Journal of Surgical Research - Articles in Press

Recovery After Open and Laparoscopic Right Hemicolectomy: A Comparison - Uncorrected Proof

2010-03-10

Background: Enhanced Recovery after Surgery (ERAS) programs have gained popularity with potential to accelerate recovery and reduce morbidity after colectomy. We were interested in comparing recovery after open right colectomy within an ERAS program compared with laparoscopic right colectomy in a standard care perioperative environment.Methods: Between October 2005 and June 2009, prospective data were collected on consecutive patients undergoing elective open right colectomy within an established ERAS setting (OpERAS). Similarly, between March 2008 and June 2009, data were collected on consecutive patients undergoing laparoscopic right hemicolectomy with conventional care (LapCon). Exclusion criteria for both groups were: ASA ≥ 4, formation of a stoma, and dementia or mental illness rendering the patient unable to comply with instructions. Perioperative variables were collected. The surgical recovery score (SRS) was used as a validated means to measure convalescence on d 1, 3, 7, 30, and 60 postoperatively.Results: There were 74 patients in the OpERAS and 39 patients in the LapCon groups. At baseline, there were no significant demographic differences except that more patients had malignancy in OpERAS group. Mean operating time was longer in the LapCon group. Median day stay was 4 (3–28) in OpERAS and 5 (2–18) in LapCon (P = 0.032). There was no statistical difference in the incidence of complications or the severity of complications. There were no significant differences in SRS after surgery at any time point.Conclusion: When perioperative care is optimized, recovery after elective open right hemicolectomy is comparable with laparoscopic resection. Studies looking at the combination of laparoscopy and ERAS are warranted.

A Small Dose of Arginine Vasopressin in Combination with Norepinephrine is a Good Early Treatment for Uncontrolled Hemorrhagic Shock After Hemostasis - Uncorrected Proof

Tao Li, Yuqiang Fang, Yu Zhu, Xiaoqing Fan, Zifu Liao, Feng Chen, Liangming Liu — 2010-03-08

Background: Limited fluid resuscitation has been proven to have a good effect on uncontrolled hemorrhagic shock. Arginine vasopressin (AVP) and norepinephrine (NE) were used to treat vasodilatory or septic shock, and were used to reduce the fluid requirement for uncontrolled hemorrhagic shock. Based on their pressor and hemodynamic stabilization effects, it is speculated that AVP and NE may be a good treatment for uncontrolled hemorrhagic shock at early stage after hemostasis.Methods: Experiments were conducted in two parts. Each part had control, lactated Ringer's solution (LR), whole blood, norepinephrine (NE), arginine vasopressin (AVP), NE+AVP, and AVP+NE+whole blood. Rats (n = 8–10/group), respectively, received LR, whole blood, NE (1 μg/kg) and AVP (0.1 U/kg) infusion alone, or in combination after 60 min hypotensive resuscitation (50 mmHg). The volume in each group was two times the volume of shed blood.Results: Whole blood improved all observed parameters, particularly the tissue blood flow and mitochondrial function of liver and kidney, and the 12-h survival (50%). NE only increased the hemodynamics. 0.1 U/kg of AVP had a similar effect with whole blood on hemodynamics, tissue blood flow, mitochondrial function, and the 12-h survival. AVP+NE significantly improved all observed variables (P < 0.05 or 0.01), the12-h survival was 70%. Whole blood further potentiated the beneficial effect of AVP+NE, and 12-h animal survival rate in this group was 80%.Conclusion: AVP+NE is a good treatment for uncontrolled hemorrhagic shock at the early stage after hemostasis if blood is unavailable. Whole blood transfusion can potentiate this beneficial effect of AVP+NE.

Effect of TachoSil in a Coagulopathic Pig Model with Blunt Liver Injuries - Uncorrected Proof

2010-03-08

Objective: In this study, we investigated the efficacy of a fibrinogen/thrombin-coated collagen patch (TachoSil) to terminate severe bleeding in a coagulopathic pig model with blunt liver injury.Methods: Following surgical preparation, which included splenectomy and cystotomy, coagulopathy was induced by exchanging 80% of the animal's blood volume with hydroxyethylstarch 130/0.4 and lactated Ringer's solution. Subsequently. a grade III liver injury was induced by a force of 238 ± 19 Newton and free bleeding was allowed for 30 s. Animals were randomly assigned to receive either a placebo patch (cotton patch) (control group, n = 7) or a fibrinogen/thrombin patch (FT patch group, n = 7), which was positioned 30 s after injury on the inflicted area. Coagulation parameters, hemodynamic variables, as well as treatment were monitored for 2 h post-injury and patch placement. Histology was obtained to evaluate the equality of liver injury and to show the morphology of the FT patch.Results: Hemostasis after hemodilution was severely impaired. Blood loss after trauma was significantly diminished in the FT patch group (419 mL ± 90 mL) compared with the control group (1775 mL ± 358 mL) (P < 0.001). All animals treated with the FT patch survived, whereas 100% of the control group died before reaching the end of the observation period (P < 0.001). Gross sectioning and histology showed an equal degree of injury with a tight adherence of the FT patch.Conclusion: TachoSil under severe coagulopathy effectively controlled bleeding and successfully prevented hemorrhagic death.

RhGH Attenuates Ischemia Injury of Intrahepatic Bile Ducts Relating to Liver Transplantation - Uncorrected Proof

Zheng Wang, Jie Zhou, Jianhua Lin, Yu Wang, Yixiong Lin, Xianghong Li — 2010-03-08

Background: To study the effect of rhGH administration on intrahepatic cholangiocytes relating to liver transplantation with ischemia of hepatic artery, and ulteriorly, clarify pathologic mechanism of the injury.Methods: Rat orthotopic autologous liver transplantation was performed first. Three hours later, the rats were grouped as followed: HAL (hepatic artery ligation) group; HAL + rhGH (hepatic artery ligation followed by rhGH administration) group; CON (without hepatic artery ligation) group. Specimen was collected after 7 d. ALT and ALP of serum were measured. The pathologic changes of bile ducts of liver tissue were observed. The number of bile ducts and blood vessels in portal area were counted. Immunochemistry for VEGF, VEGFR-2, VEGFR-3, GHR, and IGF-1R of intrahepatic cholangiocytes was performed. Cholangiocytes apoptosis was evaluated by TUNEL analysis. Cholangiocytes proliferation was evaluated by PCNA immunolabeling.Results: ALT and ALP of HAL + rhGH group were significantly ameliorated compared with untreated animals (P < 0.05). ALT and ALP of HAL group were significantly higher compared with CON group (P < 0.05). In HAL group, the main injury of bile ducts was not reversible, whereas it was reversible in CON and rhGH groups. In HAL group, the number of bile ducts in portal area decreased, while the number of bile ducts not accompanying blood vessels increased (P < 0.05). In rhGH group, the number of bile ducts in portal area increased, while the number of bile ducts accompanying blood vessels increased compared with HAL group (P < 0.05). The expression of VEGF, VEGFR-2, VEGFR-3, GHR, and IGF-1R was significantly lower in HAL group than in CON group (P < 0.05). Following administration of rhGH to HAL rats, the expression of VEGF, VEGFR-2, VEGFR-3, IGF-1R, and GHR was significantly higher (P < 0.05). Administration of rhGH prevented increase in cholangiocytes apoptosis induced by HAL (P < 0.05). Administration of rhGH promoted increase in cholangiocytes proliferation held by HAL (P < 0.05).Conclusions: Administration of rhGH appears to attenuate ischemia injury of intrahepatic bile ducts relating to liver transplantation. This function is partly related to the capacity that rhGH inhibits the apoptosis of intrahepatic cholangiocytes and prompts the proliferation and angiogenesis by increasing the expression of VEGF, VEGFR2, VEGFR3, GHR, and IGF1-R.

Noninvasive assessment of intra-abdominal pressure by measurement of abdominal wall tension1 - Uncorrected Proof

2010-03-08

Background: Sustained increased intra-abdominal pressure (IAP) has negative effects. Noninvasive IAP measurement could be beneficial to improve monitoring of patients at risk and in whom IAP measurements might be unreliable. We assessed the relation between IAP and abdominal wall tension (AWT) in vitro and in vivo.Materials and methods: The abdomens of 14 corpses were insufflated with air. IAP was measured at intervals up to 20 mm Hg. At each interval, AWT was measured five times at six points. In 42 volunteers, AWT was measured at five points in supine, sitting, and standing positions during various respiratory manoeuvres. Series were repeated in 14 volunteers to measure reproducibility by calculating coefficients of variation (CV). ANOVA was used for analyses.Results: In corpses, all points showed significant correlations between IAP and AWT (P < 0.001 for points 1–4 in the upper abdomen, P = 0.017 for point 5 and P = 0.008 for point 6 in the lower abdomen). Mean slopes were greatest at points across the epigastric region (points 1–3). In vivo measurements showed that AWT was on average 31% higher in men compared to women (P < 0.001), and increased from expiration to inspiration to Valsalva's manoeuvre (all P < 0.001). AWT was highest at points 1 and 2 and in standing position, followed by supine and sitting positions. BMI did not influence AWT. Mean CV of repeated measurements was 14%.Conclusions: AWT reflects IAP. The epigastric region appears most suitable for AWT measurements. Further longitudinal clinical studies are needed to assess usefulness of AWT measurements for monitoring of IAP.

A Membrane Slurry Reduces Postoperative Adhesions in Rat Models of Abdominal Surgery - Uncorrected Proof

2010-03-08

Background: Sodium hyaluronate and carboxymethylcellulose (HA-CMC) membrane is an effective barrier material for limiting postoperative adhesions, but can be difficult to apply in certain situations due to its physical properties. We tested whether HA-CMC membrane hydrated in saline (slurry) is an effective alternative to HA-CMC membrane for preventing surgical adhesions in rat models of abdominal surgery.Materials and methods: All studies were performed in rat cecal abrasion or sidewall defect models of adhesion formation. Adhesions were examined 7 d after surgery. In separate studies, the effects of variations in slurry composition, volume, and site of application on anti-adhesive properties were studied and compared with untreated controls. Finally, the effectiveness of HA-CMC membrane slurry for preventing adhesions was compared with that of conventional HA-CMC membrane.Results: Application of HA-CMC membrane slurry to traumatized tissue resulted in a significant reduction in the incidence of adhesions compared with untreated controls in both rat surgery models. Slurry was equally effective when applied in low and high film-to-volume formulations, but had minimal effect when applied in a small volume or at a location distal to the injury. Comparison of HA-CMC membrane slurry and conventional HA-CMC membrane indicated similar efficacy for reducing postoperative adhesions.Conclusions: In rat models of abdominal surgery, HA-CMC membrane slurry reduced postoperative adhesion formation and may be an effective alternative for HA-CMC membrane in situations where its use is limited by its physical properties.

The Expression of Claudin-1, Claudin-2, Claudin-3, and Claudin-4 in Gastric Cancer Tissue - Uncorrected Proof

Hun Jung, Kyong Hwa Jun, Ji Han Jung, Hyung Min Chin, Woo Bae Park — 2010-03-08

Background: The claudins (CLDNs) are a family of functional tight junction proteins, and are involved with the epithelial-to-mesenchymal transition (EMT). The claudin proteins have a significant influence on the biological behavior of tumor progression in several types of cancers. In this study, we aimed to evaluate the expression pattern of claudin-1, claudin-2, claudin-3, and claudin-4 in gastric cancer tissue.Materials and methods: Tissue was obtained from surgically resected specimens of 72 patients who were diagnosed with gastric adenocarcinoma at a single institution. The expressions of claudin-1, claudin-2, claudin-3, and claudin-4 were determined by immunohistochemical staining with the ABC method.Results: Claudin-2 demonstrated the highest expression rate (73.6%) and claudin-4 demonstrated the lowest expression rate (44.4%). The expression of claudin-1 was significantly lower in cases of intestinal type adenocarcinoma based on the Lauren classification. The expressions of claudin-3 and claudin-4 were significantly lower in cases with positive lymphatic invasion. The expression of claudin-3 was significantly lower in cases with an advanced T-stage (T3 and T4). The expression of claudin-3 showed significantly positive correlations with the expression of the other claudin proteins. In survival analysis, the expression of claudin-4 was related to good overall survival rate with significance (P = 0.046).Conclusion: We suggest that claudin-3 and claudin-4 represent useful molecular markers for gastric cancer. Claudin-3 and claudin-4 would be the most important proteins related to the lymphatic invasion process, and claudin-4 would be useful with prognostic marker based on our results. Further investigations with a greater number of subjects are required to identify the action mechanism of claudin in gastric cancer.

Resection of Type I Gastric Carcinoid: When and Why? - Uncorrected Proof

John C. Mansour — 2010-03-08

Type I gastric carcinoid is a disease associated with atrophic gastritis, hypergastrinemia, and hyperplasia of enterochromaffin-like (ECL) cells. Unfortunately, type I gastric carcinoid is also associated with a healthy bit of confusion regarding its management and natural history. Unlike the MEN- or gastrinoma-associated type II carcinoids or the sporadic type III gastric carcinoids, the rate of nodal or distant metastases among patients with type I gastric carcinoid is extremely low. This finding has been reported by both Rappel et al. and Gladdy et al. . Rappel reports that among the 86 patients managed nonoperatively, none of the patients had developed metastases or died from the carcinoid tumor despite median follow-up greater than 6 y . The more recent series supports this finding with a disease-specific survival of 100% for patients managed with either surgical resection or endoscopic surveillance .

Upper Gastrointestinal Carcinogenesis: H. pylori and Stem Cell Cross-Talk - Uncorrected Proof

Ioannis Pilpilidis, Jannis Kountouras, Christos Zavos, Panagiotis Katsinelos — 2010-03-08

Chronic inflammation of the gastric epithelium has been associated with the pathogenesis of gastric cancer, as it was postulated by Corea's model of gastric carcinogenesis. Helicobacter pylori (Hp) regulates this inflammatory process and promotes gastric carcinogenesis through induction of gene mutations and protein modulation. Recent data raise the cancer stem cell hypothesis, which implies a central role of multipotent cancer cells in oncogenesis of various solid tumors. This review provides a synopsis of gastric cancer initiation and promotion through Hp and stem cell signaling pathways. The expanding research field of Hp-related cancer stem cell biology may offer novel implications for future treatment of upper gastrointestinal cancer.

Glucose-Induced Intestinal Vasodilation Via Adenosine A1 Receptors Requires Nitric Oxide but not K+ATP Channels - Uncorrected Proof

Paul J. Matheson, Na Li, Patrick D. Harris, El Rasheid Zakaria, R. Neal Garrison — 2010-03-08

Background: Both nitric oxide (NO) and adenosine A1 receptor activation mediate microvascular vasodilation during intestinal glucose absorption. Our overall hypothesis is that adenosine triphosphate (ATP) utilization during glucose absorption would increase adenosine metabolite release, which acts on adenosine A1 receptors to alter endothelial production of NO and/or activate ATP-dependent potassium channels (K+ATP) to dilate intestinal microvessels.Methods: Intravital videomicroscopy of the rat jejunum was used to record the vascular responses of inflow (termed 1A) arterioles, proximal (p3A), and distal (d3A) premucosal arterioles during exposure to isotonic glucose or mannitol solutions alone or in the presence of the selective nitric oxide synthase (NOS) inhibitor (L-NMMA), an adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX)), or a K+ATP channel inhibitor (glibenclamide).Results: As expected, glucose exposure caused rapid dilation of both p3A and d3A arterioles, while mannitol exposure had no effect on microvascular diameters. Adenosine A1 receptor blockade completely prevented glucose-induced dilation of the premucosal arterioles. NOS inhibition significantly blunted the glucose-induced vasodilation of the premucosal arterioles, but had little effect in the mannitol group. Simultaneous application of both the NOS inhibitor and the adenosine A1 receptor antagonist gave the same reduction in glucose-induced dilation of the premucosal arterioles as the adenosine A1 receptor antagonist alone. Blockade of K+ATP channels with glibenclamide did not attenuate glucose-induced vasodilation of the premucosal arterioles.Conclusion: These data suggest that glucose-induced vasodilation of premucosal jejunal arterioles is mediated through adenosine A1 receptors, and NO at least partially mediates the adenosine A1 receptor-induced vasodilation. In addition, K+ATP channels are not involved in premucosal arteriolar vasodilation during intestinal glucose exposure.

ETS-GS, a New Antioxidant, Ameliorates Renal Ischemia-Reperfusion Injury in a Rodent Model - Uncorrected Proof

2010-02-24

Background: Ischemia-reperfusion (I/R) contributes to acute kidney injury (AKI). Antioxidants are being investigated as potential therapeutics given that reactive oxygen species (ROS) can exacerbate I/R injury. The current study examined whether a new antioxidant, ETS-GS, inhibits ROS generation and thereby prevents renal I/R injury in rodent models.Methods: Rats with experimentally-induced renal I/R injury were treated concurrently with an intravenous injection of either ETS-GS or saline. Anesthesia was induced with sevoflurane.Results: Histologic examination revealed marked reduction of interstitial congestion, edema, inflammation, and hemorrhage in kidney tissue harvested 24 h after ETS-GS treatment. Renal I/R-induced secretion of nitric oxide (NO) in serum was inhibited by ETS-GS treatment. Furthermore, malondialdehyde (MDA) levels in the kidney were significantly lower in ETS-GS-treated rats with renal I/R. Moreover, when murine macrophage-like RAW264.7 cells were stimulated with antimycin A in the presence or absence of simultaneous ETS-GS treatment, ETS-GS decreased ROS levels.Conclusions: Thus, ETS-GS lowered ROS levels in cultured cells, reduced serum NO levels, decreased renal MDA levels, and protected rats against I/R-induced kidney injury. Given these in vitro and in vivo findings, ETS-GS is a strong candidate for future exploration of therapeutic potential in various human I/R diseases.

Factor Xa Induces Tissue Factor Expression in Endothelial Cells by P44/42 MAPK and NF-κB-Dependent Pathways - Uncorrected Proof

2010-02-24

Background: Tissue factor (TF) is an initiator of coagulation. The serine protease factor Xa (FXa) is the convergence point of the extrinsic and intrinsic components of the coagulation cascade. In addition to its hemostatic function, FXa elicits inflammatory responses in endothelial cells that may be important in surgical procedures in which inflammation is triggered. This study tested the hypothesis that FXa can up-regulate TF on vascular endothelial cells by a mitogen-activated protein kinase (MAPK)- and NF-κB-dependent pathway.Methods and Results: Incubation of cultured human umbilical vein endothelial cells (HUVECs) with FXa increased TF protein expression and activity in a dose-dependent manner. Pre-incubation of HUVECs with the serine protease inhibitor antithrombin, which targets not only thrombin but also FXa and FIXa, inhibited FXa-induced TF expression, but the selective thrombin inhibitor hirudin did not inhibit FXa-induced TF expression, ruling out a thrombin-mediated pathway. After 10 min incubation with HUVECs, FXa rapidly induced P44/42 MAPK activation (immunoblotting of phosphorylated P44/42 MAPK) with a peak at 30 min. The MEK 1/2 inhibitor PD98059 partially reduced FXa-induced TF expression and activity (3.82 ± 0.11 vs 6.54 ± 0.08 fmol/min/cm2, P < 0.05). NF-κB was activated by FXa, confirmed by cytoplasmic IkBα degradation and increased NF-κB P65 nuclear translocation. Interruption of the NF-κB pathway by the IkBα phosphorylation inhibitor Bay 11-7802 abrogated FXa-induced TF protein expression and activity (1.93 ± 0.02 versus 6.54 ± 0.08 fmol/min/cm2, P < 0.05). However, inhibition of PI3 kinase by LY 294002 did not attenuate FXa-induced TF protein expression and activity.Conclusions: (1) FXa up-regulates TF protein expression and activity in HUVECs, (2) FXa-induced up-regulation of TF is independent of the thrombin-PAR1 pathway, and (3) the MAPK and NF-κB pathways, but not PI3 kinase pathway, are involved in FXa-induced TF expression on human umbilical endothelial cells. FXa may be a feed-forward alternative mechanism of activating TF expression and activity, thereby increasing a procoagulant state or inflammation. This mechanism may be important in the pro-inflammatory state initiated by cardiac surgical procedures.

Transfer of Bone Marrow Progenitors Prevents Coronary Insufficiency and Systolic Dysfunction in the Mechanical Unloaded Heart in Mice - Uncorrected Proof

2010-02-24

Background: Left ventricular-assist device (LVAD) can lead to improvement of cardiac performance in a subset of patients, but chronic mechanical unloading in this fashion may result in left ventricular (LV)-atrophy and impaired functional recovery. Here, we evaluate the efficacy of transferring bone-marrow KSL cells (Lin-/c-kit+/Sca1+), a fraction containing endothelial progenitor cells, for preventing LV-atrophy and malfunction in a mouse model of mechanical unloading of the heart.Materials and Methods: Recipients of an isogenic heart transplant received intramyocardial isogenic KSL cells or PBS in three different locations of the left ventricle (LV). Coronary blood flow and LV systolic function were evaluated by echocardiography, and morphologic changes were analyzed on d 7 and 56.Results: PBS-treated mice showed severe systolic dysfunction and large thrombi in LV at both time points. In contrast, KSL cell transfer markedly reduced systolic dysfunction and thrombus size. Furthermore, in comparison with PBS control, KSL recipients had increased coronary blood flow (3-fold, P < 0.01) accompanied by increased LV capillary density and muscle mass.Conclusions: These results indicate that intramyocardial transfer of bone marrow KSL cells significantly protects against coronary insufficiency and systolic dysfunction in the chronic LV-unloading heart, suggesting that this approach may have clinical potential as a combination therapy with LVAD.

Hemostatic Effectiveness of Fibrin Pad after Partial Nephrectomy in Swine - Uncorrected Proof

2010-02-22

Background: Current management of severe surgical or traumatic bleeding is often achieved by manual tamponade or occlusion using devices such as tourniquets or ligatures. There are some clinical scenarios where these options are either marginally effective or impractical. The present study evaluates a new combination device (Fibrin pad) consisting of biologically active components (human thrombin and fibrinogen) delivered to the targeted site by an absorbable synthetic matrix (oxidized regenerated cellulose and polyglactin 910) in a swine severe bleeding model. In this model, severe bleeding can be managed by concurrent use of several currently available treatments, or a more convenient option that offers performance and safety advantages.Materials and Methods: Partial nephrectomies were performed on swine and treated with either Fibrin pad (FP) or conventional therapy (CTR)-temporary occlusion of renal artery, electrocautery, SURGIFLO, EVITHROM, SURGICEL NU-KNIT, and PDS II suture). After intraoperative hemostasis was confirmed, the animals were closed and recovered, then survived for 2, 14, or 56 d.Results: Hemostasis was achieved at surgery and maintained in all FP and CTR treated animals. FP was as effective as CTR at establishing durable hemostasis. Treatment with FP did not require temporary occlusion of the renal artery and decreased the total treatment time by half. No animals in either group had complications related to postoperative bleeding at any time during the study. There was no evidence of pulmonary thrombi or evidence of thrombotic complications. No biologically significant adverse local tissue response was present in association with the Fibrin pad at any study interval, and no biologically relevant or consistent changes in blood parameters were identified.Conclusions: Fibrin pad was as effective as CTR for the primary management of severe bleeding without occlusion of the renal artery and a shorter surgical time. No evidence of a systemic or local adverse response was identified due to exposure to the Fibrin pad.

Hypothermic Machine Preservation Attenuates Ischemia/Reperfusion Markers after Liver Transplantation: Preliminary Results - Uncorrected Proof

2010-02-22

Background: Hypothermic machine perfusion (HMP) has shown significant benefits in renal transplantation but is still in its infancy in liver transplantation. Potential benefits include diminished preservation injury and improved early graft function.Methods: We analyzed liver tissue and effluent collected during our Phase 1 trial of liver HMP. HMP was performed for 4–7 h using dual centrifugal perfusion with Vasosol solution at 4–8°C were transplanted and compared with cold stored (CS) transplant controls. Histology, reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry on liver biopsies compared histology and expression of early proinflammatory cytokines, IL-8 and TNF-α, and intracellular adhesion molecule-1 (ICAM-1). Gel electrophoresis was used to evaluate effluent protein content representing residual metabolism.Results: We saw no differences between HMP and CS in early histologic findings after reperfusion. RT-PCR of reperfusion biopsy samples in the CS group showed high expression of proinflammatory cytokines and ICAM-1. This up-regulation was significantly attenuated by HMP (ICAM-1; P = 0.0152) (IL-8; P = 0.0014) (TNF-α; P = 0.0284). This was confirmed with immunohistochemistry. Albumin was identified in the perfusate throughout HMP.Conclusions: HMP significantly reduced proinflammatory cytokine expression compared with CS controls. Further studies of human liver HMP with detailed molecular investigations are now warranted to elucidate benefits of HMP in liver transplantation.

Preservation of Amputated Extremities by Extracorporeal Blood Perfusion; a Feasibility Study in a Porcine Model - Uncorrected Proof

2010-02-22

Background: Successful extremity transplantations and replantations have to be performed within 6 h of amputation to avoid irreversible tissue loss. This study investigates ex vivo the technical feasibility and the limb preservation potential of extracorporeal whole blood perfusion in a porcine model.Methods: Forelimbs of eight large white pigs were divided into paired groups: I perfusion group, II contralateral cold ischemia controls. In group I axillary arteries and veins were cannulated and perfusion with anticoagulated autologous blood was performed for 12 h; O2, CO2, Hb, lactate, potassium, pH, and muscle contractility were monitored. Tissue biopsies were examined by histology and immunofluorescence. Group II was stored at 4°C.Results: Continuous limb perfusion could be performed in all extremities of group I for 12 h. pH was maintained normal and potassium controlled with insulin and glucose. Lactate levels increased initially during perfusion due to the lack of a metabolizing liver. Muscle stimulation was possible throughout the entire perfusion, whereas a complete loss of response was noted in cold ischemia controls. Minor tissue damage was observed histologically and by immunofluorescence in group I, whereas the samples of group II were apparently preserved with the exception of a loss of endothelial heparan sulfate.Conclusions: The tissue preserving potential and the feasibility of extremity perfusion using common extracorporeal blood circulation techniques was demonstrated in this ex vivo study. The results encourage further investigations in prolonged perfusion followed by limb replantation. This approach harbors promising clinical potential for extremity preservation in extremity transplantation and replantation.

VEGF Modulates Angiogenesis and Osteogenesis in Shockwave-Promoted Fracture Healing in Rabbits - Uncorrected Proof

2010-02-22

Objective: Strong vascular endothelial growth factor (VEGF) expression of osteoprogenitors was found in callus site during fracture healing. The aim of this study was to investigate whether VEGF modulates the angiogenesis and osteogenesis in shockwave-promoted fracture healing in rabbits.Materials and Methods: Twenty-seven Japanese rabbits were used in the study. A fracture of left tibia with 5 mm gap was created, and the fracture was stabilized with an external fixator. The rabbits were randomly divided into three groups. Group I was the control group and received no shockwave therapy. Group II received shockwave therapy, and group III was pretreated with bevacizumab, a monoclonal antibody against VEGF, before receiving shockwave. Radiographs of the tibia were obtained at 1, 4, and 8 wk. Bone mineral density was performed at 8 wk. The rabbits were euthanized at 8 wk, and the bone specimens were subjected to histomorphological examination and immunohistochemical analysis.Results: At 8 wk, radiographs showed considerably better bone healing and remodeling of the fracture in group II compared with groups I and III, whereas no discernable difference was noted between group I and group III. The BMD values were significantly higher in group II than groups I and III, but no difference noted between group I and group III. In histomorphological examination, significant increases in bone tissue was were noted in group II compared with groups I and III, but no difference was noted between group I and group III. In immunohistochemical analysis, significant increases in VEGF, vWF, PCNA, BMP-2 and osteocalcin, and a decrease in TUNEL expression were observed in group II compared with groups I and III, but no statistical difference was noted between group I and group III.Conclusion: Significant increases in VEGF and angiogenic and osteogenic growth factors were noted in shockwave-promoted bone healing. Pre-treatment with bevacizumab inhibited VEGF and in turn, attenuated the effect of shockwave. It appears that VEGF modulates angiogenesis and osteogenesis in shockwave-promoted bone healing in rabbits.

The Therapeutic Potential of Pyruvate - Uncorrected Proof

Mitchell P. Fink — 2010-02-22

Pyruvate, the anionic form of a simple α-keto acid, plays a key role in intermediary metabolism, being the end-product of glycolysis and the starting substrate for the tricarboxylic acid (TCA) cycle. Additionally, pyruvate reacts rapidly and non-enzymatically with the reactive oxygen species (ROS), hydrogen peroxide (H2O2). And scavenging of H2O2 by endogenously generated pyruvate is probably a key cellular defense against oxidative stress, particularly in proliferating cells .

Protective Role of Simvastatin on Lung Damage Caused by Burn and Cotton Smoke Inhalation in Rats - Uncorrected Proof

2010-02-17

Background: Smoke inhalation injury is a major comorbid factor in patients with thermal injury and occurs in about 30% of patients with major burns. In addition, inhalation injury reportedly accounts for 20%–84% of the mortality in burned individuals and is associated with higher mortality rates for every age and burn size category. The aim of the present study was to investigate the effects of simvastatin on lung damage with burn and cotton smoke inhalation.Methods: Wistar rats were randomly assigned to three groups: saline treated control group, via an orogastric route (group 1, n = 6), burn (30%) and cotton smoke inhalated group (group 2, n = 6), and simvastatin treated (25 mg/kg/d, via an orogastric route) burn (30%) and cotton smoke inhalated group (group 3, n = 6). Rats were sacrificed at 48 h of the treatments and the trachea and lungs were removed completely. Tissue samples were taken for histopathologic, immunohistopathologic, and biochemical analyses. Univariate analysis of variance coupled with Duncan's post-hoc test was performed for statistical evaluation.Results: Lung parenchymal and tracheoepithelial damage was confirmed in group 2 by histopathologic examination. Lung malonedialdehyde (MDA) levels were significantly decreased (P < 0.001), while glutathione (GSH) concentration did not alter in group 2 compared with group 1. Also, immunopathologic data revealed that epithelial iNOS level was elevated, while no modulation was detected in the level of myeloperoxidase (MPO). Simvastatin administration resulted in decreasing the lung parenchymal and tracheoepithelial damage. Tissue MDA levels were decreased significantly (P < 0.001), whereas GSH concentrations were elevated in group 3 compared with group 1 and group 2 (P < 0.001). Simvastatin treatment caused a decrease in epithelial iNOS levels, while MPO levels were not modulated. In addition, simvastatin significantly reduced pulmonary apoptosis in lung injury.Conclusions: Our results have indicated that simvastatin administration seems to play beneficial role in lung injury of rats promoted by combined burn and smoke inhalation. Thus, simvastatin may represent a potential approach to prevent smoke inhalation-associated lung dysfunction. However, the significant decrease in basal oxidant production may cause impairment in cellular signalling processes.

Anti-Apoptotic Effect of Hyperbaric Oxygen Preconditioning on a Rat Model of Myocardial Infarction - Uncorrected Proof

Qiang Sun, Qing Sun, Yun Liu, Xuejun Sun, Hengyi Tao — 2010-02-17

Background: In our previous study, it was indicated that hyperbaric oxygen preconditioning (HOP) could induce a preconditioning against myocardial infarction and promote neovascularization. In this study, attempts were made to investigate whether a modified short-term pre-exposure protocol could also induce cardioprotection, and its potential mechanisms.Materials and methods: Adult male Sprague Dawley rats were divided into seven groups; group 1 was sham surgery (SHAM) and group 2 was pre-exposed to normal air (CTL), and the other groups to HOP 1, 6, 24, 48, and 72 h (H1, H6, H24, H48, H72 groups) before permanent ischemia. The infarct size was measured by triphenyltetrazolium chloride staining, and left ventricular function parameters were recorded. The extent of apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive staining. Caspase-3 activity, Bcl-2, and Bax expression were also measured.Results: Compared with CTL group, myocardial infarct size was significantly decreased as well as cardiac cell apoptosis in area at risk zones (AAR) in H48 group. Meanwhile, the activity of caspase 3 was reduced, the ratio of Bcl-2/Bax expression was up-regulated, and the heart function parameters, including left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVEDP), +(dP/dt)max, and –(dP/dt)max were also significantly improved after preconditioning in H48 group.Conclusion: The results indicate that short-term HOP could induce cardioprotection and may not last for more than 24 h. HOP prevents myocardium from permanent ischemia injury by suppression of apoptotic pathways.

Multifactorial Comparison of Modified and Conventional Perfusion Strategies in A Porcine Model of Cardiopulmonary Bypass - Uncorrected Proof

2010-02-17

Background: Utilization of thromboresistant circuits in cardiopulmonary bypass (CPB) surgery has been controversial. However, due to the advantages associated with these types of circuits, we sought to evaluate the efficacy of use of low-dose heparin in conjunction with thromboresistant surfaces, closed perfusion system, elimination of blood-gas interface, maintenance of hematocrit to >25%, and systemic normothermia, with respect to the conventional strategy of non-thromboresistant open circuits with high-dose heparin, during 3 h of CPB in an animal model.Methods: Using an open-chest swine model, animals were placed on CPB for 3 h with additional monitoring for 1 h post-CPB. Pigs were randomized into either a heparin-bonded circuit (HBC) group (n = 10) or a non-HBC (NHB) group (n = 10). Hemodynamic, hematologic, and biochemical parameters and multiphoton microscopy were used to compare the two groups.Results: Pigs in the HBC group showed a 38.4% reduction in post-CPB blood loss in comparison with the NHB group (P = 0.0007). Additionally, compared with the HBC group, the NHB group exhibited a 32.7% post-CPB reduction in platelets (P < 0.001) and significant increases in alkaline phosphatase, aspartate aminotransferase, and creatine phosphokinase enzymes (P < 0.0202, P = 0.0015, P < 0.0001; respectively). Multiphoton imaging of the arterial filters revealed no entrapment of RBC, WBC, and platelets in the HBC group, while the filters in the NHB group were clogged by these cells.Conclusion: Utilization of modified perfusion strategy employing low-dose heparin and closed thromboresistant circuits is successful in ameliorating the potential adverse hematologic and pro-inflammatory elements induced with open perfusion system of non-thromboresistant circuits most commonly used in cardiac surgery.

A CXCR4 Antagonist CTCE-9908 Inhibits Primary Tumor Growth and Metastasis of Breast Cancer - Uncorrected Proof

2010-02-16

By Eugene H. Huang, M.D., Balraj Singh, Ph.D., Massimo Cristofanilli, M.D., Juri Gelovani, M.D., Ph.D., Caimiao Wei, Ph.D., Laura Vincent, B.S., Kendra R. Cook, B.S., and Anthony Lucci, M.D.

Topical Heparin: A Promising Agent for the Prevention of Tracheal Stenosis in Airway Surgery - Uncorrected Proof

2010-02-16

By Serdar Sen, M.D., Ibrahim Meteoglu, M.D., Mustafa Ogurlu, M.D., Selda Sen, M.D., Onur Ozgun Derincegoz, Ph.D., and Sabri Barutca, M.D. Journal of Surgical Research 157, e23–e29 (2009)

HB-EGF Improves Intestinal Microcirculation after Hemorrhagic Shock - Uncorrected Proof

Hong-yi Zhang, Andrei Radulescu, Yan Chen, Gail E. Besner — 2010-02-12

Background: The goal of this study was to determine the role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) as a mediator of gut microcirculation after hemorrhagic shock and resuscitation (HS/R) in mice.Materials and Methods: HS/R was induced in HB-EGF knockout (KO) and wild type (WT) mice. Ink-gelatin injection and vascular corrosion casting were performed to visualize the gut microvasculature. The degree of gut microcirculatory injury was graded using five patterns of injury (1<194>5) according to the severity of microvascular hypoperfusion. Statistical analyses were performed using linear mixed models with P < 0.05 considered statistically significant.Results: HB-EGF KO mice subjected to HS/R had significantly decreased perfusion of the gut microvasculature compared with WT mice subjected to HS/R (P = 0.0001). HB-EGF KO mice subjected to HS/R and treated with exogenous HB-EGF had significantly increased gut microvascular perfusion compared with non-HB-EGF treated KO mice (P = 0.01). Lastly, WT mice subjected to HS/R and treated with HB-EGF had significantly increased gut microvascular perfusion compared with non-HB-EGF-treated WT mice (P = 0.04).Conclusions: HB-EGF improves gut microcirculation after HS/R. These findings support the clinical use of HB-EGF in protection of the intestines from disease states associated with intestinal hypoperfusion injury.

Cepharanthine Improves Renal Ischemia-reperfusion Injury in Rats - Uncorrected Proof

2010-02-12

Background: Acute renal damage has numerous causes, including renal ischemia-reperfusion injury. Due to its diverse actions, cepharanthine is used to treat many acute and chronic diseases, including pit viper bites, alopecia areata, and leucopenia in radiation therapy. In this study, we examined whether cepharanthine provides a renal-protective effect in a renal ischemia-reperfusion model.Materials and Methods: Male Wistar rats were divided into four groups that received the following treatments: induction of renal ischemia-reperfusion (I/R group); subcutaneous injection of cepharanthine (10 mg/kg) followed 1 h later by induction of renal ischemia-reperfusion (Cepha + I/R group); subcutaneous injection of cepharanthine (10 mg/kg) (Cepha group); and subcutaneous injection of saline followed 1 h later by sham treatment (control group). Rats were sacrificed 24 h after renal ischemia-reperfusion or sham treatment. Serum blood urea nitrogen (BUN) and creatinine (Cre) concentrations were determined, histologic examination was performed, and oxidative stress was evaluated in kidney tissue. In addition, antimycin A (AMA)-stimulated RAW264.7 cells were treated with cepharanthine to determine its antioxidant effects.Results: Serum BUN and Cre levels were increased in the I/R group; however, these increases were significantly inhibited in the Cepha + I/R group. Similarly, kidney tissue damage observed in the I/R group was attenuated in the Cepha + I/R group. In vitro, cells treated with both cepharanthine and AMA showed reduced reactive oxygen species activity compared with cells treated with AMA alone.Conclusions: Our findings suggest that cepharanthine may be effective in the treatment of various types of ischemia-reperfusion injuries.

In Vivo Assessment of the Effects of Ginsenoside Rb1 on Intimal Hyperplasia in ApoE Knockout Mice - Uncorrected Proof

Hong Chai, Geoff Schultz, Kamran Aghaie, Wei Zhou — 2010-02-12

Objective: This study investigated the effects of ginsenoside Rb1 (Rb1) on injury-induced intimal hyperplasia in ApoE knock out (ApoE –/–) mice. We also examined the value of an ultrasound micro-image system in dynamic monitoring of lumen diameter and flow velocity.Methods: After guide wire injury of the distal left common carotid artery (CCA), ApoE–/– mice were treated with intraperitoneal infusion of normal saline (NS), homocysteine (Hcy), ginsenoside Rb1 (Rb1), or Hcy+Rb1 for 4 wk. Bilateral CCA luminal diameters and flow velocities were measured with an ultrasound micro-image system before surgery and weekly afterwards. Following the final ultrasound, CCAs were harvested and analyzed for intima-medium thickness ratios.Results: Progressive reduction in luminal diameters and increase in flow velocity of the injured left distal CCA segment were observed using ultrasound micro-imaging system in all groups compared with the relatively stable left proximal CCA and right CCA. The NS and Hcy groups had significantly higher degree of diameter reduction compared with the Rb1 and Rb1+Hcy groups. The ultrasound findings were consistent with histology analyses at 4 wk post-op.Conclusions: The study suggested that Rb1 attenuated the effects of Hcy on injured carotid arteries of ApoE –/– mice. The study also showed that ultrasound micro-image system was a reliable tool in monitoring luminal reduction after injury in murine model. This study establishes a fundamental step of in vivo monitoring of the therapeutic effects of agents in a murine model without sacrificing the animals.

A Pilot Study Assessing the Feasibility of a Short Period of Normothermic Preservation in an Experimental Model of Non Heart Beating Donor Kidneys - Uncorrected Proof

2010-02-12

Background: Restoring metabolism to an organ after hypothermic storage and before transplantation could reverse some of the detrimental effects of ischemic injury. This may be particularly beneficial for kidneys from non-heart-beating (NHBD) donors that sustain significant periods of warm and cold ischemic injury. This pilot study assessed the feasibility of a short period of normothermic preservation (NP) in a porcine autotransplant model.Methods: Kidneys were subjected to 30 min of warm ischemia, then preserved by hypothermic machine perfusion (HMP) for 22 h or 20 h HMP followed by 2 h of NP using autologous blood. Kidneys were then re-implanted, a contralateral nephrectomy performed, and renal function measured over 10 d.Results: Post-transplant, 4/6 animals survived in the NP group compared with 5/6 in the HMP group (P = 1.00). Creatinine levels fell below 250 μmol/L in all four of the surviving animals in the NP group compared with 2/5 in the HMP group (P = 0.608). There was no difference in levels of renal function (peak creatinine, HMP= 1736 ± 866 versus NP =1553 ± 516 μmol/L; P ≥ 0.990). Levels of lipid peroxidation were significantly lower 60 min post-transplant in the NP group (NP = 477 ± 118.0 versus HMP = 671 ± 99.4 pg/mL; P = 0.026).Conclusion: A period of NP at the end of the renal preservation period in NHB kidneys is a feasible method of kidney preservation. NP could prove to be a useful technique to predetermine graft function and allow pre-transplant modification of organs.

Effects of Nuclear Factor κB Inhibitors on Colon Anastomotic Healing in Rats1 - Uncorrected Proof

Abdulkadir Bedirli, Bulent Salman, Hatice Pasaoglu, Ebru Ofluoglu, Omer Sakrak — 2010-02-12

Background: Nuclear factor (NF)-κB plays an essential role in inflammation. We tested this role by administering NF-κB-inhibitors into rats undergoing a well-established model of colonic anastomotic healing.Methods: Wistar rats underwent laparotomy, descending colonic transection, and handsewn reanastomosis. The animals were randomized to receive either a selective NF-κB inhibitor (parthenolide 0.5 mg/kg or resveratrol 0.5 mg/kg) or an equal volume of water by gavages before operation and then daily after surgery. Animals were sacrificed either immediately after anastomotic construction (d 0) or at the third, fifth, or seventh postoperative day.Results: Both parthenolide and resveratrol treatment led to early significant increases in plasma levels of IL-6. On d 7, hydroxyproline levels were significantly higher in the parthenolide and resveratrol groups. A similar pattern was observed with the bursting pressure. In contrast, gelatinase activity (MMP-2 and MMP-9 expression) was significantly higher in the control group on postoperative d 3. On d 3, expression of NF-κB activity was up-regulated in the anastomotic area. Both parthenolide and resveratrol completely attenuated NF-κB activity. Study groups also developed more marked inflammatory cell infiltration and collagen deposition on histology analysis.Conclusions: Parthenolide and resveratrol significantly improved healing and mechanical stability of colonic anastomoses in rats during the early postoperative period. Both agents may be acting to accelerate the host reparative process as well as to enhance protection of the anastomotic wound bed.

Normothermic Versus Hypothermic Ex Vivo Flush Using a Novel Phosphate-Free Preservation Solution (AQIX) in Porcine Kidneys - Uncorrected Proof

2010-02-10

Background: The initial flush of an organ is important to remove any cellular components from the microcirculation before storage. The aim of this study was to assess graft function after an ex vivo warm flush with a novel non-phosphate buffered preservation solution AQIX RS-I (AQIX) compared with a traditional cold flush.Methods: Porcine kidneys were either warm-flushed with AQIX RS-I at 30°C, or cold-flushed at 4°C with University of Wisconsin solution (UW) or hyperosmolar citrate (HOC) preservation solution at a pressure of 100 mmHg (n = 6). Renal function was measured ex vivo by perfusing the organs with autologous blood at 37°C on an isolated organ perfusion system.Results: The AQIX group flushed significantly quicker than the cold stored groups (22 ± 1.8 versus UW 4.9 ± 1.6 versus HOC 10 ± 1.6 mL/min/100g; P = 0.001) and gained less weight than the UW group (19 ± 2.9 versus UW 30 ± 3.4 versus HOC 21% ± 7.7%; P = 0.025). The AQIX group also had superior acid-base homeostasis. Functional results, histologic analysis, and ADP: ATP levels were comparable between the groups.Conclusion: Flushing kidneys with AQIX at 30°C cleared the renal microcirculation of blood more rapidly without any detrimental effects when compared to traditional cold flushing with UW or HOC at 4°C. Warm initial flushing has potential to be developed as part of normothermic renal preservation techniques.

Melatonin Attenuates I/R-Induced Mitochondrial Dysfunction in Skeletal Muscle - Uncorrected Proof

2010-02-10

Background: Our recent studies have shown that ischemia/reperfusion (I/R) produces significant necrosis and apoptosis in the cells of skeletal muscle. Our previous studies also demonstrated that melatonin provides significant protection against superoxide generation, endothelial dysfunction, and cell death in the skeletal muscle after I/R. Mitochondria are essential for cell survival, because of their roles as ATP producers as well as regulators of cell death. However, the efficacy of melatonin on I/R-induced mitochondrial dysfunction in the skeletal muscle in vivo has not been demonstrated in the literature.Materials and Methods: Vascular pedicle isolated rat gracilis muscle model was used. After 4 h of ischemia followed by 24 h of reperfusion, gracilis muscle was harvested, and mitochondrial as well as cytosolic fractions were isolated. Mitochondrial dysfunction was determined by the alteration of mitochondrial membrane potential and the release of the proapoptotic protein, cytochrome c. Three groups were designed; sham I/R, I/R-V (I/R with vehicle), and I/R-Mel (I/R with melatonin). Melatonin or vehicle was given intravenously 10 min prior to reperfusion and 10 min after reperfusion.Results: We found that the capability of uptake of fluorescent JC-1 dye in skeletal muscle cells was substantially improved in I/R-Mel group compared with I/R-V group. Melatonin significantly inhibited the outflow of cytochrome c from mitochondria to cytoplasm, which was demonstrated in the I/R-V group.Conclusions: Melatonin significantly attenuates I/R-induced mitochondrial dysfunction, such as the depolarization of mitochondrial membrane potential and the release of the proapoptotic protein, cytochrome c, from the mitochondria.

The Impact of Duty Hours on Surgical Resident Education: Are Operative Logs Appropriate Surrogates for Surgical Competence? - Uncorrected Proof

Julie A. Margenthaler — 2010-02-10

The Accreditation Council for Graduate Medical Education mandated residency training programs to institute restricted duty hours July 1, 2003. Since that time, much has been written regarding the impact on surgical residents' training experiences and quality of life, as well as the ultimate effect on patient safety and care. A major concern of both residents and faculty was the assumption that this restriction would impact different specialties in unique ways. Specifically, surgeons feared that this would decrease the residents' operative experience and have a detrimental impact on technical skills. However, evidence is mounting that this is not the case. In fact, the current article by Shin and colleagues suggests that the operative experience may be better allocated and enhanced in the setting of restricted duty hours.

Cepharanthine Exerts Anti-Inflammatory Effects Via NF-κB Inhibition in a LPS-Induced Rat Model of Systemic Inflammation - Uncorrected Proof

2010-02-08

Background: Systemic inflammatory response syndromes involving sepsis continue to have extremely high mortality rates. Inflammation is difficult to control when it spreads throughout the body and often progresses into multiple organ dysfunction, eventually leading to death. Cepharanthine (CE) is a plant alkaloid that possesses bioactive properties, with various known actions. In the present study, we investigated protective effects of CE in a lipopolysaccharide (LPS)-induced systemic inflammatory response model and examined underlying mechanisms.Materials and Methods: We intravenously administered LPS (7.5 mg/kg) to male Wistar rats after intraperitoneal injections of either physiologic saline (LPS group) or CE (10 mg/kg; CE + LPS group), or 2 h before intraperitoneal injection of CE (post-CE + LPS group). We then compared changes in serum cytokine and nitrogen oxide levels over time, and performed histologic examinations of the lungs and liver in each group. Using mouse macrophage RAW264.7 cells, we determined the effect of CE on LPS-induced cytokine secretion into the cell culture medium, as well as NF-κB activity.Results: The increase in LPS-induced cytokine levels in rat serum was significantly inhibited by CE treatment; this effect was also seen in the post-CE + LPS group. In addition, we observed histologic improvements with CE co-treatment. In vitro, CE inhibited NF-κB activation by inhibiting the IKK pathway.Conclusions: These results suggest that CE exerts protective effects, at least in part, via NF-κB inhibition. CE may thus be a potential agent for treating systemic inflammatory response syndromes such as sepsis.

Study on Construction of nano tPA Plasmid to Prevent Thrombosis After Mechanical Valve Replacement in Dogs - Uncorrected Proof

2010-02-08

Background: Mechanical valve is inclined to induce thrombosis. We intend to elucidate the transfection of nano tissue-type plasminogen activator (tPa) gene plasmid to prevent thrombosis after tricuspid mechanical valve replacement in dogs.Methods: A dog model of mechanical tricuspid valve replacement was constructed. A constructed chitosan nano tPA gene plasmid was used to transfect the dog cardiocytes at the same time of tricuspid valve replacement. The effect of this gene on the survival of dogs, anticoagulation (prothrombin time, INR and D-dimer contents, thrombosis in heart), and the expressions of tPA were observed.Results: Nano tPA gene plasmid was successfully constructed and transfected into cardiocytes. The gene could significantly increase the survival of animals and the contents of D-dimer (P < 0.01), and could prevent thrombus formation on mechanical valves, but there was no significant difference of prothrombin time and INR between two groups (P > 0.05).Conclusion: The constructed nano tPA gene plasmid could prevent thrombus formation after mechanical valve replacement, which provides a clue for clinical use.

The Impact of the Intra-Abdominal Space on Liver Regeneration After a Partial Hepatectomy in Rats - Uncorrected Proof

2010-02-08

Background: Little is known about the relationship between intra-abdominal space and liver regeneration. The present study was experimentally designed to investigate the influence of the “occupied space” or the “loss of occupied space” on a regenerating liver.Methods: Experiment 1: Rats were randomly assigned to two groups: SO (space occupied) rats (n = 40); occupancy of intra-abdominal space followed by a two-thirds partial hepatectomy (PH) and control rats (n = 40); A PH alone. The rats in both groups were euthanized at 24, 48, 96, and 168 h after the operation. Computed tomography (CT) images were analyzed to evaluate the regenerating-direction and the shape of the regenerated remnant liver. The liver to body weight ratio and the proliferating cell nuclear antigen (PCNA) labeling index were measured at each time point. Experiment 2: A second laparotomy was performed at 168 h after the PH in both groups; occupier-removal for the SO rats and a sham operation for the control rats. The rats in both groups were euthanized at 24 and 168 h after the second operation. The liver to body weight ratio and PCNA labeling index were measured at each time point.Results: Experiment 1: The remnant liver of the SO rats enlarged toward the dorsal and caudal side because liver regeneration toward the ventral side in the SO rats was inhibited with the occupier in the abdominal space at 96 h, and later, after the PH. CT images showed a statistically significant difference in the shape of the regenerated remnant liver between the control group and the SO group. The liver/body weight ratio was significantly decreased in the SO rats at 96 and 168 h after PH (P < 0.05). There was no significant difference between the groups in the PCNA labeling index. The SO rats showed a significant increase of the PCNA labeling of the inferior right lobe (10.6%) in comparison with the index of the superior right lobe (7.8%), which came in direct contact with the occupier, at 96 h after the operation (P < 0.05). The cell density of superior right lobe of the SO rats group was significantly higher than that of the control group at 168 h after operation (P < 0.05). Experiment 2: There was no statistically significant difference in the liver/body weight ratio at 168 hrs after the second operation between the groups. However, there was a statistically significant increase of the PCNA labeling index 24 h after the second operation in the occupier-removal rats in comparison with the control rats (P < 0.05).Conclusion: The occupied intra-abdominal space was therefore found to suppress liver regeneration after a partial hepatectomy, while the removal of such an occupied space stimulated the regeneration of the liver.

Tissue Proteolysis in Appendicitis with Perforation - Uncorrected Proof

2010-02-08

Background: Matrix metalloproteinases (MMPs) and serine proteases are able to degrade the extracellular matrix (ECM) and modulate immune responses in the gastrointestinal tract. The purpose of this study was to investigate local proteolysis in perforated appendicitis and its association with the appendix perforation.Materials and Methods: Biopsies were taken at the sites of perforation (n = 15) with a gradually increased distance from it. The expression and distribution of MMP-1, -2, and -9, the tissue inhibitor of metalloproteinases type (TIMP-1), plasminogen activator inhibitor type1 (PAI-1), and urokinase plasminogen activator (uPA) were measured by ELISA. The distribution of MMP-9, TIMP-1, uPA, and PAI-1 in perforated, nonperforated, and uninflamed appendix was investigated by immunohistochemistry with monoclonal antibody technique.Results: MMP-1 expression was highest close to the perforation and was gradually decreased in biopsies in more distal locations (P < 0.01). MMP-9 showed a similar pattern being highest at the sites for perforation (P < 0.05), while MMP-2 expression showed a trend in the opposite direction without statistically significance. The expression of TIMP-1 trended lower at the sites of perforations. PAI-1 was highest at the sites of perforation (P < 0.01) and the uPA expression was similarly elevated close to and at the perforation.Conclusions: These data indicate a key role of MMP in the pathogenesis of appendix perforation. A local imbalance between MMP-9 and the inhibitor TIMP-1 could potentially contribute to the tissue injury leading to an appendix perforation. The overexpression of PAI-1 at the sites of perforations may also contribute to tissue damage.

Super Hydrophilic Thin Film Nitinol Demonstrates Reduced Platelet Adhesion Compared with Commercially Available Endograft Materials - Uncorrected Proof

2010-02-08

Background: Thin film nitinol (TFN) is a novel material with which to cover stents for the treatment of a wide range of vascular disease processes. This study aimed to show that TFN, if treated to produce a super hydrophilic surface, significantly reduces platelet adhesion, potentially rendering covered stents more resistant to thrombosis compared to commercially available materials.Materials and Methods: TFN was fabricated using a sputter deposition process to produce a 5-μ thin film of uniform thickness. TFN then underwent a surface treatment process to create a super hydrophilic layer. Platelet adhesion studies compared surface treated TFN (S-TFN) to untreated TFN, polytetrafluoroethylene, Dacron, and bulk nitinol. In vivo swine studies examined the placement of an S-TFN covered stent in a 3.5 mm diameter external iliac artery. Angiography confirmed placement, and repeat angiography was performed at 2 wk followed by post mortem histopathology.Results: S-TFN significantly reduced platelet adhesion without any evidence of aggregation compared with all materials studied (P < 0.05). Furthermore, in vivo swine studies demonstrated complete patency of the S-TFN covered stent at 2 wk. Post mortem histopathology showed rapid endothelialization of the S-TFN without excessive neointimal hyperplasia.Conclusions: These results demonstrate that S-TFN significantly reduces platelet adhesion and aggregation compared with commercially available endograft materials. Furthermore, the hydrophilic surface may confer thromboresistance in vivo, suggesting that S-TFN is a possible superior material for covering stents.

Early Postoperative Oral Intake Accelerates Upper Gastrointestinal Anastomotic Healing in the Rat Model - Uncorrected Proof

2010-02-04

Background: In our previous study, we reported that early postoperative oral feeding accelerated upper gastrointestinal anastomotic healing in rats. To investigate its underlying mechanism, we performed in vivo and in vitro experiments.Materials and Methods: Rats that received proximal jejunal anastomosis were divided into four groups: the enteral nutrition (EN) group were fed via gastrostomy, the total parental nutrition (TPN alone) group were fed via a venous catheter, the TPN + saline group received an additional administration of normal saline solution via gastrostomy, and the TPN + water group received an additional administration of distilled water via gastrostomy. The anastomotic bursting pressure (ABP) and the hydroxyproline content of the anastomotic tissue were measured 5 d postoperatively. In an in vitro setting, the rat gastrointestinal fibroblasts were subjected to uniaxial stretching for 60 min, and the expression of type I and type III collagen mRNA was evaluated.Results: The ABP and hydroxyproline content in the EN group, the TPN + saline group, and the TPN + water group were significantly higher than those in the TPN alone group (ABP; 214.6 ± 42, 199.4 ± 36, and 187.3 ± 29 versus 149.5 ± 49 mmHg; P < 0.01, hydroxyproline; 63.5 ± 10, 67.8 ± 13, and 64.1 ± 14 versus 50.5 ± 12 μmol/g dry tissue; P < 0.01). The mRNA levels of type I and type III collagen were increased by stretch stimulation.Conclusions: These results suggest that mechanical loading plays a key role in anastomotic healing. Further investigations are necessary to confirm this suggestion.

Laparoscopic Antrectomy for the Treatment of Type I Gastric Carcinoid Tumors - Uncorrected Proof

2010-02-04

Background: While the optimal treatment for type I gastric carcinoid tumors remains controversial, there is evidence to suggest that in multifocal disease, antrectomy may not only control local disease but also may lead to enterochromaffin-like cell (ECL) hyperplasia regression compared to medical and endoscopic treatments.Materials and Methods: A single institution retrospective review of eight consecutive patients with multifocal type I gastric carcinoid tumor patients with no evidence of metastatic disease was performed from 2005 to 2006. All of these patients underwent laparoscopic antrectomy with Billroth II reconstruction. Patients' preoperative gastrin, chromogranin A levels, and biopsy and surgical specimen slides were compared with postoperative laboratory and biopsy slides. Pathology slides were reanalyzed by a blinded pathologist from our institution for evidence of tumor and ECL hyperplasia regression.Results: All patients tolerated the procedure well with no reoperations or mortalities. Six of eight patient complained of mild reflux which was treated medically. One of eight had a mild wound infection which resolved with a course of cephalexin. Gastrin levels significantly decreased (98.9%) in all patients (P = 0.001). Furthermore, chromogranin A levels also significantly decreased (81.4%). Eight of eight patients showed no evidence of carcinoid tumor after surgery at mean biopsy follow-up of 17 mo (range 2–35 mo), however there was ECL hyperplasia after resection. Four of eight patients (50%) showed regression of ECL hyperplasia on postop biopsy, while the remaining four of eight showed no evidence of regression.Conclusions: This is the largest case series to investigate the surgical, clinical, and histologic outcomes of laparoscopic antrectomy in type I gastric carcinoid. Our data suggest that laparoscopic antrectomy is a safe and minimally invasive approach to treat nonmetastatic type I gastric carcinoid. All patients had no evidence of gross or microscopic disease at follow-up biopsy and almost half had regression of ECL hyperplasia at follow-up suggesting that antrectomy may be sufficient to prevent tumor recurrence. However, continued regular endoscopic surveillance and medical follow-up of patients with ECL hyperplasia are recommended.

The Feasibility of FS Mesh Fixation by a Transgastric Approach—An Important Benefit in Future NOTES Procedures? - Uncorrected Proof

2010-02-04

Background: Preserving the integrity of the abdominal wall is a major benefit in NOTES procedures. It may result in a decrease of postoperative (postOP) pain, infection, and port site hernia. This experimental study on intra-peritoneal onlay mesh (IPOM) repair was designed to apply meshes by a transgastric access (TGA) and to use a combination of transfascial sutures and fibrin sealant as fixation.Materials and Methods: Four abdominal wall defects were created by TGA under laparoscopic control in five nonsurvival and three survival pigs (4, 11, and 22 d observation period). Titanized polypropylene meshes were fixed transfascially by four polypropylene sutures using a “suture passer” device. Meshes were additionally fixed with 0.2 mL of fibrin sealant (FS) by an endoscopic application. TGA was closed with endoclips in the nonsurvival model and with laparoscopic suturing in survival pigs.Results: The three survival pigs were euthanized on the d 4, 11, and 22 postOP. The macroscopic evaluation revealed excellent integration of the meshes without signs of shrinkage, dislocation, or inflammation. Histology confirmed macroscopic findings.Conclusions: Our findings confirm that IPOM repair of ventral hernia in an experimental NOTES hybrid procedure is feasible. This study also demonstrates the technical feasibility and the potential advantages of FS mesh fixation to further reduce trauma to the abdominal wall following the key principles of the NOTES approach.

Targeted Gene Delivery to Selected Liver Segments Via Isolated Hepatic Perfusion - Uncorrected Proof

2010-02-04

Background: Development of targeted gene transfer technologies is essential for in vivo gene therapy. In this study, we examined the feasibility of physically targeting an adenoviral vector to selected liver segments in rats by isolating the hepatic perfusion (IHSP) and clamping the portal vein between the upper and lower segments.Materials and Methods: The rats were divided into two groups: IHSP group and the inferior vena cava (IVC) group. The adenoviral vector, which harbored the β-galactosidase (β-gal) gene, was administered via the portal vein, after which unbound vector particles were washed out with phosphate-buffered saline (PBS) and removed via the cannulated inferior vena cava (IVC) in IHSP group, while the IVC group received the transgene directly via the IVC without isolation of the hepatic perfusion.Results: With this configuration (IHSP group), >99% of the β—gal activity was limited to the targeted hepatic lobes, findings which were confirmed by histochemical staining with X-gal. We also found there to be significant differences in transgene expression among the hepatic lobes in the IVC group.Conclusions: Taken together, these results indicate that the IHSP technique is useful for local gene delivery to selected liver segments, and that when evaluating the efficacy of IHSP in the treatment of liver disease (e.g., nonresectable tumors), interlobar differences must be given careful consideration to ensure that sufficient drug or vector is delivered to all targeted hepatic lobes.

Monitoring of Loss of Heterozygosity in Serum Microsatellite DNA Among Patients with Gastrointestinal Stromal Tumors Indicates Tumor Recurrence - Uncorrected Proof

2010-01-28

Background: Patients with gastrointestinal stromal tumors (GIST) harbor increased levels of circulating tumor DNA in their peripheral blood. In the current study, the aim was to investigate whether the frequency of loss of heterozygosity (LOH) on cell-free DNA in blood may reflect tumor stage and recurrent disease of these patients.Materials and Methods: Serum DNA and follow-up samples of 92 patients suffering from recurrent GIST were analyzed by a PCR-based fluorescence microsatellite analysis using a panel of 12 polymorphic markers. The data were correlated with established risk factors, and patients were followed-up over 4 y.Results: Microsatellite analysis demonstrated a positive LOH score on cell-free DNA of 30/92 patients. A significant correlation with recurrence in CT imaging showed that a positive LOH score (n ≥ 2) was detected in 58% (11/19) of patients with recurrent disease (P = 0.030, χ2 test), but only in 25% of patients were clinically free of recurrence. No prognostic significance of a positive LOH score was observed after a median observation time of 48 mo.Conclusion: Our findings show that LOH on circulating serum DNA correlates with the tumor status and is a frequent event in GIST patients with recurrent disease.

Protection of Human Myocardium by Bone Marrow Cells: Role of Long-Term Administration of the Mitochondrial KATP Channel Opener Nicorandil - Uncorrected Proof

Vien Khach Lai, Manuel Galiñanes — 2010-01-25

Background: We have previously demonstrated that bone marrow cells (BMCs) afford myocardial protection as potent as ischemic preconditioning (IP) and also that the myocardium of patients treated with the mitoKATP channel opener nicorandil cannot be protected by IP. Here, we investigated whether nicorandil influences the cardioprotection elicited by BMCs and whether any loss in protection can be rescued by naïve allogenic BMCs.Materials and Methods: BMCs and right atrial appendage were obtained from patients on long-term treatment and nontreated with nicorandil. The atrial myocardium was subjected to 90 min ischemia/120 min reoxygenation at 37°C in the presence and absence of autologous and allogenic BMCs. Some muscles were subjected to IP prior to ischemia and served as positive controls. Tissue injury was assessed by creatine kinase released during reoxygenation, and cell necrosis and apoptosis were determined by propidium iodide and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).Results: Creatine kinase (CK) release and cell necrosis and apoptosis induced by ischemia were not significantly reduced by IP in the myocardium from nicorandil subjects and values were also unaffected by the co-incubation with autologous or allogenic BMCs from subjects not treated with nicorandil (naïve BMCs). However, when the myocardium from subjects not treated with nicorandil was co-incubated with autologous BMCs or with allogenic BMCs from subjects treated with nicorandil, there was a similar significant reduction in CK release, cell necrosis and apoptosis.Conclusions: The cardioprotective properties of BMCs from subjects treated with the mitoKATP channel opener nicorandil are preserved; however, the myocardium of these patients cannot benefit from the cardioprotective effect of BMCs due to an unresponsive myocardium.

Analysis of Second Primary Lung Cancers in the SEER Database - Uncorrected Proof

2010-01-25

Background: We sought to examine the outcomes of second primary lung cancers in the large population-based Surveillance Epidemiology and End Results (SEER) database. We also sought to study the outcomes of synchronous second non-small-cell lung cancers (NSCLCs), classified as stage IVA (M1A) according to the seventh edition of the TNM staging for lung cancer.Methods: Data of patients with at least two primary lung cancers were obtained. All available variables potentially associated with the incidence of a second primary lung cancer were examined. The overall survival of patients with synchronous NSCLC was compared with those with metachronous and stage IV NSCLC.Results: A small proportion (1.5%) of patients with lung cancer developed a second primary. A second primary is associated with younger age, female gender, earlier stage, and white race. The median survival of patients with metachronous NSCLCs (n = 3352) was worse than those with synchronous NSCLCs (n = 1858) (median survival 22 mo versus 29 mo, respectively; P < 0.01). After adjusting for age, race, gender, stage, and histology of both primaries, this difference in survival between patients with synchronous and metachronous second primary lung cancers was not statistically significant, but was better than those with stage IV NSCLC (n = 127,654; median survival 4 mo).Conclusions: The incidence of second primary lung cancer is lower than that previously reported. Factors associated with good prognosis predict a second primary. Synchronous NSCLCs have an outcome better than a stage IV (M1a) designation. These patients should receive appropriate stage-specific multi-modality therapy suitable for the independent stage of each cancer without considering them unresectable.

Detrimental Functions of IL-17A in Renal Ischemia-Reperfusion Injury in Mice - Uncorrected Proof

2010-01-25

Background: Renal ischemia-reperfusion (I/R) injury, as a common and clinically important problem, starts with direct damage caused by chemokines and inflammatory cytokines, which is aggravated by specific and nonspecific immune reactions. Recently, IL-17A has been considered to be in a uniquely powerful position between adaptive and innate immunity. The present study investigated the role of IL-17A in renal I/R injury in mice.Methods: We measured the time-course of changes in plasma and renal IL-17A levels using a murine model of renal I/R injury. Then, the protective effect of monoclonal anti-IL-17A antibody, given intravenously at 30 min before or after renal I/R operation, on renal I/R injury was investigated. In addition, the levels of plasma and renal pro- and anti-inflammatory cytokines and chemokines were assessed.Results: IL-17A was significantly increased in plasma and kidneys after renal I/R injury in mice. Furthermore, intravenous administration of neutralizing monoclonal anti-IL-17A antibody attenuated renal I/R injury by evaluating renal function and histopathology. In addition, administration of anti-IL-17A antibody substantially reduced the plasma and renal levels of many pro-inflammatory mediators (TNF-α, IL-6, high-mobility group box 1 (HMGB1), IL-1β, IL-17A, macrophage inflammatory protein-1α (MIP-1α), and monocyte chemoattractant protein-1 (MCP-1), as well as increased the plasma and renal levels of anti-inflammatory cytokines IL-10 and transforming growth factor β (TGF-β).Conclusion: The above data suggest that IL-17A has a detrimental effect on renal I/R injury via facilitating the production of pro-inflammatory cytokines and chemokines as well as hampering the production of anti-inflammatory cytokines.

Book Review - Uncorrected Proof

Joel T. Adler, Heather B. Neuman — 2010-01-18

The fourth edition of The Breast: Comprehensive Management of Benign and Malignant Diseases comes 3 years after the publication of the previous edition. Since the publication of the first edition in 1991, this resource has proven to be a highly respected reference. The pace of basic, translational, and clinical breast cancer research is rapid, and this fourth edition is the latest attempt to summarize the current understanding. In short, it represents an authoritative summary of current research and treatment for breast disease.

Adenovirus-Mediated SiRNA Targeting c-Met Inhibits Proliferation and Invasion of Small-Cell Lung Cancer (SCLC) Cells - Uncorrected Proof

Zhao-Xia Wang, Bin-Bin Lu, Jin-Song Yang, Ke-ming Wang, Wei De — 2010-01-18

Background: The hepatocyte growth factor receptor c-Met and its ligand hepatocyte growth factor (HGF) have been reported to be involved in cellular motility, growth, and invasion by activating mitogenic signaling pathways. The overexpression of c-Met gene has been found in many malignant cancers, but the roles of c-Met overexpression in SCLC tumors still remain unclear. The aim of the present study was to explore its roles and potential as a therapeutic target for SCLC.Methods: Quantitative real-time RT-PCR and immunohistochemistry assays were performed to detect the expression of c-Met mRNA and protein in SCLC tissue or corresponding non-tumor lung tissue samples. Adenovirus-mediated small interfering RNA (siRNA) was employed to down-regulate the expression of c-Met gene in SCLC cell line (NCI-H446). MTT and colony formation assays were performed to detect in vitro proliferation of NCI-H446 cells. In vitro wound-healing and transwell invasion assays were performed to detect in vitro invasion and metastasis of NCI-H446 cells. Finally, in vivo tumorigenicity and metastasis assays were done to analyze in vivo proliferation and metastasis of NCI-H446 cells in a xenograft model.Results: We showed that the levels of c-Met mRNA expression were significantly higher in SCLC tissue samples (0.97±0.08) than those in corresponding non-tumor lung tissue samples (0.21±0.02; P<0.05). Additionally, the immunostaining of c-Met protein in SCLC tissues was stronger than that in corresponding non-tumor tissues. Adenovirus-mediated siRNA targeting c-Met could significantly down-regulate c-Met expression, and the specific down-regulation of c-Met expression in SCLC cells could strongly inhibit proliferation of SCLC cells both in vitro and in vivo. Moreover, c-Met down-regulation could also reduce invasion capacity in vitro and metastasis capacity in vivo of SCLC cells.Conclusions: Taken together, our results indicated that the overexpression of c-Met gene played an important role in the progression and development of SCLC, and adenovirus-mediated siRNA targeting c-Met could potentially be an experimental approach for SCLC gene therapy.

Opioid δ1 and δ2 Receptor Agonist Attenuate Myocardial Injury Via mPTP in Rats With Acute Hemorrhagic Shock - Uncorrected Proof

2010-01-18

Background: Studies have documented the beneficial roles of δ opioid receptor (OR) agonist for hemorrhagic shock. However, the myocardial protection roles and the mechanisms of hemodynamic stability during resuscitation of δ-OR agonist have not been explored. This study was designed to investigate myocardial protective effects and the mechanisms of high selective δ1 and δ2-OR agonists during resuscitation of acute hemorrhagic shock.Materials and Methods: Forty-eight adult male SD rats were adapted for 60-min hemorrhagic shock through removing 30% (5mL) of the total blood volume, and followed by 2-h resuscitation with shed blood and L-lactated Ringer's solution. At the end of shock and prior to resuscitation, NS, δ1-OR agonist TAN-67 (10mg/kg), and antagonist BNTX (3mg/kg), DMSO, δ2-OR agonist deltorphin II, (1mg/kg) and antagonist NTB (2mg/kg) in 0.5mL were administrated. Left ventricular function parameters were measured during the whole experimental period. Myocardial mitochondria were isolated to determine opening of mitochondrial permeability transition pore (mPTP). Morphologic changes in myocardium and mitochondria were observed by electron microscope.Results: The hemodynamic indexes in group TAN-67 and group deltorphinII were higher than control group at each time point during resuscitation, respectively (P<0.05). TAN-67 and deltorphin II decrease but their antagonists BNTX and NTB increase the opening of mPTP (P<0.05). Myocardial and mitochondrial damage were attenuated in group TAN-67 and group deltorphin II.Conclusions: δ1-OROR agonist TAN-67 and δ2-OROR agonist deltorphin II protect the heart by targeting the mPTP in rats with acute hemorrhagic shock.

Kallikrein-Kinin System: A Surgical Perspective in Post-Aprotinin Era - Uncorrected Proof

Pankaj Saxena, Philip Thompson, Yves d'Udekem, Igor E. Konstantinov — 2010-01-18

Kallikrein-kinin system (KKS) plays an important role in inflammation, ischemia-reperfusion (IR) injury, and development of neoplasia. There is evidence to suggest that KKS plays an important role in organ protection during preconditioning. Aprotinin is a nonspecific serine protease inhibitor, which has been extensively used in cardiac surgery for the control of post operative bleeding. The anti-inflammatory effects of aproprotin are due to its inhibitory effect on the kallikrein-kinin system (KKS). We herein review KKS and its role as applied to the practice of surgery.

A Comparison of Woven Versus Nonwoven Polypropylene (PP) and Expanded Versus Condensed Polytetrafluoroethylene (PTFE) on Their Intraperitoneal Incorporation and Adhesion Formation - Uncorrected Proof

2010-01-14

Objective: To compare known and novel synthetic materials useful for incisional hernia repair and to test independently, whether they justify common perceptions related to their use.Methods: Four types of synthetic materials were implanted in to 12 pigs to compare incorporation histology and adhesion formation 90 d after placement. Woven polypropylene (WPP), nonwoven polypropylene (NWPP), expanded polytetrafluoroethylene (ePTFE). and condensed polytetrafluoroethylene (cPTFE) were placed intraperitoneally (IP).Results: Intraperitoneally, WPP became fully peritonealized, but generated thick and plentiful adhesions. NWPP became fully peritonealized and generated filmy and far less numerous adhesions. ePTFE formed some filmy adhesions and did not peritonealize. cPTFE and WPP became fully peritonealized. However, bowel became adherent on raised edges of cPTFE and WPP.Conclusion: We conclude that NWPP incorporates extremely well intraperitoneally, promotes few adhesions, and its use is likely to be suitable for hernia repair. cPTFE performs well and promotes few adhesions, but to minimize potentially serious complications, its edges must be secured around its entire circumference.

Inhibition of NF-κB Activation by β-Glucan Is Not Associated with Protection from Global Ischemia-Reperfusion Injury in Pigs - Uncorrected Proof

2010-01-14

Background: Pretreatment with β-glucan has been shown to protect against regional ischemia-reperfusion injury, through inhibition of myocardial NF-κB activation. The aim was to examine whether β-glucan pretreatment could protect against global ischemia-reperfusion injury, which is encountered in the clinical setting during open heart surgery.Materials and Methods: Twenty-one pigs were randomized to pretreatment with oral β-glucan (SBGo, n = 7), pretreatment with i.p. β-glucan (SBGip, n = 7), and untreated controls (n = 7). The pigs were subjected to cardiopulmonary bypass (CPB) with 1 h of global cardioplegic ischemia followed by wean from CPB and reperfusion for 4 h. Cardiac function was determined by a conductance catheter, and troponin T was sampled from the coronary sinus. Atrial biopsies obtained at baseline, following 30 min, and 3 h of reperfusion were analyzed for phosphorylated NF-κB by Western blot.Results: Following reperfusion, phosphorylated NF-κB increased by 210% in the control group, 197% in the SBGo group, but was reduced by 5% in the SBGip group (P < 0.01 versus control). After 4 h of reperfusion, preload recruitable stroke work dropped by 19% in the control group and 25% in the SBGo group compared with 60% in the SBGip group (P < 0.01 versus control). The area under the curve for troponin T was larger in the SBGip group compared with the control group (P < 0.05) and the SBGo group (P < 0.01).Conclusion: Inhibition of NF-κB activation by i.p. β-glucan does not protect against ischemia-reperfusion injury in pigs subjected to global ischemia and reperfusion, and may be associated with aggravation of ischemia-reperfusion injury.