猪胃生长抑素阳性细胞和盐酸细胞发育的研究

应用免疫组织化学技术和组织学方法分别研究猪胃生长发育过程中生长抑素(SS)阳性细胞和盐酸细胞数量的变化。结果表明,胃底腺盐酸细胞数量刚出生时很少,但从3日龄开始一直处于上升趋势,直到120日龄才开始下降。从出生1～3日龄,盐酸细胞数量呈极显著增加(P<0 01);在20日、45日龄和90日龄时,盐酸细胞数量仍均呈显著或极显著增加(P<0 05,P<0 01)。然后于120日龄,盐酸细胞数量呈极显著减少(P<0 01)。胃底腺中SS阳性细胞发育与盐酸细胞正相反,从刚出生(1日龄)到3日龄,SS阳性细胞极显著增加(P<0 01),然后从3日龄以后SS阳性细胞逐渐减少,一直持续到120日龄。表明猪胃底腺中SS阳性细胞的发育可能对盐酸细胞的发育具有调节作用。

乳酸菌在不同开食制度下对新生仔猪胃肠道发育的影响

将12窝仔猪随机分为4组,即在饲喂与不饲喂开食料2种饲养制度下,分别设饲喂乳酸菌剂组和饲喂脱脂乳的对照组,每组3个重复.仔猪于7日龄开食,21日龄断奶,开食早期饲喂乳酸菌剂或脱脂乳.于仔猪7、14、21、24、35日龄每窝屠宰一头,取胃底、十二指肠、空肠组织进行组织形态学观察.结果表明:乳酸菌促进断奶后仔猪胃底腺盐酸细胞的增加(P<0.01),开食促进断奶前后胃底腺盐酸细胞的增加(P>0.05);乳酸菌和开食可促进断奶前十二指肠肠绒毛高度的维持,前者作用较短暂,后者的作用则更为明显,但两者对空肠肠绒毛无显著影响;添加乳酸菌与开食之间不存在互作效应.

大豆苷元对断奶仔猪胃肠道发育的影响

试验选用3窝新生仔猪,每窝内随机分为两组:大豆苷元组和对照组,于7、9、11日龄每头仔猪分别饲喂1、2和3mg.mL-1大豆苷元脱脂乳溶液1mL或等体积脱脂乳;所有仔猪于21日龄断奶;于14、21、24和35日龄,每窝随机抽取大豆苷元组和对照组仔猪各一头称重,屠宰,称量脾脏和胸腺重;取胃底部、十二指肠前端、空肠前端用于组织形态学观察;测定空肠和回肠组织组胺以及血清皮质醇含量。结果表明:大豆苷元显著增加断奶仔猪胃底腺盐酸细胞数量(P<0.05),但对胃底腺厚度和肠绒毛高度无显著影响;大豆苷元既可以阻止断奶造成的胃底腺肥大细胞募集(P<0.05),又可以维持肥大细胞的平稳增加;此外大豆苷元还可以降低断奶后回肠组胺水平(P<0.05);皮质醇在所有采样时间都无显著差异,说明大豆苷元对肥大细胞和组胺的作用可能与皮质醇无关;除35日龄大豆苷元组胸腺重高于对照组(P<0.05)外,大豆苷元对断奶仔猪胸腺和脾脏质量无显著影响。

Effects of glutamine supplementation on splenocyte cytokine mRNA expression in rats with septic peritonitis

AIM: To investigate the effects of glutamine (GLN)-enriched diets before and GLN-containing total parenteral nutrition (TPN) after sepsis or both on the secretion of cytokines and their mRNA expression levels in splenocytes of rats with septic peritonitis.METHODS: Rats were assigned to a control group and 4experimental groups. The control group and experimental groups 1 and 2 were fed a semipurified diet, while experimental groups 3 and 4 had part of the casein replaced by GLN which provided 25% of the total nitrogen.After rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), whereas the control group underwent a sham operation, at the same time, an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. The control group and experimental groups 1 and 3 were infused with conventional TPN, while the TPN in experimental groups 2 and 4 was supplemented with GLN, providing 25% of the total nitrogen in the TPN solution. All rats were kiued 3 d after sham operation or CLP to examine their splenocyte subpopulation distribution and cytokine expression levels.RESULTS: Most cytokines could not be detected in plasma except for IL-10. No difference in plasma IL-10 was observed among the 5 groups. The IL-2, IL-4, IL-10, and TNF-α mRNA expression levels in splenocytes were significantly higher in experimental groups 2 and 4 than in the control group and group 1. The mRNA expression of IFN-γ was significantly higher in the GLN-supplemented groups than in the control group and experimental group 1. The proportion of CD45Ra+ was increased, while those of CD3+ and CD4+ were decreased in experimental group 1 after CLP was performed. There were no differences in spleen CD3+ lymphocyte distributions between the control and GLN-supplemented groups.CONCLUSION:GLN supplementation can maintain Tlymphocyte populations in the spleen and significantly enhance the mRNA expression levels of Th1 and Th2cytokines and TNF-α in the spleen of rats with septic peritonitis.

Response of cellular stoichiometry and phosphorus storage of the cyanobacteria A phanizomenon flos-aquae to smallscale turbulence

Turbulent mixing, in particular on a small scale, aff ects the growth of microalgae by changing diff usive sublayers and regulating nutrient fluxes of cells. We tested the nutrient flux hypothesis by evaluating the cellular stoichiometry and phosphorus storage of microalgae under dif ferent turbulent mixing conditions. A phanizomenon flos-aquae were cultivated in dif ferent stirring batch reactors with turbulent dissipation rates ranging from 0.001 51 m2/s 3 to 0.050 58 m 2/s 3, the latter being the highest range observed in natural aquatic systems. Samples were taken in the exponential growth phase and compared with samples taken when the reactor was completely stagnant. Results indicate that, within a certain range, turbulent mixing stimulates the growth of A. flos-aquae. An inhibitory ef fect on growth rate was observed at the higher range. Photosynthesis activity, in terms of maximum ef fective quantum yield of PSII(the ratio of F v/F m) and cellular chlorophyll a, did not change significantly in response to turbulence. However, Chl a/C mass ratio and C/N molar ratio, showed a unimodal response under a gradient of turbulent mixing, similar to growth rate. Moreover, we found that increases in turbulent mixing might stimulate respiration rates, which might lead to the use of polyphosphate for the synthesis of cellular constituents. More research is required to test and verify the hypothesis that turbulent mixing changes the dif fusive sublayer, regulating the nutrient flux of cells.

Bile salts inhibit growth and induce apoptosis of culture human normal esophageal mucosal epithelial cells

AIM： To investigate the effect of six bile salts： glycocholate （GC）, glycochenodeoxycholate （GCDC）, glycodeoxycholate （GDC）, taurocholate （TC）, taurochenodeoxycholate （TCDC）, taurodeoxycholate （TDC）, and their mixture on cultured human normal esophageal rnucosal epithelial cells. METHODS： Human normal esophageal mucosal epithelial cells were cultured with serum-free keratinocyte medium. 3-[4,5-Dimethylthiaolyl]-2,5- diphenyl-tetrazolium bromide assay was applied to the detection of cell proliferation. Apoptotic morphology was observed by phase-contrast video microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） assay. Sub-G1 DNA fragmentations and early apoptotic cells were assayed by flow cytometry （FCI） with propidium iodide （PI） staining and annexin V-FITC conjugated with PI staining. Apoptotic DNA ladders on agarose gel electrophoresis were observed. RESULTS： Except for GC, GCDC, GDC, TC, TCDC, TDC and their mixture could initiate growth inhibition of esophageal mucosal epithelial cells in a dose- and time-dependent manner. TUNEL and FCM assays demonstrated that the bile salts at 500 μmol/L and their mixture at 1 500 μmol/L induced apoptosis except for GC. The percentage of sub-G1 detected by FCM with PI staining was 83.5% in cells treated with 500 μmol/L TC for 2 h, and 19.8%, 20.4%, 25.6%, 13.5%, and 75.8% in cells treated with 500 μmol/L GCDC, TCDC, GDC, TDC, and 1 500 μmol/L mixture for 24 h, respectively, which were higher than that of the control （1.5%）. The percentage was 1.4% in cells with 500 μmol/L GC for 24 h. DNA ladders on agarose gel electrophoresis were seen in cells treated with 500 μmol/L TC for 2 h and i 500 μmnol/L mixture for 24 h. CONCLUSION： All GCDC, GDC, TC, TCDC, TDC and their mixture can inhibit growth and induce apoptosis of cultured human normal esophageal mucosal epithelial cells, but GC is well tolerated by the cells.

Evaluation of leukocyte esterase and nitrite strip tests to detect spontaneous bacterial peritonitis in cirrhotic patients

AIM： To investigate the diagnostic efficacy of leukocyte esterase and nitrite reagent strips for bedside diagnosis of spontaneous bacterial peritonitis （SBP）. METHODS： A total of 63 consecutive patients with cirrhotic ascites （38 male, 25 female） tested between April 2005 and July 2006 were included in the study. Bedside reagent strip testing was performed on ascitic fluid and the results compared to manual cell counting and ascitic fluid culture. SBP was defined as having a polymorphonuclear ascites count of ≥ 250/mm^3. RESULTS： Fifteen samples showed SBP. The sensitivity, specificity, positive and negative predictive values of the leukocyte esterase reagent strips were; 93%, 100%, 100%, and 98%, respectively. The sensitivity, specificity, positive and negative predictive value of the nitrite reagent strips were 13%, 93%, 40%, and 77%, respectively. The combination of leukocyte esterase and nitrite reagents strips did not yield statistically significant effects on diagnostic accuracy. CONCLUSION： Leukocyte esterase reagent strips may provide a rapid, bedside diagnostic test for SBP.

Apoptotic effect of Epigallocatechin-3-gallate on the human gastric cancer cell line MKN45 via activation of the mitochondrial pathway

To investigate whether Epigallocatechin-3-gallate （EGCG） can induce apoptosis of the gastric cancer cell line MKN45 and its apoptotic pathway.METHODS： To determine this, apoptotic rates of MKN45 cells after EGCG treatment with or without caspase-3 inhibitor were evaluated by Annexin V-FITC ＋ PI staining The influence of EGCG on the activity of caspase-3 in the MKN45 cells was determined by ELISA. By Rhodamine123 staining, the membrane potential change of the mitochondrion was also investigated, and mRNAs and protein expression of the bcl-2 family were analyzed by RT-PCR and Western blot.RESULTS： EGCG can induce apoptosis of MKN45 cells in time- and dose-dependent manner. Eight hours after EGCG treatment, the activity of caspase-3 in the MKN45 increased, especially 12 h after treatment. The mitochondrial membrane potential was significantly weakened 4 h after EGCG insult. The mRNA and protein expression levels of pro-apoptotic members, such as Bax, Bid and Bad, were upregulated gradually as treated time increased. Moreover, the mRNA and protein expression levels of anti-apoptotic members, such as Bcl-xL and Bcl-2, were inhibited. CONCLUSION： These data support that EGCG can induce apoptosis of the human gastric cancer cell line MKN45, and the effect is in a time- and dose-dependent manner. The apoptotic pathway triggered by EGCG in MKN45 is mitochondrial-dependent.

Surface plasmon resonance analysis to evaluate the importance of heparin sulfate groups＇ binding with human aFGF and bFGF

Human acidic and basic fibroblast growth factors (aFGF and bFGF) are classic and well characterized members of the heparin binding growth factor family. Heparin is generally thought to play an extremely important role in regulating aFGF and bFGF bioactivities through its strong binding with them. In order to unravel the mechanism of the interactions between heparin and FGFs, and evaluate the importance of heparin sulfate groups' binding with FGFs, surface plasmon resonance analyses were performed using IAsys Cuvettes System. Heparin and its regioselectively desulfated derivatives were immobilized on the cuvettes. aFGF and bFGF solutions with different concentrations were pipetted into the cuvettes and the progress of the interaction was monitored in real\|time by Windows based software, yielding kinetic and equilibrium constants for these interactions. In addition, in order to reduce the delicate difference among the cuvettes, inhibition analyses of mixture of FGFs and immobilized native heparin by modified heparins were also done. The data from these two methods were similar, indicating that all sulfate groups at 2 O, 6 O and N in heparin were required for the binding to aFGF; and that their contribution to the binding was in the order 2 O, N and 6 O sulfate group. In contrast, definite contribution of the 6 O sulfate group to the binding with bFGF was most apparent, while the other two sulfate groups appeared to be necessary in the order 2 O and N sulfate group. These methods established here can be used for analysing the effect of sulfate groups in heparin on the binding with other human FGF members or other heparin binding proteins.

Berbamine induces apoptosis in human hepatoma cell line SMMC7721 by loss in mitochondrial transmembrane potential and caspase activation

Objective： To investigate the effect ofberbamine on human hepatoma cell line SMMC7721. Methods： The effects of 24 h and 48 h incubation with different concentrations （0-64 μg/ml） of the berbamine on SMMC7721 cells were evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide （MTT） assay. Hoechst 33258 staining was conducted to distinguish the apoptotic cell, and the appearance of sub-G1 stage was determined by PI （propidium iodide） staining, the percentage of apoptotic cell was determined by flow cytometry following annexin V/PI staining. Flow cytometry was performed to analyze the cell cycle distribution and the mitochondrial membrane potential （△ψm）, the expression of activated caspase3 and caspase9 was analyzed by Western-blot. Results： The proliferation of SMMC7721 was decreased after treatment with berbamine in a dose- and time-dependent manner. Berbamine could induce apoptosis in SMMC7721 cells and could cause cell cycle arrest in G0/G1 phase, to induce loss of mitochondrial membrane potential （AVm） and activate caspase3 and caspase9. Berbamine-induced apoptosis could be blocked by the broad caspase inhibitor z-VAD-fmk. Conclusion： Berbamine exerts antiproliferative effects on human hepatocellular carcinoma SMMC7721 cells. The anticancer activity of berbamine could be attributed partly to its inhibition of cell proliferation and induction of apoptosis in cancer cells through loss in mitochondrial transmembrane potential and caspase activation.

Glutamine-supplemented total parenteral nutrition attenuates plasma interleukin-6 in surgical patients with lower disease severity

AIM： To evaluate whether the effect of Gin dipeptideenriched total parenteral nutrition （TPN） on postoperative cytokine alteration depended on the disease severity of surgical patients. METHODS： Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous （0.228 g nitrogen/kg per d） and isocaloric （30 kcal/kg per d） TPN for 6 d. Control group （Cony） using conventional TPN solution received 1.5 g amino acids/kg per day, whereas the test group received 0.972 g amino acids/kg per day and 0.417 g L-alanyI-L-glutamine （Ala-GIn）/kg per day. Blood samples were collected on d 1 and d 6 postoperatively for plasma interleukin （IL）-2, IL-6, IL-8, and interferon （IFN）-γ analysis. RESULTS： Plasma IL-2 and IFN-γ were not detectable. IL-6 concentrations were significantly lower on the 6^th postoperative day in the Ala-GIn group than those in the Cony group in patients with APACHE Ⅱ≤6, whereas no difference was noted in patients with APACHE Ⅱ〉6. There was no difference in IL-8 levels between the two groups. No difference in cumulative nitrogen balance was observed on d 2-5 after the operation between the two groups （Ala-GIn -3.2±1.6 g vs Cony -6.5±2.7 g）. A significant inverse correlation was noted between plasma IL-6 levels and cumulative nitrogen balance postoperatively in the Ala-GIn group, whereas no such correlation was observed in the Conv group. CONCLUSION： TPN supplemented with Gin dipeptide had no effect on plasma IL-8 levels after surgery. However, Gin supplementation had a beneficial effect on decreasing systemic IL-6 production after surgery in patients with low admission illness severity, and lower plasma IL-6 may improve nitrogen balance in patients with abdominal surgery when Gin was administered.

Effect of Mono- and Di-ethanolammonium Formate Ionic Liquids on the Volatility of Water, Ethanol, and Methanol

Vapor pressures were measured for six binary systems containing water, ethanol, or methanol with one of the two ionic liquids(ILs) at different component concentrations and temperatures using a quasi-static ebulliometer,with the ILs mono-ethanolammonium formate([HMEA][HCOO]) and di-ethanolammonium formate([HDEA][HCOO]).The vapor pressures of the IL-containing binary systems are well correlated using the NRTL model with an overall average absolute relative deviation(AARD) of 0.0062. The effect of ILs on the vapor pressure depression of solvents at 0.050 mole fraction of IL is that [HDEA][HCOO]>[HMEA][HCOO], and the vapor pressure lowering degree follows the order of water>methanol>ethanol. Further, the activity coefficients of three solvents(viz. water,ethanol, and methanol) for the binary systems {solvent(1) + IL(2)} predicted based on the fitted NRTL parameters at T 333.15 K indicate that the two ILs generate a negative deviation from Raoult's law for water and methanol and a positive deviation for ethanol to a varying degree, change the relative volatility of a solvent. [HMEA][HCOO]may be a promising entrainer to efficiently separate ethanol aqueous solutions by special rectification.

Effect of salvianolate on intestinal epithelium tight junction protein zonula occludens protein 1 in cirrhotic rats

AIM:To study the effect of salvianolate on tight junctions(TJs) and zonula occludens protein 1(ZO-1) in small intestinal mucosa of cirrhotic rats.METHODS:Cirrhosis was induced using carbon tetrachloride.Rats were randomly divided into the untreated group,low-dose salvianolate(12 mg/kg) treatment group,medium-dose salvianolate(24 mg/kg) treatment group,and high-dose salvianolate(48 mg/kg) treatment group,and were treated for 2 wk.Another 10 healthy rats served as the normal control group.Histological changes in liver tissue samples were observed under a light microscope.We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system.Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy.The changes in ZO-1 expression,a tight junction protein,were analyzed by immunocytochemistry.The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.RESULTS:In the untreated group,hepatocytes showed a disordered arrangement,fatty degeneration was extensive,swelling was obvious,and disorganized lobules were divided by collagen fibers in hepatic tissue,which were partly improved in the salvianolate treated groups.In the untreated group,abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts,and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment.Compared with the untreated group,no differences in intestinal villi width between the five groups were observed.The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group(P < 0.01).The number of microvilli decreased and showed irregular lengths and arrangements in the untreated group.The intercellular space between epithelial cells was wider.The TJs were discontinuous,which indicated disruption in TJ morphology in the untreated group.In the treated groups,the microvilli in the intestinal epithelium were regular and the TJs were gradually integrated and distinct.The expression of ZO-1 decreased in the small intestine of the untreated cirrhotic rats.The high expression rate of ZO-1 in ileal mucosa in the untreated group was significantly lower than that in the medium-dose salvianolate group(21.43% vs 64.29%,χ 2 = 5.25,P < 0.05),high-dose salvianolate group(21.43% vs 76.92%,χ 2 = 8.315,P < 0.01) and normal group(21.43% vs 90%,χ 2 = 10.98,P < 0.01).CONCLUSION:Salvianolate improves liver histopathological changes,repairs intestinal mucosa and TJ structure,and enhances ZO-1 expression in the small intestinal mucosa in cirrhotic rats.

Effect of vitamin E succinate on the proliferation of human breast cancer cells

Objective：Tn investigate the growth inhibition and apoptosis induced by vitamin E suceinate （VES） on human breast cancer cells and to analyze the possible mechanism in this process. Methods： Human breast cancer cell line Bcap-37 was treated with VES for 12, 24 and 48 h at the concentrations of 5, 10and 20 μg/ml. Then MTT assay was employed to detect the inhibitory effect of VES on the growth of breast cancer cells. Flow cytometry was used to analyze the cell cycle and apoptosis. To find out whether the Fas/FasL pathway was involved in this process, RT-PCR and flow cytometry assay were used to detect the Fas expression at the mRNA and protein level. Results： VESexhibited a significant inhibitory effect on the growth of human breast cancer cells, presenting in a dose- and time-dependant manner. The apoptotic rate of Bcap 37 cells was 0.6%, rose to 21.0% and 37.5% after treated with VES for 24 and 48 h at the concentration of 20 μg/ml. Fas mRNA transcription was upregulated after VES treatment and cell surface Fas expression increased according to the flow cytometry assay. Concluslon：Significant growth inhibition and apoptosis are induced in human breast cancer cells after treated with VES. The modulation of Fas/FasL pathway may related to the upregulation of Fas molecule on the cancer cell surface.

Is the required therapeutic effect always achieved by racemic switch of proton-pump inhibitors?

Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.

Removal of Co(Ⅱ) from aqueous solutions by NKC-9 strong acid resin

A strong acidic ion exchange resin(NKC-9)was used as a new adsorbent material for the removal of Co(Ⅱ)from aqueous solutions.The adsorption isotherm follows the Langmuir model.The maximum adsorption capacity of the resin for Co(Ⅱ)is evaluated to be 361.0 mg/g by the Langmuir model.It is found that 0.5 mol/L HCl solution provides effectiveness of the desorption of Co(Ⅱ)from the resin.The adsorption rate constants determined at 288,298 and 308 K are 7.12×10-5,8.51×10-5and 9.85×10-5s-1, respectively.The apparent activation energy(Ea)is 12.0 kJ/mol and the adsorption parameters of thermodynamic are-H Θ=16.1 kJ/mol,-SΘ=163.4 J/(mol·K),-G Θ 298 K=-32.6 kJ/mol,respectively.The adsorption of Co(Ⅱ)on the resin is found to be endothermic in nature.Column experiments show that it is possible to remove Co(Ⅱ)ions from aqueous medium dynamically by NKC-9 resin.

IMMUNOMODULATING EFFECTS OF THE FUCOIDAN-GALACTOSAN SULFATE (F_12) ON MACROPHAGES IN MICE

The immunomodulating effects of F12 on mouse peritoneal macrophages was intended to be studied with different doses of 20, 40, 80 and 120mg/Kg. F12 increased peroxidase activity in dexc dependent mammer from 0.02±0.001 to 0.175±0.038, 0.211±0.041, 0.137±0.045 and 0.078±0.036, respectively, increased cytotoxicity from 127.33±22.96 to 162.74±19.53, 237.30±25.15 , 178.62±36.22 and 158.66±42.75dpm, respectively, promoted phagocytic activity from 0.03±0.01 to0.21±0.016, 0.43±0.041, 0.40±0.032 and 0.30±0.160b. Furthermore, F12 in a concentration of 15, 30,60,120μg/ml enhanced IL-1 production from 0.15±0.02 to 0.20±0.005b 0.21±0.02,0.22±0.005,0.24±0.002 and 0.22±0.02,respectively. Thus F12 can be considered as an effective stimulator of macrophages.

FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts

AIM: To evaluate the efficacy and safety of the FOLFIRI regimen in patients with metastatic pancreatic adenocarcinoma (PAC) after the failure of gemcitabine and platinum salts. METHODS: All consecutive patients with histologically confirmed, metastatic PAC and World Health Organiza-tion performance status (PS) ≤ 2 received FOLFIRI-1 [irinotecan 180 mg/m2 on day 1 and leucovorin 400 mg/m2 followed by 5-fluorouracil (5-FU) 400 mg/m2 bolus, then 5-FU 2400 mg/m2 as a 46-h infusion, biweekly] or FOLFIRI-3 (irinotecan 100 mg/m2 on day 1 and leucovorin 400 mg/m2, then 5-FU 2400 mg/m2 as a 46-h infusion and irinotecan 100 mg/m2 repeated on day 3, biweekly) after failure of gemcitabine and platinum-based chemotherapies as a systematic policy in two institutions between January 2005 and May 2010. Tumor response, time to progression (TTP), overall survival rate (OS) and grade 3-4 toxicities were retrospectively studied. Subgroup analyses were performed to search for prognostic factors. RESULTS: Sixty-three patients (52.4% male, median age 59 years) were analyzed. Among them, 42.9% were PS 0, 38.1% were PS 1 and 19.0% were PS 2. Fifty one patients (81.0%) had liver metastases. Before the FOLFIRI regimen, patients had received 1 line (n = 19), 2 lines (n = 39) or 3 lines (n = 5) of chemotherapy. Median TTP obtained with the line before FOLFIRI was 3.9 mo (95% CI: 3.4-5.3 mo). A total of 480 cycles was completed (median: 6 cycles, range: 1-51 cycles). The main reason for discontinuing FOLFIRI was tumor progression (90.3%). Tumor control was achieved in 25 patients (39.7%) (partial response: n = 5, stable disease: n = 20) with FOLFIRI. Median TTP was 3.0 mo (95% CI: 2.1-3.9 mo) and median OS was 6.6 mo (95% CI: 5.3-8.1 mo). Dose adaptation was required in 36 patients (57.1%). Fifteen patients (23.8%) had grade 3-4 toxicities, mainly hematological (n = 11) or digestive (n = 4). Febrile neutropenia occurred in 3 patients. There was no toxic death. PS 2 was significantly associated with poor TTP [hazard ratio (HR): 16.036, P < 0.0001] and OS (HR: 4.003, P = 0.004). CONCLUSION: The FOLFIRI regimen had an acceptable toxicity and an interesting efficacy in our study, limited to patients in good condition (PS 0-1).

Effects of Pilocarpine Hydrochloride on the Hyposalivation Induced by Psychotropic Drugs

The aim was to study the secretagogue action of pilocarpine on the murine parotid glands submitted to chronic treatment with psychotropic drugs by salivary flow rate determinations and histological alterations. Fifty four male Wistar rats were equally divided in three groups： C group （control） received saline solution for 30 days; AD group （n = 18） received AmitriptylineR and DiazepamR for 30 days, and ADP group （n = 18） received Amitriptyline R and DiazepamR for 30 days and AmitriptylineR, DiazepamR and pilocarpine for further 30 days, resulting in 60 days of treatment. Saliva samples were collected 30 h after the end of treatment. Parotids were removed and processed for hematoxylin-eosin histological analysis. Dedicated software for image processing allowed the determination of cell number and volume. Significant differences between paired-groups C-AD （P 〈 0.01） and AD-ADP （P 〈 0.01） were observed for glands size and weight. The volume of serous cells was greater in AD, suggesting a hypertrophy of the salivary glands. For salivary flow rate, C group showed the highest average. The number of serous cells was similar between groups ADP and C, with the lowest average being found in AD group （P 〈 0.05）.

Inositol 1,4,5-trisphosphate 3-kinases:functions and regulations

Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP3K) plays an important role in signal transduction in animal cellsby phosphorylating inositol 1,4,5-trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP4). Both IP3 and IP4 arecritical second messengers which regulate calcium (Ca2+) homeostasis. Mammalian IP3Ks are involved in many biologicalprocesses, including brain development, memory, learning and so on. It is widely reported that Ca2+ is a canonicalsecond messenger in higher plants. Therefore, plant IP3K should also play a crucial role in plant development. Recently,we reported the identification of plant IP3K gene (AtIpk2β/AtIP3K) from Arabidopsis thaliana and its characterization.Here, we summarize the molecular cloning, biochemical properties and biological functions of IP3Ks from animal, yeastand plant. This review also discusses potential functions of IP3Ks in signaling crosstalk, inositol phosphate metabolism,gene transcriptional control and so on.