University of Colorado Denver

About: University of Colorado Denver is a education organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Population & Health care. The organization has 27444 authors who have published 57213 publications receiving 2539937 citations. The organization is also known as: CU Denver & UCD.

Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure

Abstract: At present, six groups of chronic pulmonary hypertension (PH) are described. Among these, group 1 (and 1') comprises a group of diverse diseases termed pulmonary arterial hypertension (PAH) that have several pathophysiological, histological, and prognostic features in common. PAH is a particularly severe and progressive form of PH that frequently leads to right heart failure and premature death. The diagnosis of PAH must include a series of defined clinical parameters, which extend beyond mere elevations in pulmonary arterial pressures and include precapillary PH, pulmonary hypertensive arteriopathy (usually with plexiform lesions), slow clinical onset (months or years), and a chronic time course (years) characterized by progressive deterioration. What appears to distinguish PAH from other forms of PH is the severity of the arteriopathy observed, the defining characteristic of which is "plexogenic arteriopathy." The pathogenesis of this arteriopathy remains unclear despite intense investigation in a variety of animal model systems. The most commonly used animal models ("classic" models) are rodents exposed to either hypoxia or monocrotaline. Newer models, which involve modification of classic approaches, have been developed that exhibit more severe PH and vascular lesions, which include neointimal proliferation and occlusion of small vessels. In addition, genetically manipulated mice have been generated that have provided insight into the role of specific molecules in the pulmonary hypertensive process. Unfortunately, at present, there is no perfect preclinical model that completely recapitulates human PAH. All models, however, have provided and will continue to provide invaluable insight into the numerous pathways that contribute to the development and maintenance of PH. Use of both classic and newly developed animal models will allow continued rigorous testing of new hypotheses regarding pathogenesis and treatment. This review highlights progress that has been made in animal modeling of this important human condition.

Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus – Mechanisms, Management, and Clinical Considerations

Abstract: Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes mellitus exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes mellitus than for those without. This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes mellitus and heart disease outside of the acute care setting.

Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy

Abstract: In cancer treatment, apoptosis is a well-recognized cell death mechanism through which cytotoxic agents kill tumor cells. Here we report that dying tumor cells use the apoptotic process to generate potent growth-stimulating signals to stimulate the repopulation of tumors undergoing radiotherapy. Furthermore, activated caspase 3, a key executioner in apoptosis, is involved in the growth stimulation. One downstream effector that caspase 3 regulates is prostaglandin E(2) (PGE(2)), which can potently stimulate growth of surviving tumor cells. Deficiency of caspase 3 either in tumor cells or in tumor stroma caused substantial tumor sensitivity to radiotherapy in xenograft or mouse tumors. In human subjects with cancer, higher amounts of activated caspase 3 in tumor tissues are correlated with markedly increased rate of recurrence and death. We propose the existence of a cell death-induced tumor repopulation pathway in which caspase 3 has a major role.

Nucleotide signalling during inflammation

Abstract: Inflammatory conditions are associated with the extracellular release of nucleotides, particularly ATP. In the extracellular compartment, ATP predominantly functions as a signalling molecule through the activation of purinergic P2 receptors. Metabotropic P2Y receptors are G-protein-coupled, whereas ionotropic P2X receptors are ATP-gated ion channels. Here we discuss how signalling events through P2 receptors alter the outcomes of inflammatory or infectious diseases. Recent studies implicate a role for P2X/P2Y signalling in mounting appropriate inflammatory responses critical for host defence against invading pathogens or tumours. Conversely, P2X/P2Y signalling can promote chronic inflammation during ischaemia and reperfusion injury, inflammatory bowel disease or acute and chronic diseases of the lungs. Although nucleotide signalling has been used clinically in patients before, research indicates an expanding field of opportunities for specifically targeting individual P2 receptors for the treatment of inflammatory or infectious diseases.

Prophylactic Administration of Respiratory Syncytial Virus Immune Globulin to High-Risk Infants and Young Children

Abstract: Background Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common respiratory illness. Methods We studied 249 infants and young children (mean age, eight months) who had bronchopulmonary dysplasia due to prematurity (n = 102), congenital heart disease (n = 87), or prematurity alone (n = 60). Respiratory syncytial virus immune globulin was given monthly to some of these children in either a high dose (750 mg per kilogram of body weight; n = 81) or a low dose (150 mg per kilogram; n = 79); 89 controls received no immune globulin. Group assignments were random. Assessments of respiratory illness and management were conducted without knowledge of the children's group assignments. Results There were 64 episodes of respiratory syncytial virus infection: 19 in the high-dose group, 16 in the ...