ALCOHOLISM, Issue 7 2002
Jason Glanz
Background Discussions between the World Health Organization (WHO) and the International Society on Biomedical Research on Alcoholism (ISBRA) identified the need for a multiple-center international study on state and trait markers of alcohol abuse and alcohol dependence. The reasoning behind the generation of such a project included the need to understand the alcohol use characteristics of diverse populations and the performance of biological markers of alcohol use in a variety of settings throughout the world. A second major reason for initiating this study was to collect DNA for well-structured and stratified association studies between genetic markers and/or "candidate" genes and behavioral/physiological phenotypes of importance to predisposition to alcohol dependence. Methods An extensive interview instrument was developed with leadership from the U.S. National Institute on Alcohol Abuse and Alcoholism (NIAAA). The instrument was translated from English to Finnish, French, German, Japanese, and Portuguese (Brazilian). One thousand eight hundred sixty-three subjects were recruited at five clinical centers (Montreal, Canada; Helsinki, Finland; Sapporo, Japan; São Paulo, Brazil; and Sydney, Australia). The subjects responded to the structured interview and provided blood and urine samples for biochemical analysis. This article focuses on the demographic characteristics of the study subjects, their drinking habits, alcohol-dependence characteristics, comorbid psychiatric and other drug variables, and predictors for seeking treatment for alcohol dependence. Multiple logistic regression models were constructed and used to explore variables that contribute to various levels of alcohol consumption, to a diagnosis of alcohol dependence, and to seeking treatment for alcohol dependence. ANOVA with post hoc comparisons, ,2, and Pearson moment calculations were used as necessary to assess additional relationships between variables. Results A number of factors previously noted in disparate studies were confirmed in our analysis. Men consumed more alcohol than women, Asians consumed less alcohol than whites or Blacks, alcohol-dependent subjects consumed more alcohol than nondependent subjects, alcohol consumption increased with age, and an increased level of education (university or postgraduate education) reduced the percentage of such individuals in the category designated as heavy drinkers (>210 g alcohol/week) and in the group who were currently in treatment for dependence. However, our analysis allowed for much more detailed comparisons; for example, although men drank more than women on a g/day basis, the differences were less pronounced on g/kg/day basis, and alcohol-dependent women drank equal amounts of alcohol as alcohol-dependent men on a g/kg/day basis. Antisocial personality characteristics or reports of trouble sleeping when an individual stops drinking were associated with higher alcohol intake. The most important of the tested factors that contributed to a DSM-IV diagnosis of dependence, however, was the report of anxiety if an individual stopped drinking. In terms of the various criteria within the DSM-IV criteria for alcohol dependence, no one criterion seemed to be prominent for individuals who sought alcohol dependence treatment, but the higher the number of criteria met by the individual, the higher was the probability that he or she would be in treatment. Conclusions This initial report is the beginning of the "data mining" of this rich data set. The cross-national/cross-cultural aspects of this study allowed for multiple comparisons of variables across several ethnic/racial groups and allowed for assessment of biochemical markers for alcohol intake and predisposition to alcohol dependence in diverse settings. [source]

Physiologic, bronchoscopic, and bronchoalveolar lavage fluid findings in young children with recurrent wheeze and cough,

PEDIATRIC PULMONOLOGY, Issue 8 2006
John Saito MD
Abstract Assessing airway disease in young children with wheeze and/or cough is challenging. We conducted a prospective, descriptive study of lung function in children <3 years old with recurrent wheeze and/or cough, who had failed empiric antiasthma and/or antireflux therapy and subsequently underwent flexible bronchoscopy. Our goals were to describe radiographic, anatomical, microbiological, and physiological findings in these children, and generate hypotheses about their respiratory physiology. Plethysmography and raised-volume rapid thoracoabdominal compression (RVRTC) techniques were performed prior to bronchoscopy. Mean Z-scores (n,=,19) were ,1.34 for forced expiratory volume at 0.5 sec (FEV0.5), ,2.28 for forced expiratory flows at 75% of forced vital capacity (FVC) (FEF75), ,2.25 for forced expiratory flows between 25,75% of FVC (FEF25,75), 2.53 for functional residual capacity (FRC), and 2.23 for residual volume divided by total lung capacity (RV/TLC). Younger, shorter children had markedly depressed FEF75 and FEF25,75 Z-scores (P,=,0.002 and P,=,<0.001, respectively). As expected, lower airway anatomical abnormalities, infection, and inflammation were common. Elevated FRC was associated with anatomical lower airway abnormalities (P,=,0.03). FVC was higher in subjects with neutrophilic inflammation (P,=,0.03). There was no association between other physiologic variables and bronchoscopic/bronchoalveolar lavage fluid findings. Half of those with elevated RV/TLC ratios (Z-score >2) had no evidence of chest radiograph hyperinflation. We conclude that in this population, plethysmography and RVRTC techniques are useful in identifying severity of hyperinflation and airflow obstruction, and we hypothesize that younger children may have relatively small airways caliber, significantly limiting airflow, and thus impairing secretion clearance and predisposing to lower airway infection. Pediatr Pulmonol. 2006; 41: 709,719. © 2006 Wiley-Liss, Inc. [source]

Pirfenidone Treatment Decreases Transforming Growth Factor-,1 and Matrix Proteins and Ameliorates Fibrosis in Chronic Cyclosporine Nephrotoxicity

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2002
Fuad S. Shihab
Chronic cyclosporine (CsA) nephrotoxicity is characterized by tubulointerstitial fibrosis. Pirfenidone (PFD) is a novel antifibrotic compound that was shown to prevent and even reverse fibrosis. The mechanism of action of PFD is unclear but involves inhibition of transforming growth factor-, (TGF-,). Salt-depleted rats were administered CsA, CsA + PFD, vehicle (VH) or VH + PFD and sacrificed at 28 days. Physiologic and histologic changes were studied in addition to TGF-,1, plasminogen activator inhibitor-1 (PAI-1) and biglycan mRNA expressions by Northern blot. TGF-,1 immunohistochemistry was also performed. Treatment with PFD ameliorated CsA-induced fibrosis by about 50% (p <,0.05). CsA-induced decrease in creatinine clearance improved with PFD but the difference was not significant. TGF-,1, PAI-1 and biglycan mRNA expressions increased with CsA (p <,0.05 vs. VH) but strikingly improved with PFD treatment (p <,0.05 vs. CsA), which brought the levels down to VH levels. PFD treatment also decreased TGF-,1 protein expression by 80%. These results demonstrate that PFD can attenuate renal fibrosis in this model. PFD was associated with a decrease in TGF-,1 expression, which, in turn, was associated with a decrease in matrix deposition. These experiments suggest that PFD can be clinically useful for preventing chronic CsA nephrotoxicity and may prove to be helpful in other progressive renal diseases. [source]

Cardiac gene expression profiling may reveal key differences between physiologic and pathologic cardiac hypertrophy

ACTA PHYSIOLOGICA, Issue 4 2005
Dr Maurice H. Laughlin
No abstract is available for this article. [source]

Somatostatin receptors and autoimmune-mediated diabetes

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2005
Xaio-Ping Wang
Abstract Somatostatin (SST) peptide is produced by various SST-secreting cells throughout the body and acts as a neurotransmitter or paracrine/autocrine regulator in response to ions, nutrients, peptides hormones and neurotransmitters. SST is also widely distributed in the periphery to regulate the inflammatory and immune cells in response to hormones, growth factors, cytokines and other secretive molecules. SST peptides are considered the most important physiologic regulator of the islet cell, gastrointestinal cell and immune cell functions, and the importance of SST production levels has been implicated in several diseases including diabetes. The expression of SST receptors has also been found in T lymphocytes and primary immunologic organs. Interaction of SST and its receptors is also involved in T-cell proliferation and thymocyte selection. SSTR gene-ablated mice developed diabetes with morphologic, physiologic and immunologic alterations in the endocrine pancreas. Increased levels of mononuclear cell infiltration of the islets are associated with the increased levels of antigen-presenting cells located in the islets and peripancreatic lymph nodes. Increased levels of SST were also found in antigen-presenting cells and are associated with a significant increase of CD8 expression levels on CD4+/CD8+ immature thymocytes. These findings highlight the crucial role of this neuroendocrine peptide and its receptors in regulating autoimmune functions. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Athletes' Heart and Echocardiography: Athletes' Heart

ECHOCARDIOGRAPHY, Issue 7 2008
B.Sc., Martin Stout M.Sc.
Sudden death of competitive athletes is rare. However, they continue to have an impact on both the lay and medical communities. These deaths challenge the perception that trained athletes represent the healthiest segment of modern society. There is an increasing frequency of such reported deaths worldwide and the visibility of this issue is underlined by the high-profile nature of each case. Differential diagnosis between pathological and the physiologic (nonpathological) responses to high levels of physical training has become clinically more important. The purpose of this review is to highlight the main echocardiograph characteristics related to different types of training/sports participation and to highlight already recognized and newer concepts in their clinical assessment. [source]

Trauma Team Activation Criteria as Predictors of Patient Disposition from the Emergency Department

ACADEMIC EMERGENCY MEDICINE, Issue 1 2004
Michael A. Kohn MD
Many trauma centers use mainly physiologic, first-tier criteria and mechanism-related, second-tier criteria to determine whether and at what level to activate a multidisciplinary trauma team in response to an out-of-hospital call. Some of these criteria result in a large number of unnecessary team activations while identifying only a few additional patients who require immediate operative intervention. Objectives: To separately evaluate the incremental predictive value of individual first-tier and second-tier trauma team activation criteria for severe injury as reflected by patient disposition from the emergency department (ED). Methods: This was a prospective cohort study in which activation criteria were collected prospectively on all adult patients for whom the trauma team was activated during a five-month period at an urban, Level 1 trauma center. Severe injury disposition ("appropriate" team activation) was defined as immediate operative intervention, admission to the intensive care unit (ICU), or death in the ED. Data analysis consisted of recursive partitioning and multiple logistic regression. Results: Of the 305 activations for the mainly physiologic first-tier criteria, 157 (51.5%) resulted in severe injury disposition. The first-tier criterion that caused the greatest increase in "inappropriate" activations for the lowest increase in "appropriate" activations was "age > 65." Of the 34 additional activations due to this criterion, seven (20.6%) resulted in severe injury disposition. Of the 700 activations for second-tier, mechanism-related criteria, 54 (7.7%) resulted in ICU or operating room admissions, and none resulted in ED death. The four least predictive second-tier criteria were "motorcycle crash with separation of rider,""pedestrian hit by motor vehicle,""motor vehicle crash with rollover," and "motor vehicle crash with death of occupant." Of the 452 activations for these four criteria, only 18 (4.0%) resulted in ICU or operating room admission. Conclusions: The four least predictive second-tier, mechanism-related criteria added little sensitivity to the trauma team activation rule at the cost of substantially decreased specificity, and they should be modified or eliminated. The first-tier, mainly physiologic criteria were all useful in predicting the need for an immediate multidisciplinary response. If increased specificity of the first-tier criteria is desired, the first criterion to eliminate is "age > 65." [source]

Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2,-deoxyguanine glycosylase

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2006
M. Ahmad Chaudhry
Abstract The human OGG1 gene encodes a DNA glycosylase that is involved in the base excision repair of 8-hydroxy-2,-deoxyguanine (8-OH-dG) from oxidatively damaged DNA. Cellular 8-OH-dG levels accumulate in the absence of this activity and could be deleterious for the cell. To assess the role of 8-oxoguanine glycosylase (OGG1) in the cellular defense mechanism in a specific DNA repair defect background, we set out to determine the expression pattern of base excision repair genes and other cellular genes not involved in the base excision pathway in OGG1-deficient human KG-1 cells after ionizing radiation exposure. KG-1 cells have lost OGG1 activity due to a homozygous mutation of Arg229Gln. Gene expression alterations were monitored at 4, 8, 12 and 24 hr in 2 Gy irradiated cells. Large-scale gene expression profiling was assessed with DNA microarray technology. Gene expression analysis identified a number of ionizing radiation-responsive genes, including several novel genes. There were 2 peaks of radiation-induced gene induction or repression: one at 8 hr and the other at 24 hr. Overall the number of downregulated genes was higher than the number of upregulated genes. The highest number of downregulated genes was at 8 hr postirradiation. Genes corresponding to cellular, physiologic, developmental and extracellular processes were identified. The highest number of radiation-induced genes belonged to the signal transduction category, followed by genes involved in transcription and response to stress. Microarray gene expression data were independently validated by relative quantitative RT-PCR. Surprisingly, none of the genes involved in the base excision repair of radiation-induced DNA damage showed altered expression. © 2005 Wiley-Liss, Inc. [source]

A review of the GOLD guidelines for the diagnosis and treatment of patients with COPD

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2008
L. Fromer
Summary Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the USA, and represents a major health, social and economic burden. COPD is underdiagnosed and often misdiagnosed, which likely contributes to the continuing increases in the prevalence, morbidity and mortality associated with this disease. This is unfortunate because whereas COPD cannot be cured, it can be treated effectively, particularly during the earlier stages of the disease. Evidence-based guidelines, developed to assist in the prevention, diagnosis and management of COPD, are available to healthcare professionals interested in learning more about COPD. These guidelines are updated and revised on a regular basis to reflect recent advances in our understanding of the pathophysiology of and treatments available for COPD. Nevertheless, primary-care physicians have reported a lack of awareness of the fundamental concepts underpinning the optimal treatment and management of COPD presented in the guidelines. Thus, the objective of this article is to summarise key physiologic, diagnostic and management concepts provided in the most recent update of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, which were published in November 2006. [source]

Original semiologic standardized evaluation of stratum corneum hydration by Diagnoskin® stripping sample

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 3 2004
P. Gasser
Synopsis In a normal and healthy skin, the regular elimination of the superficial corneocytes, called desquamation, is a fundamental physiologic process intended to protect the barrier function of the skin. This invisible loss of corneocytes, individually or in small groups, is incessantly compensated by the divisions of the proliferative layer and the upward cellular maturation in order to maintain the harmonious renewal of the epidermis and the integrity of the stratum corneum. The harmony of this desquamation process is intimately conditioned by a sufficient hydration of the stratum corneum: (i) an abnormal desquamation leads to a disruption of the water barrier function and consequently to a dehydration tendency of the stratum corneum, and (ii) a cutaneous dryness (whatever the cause) is able to disturb the desquamation process. Protecting the water content of the stratum corneum has always been a major preoccupation of the cosmetic industry scientists. Consequently, the moisturizing properties of a cosmetic product are objectively measured by various explorations directly targeted on the hydration (corneometry) and on the level of the water barrier function (transepidermal water loss (TEWL) measurements), which depends directly on the skin hydration state. This intimate linkage of the desquamation process and the water content of the stratum corneum enable us to suggest an indirect assessment of the hydration from a direct study of the desquamation by examining a skin-stripping sample (D-Squames®) by an optical microscope (linked to a computer). We will describe this already known technique and mainly its new and unpublished semiologic exploitation, named Diagnoskin®, whose advantages are its simplicity and its reproducibility particularly interesting in the case of sequential appraisal of dermatologic or cosmetic treatments. Résumé Sur une peau normale et saine, l'élimination régulière des cornéocytes superficiels, appelée desquamation, est un processus physiologique fondamental destinéà préserver la fonction barrière de la peau. La perte invisible des cornéocytes, individuellement ou par petits paquets cellulaires, est sans cesse compensée par les divisions de la couche germinative et la maturation cellulaire ascensionnelle afin de maintenir le renouvellement harmonieux de l'épiderme et l'intégrité du stratum corneum. L'harmonie de ce processus de desquamation est intimement conditionnée par une hydratation suffisante du stratum corneum: une desquamation anormale aboutit à une perturbation de la fonction barrière et donc à une tendance à la déshydratation du stratum corneum, Une sècheresse cutanée (quelle qu'en soit la cause) va perturber la desquamation. Préserver la teneur en eau du stratum corneum est depuis toujours une préoccupation majeure pour le scientifique de l'industrie cosmétique. L'appréciation objective du caractère hydratant d'une crème cosmétique est d'ailleurs mesuré par diverses explorations directement ciblées sur l'hydratation (cornéométrie) et sur l'état de la fonction barrière (Perte Insensible en Eau ,PIE) qui dépend directement de l'état d'hydratation de la peau. Cette liaison intime du niveau d'hydratation du stratum corneum et du phénomène de desquamation nous a fait proposer une évaluation indirecte de l'hydratation à l'aide d'une étude directe de la desquamation par observation au microscope (reliéà un ordinateur) des prélèvements par stripping des cornéocytes superficiels (D-Squames®). Nous décrirons cette technique déjà connue et surtout son exploitation sémiologique nouvelle et inédite, appelée Diagnoskin® dont les avantages sont sa simplicité et son caractère reproductible particulièrement intéressants pour l'évaluation séquentielle de traitements dermatologiques ou cosmétiques. [source]

Nursing Diagnosis: Is It Time for a New Definition?

INTERNATIONAL JOURNAL OF NURSING TERMINOLOGIES AND CLASSIFICATION, Issue 1 2008
T. Heather Herdman PhD
PURPOSE. The Diagnosis Development Committee (DDC) of NANDA International frequently receives proposed "physiologic" and "surveillance diagnosis" submissions that may not meet the current definition of nursing diagnosis (NANDA, 2007, p. 332). There has been a request for a vote on newly proposed definitions of nursing diagnosis, risk diagnosis, and syndromes. The purpose of this article is to provide information which enables members and interested nurses to continue the dialogue and to share their thoughts and also to consider the thoughts and information generated by the participants in the NANDA-I interest survey on the definition of nursing diagnoses. DATA SOURCES. An electronic survey of the current NANDA-I definitions, and potential changes to those definitions, was distributed via the NANDA-I Web site. This article summarizes the overall findings of that survey and provides an overview of commentary received from the 269 participants. CONCLUSIONS. It is necessary to continue the dialogue on this important decision and to provide a mechanism for input from members and interested nurses before reaching any conclusions on this subject. NURSING IMPLICATIONS. NANDA-I has been recognized as the leader in the development and implementation of nursing diagnoses and must act responsibly in assessing the changing and emerging trends in nursing practice and in responding to these trends. [source]

Use of NANDA, NIC, and NOC in a Baccalaureate Curriculum

INTERNATIONAL JOURNAL OF NURSING TERMINOLOGIES AND CLASSIFICATION, Issue 2003
Cynthia Finesilver
BACKGROUND For the last 8 years, NANDA, NIC, and NOC have been successfully introduced to students in fundamentals courses at Bellin College of Nursing. As students progress through the curriculum, the classifications are expanded and applied to various client populations in all settings. The faculty expect students to use NANDA, NIC, and NOC in a variety of ways: during preparation for care of clients, documentation of client care, discussion of clients in postconference; in formal nursing process papers; and in the college laboratory setting. MAIN CONTENT POINTS Through the use of standardized languages, which address all steps of the nursing process, students have been able to plan, implement, and evaluate nursing care in all settings, from primary care to specialty care areas. Application of the NANDA, NOC, and NIC frameworks into a baccalaureate curriculum is desirable because the classifications are research based, comprehensive, and based on current nursing practice. NOC and NIC include physiologic, psychosocial, illness prevention and treatment, health promotion, and alternative therapies. Because of the universal and clinically meaningful language, students are able to communicate and document nursing activities in diverse settings and better define the unique actions and value of nursing. Feedback from students and faculty has been positive. Faculty members are encouraged to refine and alter course expectations related to NANDA, NOC, and NIC as needed. Students in the fundamentals courses adapt easily to NANDA, NOC and NIC during small group work and during discussion of common client problems, such as constipation. CONCLUSIONS Although the frameworks are not used as part of the organizing framework, they are used to teach nursing process and increase students' critical thinking and problem-solving capabilities. [source]

Cigarette smoke extract affects functional activity of MRP1 in bronchial epithelial cells

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2007
Margaretha van der Deen
Abstract Cigarette smoke is the principal risk factor for development of chronic obstructive pulmonary disease (COPD). Multidrug resistance-associated protein 1 (MRP1) is a member of the ATP-binding cassette (ABC) superfamily of transporters, which transport physiologic and toxic substrates across cell membranes. MRP1 is highly expressed in lung epithelium. This study aims to analyze the effect of cigarette smoke extract (CSE) on MRP1 activity. In the human bronchial epithelial cell line 16HBE14o,, MRP1 function was studied flow cytometrically by cellular retention of carboxyfluorescein (CF) after CSE incubation and MRP1 downregulation by RNA interference (siRNA). Cell survival was measured by the MTT assay. Immunocytochemically, it was shown that 16HBE14o, expressed MRP1 and breast cancer resistance protein. Coincubation of CSE IC50 (1.53% ± 0.22%) with MK571 further decreased cell survival 31% (p, = 0.018). CSE increased cellular CF retention dose dependently from 1.7-fold at 5% CSE to 10.3-fold at 40% CSE (both p < 0.05). siRNA reduced MRP1 RNA expression with 49% and increased CF accumulation 67% versus control transfected cells. CSE exposure further increased CF retention 24% (p = 0.031). A linear positive relation between MRP1 function and CSE-modulating effects (r = 0.99, p =0.089) was shown in untransfected, control transfected, and MRP1 downregulated 16HBE14o, cells analogous to blocking effects with MRP1 inhibitor MK571 (r = 0.99, p = 0.034). In conclusion, cigarette smoke extract affects MRP1 activity probably competitively in bronchial epithelial cells. Inhibition of MRP1 in turn results in higher CSE toxicity. We propose that MRP1 may be a protective protein for COPD development. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:243,251, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20187 [source]

Quantification of the expression and inducibility of 12 rat cytochrome P450 isoforms by quantitative RT,PCR

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2006
Etienne Caron
Abstract The administration of xenobiotics may significantly alter the expression of cytochromes P450 (CYPs), thereby leading to potentially toxic cellular, physiologic, and pharmacologic responses. Indeed, an important task in the development of new therapeutic entities is to evaluate efficiently and quantitatively their potential effects on the expression level of different CYPs. In this report, reverse transcriptase polymerase chain reaction (RT,PCR) was used to measure basal and induced mRNA of a wide range of rat CYP isoforms. Rats (n = 3 per treatment) were treated with five prototype inducers of CYP isoforms or with vehicle only. RT and PCR efficiencies were determined using appropriate RNA and DNA standards. Messenger RNA was quantified by PicoGreen standard curves and normalized to cyclophilin. Quantitative RT,PCR was used successfully to demonstrate that CYP isoforms were induced at the mRNA level following drug administration. Notably, phenobarbital resulted in significant induction of CYP2B1, CYP2B2, CYP2C6, CYP2C13, CYP2E1, CYP3A1, and CYP3A2. 3-Methylcholanthrene induced CYP1A1, CYP1A2, and CYP1B1. CYP2C11 expression was highly variable and suppressed by pyridine, whereas the expression of CYP2E1 was suppressed by dexamethasone. We demonstrated that quantitative RT,PCR can be used to evaluate efficiently the effect of compounds on the expression of a wide range of CYP isoforms. The technique is advantageous over others in that it is very sensitive, efficient and applicable to highly homologous CYP isoforms. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:368,378, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20103 [source]

In Silico Modeling and Simulation of Bone Biology: A Proposal

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005
Nadine A Defranoux
Abstract Contemporary, computer-based mathematical modeling techniques make it possible to represent complex biological mechanisms in a manner that permits hypothesis testing in silico. This perspective shows how such approaches might be applied to bone remodeling and therapeutic research. Currently, the dominant conceptual model applied in bone research involves the dynamic balance between the continual build-up and breakdown of bone matrix by two cell types, the osteoblasts and osteoclasts, acting together as a coordinated, remodeling unit. This conceptualization has served extraordinarily well as a focal point for understanding how mutations, chemical mediators, and mechanical force, as well as external influences (e.g., drugs, diet) affect bone structure and function. However, the need remains to better understand and predict the consequences of manipulating any single factor, or combination of factors, within the context of this complex system's multiple interacting pathways. Mathematical models are a natural extension of conceptual models, providing dynamic, quantitative descriptions of the relationships among interacting components. This formalization creates the ability to simulate the natural behavior of a system, as well as its modulation by therapeutic or dietetic interventions. A number of mathematical models have been developed to study complex bone functions, but most include only a limited set of biological components needed to address a few specific questions. However, it is possible to develop larger, multiscale models that capture the dynamic interactions of many biological components and relate them to important physiological or pathological outcomes that allow broader study. Examples of such models include Entelos' PhysioLab platforms. These models simulate the dynamic, quantitative interactions among a biological system's biochemicals, cells, tissues, and organs and how they give rise to key physiologic and pathophysiologic outcomes. We propose that a similar predictive, dynamical, multiscale mathematical model of bone remodeling and metabolism would provide a better understanding of the mechanisms governing these phenomena as well as serve as an in silico platform for testing pharmaceutical and clinical interventions on metabolic bone disease. [source]

Bridge to Transplant with the HeartMate Device

JOURNAL OF CARDIAC SURGERY, Issue 4 2001
William Piccione Jr.
The incidence and prevalence of chronic heart failure continues to increase, with an estimated 400,000 new cases per year in the United States. Cardiac transplantation is an effective therapy but is severely limited to approximately 2300 patients per year due to the donor shortage. With ever increasing waiting times, a significant number of patients become severely debilitated or expire prior to transplantation. A mechanical circulatory support device was first used as a "bridge to transplantation" in 1969. Since then, mechanical devices have increased tremendously in reliability and efficaciousness. The HeartMate left ventricular assist device (LVAD) has been utilized extensively in a bridge to transplant application with excellent results. Patients refractory to aggressive medical management can be sustained reliably until transplantation. In addition, bridging allows for the correction of physiologic and metabolic dearrangements often seen in these severely ill patients prior to transplantation. Nutritional, economic, and quality-of-life issues also favor earlier LVAD placement in refractory patients. This report summarizes the overall bridging experience with the HeartMate LVAD and focuses on our experience with this device at Rush-Presbyterian-St. Luke's Medical Center. [source]

The effects of osmotic stress on the structure and function of the cell nucleus

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010
John D. Finan
Abstract Osmotic stress is a potent regulator of the normal function of cells that are exposed to osmotically active environments under physiologic or pathologic conditions. The ability of cells to alter gene expression and metabolic activity in response to changes in the osmotic environment provides an additional regulatory mechanism for a diverse array of tissues and organs in the human body. In addition to the activation of various osmotically- or volume-activated ion channels, osmotic stress may also act on the genome via a direct biophysical pathway. Changes in extracellular osmolality alter cell volume, and therefore, the concentration of intracellular macromolecules. In turn, intracellular macromolecule concentration is a key physical parameter affecting the spatial organization and pressurization of the nucleus. Hyper-osmotic stress shrinks the nucleus and causes it to assume a convoluted shape, whereas hypo-osmotic stress swells the nucleus to a size that is limited by stretch of the nuclear lamina and induces a smooth, round shape of the nucleus. These behaviors are consistent with a model of the nucleus as a charged core/shell structure pressurized by uneven partition of macromolecules between the nucleoplasm and the cytoplasm. These osmotically-induced alterations in the internal structure and arrangement of chromatin, as well as potential changes in the nuclear membrane and pores are hypothesized to influence gene transcription and/or nucleocytoplasmic transport. A further understanding of the biophysical and biochemical mechanisms involved in these processes would have important ramifications for a range of fields including differentiation, migration, mechanotransduction, DNA repair, and tumorigenesis. J. Cell. Biochem. 109: 460,467, 2010. © 2009 Wiley-Liss, Inc. [source]

LDL lipid apheresis rapidly increases peripheral endothelial progenitor cell competence

JOURNAL OF CLINICAL APHERESIS, Issue 5 2009
Daniel Patschan
Abstract Background and Aim: Endothelial progenitor cells (EPCs) have been shown to promote neovascularization under physiologic and pathologic conditions. Statins have been documented to increase the total number of circulating EPCs in long-term treated patients. Lipid apheresis is used to treat patient with refractory hyperlipidemia. The aim of our study was to evaluate whether lipid apheresis is associated with EPC mobilization. Methods: Thirteen patients with refractory hyperlipidemia (analysis at the beginning and at the end of a single lipid apheresis treatment) and 10 healthy controls were included into the study. For quantifying total peripheral EPCs, CD133+/Flk-1+ myelo-monocytic blood cells were enumerated by flow cytometry. The proliferative potential of EPCs was evaluated by a "colony-forming unit" assay. In some patients, EPC eNOS expression was evaluated before and after treatment. Results: Circulating EPCs and the cells' proliferative activity were lower in hyperlipidemia patients as compared to controls (0.14 ± 0.07 vs. 0.6 ± 0.14, P = 0.01, and 13.9 ± 4.9 vs. 45.6 ± 8.1, P = 0.0007). Lipid apheresis treatment was not associated with an increase in total EPCs. The cells' proliferative activity was strongly stimulated by lipid apheresis as reflected by an increase in the number of EPC colonies (13.9 ± 4.9 to 34.1 ± 7.3, P = 0.035). Analysis of EPC eNOS expression revealed a threefold increase in the cellular expression intensity after lipid apheresis. Conclusions: Patients with refractory hyperlipidemia exhibit lower peripheral EPC numbers and a lower proliferative activity of circulating EPCs than healthy controls. A single lipid apheresis treatment significantly stimulates EPC proliferation, it furthermore increases cellular eNOS. In summary, these results show that lipid apheresis mediates beneficial effects on the EPC system as an essential element in the process of vascular repair in the human organism. J. Clin. Apheresis 2009. © 2009 Wiley-Liss, Inc. [source]

Evaluation of metalloproteinases 2 and 9 and their inhibitors in physiologic and pre-eclamptic pregnancy

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2009
Martina Montagnana
Abstract Matrix metalloproteinases (MMPs) are a family of zinc and calcium-dependent endopeptidases involved in remodeling and physiological homeostasis of extracellular matrix (ECM). The metalloproteinases activity is predominantly modulated by specific tissue inhibitors of matrix metalloproteinases (TIMPs). The balance between MMPs and TIMPs is likely to play an important role in remodeling uterine arteries in pregnancy, and it may represent means by which vasodilatation is maintained in later pregnancy. Moreover, increased levels of MMPs and in particular MMP-2 play a role in the vascular alterations induced by hypertension. The aim of this study was the evaluation of MMP-2 and -9, along with their inhibitors TIMP-1 and -2, in pre-eclamptic women compared with normotensive pregnancy and non-pregnant women. Fourteen pre-eclamptic women were compared with 37 normotensive women in different gestational age and 21 non-pregnant women. Multiplexed sandwich enzyme-linked immunosorbent assay was used to measure MMPs and TIMPs simultaneously. MMP-2 levels were significantly higher in pre-eclamptic women vs. both non-pregnant and physiologic pregnant women. MMP-9 concentrations were significantly higher in physiologic pregnant vs. non-pregnant women. The serum levels of TIMP-1 were significantly higher in pre-eclamptic vs. both non-pregnant and physiologic pregnant women. TIMP-2 values were higher in physiologic pregnant women and pre-eclamptic women vs. non-pregnant women. A positive correlation between MMP-9 values and gestational age was observed in normal pregnant women. Results of the present investigation confirm that MMP-2 and TIMP-1 values are significantly higher in preeclampsia. We confirm that the modification of the fine balance between MMPs and their inhibitors plays a greater role in the structural and functional vascular changes of women with complicated pregnancies. J. Clin. Lab. Anal. 23:88,92, 2009. © 2009 Wiley-Liss, Inc. [source]

Genetic, physiologic and ecogeographic factors contributing to variation in Homo sapiens: Homo floresiensis reconsidered

JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 6 2006
GARY D. RICHARDS
Abstract A new species, Homo floresiensis, was recently named for Pleistocene hominid remains on Flores, Indonesia. Significant controversy has arisen regarding this species. To address controversial issues and refocus investigations, I examine the affinities of these remains with Homo sapiens. Clarification of problematic issues is sought through an integration of genetic and physiological data on brain ontogeny and evolution. Clarification of the taxonomic value of various ,primitive' traits is possible given these data. Based on this evidence and using a H. sapiens morphological template, models are developed to account for the combination of features displayed in the Flores fossils. Given this overview, I find substantial support for the hypothesis that the remains represent a variant of H. sapiens possessing a combined growth hormone,insulin-like growth factor I axis modification and mutation of the MCPH gene family. Further work will be required to determine the extent to which this variant characterized the population. [source]

Enzymatic Degradation Protects Neurons from Glutamate Excitotoxicity

JOURNAL OF NEUROCHEMISTRY, Issue 3 2000
Christopher C. Matthews
Abstract: Several enzymes with the capacity to degrade glutamate have been suggested as possible neuroprotectants. We initially evaluated the kinetic properties of glutamate pyruvate transaminase (GPT; also known as alanine aminotransferase), glutamine synthetase, and glutamate dehydrogenase under physiologic conditions to degrade neurotoxic concentrations of glutamate. Although all three enzymes initially degraded glutamate rapidly, only GPT was able to reduce toxic (500 ,M) levels of glutamate into the physiologic (<20 ,M) range. Primary cultures of fetal murine cortical neurons were subjected to paradigms of either exogenous or endogenous glutamate toxicity to evaluate the neuroprotective value of GPT. Neuronal survival after exposure to added glutamate ranging from 100 to 500 ,M was improved significantly in the presence of GPT (,1 U/ml). Cultures were also exposed to the glutamate transporter inhibitor L- trans -pyrrolidine-2,4-dicarboxylate (PDC), which produces neuronal injury by elevating extracellular glutamate. GPT significantly reduced the toxicity of PDC. This reduction was associated with a reduction in the PDC-dependent rise in the medium concentration of glutamate. These results suggest that enzymatic degradation of glutamate by GPT can be an alternative to glutamate receptor blockade as a strategy to protect neurons from excitotoxic injury. [source]

Effects of EP1 receptor on cerebral blood flow in the middle cerebral artery occlusion model of stroke in mice

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2007
Sofiyan Saleem
Abstract The lipid mediator prostaglandin E2 (PGE2) exhibits diverse biologic activity in a variety of tissues. Four PGE2 receptor subtypes (EP1,4) are involved in various physiologic and pathophysiologic conditions, but differ in tissue distribution, ligand-binding affinity, and coupling to intracellular signaling pathways. To characterize the role of the EP1 receptor, physiologic parameters (mean arterial blood pressure, pH, blood gases PaO2 and PaCO2, and body temperature), cerebral blood flow (CBF), and neuronal cell death were studied in a middle cerebral artery occlusion model of ischemic stroke in wild-type (WT) and EP1 knockout (EP1,/,) mice. The right middle cerebral artery was occluded for 60 min, and absolute CBF was measured by [14C] iodoantipyrine autoradiography. The effect of EP1 receptor on oxidative stress in neuronal cultures was investigated. Although no differences were observed in the physiologic parameters, CBF was significantly (P < 0.01) higher in EP1,/, mice than in WT mice, suggesting a role for this receptor in physiologic and pathophysiologic control of vascular tone. Similarly, neuronal cultures derived from EP1,/, mice were more resistant (90.6 ± 5.8% viability) to tert -butyl hydroperoxide-induced oxidative stress than neurons from WT mice (39.6 ± 17.2% viability). The EP1 receptor antagonist SC-51089 and calcium channel blocker verapamil each attenuated the neuronal cell death induced by PGE2. Thus, the prostanoid EP1 receptor plays a significant role in regulating CBF and neuronal cell death. These findings suggest that pharmacologic modulation of the EP1 receptor might be a means to improve CBF and neuronal survival during ischemic stroke. © 2007 Wiley-Liss, Inc. [source]

Women With High-Risk Pregnancies, Problems, and APN Interventions

JOURNAL OF NURSING SCHOLARSHIP, Issue 4 2007
Dorothy Brooten
Purpose: To (a) describe women's prenatal and postpartum problems and advanced practice nurses (APN) interventions; and (b) determine if problems and APN interventions differed by women's medical diagnosis (diabetes, hypertension, preterm labor). Design and Methods: Content analysis of 85 interaction logs created by APNs during a randomized clinical trial in which half of physician-provided prenatal care was substituted with APN-provided prenatal care in the women's homes. Patients' problems and APN interventions were classified with the Omaha Classification System. Findings: A total of 212,835 health problems and 212,835 APN interventions were identified. The dominant antenatal problems were physiologic (59.2%) and health-related behaviors (33.3%); postpartum were physiologic (44.0%) and psychosocial problems (31.6%). Antenatally, women with diabetes had significantly more health-related behavior problems; women with preterm labor had more physiologic problems. APN surveillance interventions predominated antenatally (65.6%) and postpartum (66.0%), followed by health teaching, guidance, and counseling both antenatally (25.4%) and postpartum (28.1%). Women with chronic hypertension required significantly more case-management interventions. Conclusions: The categories of women's problems were largely similar across medical diagnostic groups. Interventions to address women's problems ranged from assessing maternal and fetal physiologic states to teaching interpersonal relationships and self-care management to assisting with transportation and housing. Data show the range of APN knowledge and skills needed to improve maternal and infant outcomes and ultimately reduce healthcare costs in women with high-risk pregnancies. [source]

Effects of Obesity on Pregnancy

JOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 2 2008
Shelia A. Smith
ABSTRACT Objectives:, To examine physiologic and psychological outcomes associated with maternal obesity in pregnancy and patterns of pregnancy weight gain. To identify effective interventions for maternal obesity. Data sources and study selection:, Search of obesity and pregnancy research conducted over the past 10 years using CIHAHL, Medline ERIC, and PyscInfo databases. Studies including the following keywords were included in the review: obesity, weight gain, body image, pregnancy weight gain, pregnancy obesity complications, preeclampsia and gestational diabetes. Articles were included based on scientific merit and research outcomes. Data synthesis and conclusions:, Maternal obesity is a serious condition that significantly impacts not only mothers' health but also the health and future of their children. It is paramount that all levels of health care providers be aware of consequences of obesity and be knowledgeable of effective interventions. No effective long-term interventions have been demonstrated to prevent or control obesity during pregnancy. The paucity of published results of pregnancy and postpartum interventions to address weight gain in pregnancy suggests the need for more community and individualized based intervention studies, especially focusing on long-term effects. [source]

The AWHONN Near-Term Infant Initiative: A Conceptual Framework for Optimizing Health for Near-Term Infants

JOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 6 2005
Barbara Medoff-Cooper
In June 2005, the Association of Women's Health, Obstetric and Neonatal Nurses launched a multiyear initiative to address the unique physiologic and developmental needs of near-term infants (NTIs) defined as those born between 34 and 37 weeks post-menstrual age. The Optimizing Care for the Near-Term Infant Conceptual Model integrates the concepts of neonatal physiologic functional status, nursing care practices, care environment, and the essential role of the family both in the hospital and beyond. The elements of the model will serve to guide program and resource development within the Near-Term Infant Initiative. Goals of the initiative are to raise awareness of the NTI population's unique needs, emphasize the need for research, encourage development and adoption of evidence-based guidelines to promote safe care, and provide resources that assist nurses and other health care professionals in risk-based assessment of NTIs. [source]

symptom Experience in Women After Hysterectomy

JOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 5 2001
Kimberly H. Kim RN
Objective: To review the literature addressing the symptom experience of women after hysterectomy. Data Sources: Computerized searches in MEDLINE and CINAHL, as well as texts and references cited in articles. Key concepts in the searches included hysterectomy, sleep disturbance and pain, hysterectomy and fatigue, hysterectomy, depression, and depressed mood. Study Selection: Articles and comprehensive works relevant to key concepts and published after 1970, with an emphasis on new findings from 1990 to 2000. Sixty-four citations were identified as useful to this review. Data Extraction: Data were organized under the following headings: women and hysterectomy, biopsychosocial perspectives, common symptoms after hysterectomy (pain, disturbed sleep, fatigue, depressed mood, anxiety), and significance of review (implications). Data Synthesis: Literature suggests that after a hysterectomy, women experience complications during the postoperative recovery period that may vary with the type of surgical procedure. During this period, the quantity and quality of sleep as well as other symptoms (pain, fatigue, anxiety, and depression) are influenced by various physiologic, psychologic, and social factors. Despite limited evidence that sleep problems may occur frequently during the recovery period, only a few researchers have systematically examined sleep patterns in women after hysterectomy. None of these studies, however, used objective sleep measures or examined multiple dimensions of these women's lives. Conclusions: This review conceptualized the women's symptom experience as the experience of specific symptoms (pain, sleep disturbance, fatigue, depressed mood, and anxiety) that were influenced by biopsychosocial factors. [source]

Focal lymphocytic infiltration in aging human palatal salivary glands: a comparative study with labial salivary glands

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2001
Marilena Vered
Abstract: Investigation of age-related prevalence of various types of focal lymphocytic infiltration (FLI) and degrees of histomorphologic changes was conducted on 120 biopsies of palatal and labial salivary glands (PSG and LSG, respectively) obtained from autopsy subjects free of salivary gland tumors/diseases. Biopsies were divided into young (<30 years, n=30), adult (30,60 years, n=45) and old (>60 years, n=45) age groups. A modified Chisholm & Mason grading system was used to record grades of FLI and a modified Greenspan et al. system was used to evaluate the severity of histomorphologic changes. The prevalence of FLI in PSG increased significantly from 10% in the young group to 46.6% in the old group (P=0.0012). No significant changes were found with aging in LSG. FLI was significantly more prevalent in the adult and old age groups in PSG as compared with LSG (P=0.015 and P=0.003, respectively). Both glands demonstrated significant histomorphologic changes among age groups (p<0.0001); however, these changes were significantly less common in the old age group in PSG as compared to LSG (P=0.003). In cases showing severe histomorphologic changes, FLI was not present. Therefore, FLI should not be considered as part of the deteriorating histomorphologic changes that are usually encountered in salivary glands with aging. The immunologic profile of these infiltrates should be further clarified to understand their role, both in physiologic and pathologic conditions. [source]

Expression of matrix metalloproteinase-1, matrix metalloproteinase-2 and extracellular metalloproteinase inducer in human periodontal ligament cells stimulated with interleukin-1beta

JOURNAL OF PERIODONTAL RESEARCH, Issue 6 2009
J. Xiang
Background and Objectives: Matrix metalloproteinases (MMPs), produced by both infiltrating and resident cells of the periodontium, play important roles in physiologic and pathologic events. Both interleukin-1beta and extracellular MMP inducer can stimulate the expression of MMPs, which in turn leads to breakdown of the periodontium. However, it is currently unknown whether interleukin-1beta up-regulates MMPs through stimulating the expression of extracellular MMP inducer. The aims of this study were to investigate the effect of interleukin-1beta on the expression of MMP-1, MMP-2 and extracellular MMP inducer in human periodontal ligament cells and to evaluate whether the regulation of MMP-1 and MMP-2 by this cytokine occurred through an effect on extracellular MMP inducer expression. Material and Methods: Cultured human periodontal ligament cells were treated with varying concentrations (0.01,10 ng/mL) of interleukin-1beta at for 6, 12 and 24 h. Reverse transcription,polymerase chain reaction, enzyme-linked immunosorbent assay, gelatin zymography and western blotting were performed to measure the mRNA and protein levels of MMP-1, MMP-2 and extracellular MMP inducer. Results: Basal levels of mRNA and protein for MMP-1, MMP-2 and extracellular MMP inducer were detected in untreated human periodontal ligament cells. Interleukin-1beta significantly up-regulated the expression of MMP-1 and MMP-2 mRNA and protein (p < 0.05); however, the levels of mRNA and protein for extracellular MMP inducer were not significantly different (p > 0.05). In the culture medium, the concentration of MMP-1 was also increased significantly, but the concentration of MMP-1 was not related to the concentration of extracellular MMP inducer (R2 = 0.2538, p > 0.05). Conclusion: Interleukin-1beta up-regulated the levels of MMP-1 and MMP-2, but it did not alter the expression of extracellular MMP inducer. Expression of MMP-1 and MMP-2 might be elevated by interleukin-1beta and extracellular MMP inducer via two different signal pathways. [source]

The antiproliferative activity of melatonin in B65 rat dopaminergic neuroblastoma cells is related to the downregulation of cell cycle-related genes

JOURNAL OF PINEAL RESEARCH, Issue 1 2008
Javier G. Pizarro
Abstract:, A potential application of melatonin is its ability to rescue many cell types from cell death, because of its antioxidant properties. Likewise, recent studies suggest that melatonin may also be used as an anti-tumor drug, due to its anti-proliferative properties in tumor cells when administered at physiologic or pharmacologic doses. In the present study, we investigated the mechanisms involved in the apoptosis induced by acute exposure to melatonin and roscovitine in the rat dopaminergic neuroblastoma B65 cell line. Cell growth studies revealed that, at 24 hr of treatment, roscovitine blocked cell growth and induced apoptosis whereas melatonin delayed cell growth and induced a slight increase in the number of apoptotic nuclei. Melatonin also increased the percentage of cells in the G1-phase of the cell cycle, whereas roscovitine blocked cells in the G2/M-phase. Both compounds significantly downregulated the transcriptional activity of cdk4, while melatonin also downregulated cdk2 and cyclin D1. Taken together, our data show that melatonin at millimolar concentrations inhibits dopaminergic B65 proliferation, induces cell apoptosis, and modulates cell cycle progression by inhibiting the transcriptional activity of cyclins and cdks related to the progression of the G1-phase. [source]

Association Between Ethanol and Sucrose Intake in the Laboratory Mouse: Exploration Via Congenic Strains and Conditioned Taste Aversion

ALCOHOLISM, Issue 3 2000
David A. Blizard
Background: A substantial body of literature indicates that intakes of "sweet' solutions and ethanol are positively correlated across inbred strains of rats and mice but there has been speculation that the correlation is fortuitous and there is no agreement on the underlying mechanism. Methods and Results: We assessed the correlation between intake of sucrose and ethanol in congenic mice created by backcrossing alleles favoring sucrose intake from the BXD RI-5 strain into DBA/2J. In addition, to probe more specifically the interrelationship between intake of the two solutions, we examined aversion generalization from sucrose to ethanol in C57BL/6J mice. Among the congenic mice, a statistically significant product-moment correlation of r= 0.36 (p < 0.02) was found between 6-hr intake of sucrose corrected for differences in baseline water intake and preference for 10% ethanol presented in a 96-hr 2-bottle test. Furthermore, C57BL/6J male mice conditioned to avoid a 0.2 M sucrose solution generalized their aversion to a 10% ethanol solution presented in the same 2-bottle test, drinking 42.1 ± 9.38% (mean ± SE) of their total fluid intake from the ethanol tube, compared with the control group mean of 69.86 ± 8.84%. Conclusions: The positive association between intake of sucrose and ethanol in congenic mice provides strong evidence that the previously demonstrated genetic correlation between intake of these solutions is not the result of fortuitous fixation of unrelated alleles and provides suggestive evidence that, at least in the B6/D2 lineage, the genetic association between intakes of the two solutions reflects close linkage or the pleiotropic effects of the same genes. The demonstration that a conditioned taste aversion to sucrose generalized to ethanol in the C57BL/6J inbred mouse strain is an extension of similar observations in outbred rats and specifically demonstrates that intake of the two solutions is controlled by some of the same physiologic or neurological processes and thus is consistent with the pleiotropic interpretation of the genetic correlation. [source]