Pheochromocytoma presented as intestinal pseudo-obstruction and hyperamylasemia

Pheochromocytoma has wide variations in alimentary presentations and complications. Here, we report a patient with pheochromocytoma who developed intestinal pseudo-obstruction and hyperamylasemia. The intestinal pseudo-obstruction responded promptly to intravenous infusions of phentolamine, an alpha-adrenergic blocker managed to control hypertensive crisis. The hyperamylasemia regressed gradually after resection of the tumor. The role of catecholamines liberated from the tumor is discussed in the associated pathogenesis. Early recognition of pheochromocytoma with gastrointestinal manifestations will facilitate proper management and prevent possible lethal outcome.     

Neural differentiation and potential use of stem cells from the human umbilical cord for central nervous system transplantation therapy

The human umbilical cord is a rich source of autologous stem and progenitor cells. Interestingly, subpopulations of these, particularly mesenchymal-like cells from both cord blood and the cord stroma, exhibited a potential to be differentiated into neuron-like cells in culture. Umbilical cord blood stem cells have demonstrated efficacy in reducing lesion sizes and enhancing behavioral recovery in animal models of ischemic and traumatic central nervous system (CNS) injury. Recent findings also suggest that neurons derived from cord stroma mesenchymal cells could alleviate movement disorders in hemiparkinsonian animal models. We review here the neurogenic potential of umbilical cord stem cells and discuss possibilities of their exploitation as an alternative to human embryonic stem cells or neural stem cells for transplantation therapy of traumatic CNS injury and neurodegenerative diseases.     

Pediatric lung transplantation for cystic fibrosis

Pediatric lung transplantation for cystic fibrosis has uncertain survival effects. Three retrospective studies disagree on survival benefit. The US Lung Allocation Score has changed patient selection for lung transplantation but confounds the analysis of survival outcomes. A prospective trial is needed to resolve clinical equipoise and explore quality-of-life effects.     

A synthetic analog of alpha-galactosylceramide induces macrophage activation via the TLR4-signaling pathways

Alpha-galactosylceramide (alpha-GalCer), a bioactive glycolipid isolated from the marine sponge Agelas mauritianus, is a potent immunomodulator with therapeutic potential for the treatment of autoimmune diseases and cancer. The Toll-like receptor 4 (TLR4), one of the promising molecular targets for immune-modulating drugs, is commonly expressed in innate immune cells especially macrophages and dendritic cells. Currently, whether alpha-GalCer can activate TLR4 signaling pathways remains unreported. In this study, we examined the effects of alpha-GalCer and its various structural analogs, CCL-1 approximately 47, on TLR4 activation. We found that one alpha-GalCer analog (CCL-34), but not alpha-GalCer itself, strongly stimulated NF-kappaB activity in RAW 264.7 cells. CCL-34 activated NF-kappaB in a TLR4-dependent manner and stimulated TNF-alpha production in bone marrow cells of TLR4-functional C3H/HeN mice but not in those of TLR4-defective C3H/HeJ mice. Furthermore, CCL-34 treatment stimulated NF-kappaB activation and IL-8 production in a 293 cell line constitutively expressing human TLR4, MD-2 and CD14. Treatment of RAW 264.7 cells with CCL-34 also activated TLR4-downstream mitogen-activated protein kinases (ERK, JNK and p38), induced expression of TLR4-downstream genes (TNF-alpha, IL-6, IL-1beta and iNOS) and promoted production of cytokines characteristic of activated macrophages. CCL-34-treated RAW 264.7 cells acquired a distinct morphology similar to that of LPS-activated macrophages and exhibited higher phagocytotic activity. Moreover, treatment with a TLR4-neutalizing antibody inhibited the CCL-34-induced morphological alteration. In summary, we identify a novel synthetic compound CCL-34 that can activate macrophages via TLR4-dependent signaling pathways. Our results suggest that CCL-34 is an immune modulator and may serve as a potential drug lead for immunotherapy.     

Eugenosedin-A amelioration of lipopolysaccharide-induced up-regulation of p38 MAPK, inducible nitric oxide synthase and cyclooxygenase-2

In this study, we investigate the protective effects of eugenosedin-A on p38 mitogen-activated protein kinase (MAPK), inflammatory nitric oxide (NO) and cyclooxygenase-2 (COX-2) pathways in a rat model of endotoxin shock. Rats were pretreated with eugenosedin-A, trazodone, yohimbine (1 mg kg(-1), i.v.), aminoguanidine or ascorbic acid (15 mg kg(-1), i.v.) 30 min before endotoxin challenge. Endotoxaemia was induced by a single i.v. injection of lipopolysaccharide (LPS, 10 mg kg(-1)). In rats not treated with eugenosedin-A, LPS increased plasma concentrations of NO and prostaglandin E(2) (PGE(2)), and levels of p38 MAPK, inducible NO synthase (iNOS) and COX-2 proteins in the liver, lung, aorta and lymphocytes. In the pre-treated rats, eugenosedin-A not only inhibited the LPS-induced NO and PGE(2) levels but also attenuated the LPS-induced increase in p38 MAPK and iNOS levels in the liver, aorta and lymphocytes. Eugenosedin-A also reduced LPS-induced COX-2 proteins in the aorta and lymphocytes. Likewise, aminoguanidine, ascorbic acid, yohimbine and trazodone were also found to decrease NO and PGE(2) concentrations after endotoxin challenge. While aminoguanidine and ascorbic acid also attenuated the LPS-induced increase in p38 MAPK, iNOS and COX-2 proteins in the aorta and lymphocytes, trazodone and yohimbine inhibited only the increase in p38 MAPK, iNOS and COX-2 proteins in lymphocytes. Finally, eugenosedin-A (10(-10)-10(-8) M) significantly inhibited the biphasic response induced by hydrogen peroxide (10(-6)-3 x 10(-5) M) in rat denudated aorta. Taken together, the results of this study indicate that eugenosedin-A, as well as ascorbic acid, can attenuate free-radical-mediated aortic contraction and relaxation. It may therefore be able to reduce the damage caused by septic shock by inhibiting formation of p38 MAPK, iNOS, COX-2 and free radicals.     

Outcomes of Extended-Infusion Piperacillin-Tazobactam: A Retrospective Analysis of Critically Ill Patients

Studies evaluating the outcomes of an extended-infusion (EI) piperacillin-tazobactam dosing strategy in specific cohorts of critically ill patients are lacking. A retrospective, pre-implementation and post-implementation study of 148 critically ill patients was conducted to compare EI and traditional infusion piperacillin-tazobactam. In this retrospective study, the EI piperacillin-tazobactam dosing strategy was associated with improved 30-day mortality. EI piperacillin-tazobactam may be an effective alternative to TI of piperacillin-tazobactam among critically ill patients treated for suspected gram-negative infections.