The effect of erythropoietin on uterus inflammation during ischemia reperfusion injury in rats.

OBJECTIVE: This experiment evaluated the influence of erythropoietin (Epo) in an animal model of uterine ischemia reperfusion using the quoting established protocol. DESIGN: The effects of erythropoietin treatment were evaluated by mean uterus inflammation (UI) lesions. UI lesions were determined at the 60th reperfusion min (for groups A and C) and at the 120th reperfusion min (for groups B and D). Groups A and B received no drugs, whereas rats from groups C and D were administered with erythropoietin. METHODS: 40 rats of mean mass 247.7 g were employed for the study. RESULTS: Epo administration non-significantly decreased the UI scores [without lesions] by 0.1 [-0.6244129 - 0.4244129] (p = 0.6294)). Reperfusion time kept non-significantly increased the UI scores by [without lesions] 0.15 [-0.60230385 - 0.50230385] (p = 0.5782). Together, Epo administration combined with reperfusion time non-significantly decreased the UI scores by [without lesions] 0.0727273 [-0.3886782 - 0.2432236] (p = 0.6439). CONCLUSIONS: Epo administration whether it interacted or not with reperfusion time non-significantly short-term decreased the UI lesions scores. Perhaps, a longer study time than two hours or a higher Epo dose may provide more significant effects.

[The Effect of the Antioxidant Drug U-74389G on Magnesium Levels During Hypoxia-Reoxygenation Injury in Rats].

OBJECTIVE: The aim of this experimental study was to examine the effect of the antioxidant drug U-74389G in a rat model of hypoxia-reoxygenation using the previously established protocol. Effects of treatments were evaluated by magnesium (Mg2+) levels in blood. METHODS: Non-randomized controlled study was performed. Mg2+ levels were determined in 60 min (groups A and C) and 120 min (groups B and D) after starting the reoxygenation. Groups A and B received no drugs, whereas rats from groups C and D were administered with U-74389G. RESULTS: 40 rats 16-18 weeks old of a mean weight of 2312 g were employed in the study. It is demonstrated that U-74389G administration did not alter the Mg2+ levels (decrease in Mg2+ concentration was 0.28±2.75%; p=0.917). Reoxygenation non-significantly increased the Mg2+ levels by 4.27±2.66% (p=0.107). Together, the U-74389G administration and reoxygenation non-significantly increased the Mg2+ levels by 0.36±1.64% (p=0.823). CONCLUSION: U-74389G administration, alone or in concert with reoxygenation did not significantly affect Mg2+ level in blood after experimental hypoxia in rats.

Anti-inflammatory effect of elemental diets with different fat composition in experimental colitis.

The aim of the present study was to evaluate the effectiveness of two isoenergetic elemental formulae with different fat content in the rat model of trinitrobenzene sulphonic acid (TNBS) colitis that mimics human inflammatory bowel disease. A total of forty-five male Wistar rats were assigned to five groups: (1) control group; (2) TNBS-induced colitis group; (3) TNBS-induced colitis group fed a long-chain TAG (LCT)-rich diet; (4) TNBS-induced colitis group fed a medium-chain TAG (MCT)-rich diet; (5) TNBS-induced colitis group fed a baseline diet and administered infliximab. Nutritional management lasted 12 d before and 4 d after rectal administration of TNBS. Subsequently, the rats were killed, and colonic tissue samples were collected for the assessment of histology, inflammation and oxidative stress. The MCT-rich diet decreased IL-6, IL-8 and intercellular adhesion molecule-1 (ICAM-1) levels and glutathione S-transferase (GST) activity, while the LCT-rich diet reduced only ICAM-1 levels and GST activity (P<0.05). Neither elemental formula affected IL-10 levels. Infliximab reduced IL-8 and ICAM-1 levels and GST activity and increased IL-10 levels (P<0.05). No significant differences were detected in oxidative stress. Histological damage scores differed significantly only between the control and the TNBS-induced colitis group. A MCT-rich formula seems to exert stronger anti-inflammatory effects than a LCT-rich formula in TNBS colitis.

Effects of early amiodarone administration during and immediately after cardiopulmonary resuscitation in a swine model.

BACKGROUND: Aim of this experimental study was to compare haemodynamic effects and outcome with early administration of amiodarone and adrenaline vs. adrenaline alone in pigs with prolonged ventricular fibrillation (VF). METHODS: After 8 min of untreated VF arrest, bolus doses were administered of adrenaline (0.02 mg/kg) and either amiodarone (5 mg/kg) or saline (n = 8 per group) after randomisation. Cardiopulmonary resuscitation (CPR) was commenced immediately after drug administration, and defibrillation was attempted 2 min later. CPR was resumed for another 2 min after each defibrillation attempt, and the same dose of adrenaline was given every 4th minute during CPR. Haemodynamic monitoring and mechanical ventilation continued for 6 h after return of spontaneous circulation (ROSC), and the pigs were euthanised at 48 h. Researchers were blinded for drug groups throughout the study. RESULTS: There was no difference in rates of ROSC and 48-h survival with amiodarone vs. saline (5/8 vs. 7/8 and 0/8 vs. 3/8, respectively). Diastolic aortic pressure and coronary perfusion pressure were significantly lower with amiodarone during CPR and 1 min after ROSC (P < 0.05). The number of electric shocks required for terminating VF, time to ROSC and adrenaline dose were significantly higher with amiodarone (P < 0.01). The incidence of post-resuscitation tachyarrhythmias tended to be higher in the saline group (P = 0.081). CONCLUSION: Early administration of amiodarone did not improve ROSC or 48-h survival rates, and was associated with worse haemodynamics in this swine model of cardiac arrest.

Investigating the signal transduction pathways underlying remote ischemic conditioning in the porcine heart.

BACKGROUND: The mechanism underlying remote ischemic conditioning (RIC) remains unclear. We investigated whether RIC protects the heart through the activation of the adenosine receptor and the PI3K-Akt pathway at the onset of myocardial reperfusion. METHODS AND RESULTS: Domestic pigs (27-35 kg) were subjected to in situ left anterior descending coronary artery ischemia (60 min) followed by reperfusion (180 min) and randomised to the following: (1) Control- No additional intervention; (2) Remote ischemic preconditioning (RIPC)- Four-5 min cycles of lower limb ischemia/reperfusion were administered prior to myocardial ischemia; (3) RIPC + Wort or 8-SPT: Wortmannin (Wort 20 µg/kg, a PI3K inhibitor) or 8-sulfophenyltheophylline (8-SPT 10 mg/kg, an adenosine receptor inhibitor) were administered intravenously 30 s before myocardial reperfusion to RIPC-treated animals; (4) Remote ischemic perconditioning (RIPerC)--Four-5 min cycles of lower limb ischemia/reperfusion were applied 1 min before myocardial reperfusion; (5) RIPerC + Wort or 8-SPT: Wort or 8-SPT were given 30 s before myocardial reperfusion to RIPerC-treated animals. Both RIPC and RIPerC reduced myocardial infarct size (13.3 ± 2.2% with RIPC, 18.2 ± 2.0% with RIPerC versus 48.8 ± 4.2% in control:P < 0.05:N ≥ 5/group). Wortmannin abolished the infarct-limiting effects of RIPC (33.2 ± 6% with RIPC + Wort versus 13.3 ± 2.2% with RIPC:P < 0.05:N ≥ 5/group) but not RIPerC (18.0 ± 3.4% with RIPerC + Wort versus 18.2 ± 2.0% with RIPerC:P > 0.05:N ≥ 5/group). 8-SPT did not influence the infarct-limiting effects of either RIPC or RIPerC. Western blot analysis confirmed Wortmannin-sensitive PI3K and Akt activation at myocardial reperfusion in RIPC-treated hearts. CONCLUSIONS: In the porcine heart, both RIPC and RIPerC both reduce myocardial infarct size and with RIPC but not RIPerC this cardioprotective effect is associated with the activation of the PI3K-Akt pathway at reperfusion.

Does VEGF have an effect on the survival of a long random skin flap by its application at the recipient area?

BACKGROUND: Vascular endothelial growth factor (VEGF) is a hormone-like molecule which has been shown to act on a specific receptor system and in this way to be the basic regulator of angiogenesis. The effect on the survival of a long random skin flap was examined by exogenous administration of this cytokine, at flap's recipient site. MATERIALS & METHODS: A standard dorsal skin flap measuring 1.5 x 7.5cm was elevated in eighteen wistar rats with the pedicle centered and attached between the lower angles of the scapulae. The length to width ratio was relatively high (5:1). The rats were divided in two groups of nine. In group A, flap was elevated and a skin defect was created next to it. Normal saline was injected into the fascia of the defect and the flap was transposed and secured over the previously created recipient site. In group B, flap was elevated and transposed to a previous created defect, as before, where, this time, injections of VEGF were applied into the fascia of the recipient bed. Seven days later the rats were euthanized and the flaps were excised. The underlying fascias of the recipient beds were also excised in the same dimensions. The specimens were measured, photographed and put into formalin 10%. Immunohistochemical staining and histological analysis followed. RESULTS: The differentiation between the surviving and the necrotic skin was macroscopically clear within seven days time. In group A, the mean flap survival percentage was 36.8%. In group B the percentage was 56.3%, respectively. Neovascularization of the fascia of the recipient bed was also demonstrated when VEGF had been injected. CONCLUSIONS: Exogenous administration of VEGF into the recipient bed of a skin flap improved the survival rate even though the flap's length was relatively high compared to its width.

Safety and efficacy of absorbable and non-absorbable fixation systems for intraperitoneal mesh fixation: an experimental study in swine.

PURPOSE: Choice of the best possible fixation system in terms of safety and effectiveness for intraperitoneal mesh placement in hernia surgery remains controversial. The aim of the present study was to compare the performance of four fixation systems in a swine model of intraperitoneal mesh fixation. METHODS: Fourteen Landrace swine were utilized in the study. The experiment included two stages. Initially, four pieces of mesh (Ventralight ™ ST) sizing 10 × 5 cm were placed and fixed intraperitoneally to reinforce 4 small full thickness abdominal wall defects created with diathermy. These defects were repaired primarily with absorbable suture before mesh implantation. Each mesh was anchored with a different tack device between Absorbatack™, Protack™, Capsure™, or Optifix™. The second stage took place after 60 days and included euthanasia, laparoscopy, and laparotomy via U-shaped incision to obtain the measurements for the outcome parameters. The primary endpoint of the study was to compare the peel strength of the compound tack/mesh from the abdominal wall. Secondary parameters were the extent and quality of visceral adhesions to the mesh, the degree of mesh shrinkage and the histological response around the tacks. RESULTS: Thirteen out of 14 animals survived the experiment and 10 were included in the final analysis. Capsure™ tacks had higher peel strength when compared to Absorbatack™ (p = 0.028); Protack™ (p = 0.043); and Optifix™ (p = 0.009). No significant differences were noted regarding the extent of visceral adhesions (Friedman's test p value 0.854), the adhesion quality (Friedman's test p value 0.506), or the mesh shrinkage (Friedman's test p value = 0.827). Four out of the ten animals developed no adhesions at all 2 months after implantation. CONCLUSION: Capsure™ fixation system provided higher peel strength that the other tested devices in our swine model of intraperitoneal mesh fixation. Our findings generate the hypothesis that this type of fixation may be superior in a clinical setting. Clinical trials with long-term follow-up are required to assess the safety and efficacy of mesh fixation systems in hernia surgery.

Xenotransplantation of hepatocytes in rats with acute liver failure using sirolimus for immunosuppression.

This study aimed to evaluate the effect of sirolimus (SRL; rapamycin) as an immunosuppressant during xeno transplantation (XT) of rabbit hepatocytes into male Wistar rats with acute liver failure (ALF; n = 72). Isolated rabbit hepatocytes were transplanted intrasplenically into rats within 24 h of chemically induced ALF. Treatment groups received monotherapy with either cyclosporine (CsA) 20 mg/kg or SRL 0.20 mg/kg, or combination therapy with CsA 20 mg/kg + SRL 0.20 mg/kg for 14 days post-transplant. One control group with ALF received no treatment and a second group with ALF received only XT. Surviving rats were euthanized after 14 days, with concurrent blood sampling and organ retrieval for morphological evaluation. Survival rates at 14 days were: no XT/no treatment, 0%; XT alone, 29%; XT + CsA, 79%; XT + SRL, 33%; and XT + CsA + SRL, 33%. Liver morphology showed statistically superior liver regeneration for groups on SRL therapy. It is concluded that, in this hepatocyte XT model, SRL offered no survival advantage for ALF management so CsA still maintains a central role in attempts to develop alternative solutions for ALF.

Remote postconditioning is more potent than classic postconditioning in reducing the infarct size in anesthetized rabbits.

PURPOSE: Postconditioning confers protection to the heart after a potentially lethal episode of prolonged ischemia. There is evidence that it may also be protective when applied at a distal artery. In the present study, we sought to determine whether remote postconditioning within the heart (local) or outside the heart (distal) is effective in salvaging the ischemic heart in vivo and to compare its effect with that of the classic postconditioning. METHODS: Twenty seven open chest New Zealand white anesthetized male rabbits were divided into four groups and were exposed to 30 min regional myocardial ischemia (isc), after ligation of a prominent coronary artery, followed by 3 h reperfusion (rep) after releasing the snare. Control group (n = 7) was subjected to no additional interventions, postC group (n = 6) was subjected to four cycles of 1 min isc/1 min rep of the same coronary artery at the beginning of reperfusion, remote local postC group (n = 7) to four cycles of 1 min isc/1 min rep of another coronary artery 30 s before the end of index isc and remote distal postC group (n = 7) to four cycles of 1 min isc/1 min rep of another (carotid) artery again 30 s before the end of index isc. Infarct size (I) and area at risk (R) were delineated with the aid of TTC staining and green fluorescent microspheres respectively and their ratio was expressed in percent (%I/R). RESULTS: Remote local and remote distal postC reduced the % I/R ratio (17.7 +/- 1.7% and 18.4 +/- 1.6%, respectively vs 47.0 +/- 2.5% in the control group, P < 0.01). Classic PostC had an intermediate protective effect (33.1 +/- 1.7%, P < 0.05 vs all the other groups). CONCLUSION: Remote postconditioning consisted of 1 min isc/1 min rep protects the ischemic rabbit heart in vivo, independently of the site of the remote artery. This intervention seems to confer a stronger protection than the classic postconditioning.

Preservation of venous outflow improves transverse rectus abdominis musculocutaneous flap survival following vascular delay.

BACKGROUND: The rat abdominal island model has proved to be a reliable and reproducible model for the study of surgical delay procedures. It has been customary to simultaneously divide both the artery and the accompanying vein to obtain maximum survival of the rat TRAM flap undergoing delay procedure. This study evaluates the effect of selective arterial interruption compared to standard vascular delay on flap survival in the rat TRAM flap model. METHODS: Thirty-six Wistar rats were randomly assigned to three groups (n=12), depending on the vascular ligation selected for the initial experimental delay stage. In group A (control group) no vessels were ligated. In group B the right deep inferior epigastric vessels were preserved and the right superior and left inferior and superior deep vessels were ligated. In group C the right inferior epigastric vessels and the left inferior epigastric vein were preserved while superior epigastric vessels and the left inferior epigastric artery were ligated. For the second stage one week later, TRAM flaps were elevated based on the right deep inferior epigastric vessels, re-inset in their original position and digitally photographed. Skin island viability was determined 96 hours later using digital photography and image-analysis software SigmaScan (SPSS, Inc., Chicago, IL). RESULTS: The percentage of flap survival in control group A was 50+/-6%, in group B 60+/-4% and in group C 85+/-4%. The occlusion of the three vascular pairs in group B improved the survival percentage in comparison to the control group A, but this did not achieve statistical significance. In contrast, the percentage of flap survival in control group C was statistically significant compared to groups A and B (p<0.05, ANOVA). Zone IV exhibited no necrosis in any group C animals. CONCLUSIONS: This indicates that delay with preservation of the venous outflow of zone IV results in increased blood supply.

In vivo models for heart failure research.

The medical treatment of heart failure (HF) is associated with 50% survival at 5 years, thus being one of the major causes of mortality in Western countries. An understanding of the pathophysiology of HF is essential for the development of novel efficient therapies. Consequently, the use of animal models is indispensable. In addition, the development of new in vivo models of HF is critical for the evaluation of treatments such as gene therapy, mechanical devices and new surgical approaches. However, every animal model has advantages and limitations and none of them is suitable to study all aspects of HF. Besides the technical determinants of a model, species, strain and gender affect the pathophysiology of a given heart pathogenesis and, therefore, have to be considered in each animal model. The most common in vivo models used in cardiology research and in particular in HF remodeling are presented.

The effect of nifedipine on the patency of microvascular anastomosis in rats.

Despite advances in microsurgical technique and experience in clinical microvascular surgery, there remains the possibility of vessel thrombosis. Factors that may contribute to vascular pedicle thrombosis include operative trauma, pedicle malposition, kinking, hypercoagulability and arterial vasoconstriction. The purpose of this study was to evaluate the effect of intravenous administration of nifedipine on the patency of the microvascular anastomosis of the femoral artery in rats. A total of 60 rats were used and divided into three groups. The first group (A) was used as a control group with no medical agent, the second group (B) was medicated with heparin, and the third group (C) was medicated with nifedipine. Patency was assessed with the distal empty refill test, one hour (1) and forty-eight hours (48) after completion of the anastomosis. The nifedipine and heparin treated groups (B & C) did not show higher patency rate compared to the control group (A). There was no statistically significant difference of patency percent after 1 hour and 48 hours among the three groups (p = 0.231/p = 0.480). Intravenous administration of nifedipine does not improve the patency of microvascular anastomosis. Surgical technique remains the most important factor for successful microvascular anastomosis.

Endoscopic transgastric procedures in anesthetized pigs: technical challenges, complications, and survival.

BACKGROUND AND STUDY AIMS: An incisionless endoscopic peroral transgastric approach to the peritoneal cavity has shown promise in animals as a potentially less invasive form of surgery. We present our experience with various endoscopic peroral transgastric procedures, reporting on the technical aspects and challenges that arose. MATERIALS AND METHODS: The following procedures were performed in 10 anesthetized pigs using a double-channel endoscope: peritoneoscopy (10 pigs), liver biopsy (one pig), cholecystectomy (six pigs), fallopian tube excision (one pig), and hysterectomy (one pig). RESULTS: All the procedures were accomplished successfully. There were six minor intraoperative complications. Complete gastric cleansing and elimination of all bacteria was found to be impossible to achieve in the porcine model. Overinflation was a common problem. The lack of adequate endoscope support was a major limitation. Safe closure of the gastrotomy incision was difficult using the available clipping devices. Six pigs made an uncomplicated recovery after a follow-up period of 4-6 weeks. Subsequent pathological examination revealed deep gastric ulceration in one animal and a gastric wall abscess in another. CONCLUSIONS: Peroral transgastric surgery is technically feasible and safe in a porcine model. Although all the procedures were performed successfully, the study highlights some technical difficulties and illustrates the need for major technical innovations and extensive animal studies in order to evaluate the merits of incisionless surgery.

The beneficial effect of genetically engineered Schwann cells with enhanced motility in peripheral nerve regeneration: review.

BACKGROUND: The importance of Schwann cells in promoting nerve regeneration across a conduit has been extensively reported in the literature, and Schwann cell motility has been acknowledged as a prerequisite for myelination of the peripheral nervous system during regeneration after injury. METHODS: Review of recent literature and retrospective analysis of our studies with genetically modified Schwann Cells with increased motility in order to identify the underlying mechanism of action and outline the future trends in peripheral nerve repair. FINDINGS: Schwann cell transduction with the pREV-retrovirus, for expression of Sialyl-Transferase-X, resulting in conferring Polysialyl-residues (PSA) on NCAM, increases their motility in-vitro and ensures nerve regeneration through silicone tubes after end-to-side neurorraphy in the rat sciatic nerve model, thus significantly promoting fiber maturation and functional outcome. An artificial nerve graft consisting of a type I collagen tube lined with the genetically modified Schwann cells with increased motility, used to bridge a defect in end-to-end fashion in the rat sciatic nerve model, was shown to promote nerve regeneration to a level equal to that of a nerve autograft. CONCLUSIONS: The use of genetically engineered Schwann cells with enhanced motility for grafting endoneural tubes promotes axonal regeneration, by virtue of the interaction of the transplanted cells with regenerating axonal growth cones as well as via the recruitment of endogenous Schwann cells. It is envisaged that mixed populations of Schwann cells, expressing PSA and one or more trophic factors, might further enhance the regenerating and remyelinating potential of the lesioned nerves.

A new technique of autogenous conduits for bridging short nerve defects. An experimental study in the rabbit.

BACKGROUND: [corrected] Nerve grafting is the most reliable used procedure to bridge a neural defect, but it is associated with donor site morbidity. In experimental surgery the search for an optimal nerve conduit led to the use of biological and artificial material. Nerve regeneration through epineural conduits for bridging short nerve defect was examined. METHODS: Four groups including 126 New Zealand rabbits were used. There were 3 study groups (A, B and C) and 1 control group (D). A 10-mm long sciatic nerve defect was bridged either with 3 variations of an epineural flap (Groups A, B and C) or with a nerve graft (Group D). Animals from all groups were examined 21, 42 and 91 days postoperatively to evaluate nerve regeneration employing light microscopy and immunocytochemistry. Nerve regeneration was studied in transverse sections at 3, 6 and 9 mm from the proximal stump. Using muscle stimulator the gastrocnemius contractility was examined at 91 days post surgery in all groups. FINDINGS: Immunohistochemical and functional evaluation showed nerve regeneration resembling the control group, especially in group A, were an advancement epineural flap was used. CONCLUSION: An epineurial flap can be used to bridge a nerve defect with success.

The prophylactic effect of L-arginine in acute ischaemic colitis in a rat model of ischaemia/reperfusion injury.

BACKGROUND/AIMS: The decreased synthesis of nitric oxide (NO) during ischaemia/reperfusion (I/R) has been implicated as the major underlying mechanism for the pathogenesis of acute ischaemic colitis (A.I.C.). The aim of this study was to investigate the prophylactic effect of L-arginine, a NO donor, on tissue injury during intestinal I/R, and compare its efficacy with that of exogenous vasodilators (molsidomine) and inert nitrogen-containing molecules (casein). MATERIAL AND METHODS: One hundred forty four Wistar rats underwent occlusion of the superior mesentery artery for 30, 60 and 90 min for induction of intestinal ischaemia, followed by 90 min of reperfusion. The rats were randomly assigned to receive L-arginine, molsidomine, or casein hydrolysate. In all groups, apart of the histological study, we determined the levels of serum malondialdehyde (MDA), a reliable marker indicating the degree of the tissue damage after intestinal I/R. RESULTS: Serum MDA levels were significantly lower in the L-arginine group compared to the untreated animals or those that had received molsidomine or casein, after a period of ischaemia of 90 minutes (p < 0.0005), as well as after a period of ischaemia of 60 or 90 minutes followed by a 90 minutes reperfusion (p = 0.011, and p < 0.0005, respectively). In addition, lesser histopathological damage was noted after the use of L-arginine compared to that caused by the administration of molsidomine and casein. CONCLUSION: These findings support a prophylactic effect of L-arginine in experimentally induced intestinal ischaemia. In short, L-arginine attenuates the degree of tissue damage in intestinal ischaemia and promotes healing of intestinal mucosa.

Simultaneous deregulation of p16 and cyclin D1 genes in pancreatic ductal adenocarcinoma: a combined immunohistochemistry and image analysis study based on tissue microarrays.

PURPOSE: Deregulation of cell cycle control molecules, such as cyclins and their inhibitors, is a crucial event in the carcinogenetic process. Our aim was to identify potential correlations between p16 and cyclin D1 expression in pancreatic ductal adenocarcinoma (PDAC) that affect the biological behavior of this neoplasm. MATERIALS AND METHODS: Using tissue microarray (TMA) technology, 50 paraffin-embedded tissue samples of histologically confirmed primary PDACs were cored twice and re-embedded to the final recipient block. Immunohistochemistry (IHC) was performed using monoclonal anti-p16 and anti-cyclin D1 antibodies. Protein expression levels were determined by performing computerized image analysis (CIA; estimation of Nuclear Labeling Index-NLI). SPSS (chi square test and interrater Cohen's kappa) was used for statistical analysis. RESULTS: Cyclin D1 overexpression was observed in 24/50 (48%) of the examined carcinomas, whereas p16 loss or reduced expression was detected in 40/50 (80%) cases. Statistical significance was noted when correlating grade to cyclin D1 (p=0.038), stage to p16 (p=0.012) and also to cyclin D1 (p=0.011). Interestingly, combined protein alterations (p16 loss and cyclin D1 overexpression) were observed in 23/50 (46%) cases associated with advanced stage (p=0.019). Overall combined expression of the two molecules demonstrated a significantly low value (kappa=0.012; 95% confidence interval-CI: 0.010-0.014). CONCLUSION: A significant proportion of PDACs is characterized by simultaneous protein alterations regarding p16 and cyclin D1 genes. This mechanism of genetic deregulation in cell cycle potentially explains in part the aggressive phenotype of this neoplasm.

The effect of antioxidant supplementation on bacterial translocation after intestinal ischemia and reperfusion.

The intestine is highly sensitive to ischemia/reperfusion (I/R) injury. Intestinal I/R may cause local tissue injury and disruption of the intestinal mucosal barrier, allowing the passage of viable bacteria and endotoxins from the gastrointestinal lumen to distant organs. This phenomenon, known as bacterial translocation (BT), may lead to systemic disorders with high morbidity and mortality. Oxidative stress mediators such as reactive oxygen species, polymorphonuclear neutrophils and nitric oxide are believed to contribute to the intestinal I/R injury. Many antioxidants have shown protective effects against I/R injury of various organs. The present article provides an overview of studies investigating the effect of antioxidant supplementation on BT after intestinal I/R.

An Experimental Model on the Biomechanical Behaviour of the Flexor Tendons in New Zealand Rabbits.

BACKGROUND: In order to introduce new pharmacological agents with the intent to inhibit the adhesion formation, it is important to test such products on laboratory animals under a protocol that can evaluate the quantitative and qualitative aspects of healing of the tendons. Most experimental models focus on the tensile strength and histological analysis of the tendons, failing to sufficiently quantify the degree of the adhesion formation. METHODS: The experiment included six male New Zealand rabbits that underwent surgery of their right forepaws. The deep flexor tendon of the middle finger was transected and repaired and after six weeks the rabbits were killed. In order to assess the extent of adhesions, the functional stiffness of the tendons and the range of motion of the specimens' fingers was studied using a tensile testing machine. The setup used allowed the simultaneous recording of the specimens' motion and the pulling force values. RESULTS: The mean values of the left and right forepaws were expressed in the same chart showing a clear difference between the operated and non operated forepaws. CONCLUSIONS: Using a relatively simple set up in the laboratory we had the chance to focus on a more elaborate analysis of the data with the help of low cost and accessible software.

Early, intracoronary growth hormone administration attenuates ventricular remodeling in a porcine model of myocardial infarction.

OBJECTIVE: Ventricular remodeling is a common corollary of myocardial infarction. We hypothesized that this process may be attenuated by growth hormone, administered as a single high-dose, selectively in the infarct zone, early postmyocardial infarction. DESIGN: In 35 pigs (29+/-4 kg), myocardial infarction was generated by inflation of an over-the-wire angioplasty balloon in the circumflex artery for 60 min and 5 further pigs were sham-operated. Ten minutes after reperfusion, the pigs were randomized (2:1) to either growth hormone (1 IU/kg) (n=23) or normal saline (n=12), delivered via the balloon catheter. All survivors were treated with captopril and were sacrificed 4 weeks after myocardial infarction. RESULTS: Compared to controls, growth hormone-treated animals displayed lower heart weight (4.1+/-0.5 g/kg body weight, versus 3.4+/-0.4 g/kg, respectively, p=0.003) and dimensions (left ventricular short axis diameter 46+/-7 mm versus 37+/-6 mm, p=0.01; right ventricular short axis diameter 38+/-7 mm versus 30+/-5 mm p=0.001). Growth hormone increased wall thickness in the infarct (6.0+/-1.8 in controls versus 9.9+/-3.7 in treated animals, p=0.004) and non-infarct zones (10.6+/-1.8 in controls versus 15.5+/-3.8 in treated animals, p=0.0006) and produced higher (p<0.05) microvascular density in both zones. CONCLUSION: Intracoronary administration of growth hormone attenuates left and right ventricular remodeling by inducing hypertrophy and by enhancing angiogenesis.