bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-Life Management of Venous Thromboembolism With Rivaroxaban: Results From EXperience VTE, an Italian Epidemiological Survey
Authors: Imberti Davide , Barillari Giovanni ,   for the eXperience VTE Italian Group
Published: July 2017

Two large randomized controlled trials examined the efficacy and safety of rivaroxaban for the treatment of venous thromboembolism (VTE). The aim of this epidemiological study was to analyze a cohort of Italian patients affected by VTE who were treated with rivaroxaban in clinical practice. The data were collected by physicians using an online electronic questionnaire. The study was performed during a 6-month period from January to June 2014. We analyzed the clinical characteristics, risk factors for VTE, comorbidities, diagnostic techniques, and treatments in the whole population and in the subgroups with deep vein thrombosis (DVT) only, pulmonary embolism (PE) only, and DVT+PE. Overall, 75.9% of patients were affected by DVT; 20% of patients had DVT and PE; and 4.8% of patients had only PE. Approximately 90% of patients were symptomatic upon diagnosis, and 46.3% of patients required hospitalization. More than half of the patients switched to rivaroxaban after receiving another anticoagulant therapy. The main reasons for changing treatment included difficulties in managing vitamin K antagonists, patient choice, and prothrombin time-international normalized ratio (PT-INR) instability. The switch to rivaroxaban occurred after a mean of 1.8 PT-INR measurements. Clinical characteristic were overall similar to those of patients enrolled in prior clinical trials evaluating the safety and efficacy of rivaroxaban.
Low Molecular Weight Heparins: Differences and Similarities in Approved Preparations in the United States
Authors: Bick Rodger L. , Fareed Jawed
Published: July 2017

There is adequate preclinical data to support the differential biochemical and pharmacological behavior of the currently approved low molecular weight heparins (LMWHs) in the United States. Initial studies on the anti-Xa, anti-IIa, and U.S. Pharmacopoeial (USP) potencies have clearly demonstrated differences among these products. Furthermore, the ratios between the anti-X and anti-IIa activities vary from one product to another. THis is primarily due to the composition of each product manufactured by using different patented methods. Studies in pharmacologic animal models, using gravimetric dosages or adjusted anti-Xa dosages of the LMWHs, produce product-specific results. The pharmacokinetics and pharmacodynamics of each product also vary markedly and are not predictable on the basis of any pharmacopoeial potency designation. These agents are capable of releasing tissue factor pathway inhibitor (TFPI), an inhibitor of the coagulation process. Its release is also dependent on the type of LMWH. In the United States enoxaprin, dalteparin, and ardeparin have been approved for DVT prophylaxis. Only enoxaparin and dalteparin have been approved for the acute coronary syndrome. Recently the clinical differentiation among these LMWHs has been demonstrated in the treatment of acute coronary syndrome. Similarly, when these drugs are used at high dosages, they are expected to produce product-specific pharmacodynamic effects. It must be noted that while these drugs may be interchangeable at clinically optimized/approved dosages, these drugs are not interchangeable at equivalent anti-Xa dosages. Even at optimized dosages, the clinical provile of each drug may be different. Thus, each of the LMWHs should be considered a distinct entity and their use in a given clinical situation should be validated in proper clinical trials.
Approximation of a simply supported plate with obstacle
Authors: Murea Cornel M , Tiba Dan
Published: July 2017

We discuss an algorithm for the solution of variational inequalities associated with simply supported plates in contact with a rigid obstacle. Our approach has a fixed domain character, uses just linear equations and approximates both the solution and the corresponding coincidence set. Numerical examples are also provided.
Hemivariational inequalities modeling electro-elastic unilateral frictional contact problem
Authors: Gamorski Piotr , Migórski Stanisław
Published: July 2017

We study a class of abstract hemivariational inequalities in a reflexive Banach space. For this class, using the theory of multivalued pseudomonotone mappings and a fixed-point argument, we provide a result on the existence and uniqueness of the solution. Next, we investigate a static frictional contact problem with unilateral constraints between a piezoelastic body and a conductive foundation. The contact, friction and electrical conductivity condition on the contact surface are described with the Clarke generalized subgradient multivalued boundary relations. We derive the variational formulation of the contact problem which is a coupled system of two hemivariational inequalities. Finally, for such system we apply our abstract result and prove its unique weak solvability.
A Multiyear Assessment of Public Response to a Statewide Drug Take-Back and Disposal Campaign, 2010 to 2012
Authors: Yanovitzky Itzhak
Published: July 2017

This study is the first to analyze public response to a drug take-back program, the American Medicine Chest Challenge, in a single state over a period of 3 years (2010-2012). The study utilized a three-wave repeated cross-sectional design and an annual phone survey conducted with a representative sample of adults ( N = 906 in 2010, N = 907 in 2011, and N = 906 in 2012), which assessed exposure to the campaign, drug disposal behaviors, possible mediators of campaign effects (risk appraisal, personal agency, normative influence, and interpersonal talk), and potential confounders. Logistic regression and causal mediation analysis were employed to estimate confounder-adjusted direct and mediated effects of the campaign. Results showed that the campaign reached a sizable portion (50% to 60%) of state adults and that campaign exposure was associated with increased likelihood of having conversations with others about this topic. About 55% of all adults in the state reported taking at least one of the actions recommended by the campaign, and campaign exposure was associated with increased likelihood of disposing of prescription drugs at a drug collection day event (adjusted odds ratio = 4) and of talking to a child about the risks associated with prescription drug abuse (adjusted odds ratio = 2). The causal mediation analysis demonstrated that the campaign influenced audiences by reinforcing their efficacy to safely dispose of prescription drugs, but also potentially by stimulating conversations among community members about this topic. Drug take-back campaigns can be an effective mechanism to decrease the availability of prescription drugs in communities.
Monozygotic Twins Discordant for Trisomy 13
Authors: McFadden Patrick , Smithson Sarah , Massaro Robert , Huang Jialing , Prado Gail T , Shertz Wendy
Published: July 2017

Monozygotic twins with discordant karyotypes for trisomy 13 are rare. We report a case of a spontaneously conceived pregnancy who presented with first-trimester ultrasound finding of umbilical cord cyst and increased nuchal translucency in Twin A and no abnormalities in Twin B. Amniocentesis revealed 47,XY,+13 karyotype in Twin A and 46,XY karyotype in Twin B. Selective fetal reduction was performed for Twin A. Twin B was delivered at 32 weeks gestation with normal phenotype. Peripheral blood karyotype revealed 15% mosaicism for trisomy 13 and skin fibroblast revealed 46,XY karyotype. The surviving twin will be monitored for potential complication of uniparental disomy 13 and mosaic trisomy 13. This case reinforces the need for early ultrasound and nuchal translucency measurements, especially in twin gestations.
How to research cross-media practices? Investigating media repertoires and media ensembles
Authors: Hasebrink Uwe , Hepp Andreas
Published: July 2017

In a time of deep mediatization, cross-media approaches to investigating media practices are becoming increasingly relevant. In this respect, we have to consider cross-media from at least two different perspectives. The first perspective considers the ‘individual’ whose cross-media use can be characterized as a particular ‘media repertoire’. The second refers to ‘social domains’ (collectivities and organizations) that can be analysed as communicative figurations characterized by a particular ‘media ensemble’. We propose to interlace both perspectives to help clarify the conceptual and empirical relationship between media use by individuals, on the one hand, and as part of the figuration of a social domain, on the other. From the perspective of the individual, media repertoires are composed of media-related communicative practices that individuals use to relate themselves to the figurations that they are involved in. From the perspective of these figurations, media ensembles are characterized by the media-related communicative practices of the actors involved in them. We argue that a methodological triangulation of media diaries, (group) interviews and sorting techniques is a productive way forward to qualitatively investigate both these perspectives.
The hipster’s dilemma: What is analogue or digital in the post-digital society?
Authors: Thorén Claes , Edenius Mats , Lundström Jenny Eriksson , Kitzmann Andreas
Published: July 2017

This article sets out to explore the phenomenon of willing digital disconnect by reconsidering and reworking some of the central ideas that currently fall under the umbrella of technological non-use. The presupposition of binary divisions between the dichotomies ‘users’–‘non-users’ and ‘analogue’–‘digital’ is put into question as the article explores the taking up of predigital technologies and the explicit and implicit disengagement from contemporary digital technologies. In short, this article asks: What does the contemporary revival of analogue technologies reveal about the social and material processes that constitute ‘use’, and what are the implications for the conceptual division of the terms analogue and digital? To answer these questions, the article draws on assemblage theory to describe the material and expressive performativity of social structure – that is, how individuals interact with technology. Empirical evidence comes from three illustrative cases where predigital technologies have replaced an existing digital alternative. Results emphasize the importance of understanding the material and expressive reconfigurations that underline technological use in a post-digital society in order to move beyond binary concepts such as analogue/digital or use/non-use as well as concepts such as the digital divide.
Intercultural citizenship through participation in an international service-learning program: A case study from Taiwan
Authors: Wu Chiu-Hui
Published: July 2017

Byram’s (2008) intercultural citizenship framework includes the following orientations: cognitive, evaluative, comparative, action, and communicative. Using this framework as a theoretical basis, this study explored the international service-learning (ISL) experiences of four Taiwanese non-native English speakers (NNES) during a two-week trip to a poor community in the Philippines. Data collected from these students’ individual reflections, interviews, and public presentations illustrate their acquisition of the knowledge, skills and attitudes of intercultural citizenship. This study thus demonstrates that ISL allowed students to engage beneficially for themselves and their hosts with other NNES, instead of following the tradition of study abroad in countries where English is spoken natively.
Innovative techniques for the repairing of cored axially loaded reinforced concrete specimens
Authors: Abd Elaty Metwally A , Taman Mohamed H , Kharoob Omnia F
Published: July 2017

Drilling and testing core specimens are considered the most common examinations for the reinforced concrete elements. This study brings out new techniques through which the original load-carrying capacity for the cored axially loaded specimens can be restored completely. These techniques consider reshaping the geometry of the circular opening of specimens before repairing to a square or to a rotated square. Moreover, different repairing materials with different compressive and bond strengths to the repaired surface, namely epoxy, grout, and ordinary Portland cement mortars, have been applied. A total of 15 investigated parameters, divided into five groups, in addition to the control specimen were investigated. The results revealed that reshaping the circular opening to a squared one normal to the load application direction, and filling it with epoxy, can completely restore the original capacity of the axially loaded specimens. The finite element model was developed and validated by comparisons with the current experimental results.
Good work ability among unemployed individuals: Association of sociodemographic, work-related and well-being factors
Authors: Hult Marja , Pietilä Anna-Maija , Koponen Päivikki , Saaranen Terhi
Published: July 2017

Aims: The aims of this study were to describe the perceived work ability of unemployed individuals and to explore the association between perceived good work ability and sociodemographic, work-related and well-being factors. Methods: The data were derived from the Finnish Regional Health and Well-being Study (ATH) collected by postal and Internet-based questionnaires in 2014–2015. The random sample was selected from the Finnish National Population Register. The present study includes data from unemployed or laid-off respondents ( n=1975) aged 20–65 years. Logistic regression was used in the statistical analysis. Perceived work ability was measured with the Work Ability Score. Results: Factors significantly associated with good work ability were having young children living in the household, short-term unemployment, low or moderate physical strain in most recent job, moderate mental strain in most recent job, satisfaction with most recent job, good self-rated health and good quality of life. Good self-rated health (odds ratio=10.53, 95% confidence interval 5.90–18.80) was the most substantial factor in the multivariate model. Conclusions:The findings provide further evidence on the factors related to good work ability of the unemployed. These factors should be considered when designing interventions for promoting work ability and to minimise the harmful effects of long-term unemployment.
Morbidity and mortality meetings at Australian major trauma centres: A proof of concept study
Authors: Bear H , Mok MT , Farrow N , Curtis K , Mitra B , Fitzgerald M , Gruen RL
Published: July 2017

Background

Morbidity and mortality meetings are held at all Australian major trauma centres and provide a forum to identify problems and improve practices. Meetings should focus on addressing factors in the system to prevent similar errors occurring, rather than individual culpability. This paper describes current meeting practices and assesses the use of a systems approach.

Methods

This proof of concept study used a convenience sample of four Australian major trauma centres. Trauma leaders at each centre were surveyed regarding morbidity and mortality meeting practices. The use of a systems approach was measured by assessing practices against the London Protocol for Systems Analysis of Clinical Incidents. Meeting participants were also surveyed regarding perceptions of the objectives and effectiveness of meetings.

Results

This study found variable utilisation of a systems approach. Cases are not routinely analysed for contributing system factors and effective processes are not always used to correct problems that are identified. Meeting practices also vary between centres in terms of frequency, case selection criteria and use of audit filters. Participants generally view quality improvement as the most important objective of meetings.

Conclusion

Morbidity and mortality meeting practices vary between Australian major trauma centres and a systems approach has not been fully adopted.
Diesel engine performance mapping using a parametrized mixing time model
Authors: Pasternak Michal , Mauss Fabian , Klauer Christian , Matrisciano Andrea
Published: July 2017

A numerical platform is presented for diesel engine performance mapping. The platform employs a zero-dimensional stochastic reactor model for the simulation of engine in-cylinder processes. n-Heptane is used as diesel surrogate for the modeling of fuel oxidation and emission formation. The overall simulation process is carried out in an automated manner using a genetic algorithm. The probability density function formulation of the stochastic reactor model enables an insight into the locality of turbulence–chemistry interactions that characterize the combustion process in diesel engines. The interactions are accounted for by the modeling of representative mixing time. The mixing time is parametrized with known engine operating parameters such as load, speed and fuel injection strategy. The detailed chemistry consideration and mixing time parametrization enable the extrapolation of engine performance parameters beyond the operating points used for model training. The results show that the model responds correctly to the changes of engine control parameters such as fuel injection timing and exhaust gas recirculation rate. It is demonstrated that the method developed can be applied to the prediction of engine load–speed maps for exhaust NOx, indicated mean effective pressure and fuel consumption. The maps can be derived from the limited experimental data available for model calibration. Significant speedup of the simulations process can be achieved using tabulated chemistry. Overall, the method presented can be considered as a bridge between the experimental works and the development of mean value engine models for engine control applications.
Does socialism need fraternity? On Axel Honneth’s The Idea of Socialism
Authors: Piromalli Eleonora
Published: July 2017

In this article, after retracing the main lines of Honneth’s The Idea of Socialism, I address two objections to it. Firstly, I question the marked substantiality of Honneth’s proposed socialist ‘community of fraternal life’, resulting from the conjunction of the idea of social freedom with the principle of fraternity he derives from the proto-socialists. On the basis of my objections, I then delineate an original theoretical model, denominated ‘socialism through convergence’ (STC). While based on Honneth’s concept of social freedom, STC can abstract from the element of fraternity. It is, by consequence, immune to the excess of substantiality of Honneth’s perspective and potentially more attractive for the members of modern, pluralistic societies. Finally, I criticize Honneth’s perspective for under-determining the element of normative social conflicts in the sphere of democracy and normalizing their expression into the forms of an orderly democratic deliberation; consequently, I show how the STC perspective can more effectively account for social struggles and political conflicts.
Dubai’s Private School Fees Framework: A Critical Discussion
Authors: Azzam Ziad
Published: July 2017

90% of the Dubai’s K-12 educational provision is in the hands of the private sector, with the majority of schools operating on a for-profit basis. Demand for private schooling is unabated. In its attempt to strike a balance between consumer protection and continuing to attract private investment to address the shortage of school places, Dubai’s newly appointed regulator, the Knowledge and Human Development Authority (KHDA), introduced the School Fees Framework (SFF) in 2012. This article explores the circumstances that led to the framework’s creation, and attempts to document its development. It also analyses the SFF’s objectives, how these relate to KHDA’s strategic aspirations, and the extent to which the SFF’s objectives are indeed achievable. Through linking fee increases with school ratings, the KHDA had hoped to achieve one of its main goals: raising educational standards. Early evidence suggests that this approach has in fact caused a widening of the achievement gap between ‘rich’ and ‘poor’ schools in an industry that is already highly stratified by pricing.
Career Resilience: An Integrated Review of the Empirical Literature
Authors: Mishra Paresh , McDonald Kimberly
Published: July 2017

In this article, we review and synthesize the empirical literature on career resilience (CR) to develop a nomological network that describes the major components of the construct, and its relationships with other constructs. Specifically, we outline the antecedents and consequences of CR and describe their theoretical basis. We discuss the implications of the nomological network for future research on CR. Finally, we describe the practical implications of our model for individuals, managers, and organizations.
Differential Patterns of Cocaine-Induced Organ Toxicity in Murine Heart versus Liver
Authors: Wang Ju-Feng , Ren Xianglin , Deangelis Joseph , Min Jiangyong , Zhang Yufeng , Hampton Thomas G. , Amende Ivo , Morgan James P.
Published: July 2017

To determine cocaine's toxicity in different organs, BALB/c mice were intraperitoneally injected daily for 15 days with either saline or cocaine: 10 mg/kg, 30 mg/kg, or 60 mg/kg. Cardiac function, hepatic pathophysiology, heart and liver apoptosis, and tumor necrosis factor (TNF-α) levels were analyzed. After administration of cocaine, cardiac function decreased. Inflammatory cell infiltration and eosinophilic contraction bands were visible in the hearts of mice treated with 60mg/kg cocaine. Moreover, histopathology demonstrated that cocaine caused hepatic necrosis. TdT-mediated dUTP nick end-labeling (TUNEL) staining and DNA ladder analysis indicated that cocaine caused apoptosis in both the heart and liver. Moreover, immunoassay showed that TNF-α levels significantly increased in the heart and liver with cocaine administration. However, our RT-PCR study showed that there was no significant difference in either the heart or liver in the levels of mRNA for TNF-α between cocaine-treated and saline control mice. The present study demonstrated that cocaine is toxic to multiple organs, and at low dose can induce hepatic damage without gross pathological injury to the heart. The results suggest that the liver is more sensitive than the heart to cocaine toxicity, and induction of apoptosis or TNF-α elevation may be a common mechanism responsible for cocaines toxicity.
Insulin-Sensitive Phospholipid Signaling Systems and Glucose Transport. Update II
Authors: Farese Robert V.
Published: July 2017

Insulin provokes rapid changes in phospholipid metabolism and thereby generates biologically active lipids that serve as intracellular signaling factors that regulate glucose transport and glycogen synthesis. These changes include: (i) activation of phosphatidylinositol 3-kinase (PI3K) and production of PIP3; (ii) PIP3-dependent activation of atypical protein kinase Cs (PKCs); (iii) PIP3-dependent activation of PKB; (iv) PI3K-dependent activation of phospholipase D and hydrolysis of phosphatidyicholine with subsequent increases in phosphatidic acid (PA) and diacyiglycerol (DAG); (v) PI3K-independent activation of glycerol-3-phosphate acylytansferase and increases in de novo synthesis of PA and DAG; and (vi) activation of DAG-sensitive PKCs. Recent findings suggest that atypical PKCs and PKB serve as important positive regulators of insulin-stimulated glucose metabolism, whereas mechanisms that result in the activation of DAG-sensitive PKCs serve mainly as negative regulators of insulin signaling through PI3K. Atypical PKCs and PKB are rapidly activated by insulin in adipocytes, liver, skeletal muscles, and other cell types by a mechanism requiring PI3K and its downstream effector, 3-phosphoinositide-dependent protein kinase-1 (PDK-1), which, in conjunction with PIP3, phosphorylates critical threonine residues in the activation loops of atypical PKCs and PKB. PIP3also promotes increases in autophosphorylation and allosteric activation of atypical PKCs. Atypical PKCs and perhaps PKB appear to be required for insulin-induced translocation of the GLUT 4 glucose transporter to the plasma membrane and subsequent glucose transport. PKB also appears to be the major regulator of glycogen synthase. Together, atypical PKCs and PKB serve as a potent, integrated PI3K/PDK-1-directed signaling system that is used by insulin to regulate glucose metabolism.
Comparisons of the Effects of Anesthesia and Stress on Release of Tumor Necrosis Factor-α, Leptin, and Nitric Oxide in Adult Male Rats
Authors: Mastronardi Claudio A. , Yu Wen H. , McCann Samuel M.
Published: July 2017

Bacterial lipopolysaccharide (LPS) stimulates massive release of tumor necrosis factor-alpha (TNF-α) together with nitric oxide (NO) and a lessor release of leptin. We hypothesized that other types of stress such as that of surgery might also release these cytokines and NO. Adult male rats were anesthetized with ketamine/acepromazine/xylazine anesthesia (90 + 2 + 6 mg/ml, respectively) and an external jugular catheter was inserted for removal of blood samples (0.6 ml) at various times postoperatively. Plasma TNF-α was almost undetectable in decapitated rats and was near zero immediately following the placement of the jugular catheter (time zero [to]). As the rats awakened from anesthesia, there was a rise in TNF-α at 30 min that peaked at 2 hr with a 400-fold increase and then precipitously declined 40-fold to a level still greater than zero at 3 hr. At 6 hr on the following morning, TNF-α values were near zero, but following connection of tubing and withdrawal of the initial blood sample, there was a 100-fold increase 1 hr later, followed by a decline over the next 3 hr. In contrast, plasma [NO3/NO2] from decapitated rats was 117 μM. Values at t0 were decreased and plummeted 4-fold within 30 min, then rose slightly in the ensuing 3 hr. At 6 hr on the next day [NO3/NO2] values were lower than at t0 and declined gradually during the next 4 hr. Leptin gradually declined from pre-operative concentrations, reaching a minimum at 3 hr and its concentration was unaffected by the bleeding stress of the second day. We conclude that release of TNF-α, [NO3/NO2], and leptin are neurally controlled since plasma levels of all three declined as a result of anesthesia. TNF-α secretion was remarkably stress responsive, whereas NO release appeared to be suppressed by the combined operative and bleeding stress, and leptin was stress unresponsive.
Changes in Rat Adipocyte and Liver Glucose Metabolism Following Repeated Restraint Stress
Authors: Zhou Jun , Shi Ming Xia , Mitchell Tiffany D. , Smagin Gennady N. , Thomas Sonyja R. , Ryan Donna H. , Harris Ruth B.S.
Published: July 2017

Rats exposed to repeated restraint weigh less than controls even 8 weeks after stress. Stress-induced weight loss is lean tissue, but the post-stress difference in weight between control and restrained rats is lean and fat mass. Whole-body glucose clearance is enhanced 1 day after stress, but adipocyte glucose utilization is inhibited and muscle glucose transport is unchanged. The studies described here demonstrated that glucose transport was increased in both restrained and pair-fed rats, but that glycogen synthesis was increased only in restrained rats, which may account for the improved whole-body glucose clearance. Adipocyte glucose transport was inhibited and adipose plasma membrane β-adrenergic receptor number was increased 1 day post-stress in restrained rats when weight loss was lean tissue, but were not different from control rats 5 days post-stress, when both fat and lean tissue were reduced. Thus, repeated restraint induces reversible changes in adipocyte metabolism that may represent a transition from the catabolic state of stress to a new energetic equilibrium in rats that maintain a reduced body weight for an extended period of time.
Collagen Characteristics and Organization during the Progression of Cholesterol-Induced Atherosclerosis in Japanese Quail
Authors: Velleman Sandra G. , McCormick Richard J. , Ely Daniel , Jarrold Bradley B. , Patterson Ruthi A. , Scott Christopher B. , Daneshvar Hamid , Bacon Wayne L.
Published: July 2017

This study reports the concentration of collagen and its hydroxypyridinoline crosslinks, collagen fibril organization in the dorsal aortas, and systolic blood pressure during the progression of atherosclerosis in Japanese quail selected for cholesterol-induced atherosclerosis. The quail were placed on either a control or 0.5% cholesterol-added diet at approximately 16 weeks of age. The concentration of total collagen did not change in the control arteries during the course of the study, whereas at 5 and 10 weeks of cholesterol feeding, collagen levels decreased in the cholesterol-fed birds. Hydroxypyridinoline concentration increased during the duration of the study in the cholesterol-fed birds and by 15 and 20 weeks of cholesterol feeding, levels were significantly increased over those observed in the control arteries. Transmission electron microscopy showed changes in the organization of collagen fibrils. Increased systolic blood pressure was noted beginning at 10 weeks of cholesterol feeding, which is suggestive of other systemic changes induced by hypercholesterolemia. These results demonstrated remodeling of the collagen component of the dorsal aorta extracellular matrix during the progression of atherosclerosis and are suggestive of other systemic cardiovascular system changes.
Intraduodenal Infusion of Lysophosphatidylcholine Restores the Intestinal Absorption of Vitamins a and E in Rats Fed a Low-Zinc Diet
Authors: Noh Sang K. , Koo Sung I.
Published: July 2017

Our previous work has shown that the lymphatic absorptions of lipids and lipid-soluble vitamins, retinol and α-tocopherol (αTP), are lowered markedly in rats fed a low-zinc (LZ) diet in parallel with lower lymphatic phospholipid outputs. Phosphatidylcholine (PC), when infused enterally, restored the absorptions of fat and retinol, but further lowered the absorption of αTP in rats fed the LZ diet. This study was conducted to determine whether a luminal infusion of lysophosphatidylcholine, a product of PC hydrolysis by pancreatic phospholipase A2(PLA2), would simultaneously restore the absorptions of retinol and αTP in LZ rats. Rats were trained to consume two meals per day and were divided into two groups. One group was fed an AIN-93G diet containing a LZ (3.0 mg Zn/kg), and the other was fed the same diet, but containing adequate zinc (AZ; 30.0 mg Zn/kg) for 6 weeks. Rats with lymph cannula were infused at 3.0 ml/hr for 8 hr with a lipid emulsion containing retinol, αTP, and14C-labeled triolein (14C-oleic acid) with or without 1-oleoyl-2-hydroxy phosphatidyicholine (lysoPC) in 24 ml of PBS (pH 6.5). When the lipid emulsion without lysoPC was infused, the absorptions of retinol and αTP were significantly lower in LZ rats (retinol, 13.2 ± 1.5 nmol; αTP, 430.6 ± 66.8 nmol) than in AZ rats (retinol, 18.2 ± 1.0 nmol; αTP, 543.8 ± 58.9 nmol). The lower absorptions of the vitamins in LZ rats occurred in parallel with a significant decrease in14C-oleic acid absorption. When the emulsion containing lysoPC was infused, however, absorptions of the vitamins (retinol, 18.4 ± 3.0 nmol; αTP, 777.2 ± 92.1 nmol) in LZ rats were restored completely to the control levels (retinol, 20.4 ± 2.8 nmol; αTP, 756.3 ± 136.1 nmol). The results suggest that the luminal hydrolysis of PC to lysoPC by PLA2may be impaired in LZ rats, resulting in impaired absorption of fat and the fat-soluble vitamins.
Alpha-fetoprotein Structure and Function: Relevance to Isoforms, Epitopes, and Conformational Variants
Authors: Mizejewski Gerald J.
Published: July 2017

Mammalian alpha-fetoprotein (AFP) is classified as a member of the albuminoid gene superfamily consisting of albumin, AFP, vitamin D (Gc) protein, and alpha-albumin. Molecular variants of AFP have long been reported in the biomedical literature. Early studies identified isoelectric pH isoforms and lectin-binding variants of AFP, which differed in their physicochemical properties, but not in amino acid composition. Genetic variants of AFP, differing in mRNA kilobase length, were later extensively described in rodent models during fetal/perinatal stages, carcinogenesis, and organ regeneration. With the advent of monoclonal antibodies in the early 1980s, multiple antigenic epitopes on native AFP were detected and categorized, culminating in the identification of six to seven major epitopes. During this period, various AFP-binding proteins and receptors were reported to inhibit certain AFP immunoreactions. Concomittantly, human and rodent AFP were cloned and the amino acid sequences of the translated proteins were divulged. Once the amino acid composition of the AFP molecule was known, enzymatic fragments could be identified and synthetic peptide segments synthesized. Following discovery of the molten globule form in 1981, the existence of transitory, intermediate forms of AFP were acknowledged and their physiological significance was realized. In the present review, the various isoforms and variants of AFP are discussed in light of their potential biological relevance.
Cholangiohepatitis and Inflammatory Bowel Disease Induced by a Novel Urease-Negative Helicobacter Species in A/J and Tac:ICR:HascidfRF Mice
Authors: Shomer Nirah H. , Dangler Charles A. , Schrenzel Mark D. , Whary Mark T. , Xu Shilu , Feng Yan , Paster Bruce J. , Dewhirst Floyd E. , Fox James G.
Published: July 2017

Helicobacter bilis and H. hepaticus, both urease-positive intestinal helicobacters of mice, have been shown experimentally to induce proliferative typhlocolitis in scid mice. We recently isolated a urease-negative Helicobacter sp. (H. sp.) that also induced proliferative typhlocolitis in pilot studies in scid mice. To determine the pathogenic potential of H. sp. in immunocompromised and immunocompetent mice, 5-week old male A/J or Tac:Icr:Ha(ICR)-scidfRF mice were inoculated by intraperitoneal (IP) injection with - 3 × 107colony-forming units (CFU) of H. sp. Mice were necropsied at various time points postinoculation (PI). Sham-inoculated mice had no clinical, gross, or histopathological lesions. In contrast, scid mice inoculated IP with H. sp. had severe hemorrhagic diarrhea and decreased weight gain at 2, 7, and 18 weeks postinoculation (PI), with severe proliferative typhlocolitis, phlebothrombosis, and hepatitis. A/J mice had no clinical signs, but had mild to moderate proliferative typhlocolitis and moderate to marked cholangiohepatitis at 7 and 24 weeks PI. A/J mice infected with H. sp. developed robust immune responses of a predominant Th1 type. This report demonstrates that infection with a urease-negative helicobacter can cause inflammatory bowel disease (IBD) and hepatitis in scid and immunocompetent A/J mice. These results provide a new model of IBD and cholangiohepatitis associated with a specific urease-negative, novel H. species.
The Vasorelaxation of Cerebral Arteries by Carbon Monoxide
Authors: Komuro Taro , Borsody Mark K. , Ono Shigeki , Marton Linda S. , Weir Bryce K. , Zhang Zhen-Du , Paik Eun , Macdonald R. Loch
Published: July 2017

Carbon monoxide (CO) is known to increase cerebral blood flow, but the effect of CO on the vascular tone of large cerebral arteries is uncertain. We tested whether CO affects cerebral artery tone by measuring tension generated by ex vivo segments of dog basilar artery upon exposure to CO. In cerebral artery segments contracted with either KCI or prostaglandin F2a, CO caused a concentration-related relaxation beginning with a concentration of 57 μM. Relaxation did not occur if CO was administered in the presence of bubbling carboxygen (95% 02:5% CO2), which reduces greater than 99% of CO from the solution. Furthermore, the CO-induced relaxation of cerebral artery segments was reduced in the presence of the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM)or the potassium channel blocker tetraethylammonium (TEA, 1 mM). Neither ODQ nor TEA completely eliminated the relaxation caused by CO and there was no additive effect if ODQ and TEA were administered together. These results suggest that cerebral arteries are directly relaxed by CO and that this relaxation depends upon the activation of guanylyl cyclase and the opening of potassium channels.
Effects of Dietary Restriction on Spontaneous Dermatitis in NC/Nga Mice
Authors: Fan WenYing , Kouda Katsuyasu , Nakamura Harunobu , Takeuchi Hiroichi
Published: July 2017

In laboratory animals, dietary restriction prolongs life span, improves physiologic function, and prevents or lessens severity of several diseases including some experimental inflammatory states. We investigated the effect of dietary restriction on a spontaneously occurring mouse model of atopic dermatitis, an inflammatory skin disease. NC/Nga mice were assigned to a group fed ad libitum or to a restricted diet group receiving 60% of the amount of food consumed by the other group. Dermatitis was characterized according to extent, intensity, and scratching time. We then used computer-assisted image analysis to quantify immunologic findings in skin sections. Extent, intensity score, and scratching time in mice with restriction increased more gradually than in mice fed ad libitum. Infiltrating Inflammatory cells (CD4-positive T cells, CD8-positive T cells, eosinophils, and mast cells) as well as interleukin-4 and −5 secreted into tissue were reduced in mice with restriction. In conclusion, dietary restriction delayed onset and progression of spontaneous dermatitis in NC/Nga mice, an effect possibly involving inhibition of inflammatory infiltration cell and cytokine secretion.
Ontogenic Regulation of Components of Ileal Bile Acid Absorption
Authors: Hwang Sandy T. , Henning Susan J.
Published: July 2017

The apical sodium-dependent bile acid cotransporter (ASBT) and the ileal bile acid binding protein (IBABP) are two components of ileal bile acid absorption. During the third postnatal week of the rat, there is a dramatic increase in ASBT and IBABP expression. The goals of this study were to examine the role of hormones on the ontogenic expression of ASBT mRNA and the role of weaning for both ASBT and IBABP mRNA. Administration of various doses of dexamethasone during the second postnatal week induced ASBT mRNA levels, and this effect was significantly increased with concomitant thyroxine treatment. Early weaning and weaning prevention were utilized to investigate the influence of dietary factors. ASBT and IBABP mRNA levels were significantly elevated by early weaning and were decreased by weaning prevention compared with littermate controls. Thus, glucocorticoids and thyroxine appear to play a role in the ontogenic expression of ASBT mRNA and weaning appears to participate in both ASBT and IBABP expression.
Transplantation of Normal Islets into the Portal Vein of Otsuka Long Evans Tokushima Fatty Rats Prevents Diabetic Progression
Authors: Katsuragi Isao , Okeda Toshimitsu , Yoshimatsu Hironobu , Utsunomiya Naoko , Ina Keisuke , Sakata Toshiie
Published: July 2017

To investigate the long-term effects of normal pancreatic islet transplantation on progression of obese type 2 diabetes mellitus (DM), 1500 normal islets (per rat) from Wistar King A rats at 8 weeks of age were transplanted into the liver through the portal vein of Otsuka Long Evans Tokushima Fatty (OLETF) rats, an animal model of obese type 2 DM, at 12 weeks of age. Body weight in the transplanted OLETF (IT) rats 8 and 28 weeks after islet transplantation did not differ from that in the corresponding sham-operated (SO) rats, but was greater than that in lean littermates (LETO rats; P < 0.05 for each group). In the early phase, 8 weeks after transplantation, rats in both IT and SO groups were normoglycemic, but hyperinsulinemic (P < 0.05 for each compared with LETO rats), probably resulting from increased body weight. In the late phase, 28 weeks after transplantation, hyperglycemia in the IT group was greatly attenuated compared with the SO group (P < 0.05), but hyperinsulinemia remained in both the IT and the SO groups compared with that in the LETO group (P < 0.05 for each). Immunohistochemical studies demonstrated that hypertrophic and fibrotic changes in pancreatic islets, together with mesangial proliferation of the glomerular matrix, an indicator for diabetic nephropathy, were attenuated predominantly in the IT group at the late phase after transplantation compared with those in the corresponding phase of the SO group. Islet transplantation into the liver of OLETF rats thus prevented further progression of obese type 2 DM. A possible mechanism is that islet transplantation may prevent development of hyperglycemia by improving abnormal hepatic glucose metabolism and consequently insulin resistance, which may lead to blockade of a vicious cycle between advancing damage to pancreatic islet cells and increased demand for insulin secretion, thus sparing original pancreatic cells from exhaustion induced by increased demand for insulin secretion.
Estrogen Synthetase (Aromatase) Immunohistochemistry Reveals Concordance Between Avian and Rodent Limbic Systems and Hypothalami
Authors: Naftolin Frederick , Horvath Tamas L. , Balthazart Jacques
Published: July 2017

During amniote evolution, an early divergence occurred about 300 million years ago between the reptilian lines leading to the appearance of birds (anapsids) and mammals (synapsids). The different functional requirements of these vertebrate groups have involved divergent evolution of their brains. Even superficial examination reveals major anatomical differences between mammalian and avian brains, such as extensive development of the optic lobes and cerebellum in birds and a highly developed cortex in mammals. It has been nearly impossible to identify avian homologs of some mammalian brain regions by standard morphological criteria. This has long frustrated efforts at clarifying hypotheses regarding the anatomical location, field size, and regulation of brain functions shared between these two classes, despite the certainty that the principles of neurobiology apply equally at the cellular level in both groups. In an effort to remove this barrier, we have sought markers of common function that despite apparent anatomical dissimilarity, can allow recognition of homologous brain structures. We illustrate here how comparative analysis of the distribution of the steroid-metabolizing enzyme estrogen synthetase (aromatase) may help to understand the differences and similarities in the limbic system and hypothalamus of birds and mammals.
The Role of Thrombospondin-1 in Tumor Progression
Authors: Sargiannidou Irene , Zhou Jing , Tuszynski George P.
Published: July 2017

The role of thrombospondin-1 (TSP-1) in tumor progression is both complex and controversial. It is clear from the literature that the function of TSP-1 in malignancy depends on the presence of other factors and the level of TSP-1 expression in the tumor tissue. High levels of TSP-1 secreted by tumors, which were engineered to overexpress TSP-1, inhibit tumor growth, while anti-sense inhibition of TSP-1 production in certain tumore also inhibits growth. Clearly, the presence of other factors in these experimental systems must be important. The role of TSP-1 in angiogenesis also depends on the levels of TSP-1, the presence and level of angiogenic stimulators such as basic fibroblast growth factor (bFGF), and the localization of TSP-1 in the tissue. Matrix-bound TSP-1 promotes capillary tube formation in the rat aorta model of angiogenesis, while TSP-1 inhibits bFGF- induced angiogenesis in the rat cornea model. The inhibitory effect also depends on the proteolytic state of TSP-1 since the amino terminus promotes angiogenesis in the cornea model, while the remaining140-kDa fragment inhibits bFGF-induced angiogenesis. Both the stimulatory and inhibitory effects of TSP-1 are likely due to upregulation of matrix-degrading enzymes and their inhibitors. These enzymes are critical for maintaining optimal matrix turnover during angiogenesis. These varied TSP-1-dependent mechanisms offer new targets for the development of anti-angiogenic therapeutics for the treatment of a variety of cancers, as well as other pathologies involving inappropriate angiogenesis such as diabetic retinopathy.
On the Mechanism of Hemozoin Production in Malaria Parasites: Activated Erythrocyte Membranes Promote β-Hematin Synthesis
Authors: Orjih Augustine U.
Published: July 2017

The ferriprotoporphyrin IX (FP) molecules released by intraerythrocytic malaria parasites during hemoglobin digestion are converted to β-hematin and are stored in the parasites' food vacuoles. It has been demonstrated in cell-free medium that the incorporation of FP into β-hematin under physiological conditions requires a catalyst from parasite lysates or pre-formed β-hematin. In the present studies, lysates of Plasmodium falciparum-infected erythrocytes were suspended in 1 M NaOH and were washed with phosphate buffer, pH 7.6. When the cell extracts were incubated with hematin in 0.5 M sodium acetate buffer, pH 5, for 20 hr at 37°C, a large quantity of β-hematin was formed. To determine whether parasite components were necessary for the β-hematin formation, normal erythrocyte ghosts were similarly treated with 1 M NaOH and then incubated with hematin. In repeated experiments it was found that, on the average, 70% of the hematin was converted to β-hematin. Membranes treated with HCI or CH3COOH also promoted the formation of β-hematin, while untreated membranes were ineffective. The possibility that metabolic activities in the food vacuoles of malaria parasites may activate membrane fragments, from hemoglobin vesicles, to promote β-hematin formation is discussed in this paper.
Telomerase Activity in Kaposi's Sarcoma, Squamous Cell Carcinoma, and Basal Cell Carcinoma
Authors: Chen Ziping , Smith Kathleen J. , Skelton Henry G. , Barrett Terry L. , Greenway Herbert T. , Lo Shyh-Ching
Published: July 2017

Patients with acquired immune deficiency syndrome (AIDS) often develop Kaposi's sarcoma (KS), an unusual skin tumor. The malignant nature of KS has long been disputed. Telomerase activity that maintains telomere length and ensures chromosomal stability, a frequently appearing marker in human malignancies, has been proposed to play a critical role in supporting continued cell growth, hence formation of tumors. We examined telomerase activity in tissue extracts from 22 KS, 10 squamous cell carcinoma (SCC), and 22 basal cell carcinoma (BCC) using the telomeric repeat amplification protocol (TRAP). All of the tumor tissues were previously cryopreserved at -80°C. In this study, all tumor samples tested were positive for telomerase activity. Consistent with the presence of the enzyme activity, the skin tumors had relatively long telomeres. Inhibitors in the tissue extracts of some samples needed to be diluted or extracted by phenol before the enzyme activity was detected in the TRAP assay. All KS as well as two other skin carcinoma samples revealed positive telomerase activity. Our finding supports telomerase's role in tumor cell immortality and suggests the true neoplastic nature of KS.