Pharmacologic Approaches (pharmacologic + approach)

Distribution by Scientific Domains


Selected Abstracts


Production of ,-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous ,039 thalassemia patients,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2009
Francesca Salvatori
In several types of thalassemia (including ,039-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying ,-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the ,039-thalassemia globin gene under control of the ,-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of ,-globin by K562 cell clones expressing the ,039-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from ,039-thalassemia patients were demonstrated to be able to produce ,-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of ,0 -thalassemia caused by stop codon mutations. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source]


Pharmacotherapy for Marijuana Dependence: A Double-blind, Placebo-controlled Pilot Study of Divalproex Sodium

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2004
Frances Rudnick Levin M.D.
There is a noticeable lack of targeted treatment options for marijuana dependence, in particular pharmacologic approaches. This is the first study evaluating a targeted pharmacologic approach for marijuana dependence. The goals of the study were to determine if such patients would seek pharmacologic treatment, whether these patients could be retained in treatment using a design previously developed for cocaine-dependent patients, and especially whether divalproex sodium showed promise as a treatment agent for marijuana dependence. We found that marijuana-dependent patients will seek treatment, and such patients can be adequately maintained in a pharmacologic trial. Regardless of treatment group, patients reported a significant reduction in their frequency and amount of marijuana use as well as a reduction in irritability. Given the lack of proven effective treatments for marijuana dependence, pharmacotherapies should be sought. The design of a preliminary clinical trial should include a psychosocial/behavioral intervention emphasizing motivation and medication compliance and a placebo control group. [source]


Early and Severe Hyperparathyroidism Associated with Hypercalcemia After Renal Transplant Treated with Cinacalcet

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2006
N. Leca
Bone disease is a common clinical problem following renal transplantation. In renal transplant recipients, multiple underlying factors determine the extent of bone loss and the subsequent risk of fractures. In addition to the well-recognized risk to bone disease posed by steroids, calcineurin inhibitors and pre-existing bone disease, persistent hyperparathyroidism (HPT) contributes to post-transplant bone loss. HPT is usually treated with vitamin D supplements combined with calcium. Patients whose HPT is associated with hypercalcemia pose a difficult therapeutic dilemma which often requires parathyroidectomy. Cinacalcet, a calcium mimetic agent, offers a unique pharmacologic approach to the treatment of patients with post-transplant hypercalcemia and HPT. In this paper, we describe the clinical course and biochemical changes in 10 renal transplant recipients with hypercalcemia and severe HPT early after renal transplantation treated with cinacalcet. Cinacalcet therapy corrected hypercalcemia and decreased parathyroid hormone (PTH) levels in all cases. A transient rise in the level of alkaline phosphatase was noted following initiation of cinacalcet therapy. In this patient population, correction of HPT was not permanent as discontinuing cinacalcet therapy led to a rapid rise in PTH level. [source]


Overproduction of reactive oxygen species in end-stage renal disease patients: A potential component of hemodialysis-associated inflammation

HEMODIALYSIS INTERNATIONAL, Issue 1 2005
Marion Morena
Abstract During the past decade, hemodialysis (HD)-induced inflammation has been linked to the development of long-term morbidity in end-stage renal disease (ESRD) patients on regular renal replacement therapy. Because interleukins and anaphylatoxins produced during HD sessions are potent activators for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an example of an enzyme that is responsible for overproduction of reactive oxygen species (ROS), this may constitute a link between leukocyte activation and cell or organ toxicity. Oxidative stress, which results from an imbalance between oxidant production and antioxidant defense mechanisms, has been documented in ESRD patients using lipid and/or protein oxidative markers. Characterization of HD-induced oxidative stress has included identification of potential activators for NADPH oxidase. Uremia per se could prime phagocyte oxidative burst. HD, far from improving the oxidative status, results in an enhancement of ROS owing to hemoincompatibility of the dialysis system, hemoreactivity of the membrane, and trace amounts of endotoxins in the dialysate. In addition, the HD process is associated with an impairment in antioxidant mechanisms. The resulting oxidative stress has been implicated in long-term complications including anemia, amyloidosis, accelerated atherosclerosis, and malnutrition. Prevention of oxidative stress in HD might focus on improving the hemocompatibility of the dialysis system, supplementation of deficient patients with antioxidants, and modulation of NADPH oxidase by pharmacologic approaches. [source]


Synovial mast cells: role in acute and chronic arthritis

IMMUNOLOGICAL REVIEWS, Issue 1 2007
Peter A. Nigrovic
Summary:, Mast cells reside in the normal synovium and increase strikingly in number in rheumatoid arthritis and other joint diseases. Given the broad spectrum of activity of this lineage, it has for decades been considered probable that mast cells are involved in the pathophysiology of synovitis. Recent work in murine arthritis has substantiated this suspicion, showing that mast cells can contribute importantly to the initiation of inflammatory arthritis. However, the role of the greatly expanded population of synovial mast cells in established arthritis remains unknown. Here we review the current understanding of mast cell function in acute arthritis and consider the potentially important influence of this cell on key processes within the chronically inflamed synovium, including leukocyte recruitment and activation, fibroblast proliferation, angiogenesis, matrix remodeling, and injury to collagen and bone. We also consider recent evidence supporting an immunomodulatory or anti-inflammatory role for mast cells as well as pharmacologic approaches to the mast cell as a therapeutic target in inflammatory arthritis. [source]


Management and prevention of postoperative Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 10 2009
Miguel Regueiro MD
Abstract Postoperative Crohn's disease (CD) recurrence is a common occurrence after intestinal resection. Currently, the optimal management of patients who have undergone surgical resection is unknown and treatment remains subjective. Clinicians in conjunction with patients must balance the risks of recurrence against the potential risks associated with treatment. For those at very low risk of recurrence, no therapy may be needed; however, for patients at moderate risk immunomodulators should be considered. For those at highest risk of recurrence, biologic therapy, specifically antitumor necrosis factor agents, have emerged as appropriate treatment. Any postoperative management strategy should include a colonoscopy 6,12 months after surgery to identify recurrence. This review discusses current evidence for various pharmacologic approaches in the prevention of postoperative recurrence and provides guidance for clarifying patient risk. (Inflamm Bowel Dis 2009) [source]


Pharmacotherapy for Marijuana Dependence: A Double-blind, Placebo-controlled Pilot Study of Divalproex Sodium

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2004
Frances Rudnick Levin M.D.
There is a noticeable lack of targeted treatment options for marijuana dependence, in particular pharmacologic approaches. This is the first study evaluating a targeted pharmacologic approach for marijuana dependence. The goals of the study were to determine if such patients would seek pharmacologic treatment, whether these patients could be retained in treatment using a design previously developed for cocaine-dependent patients, and especially whether divalproex sodium showed promise as a treatment agent for marijuana dependence. We found that marijuana-dependent patients will seek treatment, and such patients can be adequately maintained in a pharmacologic trial. Regardless of treatment group, patients reported a significant reduction in their frequency and amount of marijuana use as well as a reduction in irritability. Given the lack of proven effective treatments for marijuana dependence, pharmacotherapies should be sought. The design of a preliminary clinical trial should include a psychosocial/behavioral intervention emphasizing motivation and medication compliance and a placebo control group. [source]