Short-Term Clinical Response to Corticosteroids Can Predict Long-Term Natural History of Ulcerative Colitis: Prospective Study Experience

Digestive Diseases and Sciences - Long-term outcome and natural history of steroid response in adult ulcerative colitis patients based on short-term response is largely unknown. To evaluate whether...     

Effect of pioglitazone on nerve conduction velocity of the median nerve in the carpal tunnel in type 2 diabetes patients

AIM To evaluate the impact of pioglitazone pharmacotherapy in median nerve electrophysiology in the carpal tunnel among type 2 diabetes patients.METHODS The study was executed in patients with type 2 diabetes, treated with oral drugs, categorized under pioglitazone or non-pioglitazone group(14 in each group), and who received electrophysiological evaluation by nerve conduction velocity at baseline and 3 mo.RESULTS At 3 mo, pioglitazone-category had inferior amplitude in sensory median nerve [8.5 interquartile range(IQR) = 6.5 to 11.5) vs non-pioglitazone 14.5(IQR 10.5 to 18.75)](P = 0.002). Non-pioglitazone category displayed amelioration in amplitude in the sensory median nerve [baseline 13(IQR = 9 to 16.25) vs 3 mo 8.5(IQR = 6.5 to 11.5)](P = 0.01) and amplitude in motor median nerve [baseline 9(IQR = 4.75 to 11) vs 3 mo 6.75(IQR = 4.75 to 10.25)](P = 0.049); and deterioration of terminal latency of in motor ulnar nerve [baseline 2.07(IQR = 1.92 to 2.25) vs 3 mo 2.16(IQR = 1.97 to 2.325)](P = 0.043). There was amelioration of terminal latency in sensory ulnar nerve [baseline 2.45(IQR = 2.315 to 2.88) vs 3 mo 2.37(IQR = 2.275 to 2.445) for pioglitazone group(P = 0.038).CONCLUSION Treatment with pioglitazone accentuates probability of compressive neuropathy. In spite of comparable glycemic control over 3 mo, patients treated with pioglitazone showed superior electrophysiological parameters for the ulnar nerve. Pioglitazone has favourable outcome in nerve electrophysiology which was repealed when the nerve was subjected to compressive neuropathy.     

Significant downregulation of platelet gene expression in metastatic lung cancer

Platelets play a major role in the metastatic dissemination of tumor cells in vivo . Recent evidence reveals megakaryocyte-derived platelet pre-mRNA is spliced to mRNA and then translated into functional proteins in response to external stimulation. Employing a human lung cancer model, we hypothesized a subset of megakaryocyte/platelet genes exists that are significantly over or underexpressed in metastasis compared with noncancer. Microarray analysis employing platelet mRNA followed by unsupervised hierarchical clustering revealed an expression profile that includes decreased expression of 197 of the 200 platelet genes with the most altered expression (p < 1.0 × 10(-4)). Among the 608 splicing events identified between the metastasis and negative control groups, 33 highly variable genes were identified with between 3 and 13 splicing events each. In conclusion, this preliminary study reveals a platelet-based gene expression signature that differentiates metastatic lung cancer from negative controls on the basis of decreased expression of 197 of the 200 genes with the most altered expression levels. Further study may yield a prognostic tool for future metastasis among subsets of early stage lung cancer patients.     

In vivo transplantation of fetal human gut‐derived enteric neural crest cells

The prospect of using neural cell replacement for the treatment of severe enteric neuropathies has seen significant progress in the last decade. The ability to harvest and transplant enteric neural crest cells (ENCCs) that functionally integrate within recipient intestine has recently been confirmed by in vivo murine studies. Although similar cells can be harvested from human fetal and postnatal gut, no studies have as yet verified their functional viability upon in vivo transplantation. We sought to determine whether ENCCs harvested from human fetal bowel are capable of engraftment and functional integration within recipient intestine following in vivo transplantation into postnatal murine colon. Enteric neural crest cells selected and harvested from fetal human gut using the neurotrophin receptor p75^NTR were lentivirally labeled with either GFP or calcium‐sensitive GCaMP and transplanted into the hindgut of Rag2^?/γc^?/C5^?‐immunodeficient mice at postnatal day 21. Transplanted intestines were assessed immunohistochemically for engraftment and differentiation of donor cells. Functional viability and integration with host neuromusculature was assessed using calcium imaging. Transplanted human fetal gut‐derived ENCC showed engraftment within the recipient postnatal colon in 8/15 mice (53.3%). At 4 weeks posttransplantation, donor cells had spread from the site of transplantation and extended projections over distances of 1.2 ± 0.6 mm (n = 5), and differentiated into enteric nervous system (ENS) appropriate neurons and glia. These cells formed branching networks located with the myenteric plexus. Calcium transients (change in intensity F/F0 = 1.25 ± 0.03; 15 cells) were recorded in transplanted cells upon stimulation of the recipient endogenous ENS demonstrating their viability and establishment of functional connections.