CD40, a tumor necrosis factor receptor superfamily member, is up-regulated on intraheptatic endothelial cells (IHEC) and epithelial cells during inflammatory liver disease, and there is evidence that the functional outcome of CD40 ligation differs between cell types. Ligation of CD40 on cholangiocytes or hepatocytes results in induction of Fas-mediated apoptosis, whereas ligation of IHEC CD40 leads to enhanced chemokine secretion and adhesion molecule expression. We now report that differential activation of two transcription factors, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), in primary human hepatocytes or IHEC, is associated with and may explain, in part, the different responses of these cell types to CD40 ligation. CD40 ligation induced a rise in NF-κB activity in hepatocytes ,which peaked at 2 h and returned to baseline by 24 h; however, IHEC CD40 ligation resulted in a sustained up-regulation of NF-κB (>24 h). In hepatocytes, CD40 ligation led to sustained up-regulation of AP-1 activity >24 h associated with increased protein levels of RelA (p65), c-Jun, and c-Fos, whereas no induction of AP-1 activity was observed in IHECs. Analysis of mitogen-activated protein kinase phosphorylation (phospho-extracellular signal-regulated kinase 1/2 and phospho-c-Jun NH2-terminal kinase 1/2) and expression of inhibitor κBα were entirely consistent, and thus confirmed the profiles of NF-κB and AP-1 signaling and the effects of the selective inhibitors assessed using electrophoretic mobility shift assay or Western immunoblotting. CD40 ligation resulted in induction of apoptosis in hepatocytes after 24 h, but on IHECs, CD40 ligation resulted in proliferation. Inhibition of (CD40-mediated) NF-κB activation prevented IHEC proliferation and led to induction of apoptosis. Selective extracellular signal-regulated kinase and c-Jun NH2-terminal kinase inhibitors reduced levels of apoptosis in (CD40-stimulated) hepatocytes by ∼50%. We conclude that differential activation of these two transcription factors in response to CD40 ligation is associated with differences in cell fate. Transient activation of NF-κB and sustained AP-1 activation is associated with apoptosis in hepatocytes, whereas prolonged NF-κB activation and a lack of AP-1 activation in IHECs result in proliferation.
Objective: To find out the outcome of stenting before ESWL in the management of upper ureteric stone. Methods and materials: This prospective comparative study was conducted in the department of urology, Sylhet Osmani Medical College Hospital from January 2011 to June 2012. Sixty two patients with upper ureteric stone, aged between 18 to 60 years irrespective of sex, unilateral radio opaque upper ureteric stone of greatest diameter 2cm, patients with normal renal function and negative urine culture and were agreed to participate in the study were selected. Selected 62 patients with upper ureteric stones were divided randomly into group-A and group-B each consisting 31 patients. The patients of group-A were treated with ESWL with a JJ stent and that of group-B without JJ stent. In the patients selected for JJ placement, a 5 fr JJ stent was placed under regional anaesthesia before ESWL. Siemens Lithotripsy ESWL machine was used to impart shock waves and 3500 shockwaves was given in a session. Both the groups were compared for stone clearance, ureteric colic, steinstrasse, fever, lower urinary tract symptoms (LUTS), number of ESWL sessions. Data were processed and analyzed using software SPSS. Results: The number ESWL session in stented group [single session 10 (32.3%) and multiple sessions 21 (67.7%)] and in non-stented group [single session 9 (29.0%) and multiple sessions 22 (71.0%)] was similar in both groups (p>0.05) Stones were cleared in 23 (74.2%) patients in stented group and 25 (80.6%) patients in non-stented group. Difference was not statistically significant (p>0.05). Ureteric colic was significantly fewer in stented group than that of non-stented group [4 (12.9%) vs 11 (35.5%); p<0.05] but surapubic pain was significantly more in stented group than that of non-stented group [13 (41.9%) vs 5 (16.1%); p<0.05]; while steinstrasse [3 (9.7%) vs 5 (16.1%); p>0.05] and fever [5 (16.1%) vs 2 (6.5%); p>0.05] did not differ statistically significant between groups. Lower urinary tract symptoms such as urinary frequency [15 (48.4%) vs 3 (9.7%); p<0.01]; urgency [17 (54.8%) vs 5 (16.1%); p<0.01] and dysuria [19 (61.3%) vs 6 (19.4%); p<0.01] were significantly more in stented group than that of non-stented group; but gross haematuria [21 (67.7%) vs 15 (48.4%); p>0.05] were more in stented group. Conclusion: ESWL is an effective and reasonable initial therapy in the management of upper ureteric stones measuring <2 cm. Pre-ESWL ureteric stenting provides no additional benefit over non-stented ESWL in their management. Moreover, stents are associated with signiûcant patient discomfort and morbidity. Bangladesh Journal of Urology, Vol. 16, No. 1, Jan 2014 p.17-22
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