Pathologic Physiology Research Articles

Role of MicroRNAs in the Trabecular Meshwork

MicroRNAs (miRNAs) are now recognized as important post-transcriptional regulators of gene expression. MiRNAs are known to modulate cellular functions relevant to the normal and pathological physiology of the trabecular meshwork (TM) such as cell contraction and extracellular matrix turnover. There is also increasing evidence supporting the role of miRNAs in the pathogenesis of multiple diseases, and their potential value as both biomarkers of disease and therapeutic targets. However, compared with other tissues, our current knowledge regarding the roles played by miRNAs in the TM is still very limited. Here, we review the information currently available about miRNAs in the TM and discuss the main challenges and opportunities to incorporate the rapid progress in miRNA biology to the understanding of the normal and pathological physiology of the TM, and to develop novel clinical applications for diagnosis and therapy of high intraocular pressure.

Prospects for improving the management tactics for patients with gastroesophageal reflux disease complicated by Barrett's esophagus

The paper presents the new principles relative to adequate diagnosis, management tactics, and rational treatment regimens in patients with gastroesophageal reflux disease (GERD) complicated by the development of Barrett's esophagus. The paper contains up-to-date, mainly original information on the pathological physiology, clinical picture, and principles of diagnosis of this form of GERD. It outlines data on approaches to the early diagnosis and prevention of neoplastic progression in Barrett's esophagus, by taking into account recent advances in pharmacotherapy.

Anesthetic experience of a patient with Prune-belly syndrome.

Anesthetic experience of a patient with Prune-belly syndrome.

A Fully Implantable Pacemaker for the Mouse: From Battery to Wireless Power

Animal models have become a popular platform for the investigation of the molecular and systemic mechanisms of pathological cardiovascular physiology. Chronic pacing studies with implantable pacemakers in large animals have led to useful models of heart failure and atrial fibrillation. Unfortunately, molecular and genetic studies in these large animal models are often prohibitively expensive or not available. Conversely, the mouse is an excellent species for studying molecular mechanisms of cardiovascular disease through genetic engineering. However, the large size of available pacemakers does not lend itself to chronic pacing in mice. Here, we present the design for a novel, fully implantable wireless-powered pacemaker for mice capable of long-term (>30 days) pacing. This design is compared to a traditional battery-powered pacemaker to demonstrate critical advantages achieved through wireless inductive power transfer and control. Battery-powered and wireless-powered pacemakers were fabricated from standard electronic components in our laboratory. Mice (n = 24) were implanted with endocardial, battery-powered devices (n = 14) and epicardial, wireless-powered devices (n = 10). Wireless-powered devices were associated with reduced implant mortality and more reliable device function compared to battery-powered devices. Eight of 14 (57.1%) mice implanted with battery-powered pacemakers died following device implantation compared to 1 of 10 (10%) mice implanted with wireless-powered pacemakers. Moreover, device function was achieved for 30 days with the wireless-powered device compared to 6 days with the battery-powered device. The wireless-powered pacemaker system presented herein will allow electrophysiology studies in numerous genetically engineered mouse models as well as rapid pacing-induced heart failure and atrial arrhythmia in mice.

H.2 - DOES PRENATAL AND ADULT METHAMPHETAMINE EXPOSURE AFFECT SPATIAL LEARNING OF FEMALE RATS?

Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University Prague, Czech Republic

Simulation Analysis on Mechanical Effect Based on ADAMS and Matlab Software

Muscle length change and mechanical effect have an important meaning to the analysis of the relationship between the muscle fatigues. It can be widely used in muscle physiology pathology research which played a role of technical guidance to cure muscle fatigue damage and prevent muscle fatigue. This paper analyzes the muscle physiology theory. It concludes that the muscle is composed of a series of muscle bundle which is made up by a set of parallel muscle fiber through the theoretical analysis. Then, it sets up a model formula of muscle length change and stress relationship based on the mechanical theory. It gets muscle movement and mechanical related parameters by measurement method. It uses the ADAMS and Mat lab software to do the simulation analysis on the muscle movement. It establishes the muscular movement speed and the 3 d graphics of muscle displacement under the action of muscle force through the Mat lab software. Through the ADMAS software it establishes the displacement curve under the action of muscle forces which changes with time and it provides a theoretical reference for the research of muscle length change and mechanical relationship based on muscle physiology theory.

Human Placental MicroRNAs and Preeclampsia1

MicroRNAs are a class of noncoding small RNAs that regulate the expression of nearly 30% of all the human genes and participate in all fundamental cell processes. Genome-wide analysis has revealed that human placenta expresses more than 600 miRNA species, including placenta-specific ones with high levels of expression. Comparative analysis also has revealed many differentially expressed miRNAs with either high or low levels of expression in human placentas from normal versus preeclamptic pregnancies, indicating an important role of miRNAs in normal and pathological placental physiology. Although limited information is currently available as to how miRNA regulates human placental development and function, there are studies suggesting that preeclampsia-associated differentially expressed miRNAs possess critical roles in regulating placental development and function via targeting specific genes with diverse known functions. Herein we summarize the current findings regarding the expression of placental miRNAs and their function, especially in the trophoblast cells. We have recently found that the angiogenesis-associated miR-17-family miRNAs are upregulated in preeclamptic compared with normotensive placentas and they target the ephrin-B2/Eph receptor B4 (EPHB4) system. Because ephrin-B2 and EPHB4 has been previously shown to play a crucial role in trophoblast invasion into maternal spiral artery and vascular patterning during early human placental development, the miR-17-ephrin-B2/EPHB4 pathway seems to be a novel miRNA pathway for regulating normal and aberrant placental development during preeclampsia.

Aortic Occlusion Hemodynamic Attenuation With Valproic Acid

Objectives: Valproic acid (VPA; a histone deacetylase inhibitor) has demonstrated significant decreases in resuscitation requirements as well as minimizing pathologic physiology following short term aortic occlusion. The purpose of this study was to compare the cardiac and hemodynamic changes with VPA administration following supraceliac aortic occlusion. Methods: 19 swine were exposed to a 35% blood volume hemorrhage followed by a supraceliac aortic cross clamp only model with valproic acid (400 mg/kg) administered as a drip continuously during supraceliac aortic cross clamping (CC, n 1⁄4 9). Hemodynamics were measured with the use of arterial blood pressure monitor and a pulmonary artery thermodilution catheter. Results: 10 swine were divided into two equal groupssham and model. In this validation, hemodynamics were significantly different as measured after hemorrhage and cross clamp by mean arterial pressure (MAP; P 1⁄4 .024), heart rate (P < .001), cardiac index (CI; P 1⁄4 .005). In the comparison arm of control and cross clamp group, there was a significant attenuation in the adverse hemodyamic response with administration of VPA (n 1⁄4 9) during cross clamp (MAP 1⁄4 87 6 28 vs CC-122 6 43 mm Hg; P 1⁄4 .02; HR 1⁄4 124 6 23 vs CC-161 6 32 bpm; P 1⁄4 .01). Additionally, throughout the cross clamp application, there was a significantly decreased hyperdynamic response with the administration of VPA (Fig). Conclusions: VPA helps attenuate the adverse hyperdynamic cardiac response following a hemorrhagic event and subsequent aortic occlusion. The hemodynamic response appeared to be not only significant at each time interval, but sustained as cross clamp times increased. Additionally, VPA seemed to minimize pathologic hemodynamic variation and provide cardiac protection through minimizing cardiac stress and work of the heart during aortic occlusion. Author Disclosures: M. W. Causey: Nothing to disclose; M. Martin: Nothing to disclose; S. Miller: Nothing to disclose; N. Singh: Nothing to disclose.

Microvolt T wave alternans in adults with congenital heart diseases characterized by right ventricle pathology or single ventricle physiology: a case control study

BackgroundAmong adults with congenital heart diseases (CHD) evaluation of sudden cardiac death (SCD) risk remains a great challenge. Although microvolt T-wave alternans has been incorporated into SCD risk stratification algorithm, its role in adults with CHD still requires investigation. We sought to determine the incidence of MTWA in this specific group and its coincidence with ventricular arrhythmia (VA) and other clinical findings presumably associated with SCD.MethodsA case–control study was performed in which 102 patients with CHD characterized by right ventricle pathology or single ventricle physiology (TGA, UVH, Ebstein’s anomaly, ccTGA, Eisenmenger syndrome, DORV, CAT, unoperated ToF) were compared to 45 age- and sex-matched controls. All subjects underwent spectral MTWA test, ambulatory ecg monitoring, cardiopulmonary test, BNP assessment. After excluding technically inadequate traces, the remaining MTWA results were classified as positive(+), negative(−) and indeterminate(ind). Due to similar prognostic significance MTWA(+) and (ind) were combined into a common group labeled ‘abnormal’.ResultsAbnormal MTWA was present more often in the study group, compared to controls (39.2% vs 2.3%, p = 0.00001). Sustained ventricular tachycardia (sVT) was observed more often among subjects with abnormal MTWA compared to MTWA(−): 19.4% vs 3.6%, p = 0.026. The patients with abnormal MTWA had a lower blood saturation (p = 0.047), more often were males (p = 0.031), had higher NYHA class (p = 0.04), worse cardiopulmonary parameters: %PeakVO2 (p = 0.034), %HRmax (p = 0.003). Factors proven to increase probability of abnormal MTWA on multivariate linear regression analysis were: sVT (OR = 20.7, p = 0.037) and male gender (OR = 15.9, p = 0.001); on univariate analysis: male gender (OR = 2.7, p = 0.021), presence of VA (OR = 2.6, p = 0.049), NYHA > I (OR = 2.06, p = 0.033), %HRmax (OR = 0.94, p = 0.005), %PeakVO2 (OR = 0.97, p = 0.042), VE/VCO2slope (OR = 1.05, p = 0.037).ConclusionsAbnormal MTWA occurs significantly more often in adults with the chosen forms of CHD than among healthy subjects. The probability of abnormal MTWA increases in patients with malignant VA, in males and among subjects with heart failure and cyanosis. MTWA might be of potential role in risk stratification for SCD in adults with CHD.

A Hospital CEO's Perspective: Radiology Should Lead the Way in Reforming Health Care Delivery

Radiology and medical imaging systems play a central role in most health care systems. As science and technology have advanced, the ability to medically image and diagnose anatomic and physiologic pathology has increased exponentially. This capability is identified as a necessary core competency of all "general hospitals" by the American Hospital Association. Medical imaging accounts for 7.5% of health care spending in the United States, with $175 billion spent annually. Accordingly, the facilities and the physicians who provide this patient care will be a central focus in the crusade for patient-centered, efficient, and transportable patient care. As the demand in hospitals and health care systems for quality, safety, and efficiency through IT and clinical systems improvement continues to accelerate, the demand for more systems that use best-practice support and discrete data results for incorporation into systems reporting initiatives will also accelerate and grow. Medical imaging and the radiologist's report are central to creating this integrated, patient-centric system with hospitals. Ancillary to the patient care component of the functional use of the data reporting systems is the ability to use the clinical reporting information efficiently to support or defend clinical decisions associated with hospital care and to provide an improved means by which required quality metrics are made available for ensuring safety and improving care in the future.

The Many Faces of C/EBPδ and their Relevance for Inflammation and Cancer

The CCAAT/enhancer binding protein delta (CEBPD, C/EBPδ) is a transcription factor that modulates many biological processes including cell differentiation, motility, growth arrest, proliferation, and cell death. The diversity of C/EBPδ's functions depends in part on the cell type and cellular context and can have opposing outcomes. For example, C/EBPδ promotes inflammatory signaling, but it can also inhibit pro-inflammatory pathways, and in a mouse model of mammary tumorigenesis, C/EBPδ reduces tumor incidence but promotes tumor metastasis. This review highlights the multifaceted nature of C/EBPδ's functions, with an emphasis on pathways that are relevant for cancer and inflammation, and illustrates how C/EBPδ emerged from the shadow of its family members as a fascinating “jack of all trades.” Our current knowledge on C/EBPδ indicates that, rather than being essential for a specific cellular process, C/EBPδ helps to interpret a variety of cues in a cell-type and context-dependent manner, to adjust cellular functions to specific situations. Therefore, insights into the roles and mechanisms of C/EBPδ signaling can lead to a better understanding of how the integration of different signaling pathways dictates normal and pathological cell functions and physiology.

Imaging of the appearance time of cerebral blood using [15O]H2O PET for the computation of correct CBF

BackgroundQuantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. Positron emission tomography (PET) with H215O (or C15O2) can quantify CBF and apply kinetic analyses, including autoradiography (ARG) and the basis function methods (BFM). These approaches, however, are sensitive to input function errors such as the appearance time of cerebral blood (ATB), known as the delay time. We estimated brain ATB in an image-based fashion to correct CBF by accounting for differences in computed CBF values using three different analyses: ARG and BFM with and without fixing the partition coefficient.MethodsSubject groups included those with no significant disorders, those with elevated cerebral blood volume, and those with reduced CBF. All subjects underwent PET examination, and CBF was estimated using the three analyses. The ATB was then computed from the differences of the obtained CBF values, and ATB-corrected CBF values were computed. ATB was also estimated for regions of interest (ROIs) of multiple cortical regions. The feasibility of the present method was tested in a simulation study.ResultsThere were no significant differences in the obtained ATB between the image- and ROI-based methods. Significantly later appearance was found in the cerebellum compared to other brain regions for all groups. In cortical regions where CBF was reduced due to occlusive lesions, the ATB was 0.2 ± 1.2 s, which was significantly delayed relative to the contralateral regions. A simulation study showed that the ATB-corrected CBF was less sensitive to errors in input function, and noise on the tissue curve did not enhance the degree of noise on ATB-corrected CBF image.ConclusionsThis study demonstrates the potential utility of visualizing the ATB in the brain, enabling the determination of CBF with less sensitivity to error in input function.

Pseudomyxoma Peritonei: Uninvited Goblet Cells, Ectopic MUC2

Pseudomyxoma peritonei (PMP) is a challenging clinical syndrome characterized by multifocal peritoneal collections of extracellular mucins. Mucins are high molecular weight, heavily glycosylated proteins differentially expressed by various types of epithelial cells. In this pathological condition, goblet cells originating from a mucinous tumor of the appendix gain access to the peritoneal cavity where they secrete mucin ectopically. Secreted mucin thus accumulates and forms the characteristic feature of the disease. Therefore, goblet cells and secreted mucins constitute the two key elements of the disease. MUC2 is the PMP's specific, predominant mucin. It is a highly viscous, gel-forming mucin that accounts for the characteristic appearance of PMP mucinous deposits as compared to the mucinous implants of ovarian origin. Mucin deposits are the real cause of PMP’s morbid complications irrespective of the site of origin, the mechanism of peritoneal spread, or the level of neoplastic transformation. In this article, role of mucin in gastrointestinal physiology and PMP pathology are reviewed and the potential of MUC2 as a therapeutic target are discussed

Respiratory ventricular area changes measured with real-time cardiac magnetic resonance: A new, accurate, and reproducible approach for the diagnosis of pericardial constriction

Demonstration of pericardial pathology and/or constrictive physiology remains the basis for the diagnosis of pericardial constriction (PC). Cardiovascular magnetic resonance (CMR) is increasingly used to depict pericardial abnormalities [1–6]. Moreover, the Society of CMR endorses visual determination of abnormal respiratory septal motion characteristic of constrictive physiology on real-time cine imaging [7], and preliminary CMR studies have attempted to quantify this sign of increased ventricular interdependence [8,9] (Fig. 1).

Long-term outcomes of Hirschsprung's disease

Despite significant developments in the understanding of the pathologic anatomy and physiology of Hirschsprung's disease (HD), the results of surgical therapy remain far from perfect. The functional defects and psychosocial difficulties that occur commonly in children with HD are passed on to adulthood in a significant proportion of patients. Recent prospective and adequately controlled cross-sectional studies reveal that constipation and fecal soiling are common late sequelae in adulthood. HD patients show uniformly lower scores of overall bowel function than healthy control subjects. Functional outcome and quality of life may be interrelated and deteriorate with increasing age. Despite these shortcomings, at adult age, most of the HD patients appear to be able to function as normal members of the society in terms of psychosocial, occupational, and recreational activities. Patients are at risk of developing related conditions, such as cancer, that require planning of specific screening programs. Many of the long-term problems that these patients experience are specific to HD. The follow-up of HD patients should be performed by medical personnel familiar with the disease, preferably in a specialized referral center, and the follow-up should continue beyond childhood.

Biomechanical overload syndrome: defining a new diagnosis

Chronic exertional compartment syndrome (CECS) was first described in 1956,1 but little research has been performed since then to confirm the pathological physiology. An assumption is made that elevated subfascial...

Type 2 Diabetes and Mild Cognitive Impairment*

Alzheimers's disease(AD) is a continuous pathological physiology process,including pre-MCI(mild cognitive impairment,MCI),MCI and dementia.For the irreversible of the clinical course of AD,finding early and treat right in the stage of preMCI or MCI are very important for slowing down or even reverse the procession of AD.Research shows that type 2 diabetes mellitus(T2DM) is an independent risk factor for MCI and AD.This manuscript is a brief review of current concepts in the mechanisms potentially linking T2DM with cognitive impairment.

Assessing the Athlete’s Heart

The initial report of the athlete’s heart dates back to the late 1890s. The concept that endurance-based exercise and strength-based exercise lead to distinctly different changes in left ventricular (LV) structure was proposed in the 1970s and has been confirmed by more recent studies. Advances in cardiac imaging, particularly echocardiography and cardiac magnetic resonance imaging, have allowed for more precise characterization of the structural changes that develop in the hearts of athletes engaged in different sporting disciplines. Despite our improved understanding of exercise-induced cardiac remodeling, the findings of: 1) increased LV chamber dimension, 2) increased LV wall thickness, and 3) increased right ventricular (RV) chamber dimension continue to be accompanied by significant diagnostic uncertainty in clinical practice. Determining whether these entities arise from exercise-induced cardiac remodeling or represent pathologic cardiomyopathy requires the integration of a number of diagnostic techniques, including evaluations with echocardiography and/or cardiac magnetic resonance imaging. Ambiguous cases require additional testing, such as cardiopulmonary exercise testing and assessing the response to a period of prescribed detraining. Novel imaging techniques coupled with physiologic provocation that assess regional LV and RV function may make the distinction between physiologic adaptation and pathology more clear in the future.

The athlete's heart

AbstractIn this article, the authors highlight the spectrum, magnitude and determinants of the athlete's heart and provide a practical guide for differentiating physiological left ventricular hypertrophy from hypertrophic cardiomyopathy. Copyright © 2012 John Wiley &amp; Sons

Boxers motor actions ranking according to their complexity

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