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At least 451 records · Page 25Linked to original sources
PubMed2006

EBV-encoded dUTPase induces immune dysregulation: Implications for the pathophysiology of EBV-associated disease.

Epstein-Barr virus (EBV) encodes for several enzymes that are involved in viral DNA replication. There is evidence that some viral proteins, by themselves, can induce immune dysregulation that may contribute to the pathophysiology of the virus infection. In this study, we focused on the EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) and present the first evidence that the dUTPase is able to induce immune dysregulation in vitro as demonstrated by the inhibition of the replication of stimulated peripheral blood mononuclear cells (PBMCs) and the upregulation of several proinflammatory cytokines including TNF-alpha, IL-1beta, IL-8, IL-6, and IL-10 produced by unstimulated PBMCs treated with purified EBV-encoded dUTPase. Depletion of CD14-positive cells (monocytes) eliminated the cytokine profile induced by EBV dUTPase treatment. The data support the hypothesis that at least one protein of the EBV early antigen complex can induce immune dysregulation and may be involved in the pathophysiology of EBV-associated disease.

Amino Acid Sequence↗
PubMed2001

Pathophysiology of chronic heart failure.

Heart failure is a changing paradigm. The hemodynamic model, which served our needs well from the 1950s through the early 1980s, has now been largely abandoned, except for the management of decompensated patients in the hospital. The pathophysiology is exceedingly complex and involves structural changes, such as loss of myofilaments, apoptosis and disorganization of the cytoskeleton, as well as disturbances in Ca(2+) homeostasis, alteration in receptor density, signal transduction, and collagen synthesis. A more contemporary working hypothesis is that heart failure is a progressive disorder of left ventricular remodeling, usually resulting from an index event, that culminates in a clinical syndrome characterized by impaired cardiac function and circulatory congestion. This change in the framework of our understanding of the pathophysiology of heart failure is predicated on the results of numerous clinical trials conducted during the past 20 years. New therapies are now evolving that are designed to inhibit neuroendocrine and cytokine activation, whereas drugs specifically designed to heighten cardiac contractility and "unload" the left ventricle have proven to be unhelpful in long-term management of patients with chronic heart failure. However, the hemodynamic model is still relevant for patients in the hospital with decompensated heart failure, where positive inotropic drugs and vasodilators are still widely used. The modern treatment of chronic heart failure is now largely based on the neurohormonal hypothesis, which states that neuroendocrine activation is important in the progression of heart failure and that inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Thus, the evolution of treatment for chronic heart failure as a result of clinical trials has provided much enlightenment for our understanding of the fundamental biology of the disorder, a reversal of the usual flow of information from basic science to clinical investigation.

Adrenergic beta-Antagonists↗
PubMed2001

Immune complex formation after xenotransplantation : evidence of type III as well as type II immune reactions provide clues to pathophysiology.

Rejection of renal and cardiac xenografts is initiated when natural antibodies of the recipient bind to donor endothelium, activating complement on the surface of endothelial cells. Pulmonary xenotransplants, however, reveal less evidence of antibody binding and complement activation and, in contrast to other xenografts, fare worse when the complement of the graft recipient is depleted. Accordingly, we asked whether distinct immunochemical reactions might occur after xenotransplantation of the lung and what implications such reactions might have for pulmonary pathophysiology. Analysis of serum from baboons after transplantation with porcine lungs revealed complexes containing baboon IgM and porcine von Willebrand factor. The baboon IgM in these complexes was specific for Galalpha1-3Gal. Immune complexes were also seen, albeit to a lesser extent, in the serum of kidney and heart xenotransplant recipients. Deposits of porcine von Willebrand factor and baboon C3 were detected in livers and spleens of transplanted baboons. These results indicate pulmonary xenotransplantation eventuates in formation of immune complexes and in the deposition of those complexes at distant sites. Immune complex formation could explain the peculiar fate of xenoreactive antibodies after pulmonary xenotransplantation and might contribute to the pathophysiology of the lung and systemic changes not previously considered a complication of xenotransplantation.

Animals↗
PubMed1994

The pathophysiology of the sickle hemoglobinopathies and implications for perioperative management.

Patients with sickle hemoglobinopathies are at risk for unique postoperative complications and increased mortality. Understanding the pathophysiology of these disorders is important for safe perioperative management. Because there is no animal model for sickle cell disease, understanding has progressed through in vitro studies and clinical observations. This review describes the clinical manifestations of the sickle hemoglobinopathies with special emphasis on current knowledge of pathophysiology. It also discusses issues of preoperative screening, transfusion, and postoperative care.

Anemia, Sickle Cell↗
PubMed2001

The role of neurotensin in the pathophysiology of schizophrenia and the mechanism of action of antipsychotic drugs.

It has become increasingly clear that schizophrenia does not result from the dysfunction of a single neurotransmitter system, but rather pathologic alterations of several interacting systems. Targeting of neuropeptide neuromodulator systems, capable of concomitantly regulating several transmitter systems, represents a promising approach for the development of increasingly effective and side effect-free antipsychotic drugs. Neurotensin (NT) is a neuropeptide implicated in the pathophysiology of schizophrenia that specifically modulates neurotransmitter systems previously demonstrated to be dysregulated in this disorder. Clinical studies in which cerebrospinal fluid (CSF) NT concentrations have been measured revealed a subset of schizophrenic patients with decreased CSF NT concentrations that are restored by effective antipsychotic drug treatment. Considerable evidence also exists concordant with the involvement of NT systems in the mechanism of action of antipsychotic drugs. The behavioral and biochemical effects of centrally administered NT remarkably resemble those of systemically administered antipsychotic drugs, and antipsychotic drugs increase NT neurotransmission. This concatenation of findings led to the hypothesis that NT functions as an endogenous antipsychotic. Moreover, typical and atypical antipsychotic drugs differentially alter NT neurotransmission in nigrostriatal and mesolimbic dopamine (DA) terminal regions, and these effects are predictive of side effect liability and efficacy, respectively. This review summarizes the evidence in support of a role for the NT system in both the pathophysiology of schizophrenia and the mechanism of action of antipsychotic drugs.

Animals↗
PubMed1999

Pathophysiology of childhood anxiety disorders.

Prior reviews on the pathophysiology of anxiety consistently note the need for more research on biological aspects of childhood social phobia, separation anxiety disorder, and generalized anxiety disorder. The current review summarizes biological research that is relevant to these three disorders. In the first part of the review, barriers that have prevented progress in this area are delineated, and recent developments are discussed that set the stage for major advances in research on childhood anxiety disorders. In the second part of the review, studies are discussed that provide insights on the pathophysiology of childhood social phobia, separation anxiety disorder, and generalized anxiety disorder. Research on each specific disorder illustrates the manner in which recent developments in biological research facilitate novel research approaches uniquely suited for answering essential clinical questions in research on both childhood and adult anxiety disorders. For example, in research on social phobia, biological studies might enhance understandings of the longitudinal associations between individual childhood and adult disorders. In research on separation anxiety disorder, biological studies might enhance understanding on family-genetic associations between childhood and adult disorders. Finally, in research on generalized anxiety disorder, biological studies might enhance understandings of comorbidities among distinct childhood and adult disorders, particularly with respect to the relationship between anxiety and depressive disorders.

Anxiety Disorders↗
PubMed1999

Pathophysiology and clinical significance of atherosclerotic plaque rupture.

Atherosclerotic plaque rupture and resulting intracoronary thrombosis are thought to account for most acute coronary syndromes. These syndromes include unstable angina, non-Q-wave myocardial infarction (MI) and Q-wave MI. In addition, many cases of sudden cardiac death may be attributable to atherosclerotic plaque disruption and its immediate complications. Our understanding of the atherosclerotic process and the pathophysiology of plaque disruption has advanced remarkably. Despite these advances, event rates after acute coronary syndromes remain unacceptably high. This review will focus on the pathophysiology underlying atherosclerotic plaque development, the sequellae of coronary plaque rupture, and current therapies designed to treat the acute coronary syndromes. It is hoped that as our understanding of the atherosclerotic plaque improves, treatment strategies for the acute coronary syndromes will advance.

Adrenergic beta-Antagonists↗
PubMed1998

Prediction by mathematical simulation of different pathophysiological effects on D-sorbitol bioavailability.

In this study a mathematical model was applied to predict how changes in hepatic extraction ratio (E), fractional portal inflow (P) and renal elimination ratio (R) may affect fractional D-sorbitol bioavailability in cirrhotic patients. D-sorbitol bioavailability was computed as the ratio between cumulative urinary outputs measured after infusion into the superior mesenteric (Uma) or the hepatic artery (Uha) and a systemic vein (Usv). The present work was aimed at explaining by mathematical simulation the very large difference observed in the regression lines when plotting Uma or Uha against Usv values. The study was performed by considering a pathophysiological model of the hepatic circulation and simulating independent variations of the above considered parameters or assuming particular pathophysiological conditions like hepatic arterialization and hepatofugal flow. Computational results account for the wide dispersion of experimental data obtained in previous studies and provide reasonable explanations of unexpected findings.

Biological Availability↗
PubMed2003

Role of reactive oxygen species in the pathophysiology of human reproduction.

OBJECTIVE: To summarize the role of reactive oxygen species (ROS) in the pathophysiology of human reproduction. DESIGN: Review of literature. SETTING: Fertility research center and obstetrics and gynecology department in a tertiary care facility. RESULT(S): ROS plays an essential role in the pathogenesis of many reproductive processes. In male-factor infertility. oxidative stress attacks the fluidity of the sperm plasma membrane and the integrity of DNA in the sperm nucleus. Reactive oxygen species induced DNA damage may accelerate the process of germ cell apoptosis, leading to the decline in sperm counts associated with male infertility. ROS mediated female fertility disorders share many pathogenic similarities with the ones on the male side. These similarities include a potential role in the pathophysiology of endometriosis and unexplained infertility. High follicular fluid ROS levels are associated with negative IVF outcomes, particularly in smokers. Moreover, oxidative stress may be responsible in hydrosalpingeal fluid mediated embryotoxicity as well as poor in vitro embryonic development. CONCLUSION(S): High levels of ROS are detrimental to the fertility potential both in natural and assisted conception states.

DNA Damage↗
PubMed2000

Update on the pathophysiology of the epilepsies.

The pathophysiology of convulsive and non-convulsive epilepsies is discussed in its primary generalised forms. Focal, clinical and experimental epilepsies, with emphasis placed on the temporal lobe epilepsies (TLE) and their pathophysiologies are also reviewed. Neurotransmitters and neuromodulators and between them, the second messenger systems are considered in the generation, maintenance or inhibition of the epileptic discharge. Action mechanisms of the more classic antiepileptic drugs are briefly summarized along with the therapeutic strategies that might achieve the final control of abnormal discharges, including genetic control as a promising alternative in the current state of research. We emphasized the study of all type of glutamate and GABA receptors and their relation with mRNA editing in the brain. Some of the genetic studies which have been so fruitful during the last ten years and which have brought new insights regarding the understanding of epileptic syndromes are summarized in this article.

Animals↗
PubMed2002

The valve bladder syndrome: pathophysiology and treatment with nocturnal bladder emptying.

PURPOSE: We determine the etiology and treat the specific pathophysiology of the valve bladder syndrome. MATERIALS AND METHODS: Defined as persisting or progressive severe hydroureteronephrosis without residual or recurrent obstruction, the valve bladder syndrome developed in 18 boys who underwent successful ablation of the posterior urethral valve. Serial radiographic, renal function, renographic, urodynamic and perfusion studies were performed for a mean time of 11 years. RESULTS: The cause of the valve bladder syndrome proved to be sustained bladder over distention due to a combination of polyuria with 24-hour urine volume greater than 2 l. in 10 boys, impaired bladder sensation in 18 and residual urine volume in 14. Treatment of over distention during the daytime alone was unsuccessful. Nocturnal bladder emptying was performed with an indwelling nighttime catheter, intermittent nocturnal catheterization and/or frequent nocturnal double voiding. Hydronephrosis markedly improved once nocturnal bladder emptying was started and was comparable to the results after urinary diversion. CONCLUSIONS: The valve bladder syndrome is not due to a permanent prenatal alteration in bladder anatomy and function. Instead, it appears to result from sustained postnatal bladder over distention due to a combination of polyuria, impaired bladder sensation and residual urine volume, which represent sequelae of prenatal valve injury. These factors synergize to prevent bladder normalization after valve ablation and progressively reduce functional bladder capacity to maintain bladder over distention. Bladder decompensation, upper tract dilation, and renal injury develop and characterize the valve bladder syndrome. Because current therapy, including intermittent catheterization, leaves the bladder full throughout the night, it remains markedly over distended. Nocturnal bladder emptying is the specific antidote for this pathophysiological situation, and results in prompt and impressive improvement or elimination of hydronephrosis in these and similar groups of patients. This response to nocturnal bladder emptying suggests that the bladder is not the primary cause for the valve bladder syndrome.

Child↗
PubMed1993

Delayed high flow priapism: pathophysiology and management.

Two cases of the management and pathophysiology of high flow arterial priapism are presented. Both cases were post-traumatic with delayed onset of priapism and both had angiographically diagnosed arteriocorporeal fistulas. Case 1 was managed with selective cavernous artery ligation and case 2 resolved spontaneously, both with excellent return of premorbid levels of erectile function. We propose that the pathophysiological mechanism involves injury to the intracavernous artery, causing ischemic necrosis. After a delay the arterial segment blows out, leading to unregulated blood flow into the corpus cavernosum. Management with surgical ligation is highly selective and nondisruptive to unaffected vessels, offering precise control of the bleeding vessel.

Adult↗
PubMed1990

Traumatic laceration of intracavernosal arteries: the pathophysiology of nonischemic, high flow, arterial priapism.

Two forms of priapism are known to occur. The more common type, veno-occlusive priapism, presents with a prolonged painful erection, and it is characterized by ischemia and pooling of blood within the corpora cavernosa. The less common form, high flow priapism, is characterized by lack of pain and ischemia. The pathophysiology of this disorder is poorly understood and the treatment is unclear. We report 2 cases of nonischemic priapism, one of which occurred after blunt perineal trauma and the other after intracavernosal self-injection with papaverine and phentolamine. Based on our 2 cases as well as a review of the literature (5 cases), we propose that the pathophysiological mechanism of this disorder is unregulated arterial inflow into the corpora, classify it as arterial priapism, and describe a diagnostic and therapeutic algorithm for its management.

Adult↗
PubMed1998

Intracellular calcium signaling systems in the pathophysiology of affective disorders.

In this paper, we show the importance of intracellular calcium (Ca2+) signaling systems in the pathophysiology of mood disorders based on our recent work. Patients with affective disorders appear to have an enhanced intracellular Ca2+ rise in response to serotonin. We have observed effects of antidepressant drugs on intracellular Ca2+ signaling in rat cultured neuronal cells and glioma cells, and found that acute application of several classes of antidepressant drugs inhibited intracellular Ca2+ signaling and Ca2+-related signaling. It is important to investigate the role of intracellular Ca2+ signaling system for an understanding of the pathophysiology of affective disorders.

Affective Disorders, Psychotic↗
PubMed1989

Pathophysiology and treatment of gallstones.

Spurred on by the discovery of "lithogenic bile" as a precursor, there has been much attention focused on the pathophysiology and treatment of gallstones. The article reviews the progress to date regarding the epidemiology, pathophysiology, diagnosis, therapy, and recurrence/prevention of gallstones.

Adult↗
PubMedDate not supplied

Pathophysiology and pharmacological approaches for prevention of coronary artery restenosis following coronary artery balloon angioplasty and related procedures.

Percutaneous transluminal coronary angioplasty (PTCA) has become a mainstay in the treatment of ischemic heart disease, with an estimated 300,000 procedures performed annually in the United States. Despite significant advances in reducing the acute complications of percutaneous revascularization procedures with periprocedural medications and better techniques, chronic restenosis of dilated lesions remains a serious and frequent problem, occurring in 30% to 50% of cases. With a peak incidence between 1 and 4 months after PTCA, restenosis has been thought to reflect an exaggerated healing response to balloon injury, in which platelets and other cells secrete mitogens that induce smooth muscle cells from the media to migrate to and proliferate in the intima, compromising the coronary lumen and invoking ischemic symptoms. Several factors, including remodeling with compensatory arterial enlargement, normalization of wall shear stress, and recoil, are also likely to play key roles. Based on these concepts, several pharmacological approaches directed at reducing the incidence of restenosis have been investigated. Although studies frequently report suppression of neointimal proliferation in animal models of balloon vascular injury, few drug approaches have met with clear success in clinical trials. This can be explained in several ways, including mistaken understandings of the pathophysiology of restenosis, gross histopathological dissimilarities between animal vascular injury models and clinical restenosis, and inadequate dosing. This report proposes to extensively review the vast literature on the subject to serve as a guide for clinicians to the pathophysiology of restenosis and the pharmacotherapeutic management of patients after PTCA and coronary atherectomy. Those drug approaches that currently show the most clinical promise and that warrant further investigation will be highlighted.

Angioplasty, Balloon, Coronary↗
PubMed2000

Myelodysplastic syndrome and aplastic anemia: distinct entities or diseases linked by a common pathophysiology?

It is often difficult to distinguish myelodysplastic syndrome (MDS) from severe aplastic anemia (SAA) because both can present with profoundly hypocellular bone marrows. The distinction matters because although both conditions are complicated by pancytopenia, the risk of progression to acute leukemia is much greater in MDS. This chapter reexamines the relationship between SAA and MDS. The clinical and morphological features and pathophysiology of AA (including moderate and severe forms of acquired AA) are compared with MDS and hypoplastic MDS, with particular reference to new observations implicating autoimmune processes in both conditions. SAA and hypoplastic MDS (HMDS) are discussed in the light of these findings and attempts to separate nonevolving bone marrow failure syndromes from marrow failure progressing to acute leukemia are reviewed. The weight of evidence supports a common pathophysiology and, more speculatively, a common etiology for at least some forms of AA and MDS.

Anemia, Aplastic↗
PubMed2001

Pathophysiology of sickle cell disease: role of cellular and genetic modifiers.

Sickle hemoglobin (HbS), caused by a point mutation in the beta-globin gene of hemoglobin, polymerizes when deoxygenated. The pathophysiology of sickle cell disease results from cellular defects caused directly by the hemoglobin mutation interacting with the environment and many other gene products--a few known, but most yet unidentified--a typical example of epistasis. How normal tissue perfusion is interrupted is complex and why the phenotype of sickle cell disease differs from patient to patient is poorly understood. We review the "classic" aspects of the pathophysiology of sickle cell disease and focus on known and potential modulators of the phenotype of this disorder.

Anemia, Sickle Cell↗