Pancreatic cancer–Palliative therapy: surgery (bypass/resection)

Objective: We compare the outcome of palliative pancreaticoduodenectomy and palliative surgical bypass in patients with advanced pancreatic carcinoma in our hospital. Recent published related articles are also reviewed. Methods: A respective analysis was performed comparing the perioperative parameters and outcome of 20 patients who underwent pancreaticoduodenectomy with a gross suspected cancer residue and 30 patients who underwent a surgical bypass, all of the patients were diagnosed as in advanced stages intra-operatively. Results: The two groups were comparable with patient characteristics, including age, gender, initial symptoms and concomitant major organ diseases. Tumors are similar in size and intra-operatively diagnosed as in advanced stages in both groups. All of the patients in the resection group were microscopically proved having cancer residue. One postoperative mortality occurred in the resection group (5%), zero in the bypass group (P > 0.05). Overall complications were significantly higher in the resection group (30% vs. 0, P < 0.01), including 2 patients developed Acute Respiratory Distress Syndrome (ARDS), zero in the bypass group (P < 0.01); hemorrhage and transfusions in the resection group were much more than that in the bypass group (P < 0.05). Hospital stay after resection was significantly longer than bypass (20 vs. 12 days, P < 0.01). Hospital fee after resection was 4 times more than after bypass (median 61.500 vs. 15. 300 yuan, P < 0.01). Survival was significantly longer after resection (median 12.2 vs. 7.1 months, P < 0.01). Conclusion: Our results show that palliative resection in advanced pancreatic carcinoma lengthens the survival time of the patients, but this is paid for significantly higher complications than bypass.     

氢气呼吸试验检测十二指肠憩室伴发小肠细菌过度生长

十二指肠憩室并发小肠细菌过度生长,常出现腹泻等症状。我们采用CM型氢气微分析仪,对23例十二指肠憩室作了氢气呼吸法-葡萄糖呼吸试验。目的是了解十二指肠憩室并发小肠细菌过度生     

Role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation and the effect of bifidobacterial supplement on gut barrier function following burns

Early multiple organ dysfunction syndrome appears to be facilitated with bacterial translocation in severely burn injury, yet the mechanisms of bacterial translocation remains in dispute. The aim of this study was to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation following burns and the effects of bifidobacterial supplement on gut barrier. Methods: Wistar rats were randomly divided into burn group (Burn, n=60),sham burn group (SB, n=10) in experiment Ⅰ , and burn + saline group (BS, n=30), burn + bifidobacteria group (BB, n=30), and sham-burn + saline group (SS, n= 10) in experiment Ⅱ. Animals in BB group were fed bifidobacterial preparation (5 × 109 CFU/ml) after burns, 1.5ml,twice daily. Animals in BS and SS were fed saline. Samples were taken on days 1, 3, and 5 in burn groups, and on day 3 in sham-burn groups. The incidence of bacteria/endotoxin translocation and counts of Bifidobacterium, Fungi and Escherichia coli in gut mucosa were determined with standard methods. The levels of sIgA in mucus of small intestine were measured by RIA. The positive sIgA expression in lamina propria and ileum mucosal injury was evaluated light microscopically by blinded examiners. Results: Our results showed that the incidence of bacterial translocation was increased after burns, which was accompanied by significant decrease in number of bifidobacteria but significant increase in E. coli and fungi in gut mucosa, and elevation of levels of plasma endotoxin and IL-6 (P<0. 001).The incidence of bacterial translocation was markedly reduced after 3- and 5-day supplementation of bifidobacteria compared with control group (P<0.05). The counts of mucosal bifidobacteria were increased by 4- to 40-fold,while E. coli and fungi were decreased by 2- to 30-fold and 10- to 150-fold, respectively, after bifidobacterial supplementation in contrast to control group. The damage of mucosa tended to be less pronounced after 3-day bifidobacteria-supplemented formula compared with control group [grade 2(0-6) vs. grade 4(3-6), P<0.05]. Moreover, the expression and release of sIgA was markedly augmented after 3-day bifidobacteria-supplementation formula and it returned to normal range on day 5. Conclusion: The decrease in counts and proportion of bifidobacteria in mucous membrane flora may play an important role in the development of bacteria/endotoxin translocation following thermal injury. The supplement of exogenous bifidobacteria could per se improve gut barriers, and attenuate bacteria/endotoxin translocation secondary to major burns.     

In vitro differentiation of human adipose-derived adult stromal cells into neuron-like cells in hippocampal astrocyte conditioned medium

BACKGROUND: At present, researches on differentiating from human adipose-derived adult stromal cells (hADASC) to neuron-like cells are focus on inducing by artificial-synthetic compound solution; however, hippocampal astrocyte conditioned medium (HCAM) can induce in vitro differentiation from hADASC to neuron-like cells is still unclear. OBJECTIVE: To observe whether HCAM can induce in vitro differentiation from hADASC to neuron-like cells. DESIGN: Randomized control study. SETTING: Department of Neurology, Taixing People's Hospital; Central Laboratory, North China Coal Medical College. MATERIALS: Donor of adipose tissue was donated by female volunteers suffering from caesarean section in the department of obstetrics & gynecology in our hospital and aged 20－35 years. Adipose tissue was collected from subcutaneous tissue of abdomen during the operation. In addition, 8 male newborn Wistar rats within 24 hours with average body mass of 20 g were provided by Animal Institute of Chinese Academy of Medical Sciences. Rabbit-anti-human Nestin polyclonal antibody, rabbit-anti-human glial fibriliary acidic protein (GFAP) polyclonal antibody, rabbit-anti-human neuro-specific enolase polyclonal antibody and mouse-anti-human microtubal associated protein 2 (MAP-2) polyclonal antibody were provided by Wuhan Boster Company. METHODS: The experiment was carried out in the Central Laboratory of North China Coal Medical College from October 2004 to June 2005. hADASC was cultured with HCAM and its growth and morphological changes were observed under inverted phase contrast microscope. Immunocytochemistry, immunofluorescence and Western blotting were used to evaluate the expressions of Nestin, which was a specific sign of nerve precursor, neuro-specific enolase and MAP-2, which was a specific sign of nerve cell, and GFAP, which was a specific sign of neuroglial cells. MAIN OUTCOME MEASURES: Nestin, which was a specific sign of nerve precursor, neuro-specific enolase and MAP-2, which was a specific sign of nerve cell, and GFAP, which was a specific sign of neuroglial cells. RESULTS: On the 3rd day of culture, partial hADASC started deformation from slender shuttle-shape cells to neuron-like cells. It suggested that cells stretched out apophysis, which were mainly double-pole or multiple-pole cells. Five days later, immunohistochemical detection suggested that expression of Nestin (10.5±0.037) was found out in cells; meanwhile, expressions of GFAP (38.4±0.052) and neuro-specific enolase (NSE) (15.7±0.023) were also found out in cells; however, expression of MAP-2 was not observed. Western blot indicated that, 5 days after effect of HCAM, Nestin was found out in hADASC; meanwhile, expressions of GFAP and neuro-specific enolase were also found out; however, expression of MAP-2 was not observed. CONCLUSION: HCAM can induce the differentiation from hADASC to neuron-like cells in vitro.     

Divergent expression and localization of aquaporin 5, an exocrine-type water channel,in the submandibular gland of Sprague-Dawley rats

By Western blot analysis, the expression level of aquaporin (AQP) 5 in the submandibular gland (SMG) was found to be different among individual rats of the Sprague-Dawley (SD) strain. Such differences were observed for AQP5 but not for AQP1 and consequently the SD strain was divided into two groups, one expressing a high level of AQP5 and the other a low one. The difference in average intensity of expression between the two groups was more than twofold. Immunohistochemical analysis of the SMG demonstrated that the AQP5 protein was localized in the basal and apical/lateral plasma membrane of acinar cells in rats expressing the high level of AQP5. In the rat expressing the low level, however, this channel protein was localized strongly in the apical/lateral plasma membrane, but only very weakly in the basal membrane of the acinar cells. Such a diverse localization of AQP5 was confirmed by Western blotting as well. Breeding between brother and sister was repeated for two times within high expressers and low expressers to obtain the third generation progenies (F2); the AQP5 level of the SMG in the third generation (F2 rats) from high expressers was significantly higher than the F2 from low expressers. Our present study suggests the existence of genetic variation in the expression of a water channel protein, AQP5, in rats.     

Induction of long-term protective effects against heterologous challenge in SIVhu-infected macaques

A group of three rhesus macaques were inoculated with SIV isolated from a human (SIVhu) accidentally exposed and infected with SIVsm. Extensive sequence analyses of SIVhu obtained from the human and macaques following infection indicated the presence of truncated nef. Not only did nef fail to repair itself in vivo postinfection (p.i.), but instead, further mutations added additional stop codons with increasing time p.i. Infection of these animals was associated with minimal acute viral replication, followed by undetectable plasma viral loads and only intermittent PCR detection up to 5 years p.i. The three SIVhu infected and three control monkeys were then challenged with the heterologous highly pathogenic SHIV89.6p. All three controls became infected and showed rapid declines in peripheral CD4(+) lymphocytes, disease, and death at 10 and 32 weeks p.i., respectively. In contrast, all three animals previously infected with SIVhu are healthy and exhibit stable CD4(+) lymphocyte levels and undetectable plasma viral loads at >20 months post-SHIV89. 6p challenge. Only transient, low levels of SHIV replication were noted in these animals. Whereas responses to SIVgag/pol were noted, no evidence for SIV/SHIV envelope cross-reactivity was detected by antibody or CTL analyses, suggesting that the protective immune mechanisms to the heterologous challenge isolate were most likely not directed to envelope but rather to other viral determinants.     

Enhancement of NF-kappaB activity by resveratrol in cytokine-exposed mesangial cells

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.     

Hyperglycemia potentiates H(2)O(2) production in adipocytes and enhances insulin signal transduction: potential role for oxidative inhibition of thiol-sensitive protein-tyrosine phosphatases

Insulin signal transduction in adipocytes is accompanied by a burst of cellular hydrogen peroxide (H(2)O(2)) that facilitates insulin signaling by inhibiting thiol-dependent protein-tyrosine phosphatases (PTPs) that are negative regulators of insulin action. As hyperglycemia is associated with increased cellular reactive oxygen species, we postulated that high glucose conditions might potentiate the H(2)O(2) generated by insulin and modulate insulin-stimulated protein phosphorylation. Basal H(2)O(2) generation was increased threefold in differentiated 3T3-L1 adipocytes by growth in 25 mM glucose versus 5 mM glucose. High glucose increased the sensitivity of the insulin-stimulated H(2)O(2) signal to lower concentrations of insulin. Basal endogenous total PTP activity and the activity of PTP1B, a PTP implicated in the negative regulation of insulin signaling, were reduced in high glucose conditions, and their further reduction by insulin stimulation was more enhanced in high versus low glucose medium. Phosphorylation of the insulin receptor, IRS-1, and Akt in response to insulin was also significantly enhanced in high glucose conditions, especially at submaximal insulin concentrations. In primary rat adipocytes, high glucose increased insulin-stimulated H(2)O(2) production and potentiated the oxidative inhibition of total PTP and PTP1B activity; however, insulin signaling was not enhanced in the primary cells in high glucose apparently due to cross-regulation of insulin-stimulated protein phosphorylation by activation of protein kinase C (PKC). These studies indicate that high glucose can enhance insulin stimulated H(2)O(2) generation and augment oxidative PTP inhibition in cultured and primary adipocytes, but the overall balance of insulin signal transduction is determined by additional signal effects in high glucose, including the activation of PKC.