismic reception system were specialized, including the large and distinct nucleus ellipticus of the periaqueductal grey matter, the enlarged lateral superior olivary nucleus, the novel transverse infrageniculate nucleus of the dorsal thalamus, the enlarged dorsal column nuclei and the ventral posterior inferior nucleus of the dorsal thalamus. These specializations, related to production and reception of infrasound, allow the proposal of a novel concept regarding the reception and localization of infrasonic sources. The orexinergic system of the hypothalamus displayed a medial hypothalamic parvocellular cluster of neurons in addition to the magnocellular clusters typical of mammals located in the lateral hypothalamus, and a novel medial division of the locus coeruleus was observed in the pons. These systems are related to appetitive drive and promotion of wakefulness, two aspects of elephant behaviour that appear to be inextricably linked. Lastly, we observed an extensive potential neurogenic lining of the ventricles throughout the brainstem that is present in even quite old elephants, although the function of these cells remains elusive. These observations combined demonstrate that, while much of the elephant brainstem is typically mammalian, certain aspects of the anatomy related to specialized behaviour of elephants are present and instructive in understanding elephant behaviour.
The Mucosal Factors Retinoic Acid and TGF-β1 Induce Phenotypically and Functionally Distinct Dendritic Cell Types
Authors: den Hartog Gerco , van Altena Christine , Savelkoul Huub F.J. , van Neerven R.J. Joost
Published: September 2013

Non-inflammatory dendritic cell (DC) subsets play an essential role in preventing massive inflammation in mucosal tissues. We investigated whether mucosa-related factors, namely retinoic acid (RA) and transforming growth factor-β (TGF-β1), can induce such DC types. DCs were differentiated from monocytes in the absence or presence TGF-β1 and RA. The phenotype as well as responsiveness to bacterial ligands was studied in detail. Compared to monocyte-derived DCs (moDCs), the expression of co-stimulatory molecule CD86 and DC maturation marker CD83 were strongly reduced by RA and TGF-β1. In addition, both RA- and TGF-β1-induced DCs showed strongly decreased responsiveness to stimulation with the bacterial ligands lipopolysaccharide and peptidoglycan, and produced significantly lower levels of the pro-inflammatory cytokines IL-12 and TNF-α compared to moDCs, whilst IL-10 production was not significantly reduced. DCs differentiated under the influence of RA uniquely expressed markers related to intestinal homing (CD103 and integrin β7). In addition, CCR7, which mediates homing to lymph nodes, was expressed by DCs differentiated in the presence of RA, and also to a lesser extent by the other DC types. Furthermore, whereas moDCs and TGF-β1-derived moDCs expressed high levels of CD32, RA-derived DCs lacked CD32 expression but expressed high levels of CD64, suggesting that RA-DCs may primarily respond to soluble proteins and moDCs, and TGF-β DCs to immune complexes. The data presented here support the hypothesis that the mucosal factors TGF-β1 and RA, which can also be provided through dietary intake of dairy products, result in functionally and phenotypically distinct DC types with non-inflammatory properties.
Human Leukocyte Antigen-G and Regulatory T Cells during Specific Immunotherapy for Pollen Allergy
Authors: Sørensen Anja E. , Johnsen Claus R. , Dalgaard Louise T. , Würtzen Peter Adler , Kristensen Bjarne , Larsen Margit Hørup , Ullum Henrik , Søes-Petersen Ulrik , Hviid Thomas Vauvert F.
Published: September 2013

Background: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4). Methods: Eleven birch and/or grass pollen-allergic patients and 10 healthy nonatopic controls were studied before and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like transcript (ILT) 2, specific IgE, and IgG4 were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with pollen extract in vitro and immune factors were evaluated. Results: During SIT, the main changes in the peripheral blood were an increase in CXCR3+CD4+CD25+CD127low/- Tregs and a decrease in CCR4+CD4+CD25+CD127low/- Tregs, an increase in allergen-specific IgG4, and a decrease in sHLA-G during the first half of the treatment period. In the PBMC in vitro experiments, the following changes were observed upon allergen-stimulation: an increase in CD4+CD25+CD127low/- Tregs and ILT2+CD4+CD25+CD127low/- Tregs, an increase in IL-10 and IL-2 levels, and an increase in sHLA-G that was most pronounced at the start of SIT. Conclusions: The changes in CXCR3+CD4+CD25+CD127low/- Treg, IgG4, and sHLA-G levels in the peripheral blood and in ILT2+ Treg, IL-10, IL-2, and sHLA-G levels upon in vitro allergen stimulation suggest an upregulation in immunomodulatory factors and, to some degree, a shift towards TH1 during SIT.
Patterns of Sensitization to Inhalant and Food Allergens - Findings from the German Health Interview and Examination Survey for Children and Adolescents
Authors: Schmitz Roma , Ellert Ute , Kalcklösch Margrit , Dahm Stefan , Thamm Michael
Published: September 2013

Background: To assess the prevalence of allergic sensitization and to analyze patterns of sensitization to common inhalant and food allergens in a nationwide representative sample of children and adolescents in Germany. Methods: Data were collected from 2003 to 2006 within the KiGGS, the national Health Interview and Examination Survey covering a representative sample of 17,641 children and adolescents in Germany. Immunoglobulin E (IgE) antibodies to 20 specific allergens (11 inhalant and 9 food allergens) were quantitatively measured in a subsample of 12,988 KiGGS participants aged 3-17 years using the ImmunoCAP system. Serum concentrations ≥0.35 kU/l indicate sensitized participants. An exploratory factor analysis was performed in order to identify sensitization patterns. Results: Sensitization to at least 1 of the 20 tested allergens was detected in 40.2% [95% confidence interval (CI) 39.0-41.4] of the participants. The highest sensitization prevalences were found for pollen from Timothy grass (22.7%; 21.5-23.9) and rye (21.2%; 20.0-22.4). Sensitization was more prevalent in boys than in girls and prevalence increased generally with increasing age. We identified seven sensitization groups, namely (in descending order of magnitude) ‘Timothy grass/rye', ‘house-dust mites', ‘food/mugwort', ‘birch/apple', ‘animals', ‘cow's milk/egg white' and ‘moulds'. Conclusions: Allergic sensitization is common in German children and adolescents. The fact that sensitization potentially leads to clinically relevant allergic diseases stresses the public health relevance of this topic. Whether the grouping reflects the propensity for persons to be sensitized to multiple allergens within a group, or whether it is due to IgE cross-reactivity between different allergens of similar structure is still being discussed.
Effect of Proinflammatory Gene Polymorphisms on the Risk of Alzheimer's Disease
Authors: Flex Andrea , Giovannini Silvia , Biscetti Federico , Liperoti Rosa , Spalletta Gianfranco , Straface Giuseppe , Landi Francesco , Angelini Flavia , Caltagirone Carlo , Ghirlanda Giovanni , Bernabei Roberto
Published: September 2013

Background: A number of studies associate Alzheimer's disease (AD) with APOE polymorphism and alleles which favor the increased expression of immunological mediators such as cytokines or acute-phase proteins. Objective: In this study we evaluated the distribution of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in individuals with AD. We also investigated whether a synergistic effect of these proinflammatory gene polymorphisms on the risk of AD could be hypothesized. Methods: In a genetic association study that included 533 AD patients and 713 controls, the following gene polymorphisms were analyzed: C-reactive protein (CRP) 1059 G/C, interleukin 6 (IL6) -174 G/C, interleukin 1β (IL1B) -31 T/C, tumor necrosis factor α (TNF-α) -308 G/A, macrophage migration inhibitory factor (MIF) -173 G/C, monocyte chemoattractant protein 1 (CCL2) -2518 A/G, intercellular adhesion molecule 1 (ICAM1) 469 E/K, E-selectin (SELE) Ser128Arg, macrophage inflammatory protein 1α (CCL3) -906 T/A, matrix metalloproteinase 3 (MMP3) -1171 5A/6A and matrix metalloproteinase 9 (MMP9) -1562 C/T. Results: We found that IL6, IL1B, CCL2, CCL3, SELE, ICAM1, MMP3, and MMP9 gene polymorphisms were significantly and independently associated with AD. The association remained significant even after the Bonferroni correction. We also found that these proinflammatory polymorphisms were associated with different levels of risk for AD, depending on the number of high-risk genotypes concomitantly carried by a given individual. Conclusion: Proinflammatory genotypes might influence the development and progression of AD exerting a potential synergistic effect.
Engineering Bone Grafts with Enhanced Bone Marrow and Native Scaffolds
Authors: Hung Ben P. , Salter Erin K. , Temple Josh , Mundinger Gerhard S. , Brown Emile N. , Brazio Philip , Rodriguez Eduardo D. , Grayson Warren L.
Published: September 2013

The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds.
Preterm Infants Have Altered Adiponectin Levels at Term-Equivalent Age Even if They Do Not Present with Extrauterine Growth Restriction
Authors: Nakano Yuya , Itabashi Kazuo , Sakurai Motoichiro , Aizawa Madoka , Dobashi Kazushige , Mizuno Katsumi
Published: September 2013

Background/Aims: This study aimed to investigate total adiponectin (T-Ad) and high-molecular-weight adiponectin (HMW-Ad) levels in preterm infants at term-equivalent age and to assess the relationship between adiponectin levels and early postnatal growth. Methods: The study included 43 term infants and 58 preterm infants born at 34 weeks' gestation or less. T-Ad and HMW-Ad levels were measured in the preterm infants at birth and at term-equivalent age, and in the term infants at birth. Adiponectin levels were statistically compared between preterm and term infants to evaluate the association between postnatal growth and changes in the adiponectin levels in preterm infants. Results: The T-Ad levels were higher and the ratio of HMW-Ad to T-Ad (HMW%) was lower in preterm infants at term-equivalent age than in term infants. Further, body weight SD score changes were positively associated with T-Ad and HMW-Ad increases in preterm infants from birth to term-equivalent age. The HMW% changes had a negative association only with HMW% in cord blood. Conclusion: Preterm infants have altered adiponectin levels at term-equivalent age. Further, postnatal growth may contribute to adiponectin increases from birth to term-equivalent age, although HMW% changes might be regulated before birth at least up to term-equivalent age in preterm infants.
Prompt Analgesic Effect of Antihistaminic Diphenhydramine Ointment on Bone-Joint-Muscle Pain as Assessed by Skin Impedance
Authors: Fujita Takuo , Ohue Mutsumi , Fujii Yoshio , Jotoku Tsuyoshi , Miyauchi Akimitsu , Takagi Yasuyuki , Tsuchiya Masahiro , Endo Yasuo
Published: September 2013

Pain is sensed, transmitted, and modified via a variety of mediators and their receptors. Histamine is a well-known mediator of pain. In addition to their antagonistic effects against histamine, classical antihistaminics possess, to various degrees, antimuscarinergic, antiserotonergic, antiadrenergic, local anesthetic, membrane-stabilizing and other pharmacologic actions. Although there have been many attempts to use classical antihistaminics as analgesics and/or analgesic adjuvants, the appearance of non-steroidal anti-inflammatory drugs discouraged such efforts. Here, we compared the analgesic effect of an ointment containing 1% diphenhydramine (a typical first-generation antihistaminic drug) with that of indomethacin (a typical non-steroidal anti-inflammatory drug) in elderly patients with osteoarthritis and/or osteoporosis who complained of bone-joint-muscle pain. Analgesic effects were evaluated by measuring skin impedance and by subjective pain assessments (using a visual recording system) before and after ointment application. Diphenhydramine ointment exerted a prompt and marked analgesic effect that lasted for several hours, as assessed by either skin impedance or subjective pain evaluation. In contrast, the analgesic effect of indomethacin ointment was marginal, and significant only an hour or more later than that of diphenhydramine. These results suggest that diphenhydramine ointment may be useful for the relief of the bone-joint-muscle pains that are common in elderly subjects.
Body Mass Index or Waist Circumference: Which Is the Better Predictor for Hypertension and Dyslipidemia in Overweight/Obese Children and Adolescents? Association of Cardiovascular Risk Related to Body Mass Index or Waist Circumference
Authors: Gröber-Grätz Dagmar , Widhalm Kurt , de Zwaan Martina , Reinehr Thomas , Blüher Susann , Schwab Karl Otfried , Wiegand Susanna , Holl Reinhard W. ,   on behalf of the APV Study Group and the German BMBF Competence Network Obesity
Published: September 2013

Background: In order to assess the relationship between hypertension or dyslipidemia and obesity, the body mass index (BMI) is usually used. Unlike waist circumference (WC), BMI does not reflect body fat distribution. The aim of this study is to investigate whether BMI or WC is a better predictor of hypertension or dyslipidemia in overweight/obese children and adolescents. Methods: As of November 2012, the APV database contained data on 81,819 patients from 189 specialized pediatric obesity institutions in Germany, Austria and Switzerland. Logistic regression analysis was conducted using odds ratios (OR) with 95% CI. Results: The average age of the youths (n = 5.978) was 13.9 ± 1.8 years. Mean BMI-SDS was 2.0 ± 0.5, and mean WC-SDS was 2.2 ± 0.5. Both BMI-SDS and WC-SDS are significant predictors of hypertension and dyslipidemia: BMI-SDS is a better predictor (OR = 2.60) for hypertension than WC-SDS (OR = 1.85), while WC-SDS (OR = 1.90) was slightly superior to BMI-SDS (OR = 1.86) in predicting adverse lipid profiles. Compared to normal-weight patients, obese patients (BMI ≥97th percentile) exhibited increased systolic (+6.3 mm Hg) and diastolic blood pressure (+3.9 mm Hg). However, this difference was only +4.8 mm Hg (systolic) and +2.6 mm Hg (diastolic) if WC >97th percentile was used. Conclusion: BMI-SDS is more closely associated with hypertension, while WC-SDS is more closely associated with dyslipidemia. However, the additional measurement of WC has only a small benefit in obese youths.
Neuroinflammatory Phenotypes and Their Roles in Alzheimer's Disease
Authors: Wilcock Donna M.
Published: September 2013

Background: Alzheimer's disease (AD) is characterized pathologically by the presence of amyloid plaques and neurofibrillary tangles in the brain. While once considered immunologically privileged due to the blood-brain barrier, it is now understood that the glial cells of the brain are capable of complex inflammatory responses. Objective: The goal of the study is to assess the neuroinflammatory state of the early and late AD brain using the macrophage categorizations of M1, M2a, M2b and M2c. Methods: We used quantitative real-time RT-PCR to assess a number of inflammatory markers in the frontal cortex and cerebellar tissue from early and late AD patients. We then used neuropathological and clinical outcomes to determine whether there were any correlations. Results: We found that the AD brain is capable of generating all macrophage-like responses. In addition, we found that early AD is distinct from late AD with respect to the inflammatory profiles expressed in the brain. Most interestingly, however, we found that the early AD samples were biased to one of two phenotypes, M1 or M2a. Conclusion: Heterogeneity in the neuroinflammatory state of the early AD brain may represent a source of variability among the AD population. It may also reflect the presence of comorbidities.
Adult Colocolic Intussusception and Literature Review
Authors: Wilson Abralena , Elias George , Dupiton Rulx
Published: September 2013

Intussusception occurs when a proximal segment of the gastrointestinal tract, called intussusceptum, telescopes into the lumen of an adjacent segment, also known as intussuscipiens. Although common in early childhood, intussusceptions are very rare in the adult population. Most intussusceptions in adults are due to a lead point, which is an identifiable pathological abnormality, in opposition to children which there are no identifiable pathological lead points. In contrast to childhood intussusception, in adults it is associated with malignant lesions, particularly in the large bowel rather than in the small bowel. Its preoperative diagnosis and treatment in adults is difficult because of nonspecific abdominal symptom and because it rarely presents with the classic triad of vomiting, abdominal pain and passage of blood per rectum. We present a 63-year-old female with an adenocarcinoma tumor being the lead point in a colocolic intussusception, who was diagnosed preoperatively with computed tomography and had a colonoscopy to rule out obstruction. She underwent right hemicolectomy with side-to-side ileocolic anastomosis and did well postoperatively. In addition, we also review the literature and discuss the value of radiological modalities, location and surgical management to try to improve the preoperative diagnosis. Computed tomography scanning with intravenous contrast is maybe the most accurate modality for diagnosis of intussusceptions in adults, and treatment is usually surgical resection without reduction, since most of the colonic lesions are malignant.
Biliary Cast Syndrome in an Opium Inhaler
Authors: Dabiri Reza , Asadzadeh Aghdae Hamid , Rajabalinia Hasan , Mohammad Alizadeh Amir Houshang
Published: September 2013

Biliary cast syndrome (BCS) is an uncommon complication which is mostly described in orthotopic liver transplantation. However, BCS has also been reported rarely in non-liver transplant patients. We describe a male long-term opium inhaler with BCS who underwent successful endoscopic cast removal by balloon enteroscopy-guided endoscopic retrograde cholangiopancreatography. A 52-year-old man, who was a known case of opium addiction, presented with the chief complaint of epigastric pain for 1 week prior to admission. Routine laboratory evaluation revealed cholestatic liver enzyme elevation. A cholestatic pattern was seen in radiographic modalities. Endoscopic retrograde cholangiopancreatography showed a linear filling defect in the intra- and extrahepatic duct. A long biliary cast was successfully removed using an extractor balloon. After removal of the biliary cast the patient is receiving ursodeoxycholic acid and does not report any problem 4 months after treatment. It seems that biliary dyskinesia due to long-term opium use can be a predisposing factor for biliary cast formation.
Acquired haemophilia A: A 2013 update
Authors: Franchini Massimo , Mannucci Pier Mannuccio
Published: September 2013

Acquired haemophilia A (AHA) is a rare but often severe bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). AHA occurs more frequently in the elderly and in association with several conditions, such as the post-partum period, malignancies, autoimmune diseases or drug exposure; however, approximately 50% of reported cases are apparently idiopathic. Beside the elimination of the underlying disorder, the therapeutic approach to AHA should be directed toward the control of acute bleed and the eradication of FVIII autoantibody production. In this narrative review, we summarise the current knowledge on the epidemiology, diagnosis and clinical features of AHA, focusing in particular on advances in the management of this challenging bleeding disorder.
Pathophysiological role of cation transport and natriuretic factors in hypertension.
Authors: Haddy F J , Pamnani M B , Clough D L
Published: September 2013

This review considers in some detail the hypothetical relationships between sodium fluxes, both active and passive, across the cell membrane, and intracellular sodium concentration in vascular smooth muscle in the animal models of hypertension. It appears that two basic types of transport defects, increased cell membrane permeability to sodium and decreased active pumping of sodium at a given internal sodium concentration, can exist in vascular smooth muscle in experimental hypertension, and that sometimes the two defects coexist, further increasing internal sodium concentration. It is possible that eventually we may find similar transport defects in vascular smooth muscle in humans with arterial hypertension. Decreased active pumping at a given internal sodium concentration appears to result from a humoral sodium pump inhibitor. Future directions for research in the area are also considered. First priority should be given efforts to determine the chemical structure of the sodium pump inhibitor(s). High priority should also be given to attempts to measure passive and active sodium fluxes and intracellular sodium concentration in vascular smooth muscle cells in vivo, and to determine the role of atrial natriuretic factor in the genesis and maintenance of hypertension.
Kinetic aspects of red blood cell sodium transport systems in essential hypertension.
Authors: Garay R P
Published: September 2013

A kinetic study of the interaction of internal sodium with four different erythrocyte sodium transport pathways (ouabain-sensitive Na+-K+ pump, bumetanide-sensitive Na+-K+ cotransport system, Na+-Li+ countertransport, and Na+leak) has facilitated the distinction of the following subgroups of patients with essential hypertension: 1) Leak (+), exhibiting increased passive sodium permeability; 2) Co (-), showing low apparent affinity of the Na+-K+ cotransport system for internal sodium; 3) Counter (+), characterized by increased maximal rates of Na+-Li+ countertransport; and 4) Pump (-), characterized by an abnormally low apparent affinity of the Na+-K+ pump for internal sodium. We present here a new and simple sodium-loading method that allows a simultaneous kinetic study of the above abnormalities. The use of this kinetic assay may improve estimation of the frequencies, clinical features, and other properties of each subgroup of hypertensive patients in different populations.
Structure and physiological actions of rat atrial natriuretic factor.
Authors: Inagami T , Misono K S , Fukumi H , Maki M , Tanaka I , Takayanagi R , Imada T , Grammer R T , Naruse M , Naruse K
Published: September 2013

Natriuretic substances were purified from rat atrium (atrial natriuretic factor, ANF) and were shown to be identical with the inhibitor of norepinephrine-induced contraction of smooth muscle. Four native forms were isolated and their amino acid sequences were determined. The presence of a high-molecular-weight prohormone was shown. Complementary DNA (cDNA) encoding for the precursor was cloned and used to deduce the amino acid sequence of the prohormone. Genomic DNA for ANF was cloned and two introns were found. Several ANF peptides were synthesized. Structure-function studies showed that the ring structure was essential for the activity. Antibodies produced against the synthetic 25-amino acid residue ANF were used to develop a radioimmunoassay. The presence of ANF in rat plasma demonstrated that ANF is a circulating hormone. ANF was also found in the hypothalamus of rats. The ANF in plasma was found to be a low-molecular form, whereas that in atria and hypothalamus consisted of both the high-molecular-weight precursor and low-molecular-weight active ANF. The presence of messenger RNA for ANF was determined using ANF cDNA as a probe and was considered as evidence for ANF synthesis in the brain, atrium, and ventricles. ANF was shown to be released from the brain. ANF administered intracerebroventricularly was shown to inhibit angiotensin II and thirst-induced dipsogenesis. In vitro and in vivo experiments showed ANF inhibits release of vasopressin from posterior pituitary and renin from the kidneys. The hypotensive effect of ANF was examined at various doses.(ABSTRACT TRUNCATED AT 250 WORDS)
The heart as an endocrine gland.
Authors: Cantin M , Genest J
Published: September 2013

The sequence of atrial natriuretic factor (ANF) has been determined, as well as the complete structure of the rat and human complementary DNA and gene. ANF and ANF messenger RNA are present not only in atria but also in ventricles. The circulating form of ANF has been identified as the C-terminal of the molecule, ANF (Ser 99-Tyr 126). The isolated secretory granules of rat atrial cardiocytes contain only pro-ANF (Asn 1-Tyr 126). An enzyme (IRCM-SP1) has been isolated from heart atria and ventricles. This enzyme is highly specific in cleaving ANF (Asn 1-Tyr 126), to yield ANF (103-126), (102-126), and (99-126). In target cells, ANF produces a rise in cyclic guanosine 3',5'-monophosphate (cGMP) due to activation of particulate guanylate cyclase, and inhibition of adenylate cyclase leading in some cases to a decrease in cyclic adenosine 3',5'-monophosphate (cAMP). ANF produces relaxation of rabbit and rat aortic strips, inhibits steroidogenesis in both zona glomerulosa and zona fasciculata cells, and inhibits the release of arginine vasopressin from the isolated rat hypothalamohypophysial preparation in vitro but decreases AVP release in vivo only at pharmacological doses. In all forms of experimental hypertension, plasma levels of ANF are increased and, at some time periods, atrial levels are also decreased. The ventricular levels of immunoreactive ANF are also increased in renal hypertension. Infusion of ANF by minipumps decreases the blood pressure near control levels in several models of experimental hypertension. In cardiomyopathic hamsters with heart failure, the atrial levels of immunoreactive ANF are decreased while the plasma and ventricular levels are increased.(ABSTRACT TRUNCATED AT 250 WORDS)
An update on the physiology of atrial natriuretic factor.
Authors: Trippodo N C
Published: September 2013

The atrial natriuretic factor (ANF) has pharmacological actions resulting in lower atrial and arterial pressures. Atrial distention stimulates ANF release, suggesting that ANF is an effector limb of a feedback loop for controlling cardiac filling pressure. To test this hypothesis it will be necessary to determine whether physiological atrial distention releases ANF in sufficient amounts to exert biological actions. Immunoblockade of endogenous ANF and attenuation of ANF release by atrial ablation inhibited volume-induced natriuresis in rats. Infusion of ANF in rats at doses mimicking those observed during experimental volume expansion produced a natriuresis sufficient to partly account for the volume-induced response. Infusion of ANF at doses expected to change plasma ANF levels minimally decreased arterial pressure in hypertensive rats over 7 days. In dogs, some studies suggest that increased plasma ANF levels following experimental changes in atrial pressure were not sufficient to exert acute cardiovascular or renal actions, whereas others support such a notion and indicate that ANF inhibited barostimulated renal renin release. This last action could alter arterial pressure in the long term by allowing sodium equilibrium at lower renal arterial pressure. Infusion of ANF in humans that produced plasma levels in the upper physiological range caused increased sodium excretion and decreased plasma renin activity. Although data are exiguous, justifying neither acceptance nor rejection of the hypothesis that ANF functions physiologically to regulate body fluid volume and arterial pressure, the current evidence slightly favors acceptance.
Effect of atrial natriuretic factor on Na+-K+-Cl- cotransport of vascular smooth muscle cells.
Authors: Owen N E , Bush E N , Holleman W , O'Donnell M E
Published: September 2013

We previously demonstrated that vascular smooth muscle cells possess a prominent Na+-K+-Cl- cotransport system that can be markedly stimulated by elevations in levels of intracellular cyclic guanosine 3',5'-monophosphate (cGMP). Since others have shown that atrial natriuretic factor (ANF) can bind to specific membrane receptors and can enhance cGMP levels in vascular smooth muscle cells, we asked whether ANF could also stimulate Na+-K+-Cl- cotransport in vascular smooth muscle cells. It was discovered that rat atriopeptin III stimulated Na+-K+-Cl- cotransport of vascular smooth muscle cells in a concentration-dependent manner. In contrast, rat atriopeptin III had no effect on two other sodium transport systems known to be present in vascular smooth muscle cells (i.e., Na+-H+ exchange and Na+-K+-adenosine triphosphatase (ATPase). These studies indicated that ANF selectively stimulates Na+-K+-Cl- cotransport of vascular smooth muscle cells. We then asked whether ANF-stimulated Na+-K+-Cl- cotransport was dependent upon the ability of ANF to enhance intracellular cGMP levels. When rat atriopeptin III-stimulated increases in cGMP were inhibited with the quinolinedione LY 83583, rat atriopeptin III could no longer stimulate Na+-K+-Cl- cotransport of vascular smooth muscle cells. Thus it appeared that the effects of ANF were dependent upon the ability of ANF to elevate intracellular cGMP levels. Finally, we asked whether ANF effects on Na+-K+-Cl- cotransport were related to the biological activity of ANF.(ABSTRACT TRUNCATED AT 250 WORDS)
The squid axon as a model for studying plasma membrane mechanisms for calcium regulation.
Authors: DiPolo R , Beaugé L
Published: September 2013

Calcium movement across plasma membranes occurs mainly by three routes: voltage-dependent calcium channels, adenosine 5'-triphosphate-driven calcium pump, and Na+-Ca2 exchange. The regulation of the intracellular ionized calcium is the consequence of two parallel calcium transport mechanisms: a high affinity, low capacity system responsible for extruding calcium during resting conditions (calcium pump) and a low affinity and high capacity system (Na+-Ca2 antiporter). This last system is designed to extrude calcium ions when intracellular calcium rises above certain levels and also to lead calcium ions into the cell under conditions that favor the reverse mode of operation of the exchanger. This short review provides an analysis of the most conspicuous features of the two membrane transport mechanisms determined in dialyzed squid axons with special emphasis on both the complexity of the Na+-Ca2+ exchange system and its marked asymmetry.