ABSTRACT
Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal condition that can be challenging for clinicians to identify in the setting of autoimmune diseases such as systemic lupus erythematosus (SLE). This difficulty is compounded when a patient presents with all of the clinical signs of a TTP-like microangiopathy, however, with near normal ADAMTS13. This case report describes a 44-year-old female with a history of SLE who was hospitalized with acute on chronic anemia, thrombocytopenia, and altered mental status. The patient's ADAMTS13 was mildly low; hence, she was initially treated for SLE-associated immune thrombocytopenic purpura without any clinical response. The patient then underwent plasmapheresis (plasma exchange [PLEX]) for treatment of a suspected TTP-like microangiopathy. She responded to PLEX with improvement in her platelet count and mental status. This case illustrates the importance of considering TTP-like microangiopathic hemolytic anemia in the differential for patients with a history of SLE presenting with clinical signs of TTP even in the setting of near-normal ADAMTS13, thus warranting prompt treatment with PLEX.
Subject(s)
Lupus Erythematosus, Systemic , Purpura, Thrombotic Thrombocytopenic , Vascular Diseases , ADAMTS13 Protein , Adult , Female , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/therapy , Plasma Exchange , Purpura, Thrombotic Thrombocytopenic/diagnosis , Purpura, Thrombotic Thrombocytopenic/therapyABSTRACT
To determine the role of 14-3-3 in colorectal cancer apoptosis induced by nonsteroidal anti-inflammatory drugs (NSAIDs), we evaluated the effects of sulindac on 14-3-3epsilon protein expression in colorectal cancer cells. Sulindac sulfide inhibited 14-3-3epsilon proteins in HT-29 and DLD-1 cells in a time- and concentration-dependent manner. Sulindac sulfone at 600 mumol/L inhibited 14-3-3epsilon protein expression in HT-29. Indomethacin and SC-236, a selective cyclooxygenase-2 (COX-2) inhibitor, exerted a similar effect as sulindac. Sulindac suppressed 14-3-3epsilon promoter activity. As 14-3-3epsilon promoter activation is mediated by peroxisome proliferator-activated receptor delta (PPARdelta), we determined the correlation between 14-3-3epsilon inhibition and PPARdelta suppression by NSAIDs. Sulindac sulfide inhibited PPARdelta protein expression and PPARdelta transcriptional activity. Overexpression of PPARdelta by adenoviral transfer rescued 14-3-3epsilon proteins from elimination by sulindac or indomethacin. NSAID-induced 14-3-3epsilon suppression was associated with reduced cytosolic Bad with elevation of mitochondrial Bad and increase in apoptosis which was rescued by Ad-PPARdelta transduction. Stable expression of 14-3-3epsilon in HT-29 significantly protected cells from apoptosis. Our findings shed light on a novel mechanism by which NSAIDs induce colorectal cancer apoptosis via the PPARdelta/14-3-3epsilon transcriptional pathway. These results suggest that 14-3-3epsilon is a target for the prevention and therapy of colorectal cancer.
Subject(s)
14-3-3 Proteins/antagonists & inhibitors , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Apoptosis/drug effects , Colorectal Neoplasms/drug therapy , 14-3-3 Proteins/genetics , 14-3-3 Proteins/metabolism , Adenoviridae/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Cyclooxygenase 2 Inhibitors/pharmacology , HT29 Cells , Humans , Indomethacin/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , PPAR delta/metabolism , Promoter Regions, Genetic , Pyrazoles/pharmacology , Sulfonamides/pharmacology , Sulindac/analogs & derivatives , Sulindac/pharmacology , bcl-Associated Death Protein/metabolismABSTRACT
A soft tissue diode laser offers an alternative technique for uncovering dental implants. This article presents two cases in which four dental implants were uncovered using a soft tissue laser. This technique provides an efficient and patient-friendly method to perform second-stage implant surgery, safely allowing a faster rehabilitative phase.