Delivery of Porphyrins Through Self-Assembling Peptide Hydrogels for Accelerated Healing of Experimental Skin Defects In Vivo.

INTRODUCTION: The care and healing of skin defects resulting from different causes has been the object of research to achieve rapid and complete skin regeneration. Hydrogels have been used for their ability to maintain hydration during wound healing, absorb wound exudate, and cover the underlying tissue without adherence while being transparent. In this study, we evaluated the efficacy of a hydrogel (H) with encapsulated porphyrin (H+P) on a rat model of surgically-induced skin defects. METHODS: Four round 6 mm diameter skin defects were performed under general anesthesia on the dorsal area of 24 three-month-old "Young" and 24 twelve-month-old "Mature" male rats. Each age group was separated into the Control, H, and H+P groups, n=8 each, where no therapy, H, or H+P was respectively applied daily for 20 days. Digital photographs and skin biopsies were taken on the third, seventh, 10th, and 20th postoperative days and evaluated by planimetry, histology, and immunohistochemistry. RESULTS: Planimetry results demonstrated significantly decreased perimeter, diameter, and area measurements (p<0.005) of group H+P compared to Control and H groups on days 10 and 20 in the young rats, while in the mature rats, the significant differences were evident earlier (perimeter third day p<0.05; diameter and area seventh day p<0.05 and p<0.005, respectively vs. H). Granulation and scar tissue formation were also reduced in the H+P groups although they were not statistically significant. CONCLUSIONS: The application of H+P on the skin defects benefited the healing process in both young and mature animal groups, as evidenced by the statistically significant findings of planimetry. The beneficial healing process was more pronounced in the mature animals, both in the level of statistical significance as well as regarding time (evident already on the third day of healing), probably due to porphyrin assisting the reduced healing rate, which is observed in organisms of advanced age.

Intrauterine growth restriction affects bone mineral density of the mandible and the condyle in growing rats.

OBJECTIVES: To investigate in growing rats the effect of intrauterine growth restriction (IUGR) on the bone mineral density of the mandible and tibia, as well as the quality of the mandibular and condylar bone. METHODS: Twelve male rats were born IUGR by mothers sustaining 50% food restriction during pregnancy. Twelve control male rats were born by mothers fed ad libitum. Dual-energy X-ray absorptiometry (DEXA) of the tibia, proximal tibial metaphysis and the mandible, biochemical markers, histology and histomorphometrical analysis on the mandibular and subchondral bone of the condyle were performed. RESULTS: IUGR significantly affected bone mineral density (BMD) of both tibial and mandibular bones. IUGR rats had significantly lower osteocalcin values (p=0.021) and phosphorus (p=0.028), but not 25-OH vitamin D (p=0.352). Bone area percentage in the mandible was significantly lower (51.21±5.54) in IUGR compared to controls (66.00±15.49), and for subchondral bone of the condyle for IUGR (47.01±6.82) compared to controls (68.27±13.37). IUGR had a significant reduction in the fibrous layer, but not the proliferating layer, with the hypertrophic layer significantly increased. CONCLUSION: Maternal restricted nutrition during gestation can affect BMD of the mandible and the tibia of the offspring animals.

Chios Mastic Gum Consumption Has a Protective Effect on Ovariectomy-Induced Bone Loss in Rats.

The purpose of this study was to examine the potential effect of Chios Mastic Gum (CMG) consumption on bone mineral density (BMD) and strength of ovariectomized rats. CMG is a known resin used from ancient times for its beneficial biological properties. Thirty mature female Wistar rats were randomized into three equal groups: sham-operated (control), ovariectomized (OVX), and ovariectomized and administered CMG per os (OVX+CMG). BMD of the total tibia, proximal tibia, and the 6th lumbar vertebra were measured at baseline and at 3 and 6 months post ovariectomy. Bone strength was assessed with three-point-bending (3pb) of the right femur. At 3 and 6 months, BMD values of the OVX+CMG group were significantly higher for the anatomical cites evaluated than those of the OVX group. Femoral thickness assessed via 3pb had intermediate values in the treated group compared to the other groups. Cytology of vaginal smears and uterine weight of the OVX+CMG group were consistent with estrogen depletion. Gastrocnemius muscle and intraperitoneal fat ratios to body weight (BW) of the OVX+CMG group did not significantly differ from the control group. Daily consumption CMG had a protective effect on BMD of the total and proximal tibia and the 6th lumbar vertebra of the rats, without causing undesirable effects on the vaginal epithelium and uterus. The 3pb results also demonstrated a favorable effect on the thickness of rat femurs. In addition, CMG was beneficial for both the muscular system and the intraperitoneal fat/BW ratio of the rats.

The effect of table olive wastewater extract administration on the adult ovariectomised rat model of osteoporosis.

Recent efforts for alternative non-pharmaceutical treatments for postmenopausal osteoporosis are focused on nutritional measures. The aim of this study was to investigate the effect of table olive wastewater extract (OE) administration on bone mineral density (BMD) and biomechanical strength in ovariectomised rats. Thirty mature 9-month-old female Wistar rats were separated into three groups of ten: Control, Ovariectomised (OVX) and OVX + OE. BMD was measured before ovariectomy, 3 and 6 months afterwards. At the end of the study, blood, both femurs and tibias, internal organs and abdominal fat were collected. After 3 months, the percentage changes from baseline of the total and proximal tibial BMD of the OVX + OE group were both higher compared with the OVX group (P < 0·005). Similar results were found after 6 months, when the percentage changes from baseline of the total and proximal tibial BMD of the OVX + OE group were both higher compared with the OVX group (P < 0·005). Biomechanical testing of the femurs did not reveal any statistically significant difference between the groups. Body weights throughout the study, organs' and abdominal fat ratios to final body weight and blood results (alanine aminotransferase (ALT), gamma-glutamyltransferase (γ-GT), total cholesterol, HDL-cholesterol, LDL-cholesterol, Ca and P) were within normal limits and did not show any significant difference between the treated and untreated groups. As a conclusion, the administration of OE for 6 months protected tibial BMD loss in comparison with the untreated OVX group without causing adverse effects.

Platelet-rich Plasma and Mesenchymal Stem Cells Local Infiltration Promote Functional Recovery and Histological Repair of Experimentally Transected Sciatic Nerves in Rats.

Introduction Platelet-rich plasma (PRP) products and mesenchymal stem cells (MSCs) seem to have a significant potential as neurogenic therapeutic modulator systems. This study aimed to investigate such biological blood derivatives that could enhance nerve regeneration when applied locally in the primary repair of peripheral nerve transection of an experimental rat model. Methods A total of 42 two-month-old male Wistar rats were divided into three "treatment" groups (control, PRP, and MSCs). All the subjects were operated under anesthesia, and the surgical site was infiltrated with either normal saline, PRP derived from the animal's peripheral blood, or MSCs derived from the animal's femoral bone marrow. All three groups were also sub-divided into two sub-groups based on the post-operative administration of Non-steroidal anti-inflammatory drugs (NSAIDs) or not in order to evaluate the effect of NSAIDs on the final outcome. Three months post-surgery, electromyography evaluation of both hind limbs (right operated and left non-operated) was performed. The animals were euthanized, and nerve repair specimens were prepared for histology. Results PRP group had a significant effect (p<0.05) on the sciatic nerve repair when compared with the control group, whereas the MSC group had a positive effect but was not statistically significant (p=0.2). The number of counted neural axons at the area distal to the nerve repair site were significantly repetitive (p<0.05) in both the PRP and MSC groups when compared with the control group. Conclusions Both PRP and MSCs appear to play an essential role in the enhancement of nerve repair in terms of functionality and histology. MSCs group demonstrated a positive effect, whereas the PRP group showed statistically significant better results.

Protective effect of Glycyrrhiza glabra roots extract on bone mineral density of ovariectomized rats.

OBJECTIVE: The aim of this study was to evaluate the potential effect of the methanolic extract of plant Glycyrrhiza glabra roots on bone mineral density and femoral bone strength of ovariectomized rats. METHODS: Thirty 10-month-old Wistar rats were randomly separated into three groups of ten, Control, Ovariectomy and Ovariectomy-plus-Glycyrrhiza in their drinking water. Total and proximal tibial bone mineral density was measured in all groups before ovariectomy (baseline) and after 3 and 6 months post ovariectomy. Three-point-bending of the femurs and uterine weight and histology were examined at the end of the study. RESULTS: No significant difference was noted in bone density percentage change of total tibia from baseline to 3 months between Control and Ovariectomy-plus-Glycyrrhiza groups (+5.31% ± 4.75 and +3.30% ± 6.31 respectively, P = non significant), and of proximal tibia accordingly (+5.58% ± 6.92 and +2.61% ± 13.62, P = non significant) demonstrating a strong osteoprotective effect. There was notable difference in percentage change of total tibia from baseline to 6 months between groups Ovariectomy and Ovariectomy-plus-Glycyrrhiza (-13.03% ± 5.11 and -0.84% ± 7.63 respectively, P < 0.005), and of proximal tibia accordingly (-27.9% ± 3.69 and -0.81% ± 14.85 respectively, P < 0.001), confirming the protective effect of Glycyrrhiza glabra extract in preserving bone density of the Ovariectomy-plus-Glycyrrhiza group. Three-point-bending did not reveal any statistically significant difference between Ovariectomy and Ovariectomy-plus-Glycyrrhiza groups. Uterine weights of the Ovariectomy-plus-Glycyrrhiza group ranged between the other two groups with no statistically significant difference to each. CONCLUSIONS: Glycyrrhiza glabra root extract notably protected tibial bone mineral density loss in Ovariectomy-plus-Glycyrrhiza rats in comparison with ovariectomized rats, but did not improve biomechanical strength.

Induction of anaesthesia with remifentanil after bolus midazolam administration in Landrace/Large White swine.

OBJECTIVE: To investigate an alternative combination for anaesthesia induction in swine. STUDY DESIGN: Randomized, 'blinded' experimental study. ANIMALS: Forty-five Landrace/Large White swine weighing 20.0±1.5 kg. METHODS: Pulse oximetry, heart rate (HR) and blood pressure were measured after premedication with ketamine, midazolam and atropine as well as after intubation following induction with a fixed dose of 0.2 mg kg-1 midazolam combined with 1, 2, 3, 4 or 5 µg kg-1 remifentanil (groups R1, R2, R3, R4 and R5, respectively). Intubation was evaluated using a numerical scoring system assessing jaw relaxation, resistance to the laryngoscope, vocal cord position, vocal cord movement and response to intubation. The time required to intubate and necessity for an additional midazolam dose were recorded. Baseline and post-intubation variables were compared with paired t tests, whereas for differences between the remifentanil groups the Spearman's rank correlation coefficient was estimated. Multivariate regression analysis was performed to disentangle the effect of remifentanil dose and the additional midazolam. RESULTS: Higher dose of remifentanil was associated with better vocal cord position (p<0.001), better response to intubation (p<0.001), shorter time required for intubation (p=0.030) and less frequent necessity for additional administration of midazolam (p=0.004). In total, 39.5% of the animals required additional midazolam. In groups R1, R4 and R5, there were decreases in HRs (p=0.009, p=0.008 and p=0.032, respectively) between baseline and post-intubation phase; in groups R3 and R4, there were decreases in systolic blood pressure (p=0.040 and p=0.019, respectively). In the multivariate analysis, remifentanil dose was not associated with the observed changes in haemodynamic variables. One animal developed apnoea and four electrocardiographic anomalies; all resolved without pharmaceutical interventions. CONCLUSIONS AND CLINICAL RELEVANCE: A combination of 0.2 mg kg-1 midazolam with 4 or 5 µg kg-1 remifentanil may provide an alternative method of anaesthesia induction for swine.

Versatile quarto stimuli nanostructure based on Trojan Horse approach for cancer therapy: Synthesis, characterization, in vitro and in vivo studies.

Nanostructured delivery and diagnostic systems that induces specific targeting properties by exploiting the local physicochemical tumour characteristics will be evaluated is the present work. It is well known that cancer cells have specific physicochemical characteristics, which can be taken into consideration for the design of a broad spectrum of drug delivery systems (DDS). Some of those characteristics including the different temperature environment their susceptibility when temperature ranges between 40 and 43°C where cell apoptosis is induced, the intra- and extra-cellular pH which varies from 6.0 to 6.8, for cancer cells, and 6.5 to 7.4 for normal cells respectively, (lysosomes acidic pH ranges 4-5). Additional significant factors are the overexpressed receptors on the tumour surface. Loading and release studies were carried out by using the anthracycline drug Doxorubicin and their cytotoxicity was evaluated by using the MTT assay in healthy and diseased cell lines. The highlight of this work is the in vitro and in vivo studies which were performed in order to evaluate different nanostructures as for their biodistribution, pharmacokinetic and toxicity per se.

Effect of ovariectomy and Sideritis euboea extract administration on large artery mechanics, morphology, and structure in middle-aged rats.

BACKGROUND: Arterial function is regulated by estrogen, but no consistent pattern of arterial mechanical remodeling in response to depleted estrogen levels is available. OBJECTIVE: To examine long-term effects of ovariectomy (OVX) on the mechanical properties, morphology, and histological structure of the carotid artery in middle-aged rats and a potentially protective effect of Sideritis euboea extract (SID), commonly consumed as "mountain tea". METHODS: 10-month-old female Wistar rats were allocated into control (sham-operated), OVX, OVX+SID, and OVX+MALT (maltodextrin; excipient used for dilution of SID) groups. They were sacrificed after 6 months and their carotid arteries were submitted to inflation/extension tests and to dimensional and histological evaluation. RESULTS: Remodeling in OVX rats was characterized by a decreased in situ axial extension ratio, along with increased opening angle, thickness, and area of the vessel wall and of its medial layer, but unchanged lumen diameter. Compositional changes involved increased elastin/collagen densities. Characterization by the "four-fiber" microstructure-motivated model revealed similar in situ biaxial response of carotid arteries in OVX and control rats. CONCLUSIONS: Carotid artery remodeling in OVX rats was largely consistent with hypertensive remodeling, despite the minor arterial pressure changes found, and was not altered by administration of SID, despite previous evidence of its osteo-protective effect.

Correlation of Impedance Threshold Device use during cardiopulmonary resuscitation with post-cardiac arrest Acute Kidney Injury.

PURPOSE: To assess whether use of Impedance Threshold Device (ITD) during cardiopulmonary resuscitation (CPR) reduces the degree of post-cardiac arrest Acute Kidney Injury (AKI), as a result of improved hemodynamics, in a porcine model of ventricular fibrillation (VF) cardiac arrest. METHODS: After 8 min of untreated cardiac arrest, the animals were resuscitated either with active compression-decompression (ACD) CPR plus a sham ITD (control group, n=8) or with ACD-CPR plus an active ITD (ITD group, n=8). Adrenaline was administered every 4 min and electrical defibrillation was attempted every 2 min until return of spontaneous circulation (ROSC) or asystole. After ROSC the animals were monitored for 6 h under general anesthesia and then returned to their cages for a 48 h observation, before euthanasia. Two novel biomarkers, Neutrophil Gelatinase-Associated Lipocalin (NGAL) in plasma and Interleukin-18 (IL-18) in urine, were measured at 2 h, 4 h, 6 h, 24 h and 48 h post-ROSC, in order to assess the degree of AKI. RESULTS: ROSC was observed in 7 (87.5%) animals treated with the sham valve and 8 (100%) animals treated with the active valve (P=NS). However, more than twice as many animals survived at 48 h in the ITD group (n=8, 100%) compared to the control group (n=3, 37.5%). Urine IL-18 and plasma NGAL levels were augmented post-ROSC in both groups, but they were significantly higher in the control group compared with the ITD group, at all measured time points. CONCLUSION: Use of ITD during ACD-CPR improved hemodynamic parameters, increased 48 h survival and decreased the degree of post-cardiac arrest AKI in the resuscitated animals.

Effect of Erythropoietin on Postresuscitation Renal Function in a Swine Model of Ventricular Fibrillation.

Purpose. To investigate the effect of EPO administration on postresuscitation renal function. Methods. Twenty-four female Landrace/Large-White piglets aged 10-15 weeks with average weight of 19 ± 2 kg were randomly assigned to 2 different groups of 12 subjects each. After the end of an 8-minute ventricular fibrillation, the control group (Group C) received saline as placebo, whereas the EPO group (Group E) received EPO 5000 U/kg. The animals were resuscitated according to the 2010 European Resuscitation Council Guidelines for Resuscitation. Results. Five animals (41.67%) from Group C and 11 animals (91.67%) from Group E achieved ROSC (p = 0.027). Eight animals (66.67%, 5 surviving and 3 nonsurviving) from Group C suffered severe kidney damage or AKI compared to animals from Group E, in which none of the swine had evidence of severe kidney damage or AKI (p = 0.001). There was a statistically significant difference in all tested biochemical markers between the two groups, as well as a positive correlation of creatinine with NGAL, L-FABP, and IL-18 (summed mean values' p = 0.049, 0.01, and 0.004, resp.). Conclusions. Administration of EPO protected swine from postresuscitation acute kidney injury.

Effects of Erythropoietin Administration on Adrenal Glands of Landrace/Large White Pigs after Ventricular Fibrillation.

Aim. To evaluate the effects of erythropoietin administration on the adrenal glands in a swine model of ventricular fibrillation and resuscitation. Methods. Ventricular fibrillation was induced via pacing wire forwarded into the right ventricle in 20 female Landrace/Large White pigs, allocated into 2 groups: experimental group treated with bolus dose of erythropoietin (EPO) and control group which received normal saline. Cardiopulmonary resuscitation (CPR) was performed immediately after drug administration as per the 2010 European Resuscitation Council (ERC) guidelines for Advanced Life Support (ALS) until return of spontaneous circulation (ROSC) or death. Animals who achieved ROSC were monitored, mechanically ventilated, extubated, observed, and euthanized. At necroscopy, adrenal glands samples were formalin-fixed, paraffin-embedded, and routinely processed. Sections were stained with hematoxylin-eosin. Results. Oedema and apoptosis were the most frequent histological changes and were detected in all animals in the adrenal cortex and in the medulla. Mild and focal endothelial lesions were also detected. A marked interindividual variability in the degree of the intensity of apoptosis and oedema at cortical and medullary level was observed within groups. Comparing the two groups, higher levels of pathological changes were detected in the control group. No significant difference between the two groups was observed regarding the endothelial changes. Conclusions. In animals exposed to ventricular fibrillation, EPO treatment has protective effects on the adrenal gland.

Effects of mechanical loading on the expression of pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta in a rat spinal deformity model.

Mechanical loading of the spine is a major causative factor of degenerative changes and causes molecular and structural changes in the intervertebral disc (IVD) and the vertebrae end plate (EP). Pleiotrophin (PTN) is a growth factor with a putative role in bone remodeling through its receptor protein tyrosine phosphatase beta/zeta (RPTPß/ζ). The present study investigates the effects of strain on PTN and RPTPß/ζ protein expression in vivo. Tails of eight weeks old Sprague-Dawley rats were subjected to mechanical loading using a mini Ilizarov external apparatus. Rat tails untreated (control) or after 0 degrees of compression and 10°, 30° and 50° of angulation (groups 0, I, II and III respectively) were studied. PTN and RPTPß/ζ expression were evaluated using immunohistochemistry and Western blot analysis. In the control group, PTN was mostly expressed by the EP hypertrophic chondrocytes. In groups 0 to II, PTN expression was increased in the chondrocytes of hypertrophic and proliferating zones, as well as in osteocytes and osteoblast-like cells of the ossification zone. In group III, only limited PTN expression was observed in osteocytes. RPTPß/ζ expression was increased mainly in group 0, but also in group I, in all types of cells. Low intensity RPTPß/ζ immunostaining was observed in groups II and III. Collectively, PTN and RPTPß/ζ are expressed in spinal deformities caused by mechanical loading, and their expression depends on the type and severity of the applied strain.

Nifekalant Versus Amiodarone in the Treatment of Cardiac Arrest: an Experimental Study in a Swine Model of Prolonged Ventricular Fibrillation.

PURPOSE: The purpose of the experiment was to compare the effects of nifekalant and amiodarone on the return of spontaneous circulation (ROSC), survival, as well as on the hemodynamic parameters in a swine model of prolonged ventricular fibrillation (VF). METHODS: After 8 min of untreated VF, bolus doses of epinephrine (adrenaline) and either nifekalant, or amiodarone, or saline (n = 10 per group), were administered after randomization. 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. RESULTS: Forty-eight hour survival was significantly higher with nifekalant compared to amiodarone (p < 0.001) and saline (p = 0.02), (9/10 vs. 0/10 vs. 3/10, respectively). Systolic aortic pressure, diastolic aortic pressure and coronary perfusion pressure were significantly higher with nifekalant during CPR and immediate post-resuscitation period (p < 0.05). The animals in the amiodarone group had a slower heart rate at the 1st and 45th min post-ROSC (p < 0.001 and p = 0.006, respectively). The number of electric shocks required for terminating VF, time to ROSC and adrenaline dose were significantly higher with amiodarone compared to nifekalant (p < 0.001). CONCLUSIONS: Nifekalant showed a more favorable hemodynamic profile and improved survival compared to amiodarone and saline in this swine model.

Levosimendan Improves Neurological Outcome in a Swine Model of Asphyxial Cardiac Arrest.

BACKGROUND: In asphyxial cardiac arrest, the severe hypoxic stress complicates the resuscitation efforts and results in poor neurological outcomes. Our aim was to assess the effects of levosimendan on a swine model of asphyxial cardiac arrest. METHODS: Asphyxial cardiac arrest was induced in 20 Landrace/Large White piglets, which were subsequently left untreated for four minutes. The animals were randomised to receive adrenaline alone (n=10, Group A) and adrenaline plus levosimendan (n=10, Group B). All animals were resuscitated according to the 2010 European Resuscitation Council guidelines. Haemodynamic variables were measured before arrest, during arrest and resuscitation, and during the first 30 minutes after return of spontaneous circulation (ROSC), while survival and neurologic alertness score were measured 24 hours later. RESULTS: Return of spontaneous circulation was achieved in six animals (60%) from Group A and nine animals (90%) from Group B (p=0.303). During the first minute of cardiopulmonary resuscitation, coronary perfusion pressure was significantly higher in Group B (p=0.046), but there was no significant difference at subsequent time points until ROSC. Although six animals (60%) from each group survived after 24 hours (p=1.000), neurologic examination was significantly better in the animals of Group B (p<0.01). CONCLUSIONS: The addition of levosimendan to adrenaline improved coronary perfusion pressure immediately after the onset of cardiopulmonary resuscitation and resulted in better 24-hour neurological outcome.

Effects of dietary Corinthian currants (Vitis vinifera L., var. Apyrena) on atherosclerosis and plasma phenolic compounds during prolonged hypercholesterolemia in New Zealand White rabbits.

Corinthian currants are a rich source of phenolic compounds, which are known to exert beneficial effects on cardiovascular disease. The hypothesis tested is whether dietary supplementation with currants attenuates atherosclerosis and affects plasma phenolics during prolonged hypercholesterolemia in rabbits. Thirty New Zealand White rabbits were fed one of four diets (normal and supplemented with 10% currants, with 0.5% cholesterol, and with 0.5% cholesterol plus 10% currants) for eight weeks. Plasma lipids, glucose and hepatic enzymes were determined. Individual phenolic compounds were identified and quantified in plasma during the dietary intervention. At the end of the study, histological examinations of aorta and liver were performed. The high-cholesterol diet resulted in hypercholesterolemia and oxidative stress, increased aspartate aminotransferase (AST) activity and induced aortic and hepatic lesion formation. Corinthian currant supplementation attenuated atherosclerotic lesions, maintained AST within the normal range and reduced oxidative stress without affecting glucose concentrations. The p-OH-benzoic and p-OH-phenylacetic acids predominated at high concentrations in plasma and remained almost constant during the study in the group that received the normal rabbit chow and the groups given food with added cholesterol either alone or supplemented with currants. Currant supplementation to the normal diet resulted in the reduced absorption of phenolic compounds, as revealed by the measurement of their plasma metabolites, suggesting a regulatory mechanism at the gut level under normal conditions.

Oncogenic Role of the Ec Peptide of the IGF-1Ec Isoform in Prostate Cancer.

IGF-1 is one of the key molecules in cancer biology; however, little is known about the role of the preferential expression of the premature IGF-1 isoforms in prostate cancer. We have examined the role of the cleaved COO- terminal peptide (PEc) of the third IGF-1 isoform, IGF-1Ec, in prostate cancer. Our evidence suggests that endogenously produced PEc induces cellular proliferation in the human prostate cancer cells (PC-3) in vitro and in vivo, by activating the ERK1/2 pathway in an autocrine/paracrine manner. PEc overexpressing cells and tumors presented evidence of epithelial to mesenchymal transition, whereas the orthotopic injection of PEc-overexpressing, normal prostate epithelium cells (HPrEC) in SCID mice was associated with increased metastatic rate. In humans, the IGF-1Ec expression was detected in prostate cancer biopsies, where its expression correlates with tumor stage. Our data describes the action of PEc in prostate cancer biology and defines its potential role in tumor growth, progression and metastasis.

Enhancement of bone regeneration with the combination of platelet-rich fibrin and synthetic graft.

INTRODUCTION: Platelet-rich fibrin (PRF) is a relatively new developed platelet concentrate with several benefits over platelet-rich plasma. The aim of this study was to compare healing properties of PRF and its combination with a ceramic synthetic material (graft) composed of hydroxyapatite and b-tricalcium phosphate in an animal model. METHODS: A bone deficit was surgically created in each femoral condyle of 15 New Zealand white rabbits. In each animal, 1 limb had (a) PRF only and the other (b) PRF plus synthetic graft material randomly implanted. Experimental animals were killed 3 months postoperatively. Histological and radiological examinations were made by means of computed tomography and peripheral quantitative computed tomography. RESULTS: Mean density of the healed bone was statistically significantly greater when synthetic material was used (P < 0.0005). Moreover, combination of PRF with the synthetic material resulted in more cortical and subcortical bone formation (P = 0.038 and P = 0.037, respectively). CONCLUSIONS: The addition of the ceramic material significantly increased the formation of new bone, providing a better substrate for bone regeneration.

A comparative anatomic and physiologic overview of the porcine heart.

Despite advances during the last 2 decades in every aspect of cardiovascular research (interventional cardiology, cardiopulmonary resuscitation, and so forth), Western societies still are plagued by the consequences of cardiovascular disease. Consequently the discovery of new regimens and therapeutic interventions is of utmost importance. Research using human subjects is associated with substantial methodologic and ethical considerations, and the quest for an appropriate animal model for the human cardiovascular system has led to swine. The porcine heart bears a close resemblance to the human heart in terms of its coronary circulation and hemodynamic similarities and offers ease of implementation of methods and devices from human healthcare facilities. A thorough comprehension of the anatomy and physiology of the porcine cardiovascular system should focus on differences between swine and humans as well as similarities. Understanding these differences and similarities is essential to extrapolating data appropriately and to addressing the social demand for the ethical use of animals in biomedical research.