Detailed radiosynthesis of [18 F]mG4P027 as a positron emission tomography radiotracer for mGluR4.

We report here the detailed radiosynthesis of [18 F]mG4P027, a metabotropic glutamate receptor 4 (mGluR4) PET radiotracer, which showed superior properties to the currently reported mGluR4 radiotracers. The radiosynthesis in the automated system has been challenging, therefore we disclose here the major limiting factors for the synthesis via step-by-step examination. And we hope this thorough study will help its automation for human use in the future.

Organomediated cleavage of benzoyl group enables an efficient synthesis of 1-(6-nitropyridin-2-yl)thiourea and its application for developing 18F-labeled PET tracers.

A novel organomediated cleavage of benzoyl group using ethane-1,2-diamine and acetic acid under neutral condition enables an efficient synthesis of 1-(6-nitropyridin-2-yl)thiourea, which previously has been challenging to prepare by conventional methods. The successful synthesis of 1-(6-nitropyridin-2-yl)thiourea as a synthon permits development of a variety of 18F labeled heterocycles as PET imaging ligands such as N-(pyridin-2-yl)thiazol-2-amine derivatives. The utility of this synthon is demonstrated with the synthesis of a 18F-labeled PET tracer for studying prion disease. In vitro autoradiography using this PET tracer on sagittal rat brain slices showed highest accumulation of radioactivity in the hippocampus, cortex, and striatum, in accordance with reported immunostaining of PrPc in rat brain.

Efficient synthesis of NIR emitting bis[2-(2'-hydroxylphenyl)benzoxazole] derivative and its potential for imaging applications.

Unassymetric bis[2-(2'-hydroxyphenylbenzoxole)] bis(HBO) derivatives with a DPA functionality for zinc binding have been developed with an efficient synthetic route, using the retrosynthetic analysis. Comparison of bis(HBO) derivatives with different substitution patterns allows us to verify and optimize their unique fluorescence properties. Upon binding zinc cation, bis(HBO) derivatives give a large fluorescence turn-on in both visible (λem ≈ 536 nm) and near-infrared (NIR) window (λem ≈ 746 nm). The probes are readily excitable by a 488 nm laser, making this series of compounds a suitable imaging tool for in vitro and in vivo study on a confocal microscope. The application of zinc binding-induced fluorescence turn-on is successfully demonstrated in cellular environments and thrombus imaging.

Improved Synthesis of the Thiophenol Precursor N-(4-Chloro-3-mercaptophenyl)picolinamide for Making the mGluR4 PET Ligand.

Recently [11C]mG4P012 (previously [11C]KALB012 and presently named as [11C]PXT012253 by Prexton Therapeutics) had been used as a biomarker during the preclinical development of a potential therapeutic drug, PXT0002331 (an mGluR4 PAM), for PD and L-dopa-induced dyskinesia. [11C]mG4P012 was shown to be a promising PET radioligand for mGluR4 in the monkey brain and for further development in human subjects. However, the previously reported multi-step synthesis of the thiophenol precursor suffered from low yields and difficult workup procedures. To support the translational research of [11C]mG4P012 and the other potential applications, we have developed a new route for synthesis of the thiophenol precursor and optimized the reaction conditions. The synthesis of N-(4-chloro-3-mercaptophenyl)picolinamide from 1-chloro-4-nitrobenzene has been greatly improved from 8% to 52% total yield with easy handling and in gram scales.

Transjugular intrahepatic portosystemic shunt versus open splenectomy and esophagogastric devascularization for portal hypertension with recurrent variceal bleeding.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) and open splenectomy and esophagogastric devascularization (OSED) are widely used to treat patients with portal hypertension and recurrent variceal bleeding (PHRVB). This study aimed to compare the effectiveness between TIPS and OSED for the treatment of PHRVB. METHODS: The data were retrospectively retrieved from 479 cirrhotic patients (Child-Pugh A or B class) with PHRVB, who had undergone TIPS (TIPS group) or OSED (OSED group) between January 1, 2010 and October 31, 2014. RESULTS: A total of 196 patients received TIPS, whereas 283 underwent OSED. Within one month after TIPS and OSED, the rebleeding rates were 6.1% and 3.2%, respectively (P=0.122). Significantly lower incidence of pleural effusion, splenic vein thrombosis, and pulmonary infection, as well as higher hepatic encephalopathy rate, shorter postoperative length of hospital stay, and higher hospital costs were observed in the TIPS group than those in the OSED group. During the follow-up periods (29 months), significantly higher incidences of rebleeding (15.3% vs 4.6%, P=0.001) and hepatic encephalopathy (17.3% vs 3.9%, P=0.001) were observed in the TIPS group than in the OSED group. The incidence of in-stent stenosis was 18.9%. The survival rates were 91.3% in the TIPS group and 95.1% in the OSED group. The long-term liver function did not worsen after either TIPS or OSED. CONCLUSION: For the patients with liver function in the Child-Pugh A or B class, TIPS is not superior over OSED in terms of PHRVB treatment and rebleeding prevention.

[Effects of RAGE on Cell Proliferation and Tumor Growth in Pancreatic Cancer].

OBJECTIVES: To investigate the effect of receptor for advanced glycation end products (RAGE) on cell proliferation and tumor growth in nude mice with pancreatic cancer. METHODS: PANC-1 cells were transfected with shRNA RAGE -1, -2, -3 to down-regulate the expression of RAGE. Cholecystokinin octopeptide-8 (CCK-8), real-time PCR and Western blot were performed to test the impact of shRNA RAGE on the expressions of mRNAs and proteins of RAGE, matrix metalloproteinase-2 (MMP-2), MMP-9, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and vascular endothelial growth factor (VEGF). Tumor growth and microvessel density in the nude mice implanted with shRNA RAGE transfected PANC-1 cells were observed using immunohistochemistry. RESULTS: The shRNA RAGE -1, -2, -3 transfected cells had lower absorbance values than the controls 24 h after transfection, and the absorbance value reached the lowest at 48 h. The specific shRNA sequences significantly inhibited the expressions of mRNA and protein of RAGE. The mice implanted with shRNA RAGE -2 had lower tumor volume and microvessel density than shRNA RAGE -1, -3. The expressions of mRNAs and proteins of RAGE, MMP-2, NF-κB, MMP-9 and VEGF were lower in the cells transfected with shRNA RAGE -2 compared with shRNA RAGE -1, -3. CONCLUSIONS: RAGE is involved in the progression of pancreatic cancerin vitro and in vivo . The RAGE expression could influence the process of tumor angiogenesis.

Clinical outcomes of combined necrotizing pancreatitis versus extrapancreatic necrosis alone.

INTRODUCTION: Extrapancreatic necrosis (EPN) alone, i.e., in the absence of pancreatic parenchyma necrosis has gradually come to be regarded as a separate entity of acute necrotizing pancreatitis (ANP). However, data regarding the prognostic significance of EPN are quite limited, and the outcomes of interventions for patients with EPN alone are not well elucidated. The aim of this study was to explore the differences in the outcomes of patients with EPN alone and patients with both the pancreatic parenchyma and extrapancreatic necrosis (combined necrosis). METHODS: From January 2009 to December 2013, a total of 334 patients with ANP who had received interventions in the West China Hospital in China were included. Based on the extent of necrosis as assessed with contrast-enhanced CT, the patients were divided into Group 1 (n = 285) in which the necrosis involved both the pancreatic parenchyma and extrapancreatic tissues (combined necrosis) and Group 2 (n = 49) in which the necrosis involved only the extrapancreatic tissues. Additionally, Group 3 included 443 patients with interstitial pancreatitis who were also included in the analyses. The demographic characteristics, support treatment information, organ failure information, infection necrosis, persistent systemic inflammatory response syndrome (SIRS) in the first week of onset, CT severity index, and intervention types, as well as the postoperative stay lengths, ICU utility, and complications were collected and compared. RESULTS: Compared with the patients in Group 1, the patients in Group 2 suffered less persistent SIRS in the first week of onset (12/24.5% vs. 145/50.9%; P < 0.05), less persistent organ failure (6/12.2% vs. 95/33.3%; P < 0.05), less persistent multiple organ failure (3/6.1% vs. 67/23.5%; P < 0.05), and less bacteremia (5/10.2% vs. 107/37.5%; P < 0.001). The intervention types were significantly different between the two groups (P < 0.001); initial open necrosectomy was performed in 174/61.6% and 8/16.3% of the patients in Groups 1 and 2, respectively, and initial percutaneous catheter drainage (PCD) was performed in 73/25.6% and 29/59.2% of the patients in the two respective groups. Second open necrosectomies following PCD were required in 61/83.5% and 9/31.0% of the patients in Groups 1 and 2, respectively (P < 0.001). A greater number of patients in Group 1 were diagnosed with infected necrosis (204/71.6% vs. 10/20.4%; P < 0.001) and had to be sent to the ICU for further postoperative care (221/77.5% vs. 23/46.9%; P < 0.001). The postoperative stay was longer for Group 1 (median: 43.0 vs. 26.5 days; P < 0.001). Residual necrotic tissue or abscess was the most common postoperative complication in both groups. The mortality was higher in Group 1 (52/18.2% vs. 1/2.1%; P < 0.05). Compared with the patients in Group 2, the patients with interstitial pancreatitis exhibited milder courses and better outcomes. Subgroup comparisons with Group 1 indicated that early multiple organ failure was significantly associated with higher mortality. CONCLUSION: The patients with EPN alone exhibited significantly better prognoses than those with combined necrosis, and EPN alone should be regarded as a separate group of acute necrotizing pancreatitis. Open necrosectomy can be avoided in the majority of patients with EPN alone, who receive PCD as the initial first intervention.

Synthesis and evaluation of N-(methylthiophenyl)picolinamide derivatives as PET radioligands for metabotropic glutamate receptor subtype 4.

In recent years, mGlu4 has received great research attention because of the potential benefits of mGlu4 activation in treating numerous brain disorders, such as Parkinson's disease (PD). A specific mGlu4 PET radioligand could be an important tool in understanding the role of mGlu4 in both healthy and disease conditions, and also for the development of new drugs. In this study, we synthesized four new N-(methylthiophenyl)picolinamide derivatives 11-14. Of these ligands, 11 and 14 showed high in vitro binding affinity for mGlu4 with IC50 values of 3.4nM and 3.1nM, respectively, and suitable physicochemical parameters. Compound 11 also showed enhanced metabolic stability and good selectivity to other mGluRs. [(11)C]11 and [(11)C]14 were radiolabeled using the [(11)C]methylation of the thiophenol precursors 20a and 20c with [(11)C]CH3I in 19.0% and 34.8% radiochemical yields (RCY), and their specific activities at the end of synthesis (EOS) were 496±138GBq/µmol (n=6) and 463±263GBq/µmol (n=4), respectively. The PET studies showed that [(11)C]11 accumulated fast into the brain and had higher uptake, slower washout and 25% better contrast than [(11)C]2, indicating improved imaging characteristics as PET radiotracer for mGlu4 compared to [(11)C]2. Therefore, [(11)C]11 will be a useful radioligand to investigate mGlu4 in different biological applications.

Re-exploring the N-phenylpicolinamide derivatives to develop mGlu4 ligands with improved affinity and in vitro microsomal stability.

In recent years, mGlu4 has received great attention and research effort because of the potential benefits of mGlu4 activation in treating numerous brain disorders, such as Parkinson's disease (PD). Many positive allosteric modulators of mGlu4 have been developed. To better understand the role of mGlu4 in healthy and disease conditions, we are interested in developing an mGlu4 selective radioligand for in vivo studies. Thus, we had synthesized and studied [(11)C]2 as a PET tracer for mGlu4, which demonstrated some promising features as a PET radioligand as well as the limitation need to be improved. In order to develop an mGlu4 ligand with enhanced affinity and improved metabolic stability, we have modified, synthesized and evaluated a series of new N-phenylpicolinamide derivatives. The SAR study has discovered a number of compounds with low nM affinity to mGlu4. The dideuteriumfluoromethoxy modified compound 24 is identified as a very promising mGlu4 ligand, which has demonstrated enhanced affinity, improved in vitro microsomal stability, good selectivity and good permeability.

Laparoscopic pancreaticoduodenectomy: single-surgeon experience.

BACKGROUND: Innovations in surgical strategies and technologies have facilitated laparoscopic pancreaticoduodenectomy (LPD). However, data regarding the short-term and long-term results of LPD are sparse, and this procedure is the primary focus of the current study. METHODS: Between October 2010 and October 2013, a total of 31 consecutive patients received LPD, including hand-assisted laparoscopic pancreaticoduodenectomy, total laparoscopic pancreaticoduodenectomy, and laparoscopic pylorus-preserving pancreaticoduodenectomy. Data regarding short-term surgical outcomes and long-term oncological results were collected prospectively. RESULTS: The median operative time was 515.0 min (interquartile range 465.0-585.0 min). The median intraoperative estimated blood loss was 260.0 mL (interquartile range 150.0-430.0 mL). Conversion to open pancreaticoduodenectomy was required in three patients (9.7%) due to intraoperative pneumoperitoneum intolerance (n = 1, 3.2%) and tumor adherence to the superior mesenteric vein (n = 2, 6.5%). No significant differences between the surgical approaches were observed in regard to intraoperative and postoperative data. Postoperative severe complications (Clavien ≥ III) were detected in three (9.7%) patients, including one grade C pancreatic fistula, one grade B postoperative bleeding event, and one afferent loop obstruction. There were no deaths within 30 days following LPD. The final pathological results revealed duodenal adenocarcinoma in 14 (45.2%) patients, ampullary adenocarcinoma in four (12.9%) patients, distal common bile duct cancer in six (19.4%) patients, pancreatic ductal adenocarcinoma in five (16.1%) patients, gastrointestinal stroma tumor in one (3.2%) patient, and chronic pancreatitis in one (3.2%) patient. All patients suffering from tumors underwent R0 resection (n = 30, 100.0%), with the optimal number of collected lymph nodes (median: 13, interquartile range 11-19). At the most recent follow-up, 20 patients were still alive, and the 1-, and 3-year overall survival for patients with duodenal adenocarcinoma were 100.0 and 71.4%, respectively. CONCLUSIONS: According to this study, LPD is feasible and technically safe for highly selected patients and can offer acceptable oncological outcomes and long-term survival.

[Effect of CD86 Gene Modified Recipient Dendritic Cell on Mix Cultured Donor-derived Islet with Recipient-derived Lymphocyte in vitro].

OBJECTIVE: To investigate the effect of CD86 gene modified recipient dendritic cell (DC) on mix cultured donor-derived islet with recipient-derived lymphocyte in vitro. METHODS: DCs were separated from bone marrow of BALB/c mice and identified by flow cytometry. Chemically synthesized CD86 siRNA was transferred into DC. Donor islets were separated from the pancreas of SD rats. Acridine orange (AO)/Propidium iodide (PI) staining was conducted to assess the viability of islets. Lymphocytes were collected from the spleen of SD rats and then co-cultured with CD86 gene modified recipient DCs. CD86 gene modified recipient DC, donor-derived islet (400 IEQ) and recipient-derived lymphocyte (1 x 10(6)) were mix cultured in vitro. Four groups were set: blank group (islets of SD rat only), control 1 group (islets of SD rat with splenic lymphocyte of BALB/c mice) , control 2 group (islets of SD rat, splenic lymphocyte of BALB/c mice with normal recipient DC) and experimental group (islets of rat, splenic lymphocyte of BALB/c mice with CD86 gene modified recipient DC). After 3 days culture, the cellular morphology of culture was observed with light inverted microscope. The levels of IL-2, IL-4, IL-10 and IFN-γ in the culture supernatant were tested, and islets viability was assessed by AO/PI staining. GSIS was conducted and stimulation index (SD was calculated. RESULTS: Typical DC morphology was found from the collected cells. The positive rates of CD1lc, CD80 and CD86 protein expression on DCs were 86.26% ± 9.73%, 72.64% ± 8.55% and 77.18% ± 10.23%, respectively. The positive rate of CD86 protein expression on DCs after transfection was 23.64% ± 5.25%. The viability of islets was over 95%. After 3 days culture, the level of IL-10 increased significantly and the levels of IL-2 and INF-γ decreased significantly in experimental group (vs. control 1 and control 2 groups, P < 0.05). The level of IL-4 was similar in control 1, control 2 and experimental groups, but the proliferation rate of lymphocyte in the experimental group was the lowest one, the viability of islets in the experimental group was the best and the SI was the highest. The levels of IL-2, IL-4, IL-10 and IFN-γ in the experimental group were higher than those in the blank group. CONCLUSION: CD86 gene modified recipient DC loaded with donor-derived antigen could protect the islet function in vitro to some extent.

The role of organ failure and infection in necrotizing pancreatitis: a prospective study.

OBJECTIVE: To clarify the roles of organ failure and infection in the outcome of necrotizing pancreatitis. BACKGROUND: Results of previous cohort studies that focused on the roles of infection and organ failure in acute pancreatitis are controversial. METHODS: In this study, we collected the medical records of 447 patients with necrotizing pancreatitis from January 2009 to June 2012. Data associated with organ failure and infection were analyzed. RESULTS: The overall mortality rate was 13% (58/447). Intervention was performed in 223 of 447 patients. Among these 223 patients, 134 were confirmed to be with infected necrosis by a positive culture. The mortality rate was 15% (13/89) in the sterile necrosis group and 18% (24/134) in the infected necrosis group (P = 0.52). A multivariate analysis of death predictors indicated that bacteremia (odds ratio [OR] = 2.76, 95% confidence interval [CI], 1.23-5.46, P < 0.001), age (OR = 1.07, 95% CI, 1.03-1.11, P < 0.001), American Society of Anesthesiologists class (OR = 3.56, 95% CI, 1.65-7.18, P = 0.001), persistent organ failure in the first week (OR = 16.72, 95% CI, 7.04-32.56, P < 0.001), and pancreatic necrosis (OR = 1.73, 95% CI, 1.14-2.98, P = 0.008) were significant factors. CONCLUSIONS: Among patients with necrotizing pancreatitis, the effects of organ failure on mortality are more critical than those of infection. Bacteremia, age, American Society of Anesthesiologists class, persistent organ failure in the first week, and pancreatic necrosis were identified as the predictors of mortality.

Triple-layer duct-to-mucosa pancreaticojejunostomy with resection of jejunal serosa decreased pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Pancreatic fistula (PF) is one of the most common complications after pancreaticoduodenectomy (PD). We described a new method of pancreaticojejunostomy (PJ) developed by combining triple-layer duct-to-mucosa PJ with resection of jejunal serosa, which was named as modified layer-to-layer PJ (MLLPJ). The aim of the present study was to observe whether the new technique would effectively reduce the PF rate in comparison with two-layer duct-to-mucosa PJ (TLPJ). METHODS: Data on 184 consecutive patients who underwent the two methods of PJ after standard PD between January 1, 2010 and January 31, 2013 were collected retrospectively from a prospective database. The primary endpoint was the PF rate. The risk factors of PF were investigated by using univariate and multivariate analyses. RESULTS: A total of 88 patients received TLPJ and 96 underwent MLLPJ. Rate of PF for the entire cohort was 8.2%. There were 11 fistulas (12.5%) in the TLPJ group and four fistulas (4.2%) in the MLLPJ group (P = 0.039). Body mass index, pancreatic texture, pancreatic duct diameter, and methods of PJ anastomosis had significant effects on the formation of PF on univariate analysis. Multivariate analysis showed that pancreatic duct diameter ≤3 mm and TLPJ were the significant risk factors of PF. CONCLUSIONS: MLLPJ effectively reduces the PF rate after PD in comparison with TLPJ. Results confirm increased PF rates in patients with pancreatic duct diameter ≤3 mm compared with pancreatic duct diameter >3 mm.

Is laparoscopic approach for pancreatic insulinomas safe? Results of a systematic review and meta-analysis.

BACKGROUND: No consensus exists as to whether laparoscopic treatment for pancreatic insulinomas (PIs) is safe and feasible. The aim of this meta-analysis was to assess the feasibility, safety, and potential benefits of laparoscopic approach (LA) for PIs. The abovementioned approach is also compared with open surgery. METHODS: A systematic literature search (MEDLINE, EMBASE, Cochrane Library, Science Citation Index, and Ovid journals) was performed to identify relevant articles. Articles that compare the use of LA and open approach to treat PI published on or before April 30, 2013, were included in the meta-analysis. The evaluated end points were operative outcomes, postoperative recovery, and postoperative complications. RESULTS: Seven observational clinical studies that recruited a total of 452 patients were included. The rates of conversion from LA to open surgery ranged from 0%-41.3%. The meta-analysis revealed that LA for PIs is associated with reduced length of hospital stay (weighted mean difference, -5.64; 95% confidence interval [CI], -7.11 to -4.16; P < 0.00001). No significant difference was observed between LA and open surgery in terms of operation time (weighted mean difference, 2.57; 95% CI, -10.91 to 16.05; P = 0.71), postoperative mortality, overall morbidity (odds ratio [OR], 0.64; 95% CI, 0.35-1.17; P = 0.14], incidence of pancreatic fistula (OR, 0.86; 95% CI, 0.51-1.44; P = 0.56), and recurrence of hyperglycemia (OR, 1.81; 95% CI, 0.41-7.95; P = 0.43). CONCLUSIONS: Laparoscopic treatment for PIs is a safe and feasible approach associated with reduction in length of hospital stay and comparable rates of postoperative complications in relation with open surgery.

Intercellular adhesion molecular-1, Fas, and Fas ligand as diagnostic biomarkers for acute allograft rejection of pancreaticoduodenal transplantation in pigs.

BACKGROUND: The early diagnosis of pancreas allograft dysfunction is crucial for the management and long-term survival of transplanted pancreases. We investigated whether intercellular adhesion molecular-1 (ICAM-1), Fas, and Fas ligand (FasL) can be used as novel biomarkers of acute pancreaticoduodenal allograft dysfunction in pigs. METHODS: Forty outbred landraces were randomly divided into three groups. In the control group (8 pigs), a sham operation was performed but no drugs were administered. In groups 1 and 2 (8 pairs each), pancreaticoduodenal transplantation was performed, with the latter administered immunosuppressive drugs and the former not administered drugs. The expression of ICAM-1, Fas, and FasL mRNA in the peripheral vein blood was assessed by flow cytometry and RT-PCR, pre-transplant and on days 1, 3, 5, and 7 after transplantation. Simultaneously, the levels of glucose, insulin, and glucagon in the serum of the recipients were evaluated. The allograft pancreas tissue was obtained to assess the pathological damage and the expression of Fas and FasL by immunohistochemistry. RESULTS: On the first 7 days after transplantation, ICAM-1, Fas, and FasL mRNA expression in the blood leukocytes of the recipient increased significantly in groups 1 and 2 compared with the control group (P < 0.01). However, the levels in group 2 were significantly lower than those in group 1 (P < 0.05). Interestingly, the FasL expression increased but the Fas expression decreased gradually in the graft pancreas tissue during the first week after transplantation in both groups 1 and 2 compared with the control group (P < 0.05). The levels of serous glucose, insulin, and glucagon in groups 1 and 2 obviously changed on day 1 after transplantation but returned to normal on day 2. The recipient's pancreas pathological sections did not exhibit any rejection changes on days 1 and 3 after transplantation but showed rejection damage on days 5 and 7. CONCLUSION: ICAM-1, Fas, and FasL were found to be sensitive biomarkers of acute pancreas allograft dysfunction after pancreaticoduodenal transplantation in pigs, and their monitoring could be used to evaluate the effectiveness of the immunosuppression therapy.

[Effects of thymosin alpha1 on immune effector molecules of mouse].

OBJECTIVE: To analysis the effects of Talpha1 on the immune effector molecules in mouse immune system. METHODS: Sixty five BABL/c mice were divided into four groups: CsA group (n=20), Talpha1 group (n= 20), CsA+Talpha1 group (n=20) and control group (n=5). In the 3 experimental groups, 10 mg/kg CsA, 400 microg/ kg Talpha1, 10 mg/kg CsA+400 microg/kg Talpha1 were respectively administrated by intraperitoneal injection daily. Luminex was performed for cytokine detection at 1 d, 7 d, 14 d, 21 d day after the above treatments. Lymphocyte culture was prepared with the mouse spleen suspension, and then treated with 0. 25 mg/mL CsA, 10 microg/mL Talpha1 or 0.25 mg/mL CsA+10 microg/mL Talpha1 in vitro, respectively. Three days later, OD values of each treated lymphocyte culture and several cytokines in the culture were measured. RESULTS: Compared with other groups, CsA+Talpha1 group had significant lower IL-1alpha, IL-2, IL-6, IL-17, and significant higher IL-10 at 1 d, 7 d, 14 d, 21 d after the treatments (P < 0.05). Three days after the culture, OD value in the control group was significantly higher than that in Talppha1 group, CsA group, and CsA+ Talpha1 group (P < 0.05). IL-1alpa and IL-6 in the control group were significantly higher than those in the experiment groups (P < 0.05), while IL-10 in the control group was significantly lower than that in the experiment groups (P < 0.05). IL-2 and IL-17 were similar. CONCLUSION: Talpha1 show regulatory effect on the immune effector molecules which could promote Th1 cells transforming to Th2 cells.

A retroperitoneal approach for infected pancreatic necrosis.

BACKGROUND: Acute pancreatitis remains associated with a high rate of complication and death. The surgery strategy for proven or suspected infected necrosis is controversial. METHODS: The present study reviews the medical records of 9,421 patients admitted with the diagnosis of acute pancreatitis from 2002 to 2009. RESULTS: The medical records of 9,421 admitted patients diagnosed with acute pancreatitis were reviewed. Among the patients, 412 received necrosectomy. Of the 412 that were identified, 108 patients underwent retroperitoneal necrosectomy, whereas the remaining 304 patients received open necrosectomy. The mortality rates were 20.4% (62/304) and 8.3% (9/108), respectively (p = 0.004). The rates of complications in the retroperitoneal group were lower than that in the open group (p < 0.05). The mean lengths of hospital stay and ICU stay after surgery were longer in the open group than those in the retroperitoneal group (48 vs. 30 days; 6 vs. 2 days, p < 0.05). Furthermore, the postoperational days in the hospital and surgical time were also significantly different (30 vs. 12 days; 167 vs. 93 min, p < 0.05). CONCLUSIONS: A retroperitoneal pancreatic necrosectomy approach reduced the rate of complications and death among patients with infected necrosis, compared with open necrosectomy.

Radiosynthesis of N-(4-chloro-3-[(11)C]methoxyphenyl)-2-picolinamide ([(11)C]ML128) as a PET radiotracer for metabotropic glutamate receptor subtype 4 (mGlu4).

N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu4 positive allosteric modulator (PAM), which is potent and centrally penetrating. 3 is also the first mGlu4 PAM to show efficacy in a preclinical Parkinson disease model upon systemic dosing. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers a possibility to investigate mGlu4 expression in vivo under physiologic and pathological conditions. We synthesized a carbon-11 labeled ML128 ([(11)C]3) as a PET radiotracer for mGlu4, and characterized its biological properties in Sprague Dawley rats. [(11)C]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2-picolinamide (2) using [(11)C]CH3I. Total synthesis time was 38±2.2min (n=7) from the end of bombardment to the formulation. The radioligand [(11)C]3 was obtained in 27.7±5.3% (n=5) decay corrected radiochemical yield based on the radioactivity of [(11)C]CO2. The radiochemical purity of [(11)C]3 was >99%. Specific activity was 188.7±88.8GBq/mol (n=4) at the end of synthesis (EOS). PET images were conducted in 20 normal male Sprague Dawley rats including 11 control studies, 6 studies blocking with an mGlu4 modulator (4) to investigate specificity and 3 studies blocking with an mGlu5 modulator (MTEP) to investigate selectivity. These studies showed fast accumulation of [(11)C]3 (peak activity between 1-3min) in several brain areas including striatum, thalamus, hippocampus, cerebellum, and olfactory bulb following with fast washout. Blocking studies with the mGlu4 modulator 4 showed 22-28% decrease of [(11)C]3 accumulation while studies of selectivity showed only minor decrease supporting good selectivity over mGlu5. Biodistribution studies and blood analyses support fast metabolism. Altogether this is the first PET imaging ligand for mGlu4, in which the labeled ML128 was used for imaging its in vivo distribution and pharmacokinetics in brain.

Does modified Braun enteroenterostomy improve alkaline reflux gastritis and marginal ulcer after pancreaticoduodenectomy?

BACKGROUND: The safety of pancreaticoduodenectomy has improved significantly. However, alkaline reflux gastritis and marginal ulcer are two substantial problems after pancreaticoduodenectomy. AIMS: To identify whether Child reconstruction with a modified Braun enteroenterostomy decreases the incidence of alkaline reflux gastritis and marginal ulcer after pancreaticoduodenectomy better than Roux-en-Y reconstruction. METHODS: Data on 57 consecutive patients who underwent standard pancreaticoduodenectomy between January 1, 2008 and January 31, 2012 were collected prospectively. Data on early and late complications of the Child reconstruction with a modified Braun enteroenterostomy and Roux-en-Y were gathered. The risk factors of alkaline reflux gastritis and marginal ulcer were also investigated by using univariate and multivariate analyses. RESULTS: Twenty-five patients received Roux-en-Y and 32 underwent Child reconstruction with a modified Braun enteroenterostomy. Early complications after the two reconstruction methods were insignificant. Significant differences in terms of later postoperative morbidity (P = 0.01) and change in body mass index (P = 0.03) were found 12 months after pancreaticoduodenectomy. No significant difference for alkaline reflux gastritis was observed between the two methods (14.8 vs. 28.6 %, P = 0.24). Marginal ulcer occurred significantly lower in patients with the modified reconstruction than in those with Roux-en-Y reconstruction (11.1 vs. 47.6 %, P = 0.01). Peptic ulcer history, diabetes mellitus, and reconstruction type had a significant effect on marginal ulcer formation. CONCLUSIONS: Child reconstruction with a modified Braun enteroenterostomy offers an advantage with respect to marginal ulcer after standard pancreaticoduodenectomy, potentially decreasing the incidence of alkaline reflux gastritis as effectively as Roux-en-Y reconstruction.

Does internal stenting for pancreaticojejunostomy decrease the rate of pancreatic fistula following pancreatic resections? A meta-analysis.

BACKGROUND/AIMS: The aim of this study is to evaluate the effectiveness of using an internal stent for pancreaticojejunostomy (PJ) on pancreatic fistula (PF) formation, as well as on the overall outcome for patients undergoing pancreatic resections. METHODOLOGY: Articles published until the end of February 2012 comparing internal stenting and no stenting for PI were included. The primary outcome of interest was PF. The secondary outcome of interest included operative time, intra-operative blood loss, overall morbidity, hospital mortality and postoperative length of hospital stay. RESULTS: Five articles were identified for inclusion. The meta-analysis revealed that internal stenting for PJ was not associated with a statistically significant reduction in PF rate (OR 1.03; 95% CI=0.70 to 1.51; p=0.88). Patients with soft pancreas had higher PF rate in stenting group, but the difference was not significant (OR=1.71; 95% CI=0.95 to 3.10; p=0.08). There was no significant difference between the two groups in operative time, intra-operative blood loss, overall morbidity, hospital mortality, and postoperative length of hospital stay. CONCLUSIONS: The current literature suggests that internal stenting for PJ following pancreatic resections does not decrease the rate of pancreatic fistula or alter overall patient's outcome.