Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Recent evidence suggests that uremic vascular calcification is an active, cell-mediated process resembling osteogenesis in bone rather than passive precipitation. We identified increased expression of bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen) and the bone-specific transcription factor core-binding factor alpha(1) (Cbfalpha(1)) in histologic sections of inferior epigastric arteries obtained from patients with stage V chronic kidney disease or calcific uremic arteriolopathy. In in vitro experiments, the addition of uremic serum to cultured vascular smooth muscle cells up-regulated osteopontin and Cbfalpha(1) expression and accelerated mineralization. ⋯ However, a lack of inhibitors of calcification may also be important. Dialysis patients with low levels of serum fetuin A, a circulating inhibitor of mineralization, have increased coronary artery calcification, and fetuin A can inhibit mineralization of vascular smooth muscle cells in vitro. Further understanding of the pathophysiology of uremic vascular calcification is needed to design effective therapeutic strategies to intervene with this devastating condition in patients with stage V chronic kidney disease.
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Chimeric antigen receptor (CAR)-T-cell therapy has sparked a wave of optimism in hematological malignancies, reflected by the successful results of early clinical trials involving patients with pre-B-cell acute lymphoblastic leukemia, B-cell lymphomas and multiple myeloma. CAR-T-cell therapy is considered to be a novel immunotherapy treatment that has the potential for curing certain hematological cancers. ⋯ These challenges include the process of manufacturing the CAR-T cells, the mechanisms of resistance that underlie disease relapse, adverse effects and cost. This review describes the published results of clinical trials and expected developments to overcome CAR-T resistance.
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Review Case Reports
Alcohol and gastric motility: pathophysiological and therapeutic implications.
Alcohol has been associated with alterations in gastric motility. The literature identifies that various factors play a role in alcohol's effect on gastric emptying including differences in alcohol concentration, osmolarity, caloric content, amino acids as well as different processing techniques (fermentation vs distillation). Additionally, chronic alcohol consumption has been shown to alter the myenteric nitrergic system resulting in impaired gastrointestinal motor function, and it also has an inhibitory effect on the release of several neurotransmitters that play a key role in gastrointestinal motility, including acetylcholine. ⋯ In the clinical setting of DS attributed to impaired vagal nerve function, there was normalization of gastric emptying and resolution of accompanying symptoms when drinking a glass of wine before and during meals. We propose that alcohol's anticholinergic effect was augmented in the setting of vagal nerve denervation resulting in slowing of gastric emptying and in alleviation of symptoms of early DS. This review article provides an in-depth analysis of the published literature on alcohol and gastric motility focusing on the accumulated knowledge that may have clinical application and relevance.
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Human adenovirus 36 (Ad-36) causes obesity with increased adiposity, in contrast, Ad-36 infection reduces glucose and lipid metabolism; the results, however, are not consistent. In the current study, the effects of Ad-36 infection on glucose and lipid profile and inflammatory markers in Wistar rats were investigated. Sixty male Wistar rats were randomly divided into infected and control groups. ⋯ There were no significant differences in inflammatory biomarkers including tumor necrosis factor-α, interleukin 6 and monocyte chemoattractant protein-1 levels between infected and control groups. This study showed that Ad-36 had favorable effects on glycemic and lipid control in infected rats, but inflammatory biomarker levels were similar for 2 groups. Ad-36 infections could potentially be a new way to develop novel antidiabetic and antihyperlipidemic therapeutic agents.