Ramon Bataller

Bio: Ramon Bataller is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Alcoholic hepatitis & Alcoholic liver disease. The author has an hindex of 72, co-authored 283 publications receiving 19316 citations. Previous affiliations of Ramon Bataller include University of Rochester & University of North Carolina at Chapel Hill.

Hepatic stellate cells as a target for the treatment of liver fibrosis.

Abstract: Following chronic liver injury of any etiology, there is progressive fibrosis. To date, removing the causative agent is the only effective therapy to stop or even reverse liver fibrosis. Therefore, the development of effective antifibrotic therapies represents a challenge for modern hepatology. In the past decade, dramatic advances have been made in the understanding of the cellular and molecular mechanisms underlying liver fibrogenesis. The identification of activated hepatic stellate cells (HSCs) as the major fibrogenic cell type in the injured liver, as well as the recognition of key cytokines involved in this process, have facilitated the design of promising new antifibrotic therapies. These therapies are aimed at inhibiting the accumulation of activated HSCs at the sites of liver injury and preventing the deposition of extracellular matrix. Although many of these approaches are effective in experimental models of liver fibrosis, their efficacy and safety in humans are still unknown. This review describes the current therapeutic approaches for liver fibrosis and discusses different features of activated HSCs as a target to design new treatments to inhibit scar formation in chronic liver diseases.

Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.

Abstract: There is no consensus definition of acute renal failure (ARF) in critically ill patients. More than 30 different definitions have been used in the literature, creating much confusion and making comparisons difficult. Similarly, strong debate exists on the validity and clinical relevance of animal models of ARF; on choices of fluid management and of end-points for trials of new interventions in this field; and on how information technology can be used to assist this process. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. We undertook a systematic review of the literature using Medline and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. We found sufficient consensus on 47 questions to allow the development of recommendations. Importantly, we were able to develop a consensus definition for ARF. In some cases it was also possible to issue useful consensus recommendations for future investigations. We present a summary of the findings. (Full versions of the six workgroups' findings are available on the internet at http://www.ADQI.net ) Despite limited data, broad areas of consensus exist for the physiological and clinical principles needed to guide the development of consensus recommendations for defining ARF, selection of animal models, methods of monitoring fluid therapy, choice of physiological and clinical end-points for trials, and the possible role of information technology.

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

Abstract: For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Abstract: Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Cellular and molecular mechanisms of fibrosis.

Abstract: Fibrosis is defined by the overgrowth, hardening, and/or scarring of various tissues and is attributed to excess deposition of extracellular matrix components including collagen. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury. Although current treatments for fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis typically target the inflammatory response, there is accumulating evidence that the mechanisms driving fibrogenesis are distinct from those regulating inflammation. In fact, some studies have suggested that ongoing inflammation is needed to reverse established and progressive fibrosis. The key cellular mediator of fibrosis is the myofibroblast, which when activated serves as the primary collagen-producing cell. Myofibroblasts are generated from a variety of sources including resident mesenchymal cells, epithelial and endothelial cells in processes termed epithelial/endothelial-mesenchymal (EMT/EndMT) transition, as well as from circulating fibroblast-like cells called fibrocytes that are derived from bone-marrow stem cells. Myofibroblasts are activated by a variety of mechanisms, including paracrine signals derived from lymphocytes and macrophages, autocrine factors secreted by myofibroblasts, and pathogen-associated molecular patterns (PAMPS) produced by pathogenic organisms that interact with pattern recognition receptors (i.e. TLRs) on fibroblasts. Cytokines (IL-13, IL-21, TGF-beta1), chemokines (MCP-1, MIP-1beta), angiogenic factors (VEGF), growth factors (PDGF), peroxisome proliferator-activated receptors (PPARs), acute phase proteins (SAP), caspases, and components of the renin-angiotensin-aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs. This review explores our current understanding of the cellular and molecular mechanisms of fibrogenesis.