Evaluation of Vitamin D-enriched Bone Graft in Surgically-induced Critical-sized Bone Defects: An Experimental Study.

BACKGROUND: Restoration of bone defects in the craniac vault may require the use of autografts, allografts, xenografts, or synthetic grafts. There are promising data that vitamin D may play a positive role in graft incorporation. The purpose of the present study is the evaluation of the impact of vitamin D addition to human-derived bone grafts in the healing of critical-sized bone defects in porcine skulls. MATERIALS AND METHODS: Four identical critical-sized defects were created in the calvaria of 8 adult Landrace Large White pigs. The first defect was left blank as control, the second defect was filled with human-derived bone graft, the third defect was filled with human-derived bone graft enriched with a low concentration of vitamin D (2 mg/mL), and the fourth defect was filled with human-derived bone graft enriched with a high concentration of vitamin D (10 mg/mL). The animals were sacrificed after 12 weeks. Harvested tissue specimens were qualitatively evaluated by histology. New bone formation (bone volume/tissue volume) was quantitatively measured by histomorphometry. RESULTS: Signs of bone formation were evident in all bone sockets. Mean values of the bone volume/tissue volume of the 4 defects were 10.91%, 11.05%, 10.40% and 10.87% respectively, at 12 weeks. In 5 animals, high concentration of vitamin D caused a significant improvement in bone formation in relation to controls. In 3 animals, a high concentration of vitamin D was associated with decreased bone formation compared with controls. No statistical difference was observed in the graft healing among the 4 graft sites ( P > 0.05). CONCLUSIONS: The results of this study have shown that the addition of vitamin D to human-derived bone grafts does not have a significant effect on bone formation and graft incorporation in critical-sized bone defects of the porcine calvaria. Further high-quality studies are needed to fully elucidate the role of vitamin D in bone formation and bone graft union.

Mechanisms and Therapeutic Approaches for Peritoneal Adhesions: A Comprehensive Review.

Peritoneal adhesions are responsible for several and sometimes severe clinical phenotypes remaining a major problem for many patients today. Adhesions are formed within the peritoneal cavity as a result of surgery, inflammation, or injury and can cause a range of clinical symptoms, including abdominal pain, small bowel obstruction, infertility, and other complications. The incidence of peritoneal adhesions remains high as it is estimated that more than 50% of patients who undergo abdominal surgery will develop adhesions. Although advancements in surgical techniques and perioperative management have been developed, the risk of adhesion formation cannot be eliminated, and thus, the development of effective prevention strategies and treatments remains a priority in the field of surgery. In this review, we summarize the cellular and molecular mechanisms involved in the peritoneal adhesions, but also the experimental therapy approaches that have been investigated toward a solution to their possible clinical phenotypes.

Effect of Aromatase Inhibitors on Serum Calprotectin Levels in an Animal Experimental Model: Trial.

BACKGROUND/AIM: Utilizing an experimental animal model, we investigated the correlation between aromatase inhibitors (AIs) (anastrozole and letrozole) and Calprotectin levels. AIs have demonstrated superior efficacy when used as adjuvant endocrine therapy or monotherapy for postmenopausal patients with hormone receptor (HR)-positive early-stage breast cancer, although various side effects have been recorded. MATERIALS AND METHODS: Fifty-five adult female Wistar rats were randomized and assigned into four groups. The control group received no intervention. The other three groups were subjected to ovariectomy, and serum Calprotectin levels were measured at baseline, 2, and 4 months. In addition, glucose, total cholesterol, very low-density lipoprotein- (VLDL-) cholesterol, low-density lipoprotein (LDL-) cholesterol, high-density lipoprotein- (HDL-) cholesterol, and triglyceride levels were measured. Histological analysis of liver tissue was carried out following rats' euthanasia. RESULTS: Aromatase inhibitors (anastrozole and letrozole) affect calprotectin levels in ovariectomized rats. Calprotectin, a marker of inflammation, was found to be affected by the use of the inhibitors. CONCLUSION: The potential of hepatotoxicity can be examined by assessing the elevation of inflammation markers such as Calprotectin, which is an indicator that should be strictly taken into consideration when administering aromatase inhibitors as treatment.

Platelet-rich Plasma Gel versus Hyaluronic Acid on Prevention of Peritoneal Abdominal Adhesion Formation in Rats.

Background: Intra-abdominal adhesion formation is still unavoidable and a cause of significant morbidity in abdominal surgery. Platelet-rich plasma gel and hyaluronic acid have been studied for their protective of therapeutic effects on adhesions. The aim of the present study is to compare Platelet-rich plasma and hyaluronic acid in adhesion prevention. Material and method: Twenty-seven Sprague-Dawley rats were randomly allocated into three equal groups(n=9). Surgical trauma was used to induce adhesion formation. After trauma, 1 ml normal saline was instilled in the peritoneal cavity in control group (n=9), 1 ml liquid Hyaluronic acid (25 mg/ml) was instilled in group A (n= 9) and 1 ml of platelet-rich plasma was instilled in group B (n = 9). Four weeks after the laparotomy, a repetitive laparotomy was performed and adhesions were examined microscopically and macroscopically. Results: Platelet-rich plasma gel and hyaluronic acid both reduce the extent and grade of adhesions macroscopically. Interestingly, PRP turns out to be superior in the reduction of tenacity and adhesion area. Moreover, platelet-rich plasma ameliorates abdominal adhesion formation by reducing neutrophils, fibrosis, and inflammation. Conclusion: The results indicate that platelet-rich plasma gel surpasses hyaluronic acid in abdominal adhesion prevention.

Epicardial Adipose Tissue as an Independent Cardiometabolic Risk Factor for Coronary Artery Disease.

During the last decades, visceral adiposity has been at the forefront of scientific research because of its complex role in the pathogenesis of cardiovascular diseases. Epicardial adipose tissue (EAT) is the visceral lipid compartment between the myocardium and the visceral pericardium. Due to their unobstructed anatomic vicinity, epicardial fat and myocardium are nourished by the same microcirculation. It is widely known that EAT serves as an energy lipid source and thermoregulator for the human heart. In addition to this, epicardial fat exerts highly protective effects since it releases a great variety of anti-inflammatory molecules to the adjacent cardiac muscle. Taking into account the unique properties of human EAT, it is undoubtedly a key factor in cardiac physiology since it facilitates complex heart functions. Under pathological circumstances, however, epicardial fat promotes coronary atherosclerosis in a variety of ways. Therefore, the accurate estimation of epicardial fat thickness and volume could be utilized as an early detecting method and future medication target for coronary artery disease (CAD) elimination. Throughout the years, several therapeutic approaches for dysfunctional human EAT have been proposed. A balanced healthy diet, aerobic and anaerobic physical activity, bariatric surgery, and pharmacological treatment with either traditional or novel antidiabetic and antilipidemic drugs are some of the established medical approaches. In the present article, we review the current knowledge regarding the anatomic and physiological characteristics of epicardial fat. In addition to this, we describe the pathogenic mechanisms which refer to the crosstalk between epicardial fat alteration and coronary arterial atherosclerosis development. Lastly, we present both lifestyle and pharmacological methods as possible treatment options for EAT dysfunction.

Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α) as a Regulator of the Angiogenic Profile of Endometriotic Lesions.

Endometriosis is a disease that affects a significant proportion of women and its infiltrative pattern is entirely dependent on the vascular supply of lesions. Several factors seem to trigger the process of angiogenesis in endometriotic lesions. During the last years, peroxisome proliferator-activated receptors (PPARs), a group of nuclear proteins that regulate gene transcription and that seem to regulate energy consumption and expenditure, have been also implicated in the pathophysiology of angiogenesis. Their ability to regulate the course of cancer and improve the survival rates of patients has been extensively studied and seems to be partially dependent on alteration of the vascular supply of malignant lesions. Research in the field of endometriosis is scarce in the international literature and mainly focused on PPAR-gamma. However, indirect evidence suggests that PPAR-alpha (PPAR-α) may also regulate the vascular supply of endometriotic lesions as well. Specifically, PPAR-α agonists seem to downregulate angiogenesis by increasing the expression of several anti-angiogenic molecules, including thrombospondin-1 (TSP-1) and gypenoside 140 (gp140), as well as factors that are involved in the mitogen-activated protein kinase cascade. In the present article, we summarize existing indirect and direct evidence that indicates the existence of an association between the expression of PPAR-α and endometriosis to help future research in this field.

Epicardial Adipocyte-derived TNF-α Modulates Local Inflammation in Patients with Advanced Coronary Artery Disease.

BACKGROUND: Epicardial Adipose Tissue (EAT) surrounds the epicardium and can mediate harmful effects related to Coronary Artery Disease (CAD). OBJECTIVE: We explored the regional differences between adipose stores surrounding diseased and non-diseased segments of coronary arteries in patients with advanced CAD. METHODS: We enrolled 32 patients with known CAD who underwent coronary artery bypass graft (CABG) surgery. Inflammatory mediators were measured in EAT biopsies collected from a region of the Left Anterior Descending Artery (LAD) with severe stenosis (diseased segment) and without stenosis (non-diseased segment). RESULTS: Mean age was 64.3±11.1 years, and mean EAT thickness was 7.4±1.9 mm. Dyslipidemia was the most prevalent comorbidity (81% of the patients). Out of a total of 11 cytokines, resistin (p=0.039), matrix metallopeptidase 9 (MMP-9) (p=0.020), C-C motif chemokine ligand 5 (CCL-5) (p=0.021), and follistatin (p=0.038) were significantly increased in the diseased compared with the non-diseased EAT segments. Indexed tumor necrosis factor-alpha (TNF-α), defined as the diseased to non-diseased cytokine levels ratio, was significantly correlated with increased EAT thickness both in the whole cohort (p=0.043) and in a subpopulation of patients with dyslipidemia (p=0.009). Treatment with lipid-lowering agents significantly decreased indexed TNF-α levels (p=0.015). No significant alterations were observed in the circulating levels of these cytokines with respect to CAD-associated comorbidities. CONCLUSION: Perivascular EAT is a source of cytokine secretion in distinct areas surrounding the coronary arteries in patients with advanced CAD. Adipocyte-derived TNF-α is a prominent mediator of local inflammation.

The Modulating Effect of Ursodeoxycholic Acid on Liver Tissue Cyclooxygenase-2 Expression Following Extended Hepatectomy.

INTRODUCTION: Hepatic regeneration is a complex process involving a multitude of well-timed molecular operations. Ursodeoxycholic acid (UDCA) is postulated to exert a protective effect against oxidative stress and enzymatic degradation of the extracellular matrix, in turn potentiating the regenerative response. The aim of the present animal study is to evaluate the impact of UDCA administration in liver tissue expression of cyclooxygenase-2 (COX-2) in a setting of acute liver failure achieved by 80% hepatectomy. MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were randomly assigned to an experimental (UDCA) and a control group. Animals in the UDCA received oral pretreatment with UDCA for 14 days via feeding tube, while animals in the control group received saline. All animals underwent resection of approximately 80% of the liver parenchyma. Tissue and blood sample collection were performed 48 hours postoperatively. RESULTS: The postoperative mitotic index and Ki-67 levels were found to be elevated in the UDCA group (43±11.4 and 13.7±24.7 versus 31±16.7 and 7.6±5.7), albeit without any statistical significance. Pretreatment with UDCA significantly decreased COX-2 expression levels (p=0.28) as well as serum tumor necrosis factor α (TNFα) levels (37.3±10.9 pg/mL versus 75.4±14.4 pg/mL, p=0.004). COX-2 expression score was observed to be weakly correlated to Ki-67 levels in both groups. Although COX-2 expression score was not correlated with serum TNFα levels in the control group, animals pretreated with UDCA exhibited moderate correlation (r=0.45). CONCLUSION: Preoperative administration of UDCA exerts a suppressive effect on tissue expression of COX-2 following 80% hepatectomy and enforces a positive correlation between COX-2 and serum TNFα levels, suggesting that UDCA preconditions liver tissue to display an enhanced regenerative response to circulating cytokines, most notably TNFα. The weak association of COX-2 with Ki-67 expression levels suggests that COX-2 may be of secondary importance during the early phases of liver regeneration.

Osseous Healing in Surgically Prepared Bone Defects Using Different Grafting Materials: An Experimental Study in Pigs.

Regeneration of large jaw bone defects still remains a clinical challenge. To avoid incomplete bone repair, bone grafts have been advocated to support the healing process. This study comparatively evaluated new bone formation among a synthetic graft substitute, a human bone derivative, and a bovine xenograft. Materials were placed in 3 out of the 4 bone cavities, while 1 deficit was left empty, serving as a control, in mono-cortical defects, surgically prepared in the porcine calvaria bone. Animals were randomized in 2 groups and euthanized at 8 and 12 weeks. Harvested tissue specimens were qualitatively evaluated by histology. New bone formation was quantitatively measured by histomorphometry. Maximum new bone formation was noticed in defects grafted with beta-tricalcium phosphate b-TCP compared to the other bone substitutes, at 8 and 12 weeks post-surgery. Bovine and human allograft induced less new bone formation compared to empty bone cavity. Histologic analysis revealed that b-TCP was absorbed and substituted significantly, while bovine and human allograft was maintained almost intact in close proximity with new bone. Based on our findings, higher new bone formation was detected in defects filled with b-TCP when compared to bovine and human graft substitutes.

gamma-H2AX: A potential biomarker in breast cancer.

Histone H2AX undergoes phosphorylation as an answer to DNA double-strand breaks, which in turn are part of the oncogenic procedure. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. The aim of this study was to evaluate the clinical significance of gamma-H2AX expression in breast cancer. Gamma-H2AX expression in tissues from 110 breast cancer patients was analyzed by immunohistochemistry and correlated with clinicopathological variables. Greater tumor size, higher grade, and the number of affected lymph nodes are significantly associated with greater values of gamma-H2AX. In addition, gamma-H2AX differs significantly among patients' International Federation of Gynecology and Obstetrics stage. Higher values of estrogen receptor and progesterone receptor are significantly associated with lower gamma-H2AX values. In conclusion, a positive association between gamma-H2AX expression and infaust histopathological parameters was observed.

Healing after Resection of Colonic Endometriosis and Growth Factor-enriched Agents: An Experimental Rat Model.

STUDY OBJECTIVE: To examine the potential beneficial effect of platelet-rich plasma (PRP) and fibrin sealant (TISSEEL; Baxter Healthcare Corporation, Deerfield, IL) on bowel wound healing after shaving of an experimentally induced endometriotic lesion. DESIGN: A single-blind, randomized study (Canadian Task Force classification I). SETTING: A certified animal research facility. ANIMALS: Thirty female Sprague-Dawley rats. INTERVENTIONS: Experimental colonic endometriosis was induced by transplanting endometrial tissue to all animals (first surgery). Thirty rats were then randomized to 1 of 3 groups according to treatment; PRP (group 1, n = 10), fibrin sealant (group 2, n = 10), or no agent (group 3, n = 10) was applied after shaving of the endometriotic nodule (second surgery). MEASUREMENTS AND MAIN RESULTS: Colonic endometriosis was successfully induced in all subjects. Four days after the second surgery, the animals were euthanized, and microscopic evaluation was performed. The pathologist was blinded to the treatment method. Histopathologic analysis revealed that compared with the control group, collagen disposition was found in a significantly higher expression in both the PRP and fibrin sealant groups (p = .011 and p = .011, respectively). Distortion of the integrity of the colon layers was statistically more pronounced in the control group compared with the fibrin sealant group (p = .033), whereas greater new blood vessel formation was observed in the fibrin sealant group compared with the control (p = .023). No histologic evidence of residual or recurrent disease was detected. CONCLUSION: Both PRP and fibrin sealant appear to be safe and associated with improved tissue healing during shaving for the excision of colonic endometriosis, attributed to the enhanced collagen disposition, neovascularization, and protection of the integrity of colon layers. Clinical trials are warranted to confirm the feasibility of PRP and fibrin sealant in the clinical setting.

The association of diabetic microvascular and macrovascular disease with cutaneous circulation in patients with type 2 diabetes mellitus.

AIMS: To study the impact of diabetic neuropathy, both peripheral sensorimotor (DPN) and cardiac autonomic neuropathy (CAN), on transcutaneous oxygen tension (TcPO2) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 163 participants were recruited; 100 with T2DM and 63 healthy individuals. Peripheral arterial disease (PAD) was defined as ankle-brachial index (ABI) values ≤0.90. Diagnosis of DPN was based on neuropathy symptom score and neuropathy disability score (NDS), while diagnosis of CAN on the battery of the cardiovascular autonomic function tests. TcPO2 was measured using a TCM30 system. RESULTS: Patients with T2DM had lower TcPO2 levels when compared with healthy individuals. Among the diabetic cohort, those who had either PAD, DPN or CAN had significantly lower TcPO2 values than participants without these complications. Multivariate linear regression analysis, after controlling for diabetes duration, diastolic blood pressure, HbA1c, albumin to creatinine ratio and CAN score, demonstrated that TcPO2 levels were significantly and independently associated with current smoking (p = 0.013), ABI (p = 0.003), and NDS (p = 0.013). CONCLUSION: Presence of DPN is independently associated with impaired cutaneous perfusion. Low TcPO2 in subjects with DPN may contribute to delay in healing of diabetic foot ulcers, irrespectively of PAD.

The Role of Angiogenesis Inhibitors in Hypertension: Following "Ariadne's Thread".

Arterial hypertension (HT) is one of the most frequently recorded comorbidities among patients under antiangiogenic therapy. Inhibitors of vascular endothelial growth factor and vascular endothelial growth factor receptors are most commonly involved in new onset or exacerbation of pre-existing controlled HT. From the pathophysiology point of view, data support that reduced nitric oxide release and sodium and fluid retention, microvascular rarefaction, elevated vasoconstrictor levels, and globular injury might contribute to HT. The purpose of this review was to present recent evidence regarding the incidence of HT induced by antiangiogenic agents, to analyze the pathophysiological mechanisms, and to summarize current recommendations for the management of elevated blood pressure in this field.

Application of adipose-derived stromal cells in fat grafting: Basic science and literature review.

Autologous fat is considered the ideal material for soft-tissue augmentation in plastic and reconstructive surgery. The primary drawback of autologous fat grafting is the high resorption rate. The isolation of mesenchymal stem cells from adipose tissue inevitably led to research focusing on the study of combined transplantation of autologous fat and adipose derived stem cells (ADSCs) and introduced the theory of 'cell-assisted lipotransfer'. Transplantation of ADSCs is a promising strategy, due to the high proliferative capacity of stem cells, their potential to induce paracrine signalling and ability to differentiate into adipocytes and vascular cells. The current study examined the literature for clinical and experimental studies on cell-assisted lipotransfer to assess the efficacy of this novel technique when compared with traditional fat grafting. A total of 30 studies were included in the present review. The current study demonstrates that cell-assisted lipotransfer has improved efficacy compared with conventional fat grafting. Despite relatively positive outcomes, further investigation is required to establish a consensus in cell-assisted lipotransfer.

gamma-H2AX: Can it be established as a classical cancer prognostic factor?

Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to double-strand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers. The prognostic value of gamma-H2AX is indicated in certain cancer types, such as breast or endometrial cancer, but further investigation is needed to establish gamma-H2AX as a prognostic marker. This review outlines the role of gamma-H2AX in cell cycle, and its formation as a result of DNA damage. We investigate the role of gamma-H2AX formation in several cancer types and its correlation with other prognostic factors, and we try to find out whether it fulfills the requirements for its establishment as a classical cancer prognostic factor.

Effects of Dietary Supplementation with Sea Buckthorn (Hippophae rhamnoides L.) Seed Oil on an Experimental Model of Hypertensive Retinopathy in Wistar Rats.

BACKGROUND/AIMS: Sea buckthorn (Hippophae rhamnoides L.) oil is a rich source of phytosterols, flavonoids, unsaturated fatty acids, and carotenoids, known for their antioxidant and neuroprotective activity. In this study, we investigated the neuroprotective and antioxidant effect of sea buckthorn oil on rat retina in hypertensive retinopathy. METHODS: Twenty-eight male 6-month-old Wistar rats were separated into 3 groups: (1) controls, (2) unilateral nephrectomized rats receiving drinking water with 1% NaCl, (3) unilateral nephrectomized rats receiving 0.5 mL sea buckthorn oil and drinking water with 1% NaCl. Systemic pressures were being measured with the tail-cuff method. The antiapoptotic effect of sea buckthorn was determined by measuring glial fibrillary acidic protein (GFAP), cleaved caspase-3, and glutamine synthetase levels with immunohistochemistry and Western blot. RESULTS: Nephrectomy and salt intake caused increases in both systolic and diastolic pressures. Both types of analysis showed that group 2 had statistically significant increases in the expression of GFAP and cleaved caspase-3, while group 3 showed no significant differences compared with the control group. The expression of glutamine synthetase showed no significant differences between the 3 groups. CONCLUSIONS: Our findings suggest that sea buckthorn could notably protect the retina from damage induced by hypertensive retinopathy.

Association of plasma fetuin-a levels with peripheral arterial disease and lower extremity arterial calcification in subjects with type 2 diabetes mellitus.

AIMS: Fetuin-A is a hepatic glycoprotein that is involved in insulin resistance and atherosclerosis. Herein we examined the association of plasma fetuin-A levels with peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: A total of 71 patients with T2DM and 57 non-diabetic individuals were recruited. Diagnosis of PAD was based on the absence of triphasic waveform at pedal arteries, while ankle-brachial index (ABI) was calculated. Radiographs of both feet and ankles were taken for the assessment of lower extremity arterial calcification (LEAC). Plasma fetuin-A levels were measured using ELISA. RESULTS: Patients with T2DM had higher fetuin-A levels than non-diabetic participants. Participants with diabetes and PAD had lower fetuin-A levels than non-PAD diabetic patients. In subjects with T2DM fetuin-A levels were associated with ABI. Multivariate analysis demonstrated that in patients with T2DM the odds of PAD increased with long diabetes duration, smoking, presence of arterial hypertension and dyslipidemia, as well as with lower fetuin-A levels. A trend towards higher fetuin-A levels in subjects with less severe LEAC was found. CONCLUSION: Plasma fetuin-A levels are lower in patients with T2DM and PAD and are associated with PAD, irrespective of traditional cardiovascular risk factors. Moreover, fetuin-A may be involved in arterial calcification.

Ultrasound and Biochemical Diagnostic Tools for the Characterization of Vulnerable Carotid Atherosclerotic Plaque.

Stroke is a leading cause of morbidity and mortality worldwide, and characterization of vulnerable carotid plaque remains the spearhead of scientific research. Plaque destabilization, the key factor that induces the series of events leading to the clinical symptoms of carotid artery disease, is a consequence of complex mechanical, structural and biochemical processes. Novel imaging and molecular markers have been studied as predictors of disease outcome with promising results. The aim of this review is to present the current state of research on the association between ultrasound-derived echogenicity indices and blood parameters indicative of carotid plaque stability and activity. Bibliographic research revealed that there are limited available data. Among the biomarkers studied, those related to oxidative stress, lipoproteins and diabetes/insulin resistance are associated with echolucent plaques, whereas adipokines are associated with echogenic plaques. Biomarkers of inflammation and coagulation have not exhibited any conclusive relationship with plaque echogenicity, and it is not possible to come to any conclusion regarding calcification-, apoptosis- and neo-angiogenesis-related parameters because of the extremely limited bibliographic data.

Apelin and Visfatin Plasma Levels in Healthy Individuals With High Normal Blood Pressure.

BACKGROUND: High normal blood pressure (BP; 130-139/85-89 mm Hg) is related with increased cardiovascular (CV) risk compared to normal BP (120-129/80-84 mm Hg) or/and optimal BP (<120/80 mm Hg). Low apelin plasma levels have been associated with arterial hypertension and atherosclerosis, while high visfatin plasma levels may promote vascular inflammation and atherosclerotic plaque destabilization and have been evaluated as a marker for identifying stages of essential hypertension. We sought to compare the apelin and visfatin plasma levels between subjects with high normal BP and subjects with normal or optimal BP matched for age, gender, smoking, and body mass index (BMI). METHODS: Twenty-five subjects with high normal BP (office BP 136±3/88±2 mm Hg, age 57±4 years, 76% males, 32% smokers, BMI 24.0±1.7 kg/m2) and 35 subjects with normal or optimal BP (office BP 118±2/78±2 mm Hg, age 55±7 years, 63% males, 29% smokers, BMI 23.2±1.4 kg/m2) were studied. The apelin and visfatin plasma levels were determined with the enzyme-linked immunosorbent assay. RESULTS: Compared to normal or optimal BP subjects, apelin levels were significantly lower (205±108 vs. 325±152 pg/ml, P < 0.001) and visfatin levels significantly higher (11.0±2.0 vs. 7.2±0.9 ng/ml, P = 0.002) in high normal BP subjects. No significant differences were found between the 2 groups (P = NS) regarding the basic clinical characteristics, the glycemic/lipid profile, and the renal function parameters. CONCLUSIONS: The emerging, from the present study, data raise the hypothesis that lower apelin and higher visfatin plasma levels in high normal BP subjects compared to normal or optimal BP individuals could partially explain the higher CV risk of the high normal BP group.

Attenuation of Oxidative Stress by Ischemic Preconditioning in an Experimental Model of Intraabdominal Hypertension.

PURPOSE: Increased intra-abdominal pressure, as used in laparoscopic surgery or seen in intraabdominal hypertension (IAH), is associated with tissue ischemia and oxidative stress. Ischemic preconditioning (IP) is a method successfully used in liver and transplant surgery, in order to attenuate the detrimental effects of ischemia and reperfusion. In this experimental study, we tested the ability of IP to modify oxidative stress induced by extremely high intraabdominal pressures. METHODS: Twenty-five female pigs were studied and divided in three groups: a control group, a pneumoperitoneum group (with pressure of 30 mmHg), and an ischemic preconditioning group (initially subjected to preconditioning with pressure of 25 mmHg for 15 min and desufflation for 15 min and then to pneumoperitoneum as in pneumoperitoneum group). Blood samples were obtained at identical time intervals in the three groups. Total oxidative capacity, total antioxidative capacity and total nitric oxide (NO), nitrite and nitrate concentrations were measured and compared between groups. RESULTS: IP increased total antioxidative capacity (p = .045) and protective mediators like nitrite (p = .022). It was also associated with a trend toward lower levels of total oxidative capacity at the end of the abdominal desufflation period but statistical significance was not met. CONCLUSIONS: IP attenuated oxidative stress induced by IAH, mainly by increasing antioxidative capacity and the levels of protective mediators. The fact that IP was effective, even when used at extremely high levels of intraabdominal pressure, reinforces the interest on this method but further studies are needed to clarify its mechanism of action and potential clinical applications.