The effect of glycine on oxidative stress, inflammation and renin-angiotensin system in kidneys and aorta of cyclosporine-administered rats.

Cyclosporine A (CsA) is an immunosuppressive drug, used in organ transplantations. Oxidative stress, inflammation and renin-angiotensin system (RAS) activation play an important role in CsA-toxicity. Glycine (Gly) has antioxidant and anti-inflammatory effects. In this study, Gly was investigated for its protective role against CsA-induced toxicity. CsA (20 mg/kg/day; subcutaneously) was administered to rats along with Gly injection (250 or 1000 mg/kg; intraperitoneally) for 21 days. Renal function markers [serum urea and creatinine and urinary protein and kidney injury molecule levels and creatinine clearance values] together with histopathological examinations were performed. Oxidative stress (reactive oxygen species, thiobarbutiric acid reactive substances, advanced oxidation products of protein, glutathione, ferric reducing anti-oxidant power and 4-hydroxynonenal levels), and inflammation (myeloperoxidase activity) were determined in kidney tissue. The RAS system [angiotensin II (Ang II) levels, and mRNA expressions of angiotensin converting enzyme (ACE), angiotensin II type-I receptor (AT1R)] and NADPH-oxidase 4 (NOX4) were measured in kidney and aorta. CsA caused significant disturbances in renal function markers, increases in oxidative stress and inflammation parameters and renal damage. Serum angiotensin II levels and mRNA expressions of ACE, AT1R and NOX4 elevated in the aorta and kidney of CsA-rats. Gly, especially its high-dose, alleviated renal function markers, oxidative stress, inflammation and renal damage in CsA-rats. Moreover, serum Ang II levels and mRNA expressions of ACE, AT1R and NOX4 decreased significantly in aorta and kidney in CsA-rats due to Gly treatment. Our results indicate that Gly may be useful for the prevention of CsA-induced renal and vascular toxicity.

May Autogenous Grafts Increase the Effectiveness of Hyalonect Membranes in Intraosseous Defects: An Experimental In Vivo Study.

Background and Objectives: Guided bone regeneration (GBR) surgeries are used for dental implant placements with insufficient bone volume. Biomaterials used in GBR are expected to produce sufficient volume and quality of bone swiftly. This study aims to histologically evaluate the effectiveness of the use of Hyalonect membranes alone or with autogenous grafts in intraosseous defects. Materials and Methods: This study is an experimental study on sheep. Surgeries were performed under general anesthesia in accordance with ethical rules. Five 10 mm defects were surgically created in each ilium of six sheep. One defect was left empty in each ilium (group ED). The defects in the experimental group were covered with Hyalonect membrane while unfilled (group HY) or after being filled with autogenous bone grafts (ABG) (group G+HY). In the control group, the defects were either covered with collagen membrane while unfilled (group CM) or after being filled with the ABG group (G+CM). The sheep were histologically and histomorphometrically evaluated after being postoperatively sacrificed in the third and sixth week (three animals in each interval). Results: All animals completed the study without any complications. No difference was found between groups in the third and sixth weeks regarding the inflammation, necrosis, and fibrosis scores. The G+CM (52.83 ± 3.06) group was observed to have a significantly higher new bone formation rate than all the other groups in the third week, followed by the G+HY group (46.33 ± 2.25). Similar values were found for HY and CM groups (35.67 ± 4.55 ve 40.00 ± 3.41, respectively, p = 0.185), while the lowest values were observed to be in group ED (19.67 ± 2.73). The highest new bone formation was observed in group G+CM (82.33 ± 4.08) in the sixth week. There was no difference in new bone formation rates between groups G+CM, G+HY (77.17 ± 3.49, p = 0.206), and CM (76.50 ± 2.43, p = 0.118). The insignificant difference was found ED group and group HY (55.83 ± 4.92, 73.50 ± 3.27, respectively, p = 0.09). The residual graft amount in the G+CM group was found to be statistically significant at 3 weeks (p = 0.0001), compared to the G+HY group, and insignificantly higher at the 6th week (p = 0.4). Conclusions: In this study, close values were observed between G+HY and G+CM groups. Further experimental and clinical studies with different graft materials are required to evaluate the effectiveness of HY in GBR.

The Effect of Concentrated Growth Factor on Calvarial Bone in Diabetic Healing.

The aim of this study was to evaluate the effect of Concentrated Growth Factor (CGF) on bone healing in diabetic rat model. Experimental diabetes was induced in 24 male Sprague-Dawley rats by streptozotocin. Twenty-four animals served as healthy controls. The animals were divided into 4 subgroups; empty bone defect, grafting with xenogenous graft (Geno-os, OsteoBiol, Turin-Italy), CGF administration, and combined application of the CGF with the xenogenous graft in critical-sized defects in the calvaria of the rats. The diabetic group was given 4 units of Neutral Protamin Hagedorn per day. After 6 weeks, all animals were sacrificed and bone healing was histologically and histomorphometrically analyzed, and the evaluation revealed that the new bone formation in diabetic animals was significantly lower than in healthy group (P: 0.001, P: 0.023). In both groups, the highest rate of ossification was observed in the combined use of xenogenous graft and CGF. When the new bone formation was examined in the graft and CGF group, no significant difference was found between control and diabetic group (P = 0.562; P > 0.05). In conclusion, in patients with diabetes mellitus, combination therapy of CGF with graft is expected to contribute positively to the healing of bone defect.

Resveratrol ameliorates the cyclosporine-induced vascular and renal impairments: possible impact of the modulation of renin-angiotensin system.

Cyclosporine, an immunosuppressive drug, exhibits a toxic effect on renal and vascular systems. The present study investigated whether resveratrol treatment alleviates renal and vascular injury induced by cyclosporine. Cyclosporine (25 mg/kg per day, s.c.) was given for 7 days to rats either alone or in combination with resveratrol (10 mg/kg per day, i.p.). Relaxation and contraction responses of aorta were examined. Serum levels of blood urea nitrogen, creatinine, angiotensin II, and angiotensin 1-7 were measured. Histopathological examinations as well as immunostaining for 4-hydroxynonenal and nitrotyrosine were performed in the kidney. RNA expressions of renin-angiotensin system components were also measured in renal and aortic tissues. Cyclosporine decreased the endothelium-dependent relaxation and increased vascular contraction in the aorta. It caused renal tubular degeneration and increased immunostaining for 4-hydroxynonenal, an oxidative stress marker. Cyclosporine also caused upregulations of the vasoconstrictive renin-angiotensin system components in renal (angiotensin-converting enzyme) and aortic (angiotensin II type 1 receptor) tissues. Resveratrol co-treatment prevented the cyclosporine-related deteriorations. Moreover, it induced the expressions of vasodilatory effective angiotensin-converting enzyme 2 and angiotensin II type 2 receptor in aorta and kidney, respectively. We conclude that resveratrol may be effective in preventing cyclosporine-induced renal tubular degeneration and vascular dysfunction at least in part by modulating the renin-angiotensin system.

Guided Bone Regeneration Using BioGlue As a Barrier Material With and Without Biphasic Calcium Phosphate.

The aim of this study was to investigate the effects of Bioglue as a mechanical barrier with or without biphasic calcium phosphate (BCP) in a rat tibia model. Sixty Sprague Dawley male rats weighing 250 ±â€Š20 g and 10 to 12 weeks of age were studied. Unicortical defects were created on the right tibia of all rats. Subjects were randomly divided into 3 groups. BioGlue group (24 rats); BioGlue alone, Graft group (24 rats); BioGlue + BCP and Control group; unfilled and uncovered (12 rats). Animals were euthanized at 7th, 21st, and 45th days postoperatively for histological and histomorphometric analyses. BioGlue material exhibited no adverse effects until the end of observation period. Bone-healing scores did not differ statistically between Control and BioGlue group, but found to be lower in Graft group on 21st and 45th days, (P < 0.001 and P < 0.01 on the 21st day and P < 0.01 and P < 0.05 on the 45th day, respectively). New bone formation in Graft group was found to be statistically different from Control group on the 7th and 21st days (P < 0.01 and P < 0.05 respectively), whereas no statistical difference was observed between BioGlue and Control group at all times. The present analysis indicates that BioGlue functioned well as a mechanical barrier allowing new bone formation. No additional benefit of combination treatment was detected in this study design and BCP did not offer any advantage for bone regeneration, thus it can serve as only a space maintainer.

Effect of betaine treatment on the regression of existing hepatic triglyceride accumulation and oxidative stress in rats fed on high fructose diet.

We investigated whether betaine has any regressive effect on existing high fructose diet (HFrD)-induced insulin resistance, dyslipidemia, inflammation as well as hepatic steatosis and oxidative stress. Rats were fed a HFrD containing 60% fructose for 8 weeks. After 8 weeks, rats were divided into two groups and fed a control diet for an additional 4-week period (regression groups). One of the regression groups received drinking water containing betaine (1%; w/v), having antioxidant and anti-inflammatory actions. HFrD feeding caused insulin resistance, elevated triglyceride (TG) and tumor necrosis factor-alfa (TNF-α) levels, alanine aminotransferase (ALT) and aspartate transaminase (AST) activities in serum. This diet increased hepatic TG, thiobarbituric acid reactive substances (TBARS) and diene conjugate (DC) levels, decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Marked macro-vesicular steatosis were detected. Serum TNF-α and ALT, hepatic TG, TBARS and DC levels and steatosis scores decreased in regression period of HFrD-fed rats. Additionally, serum TNF-α, hepatic TG, TBARS and DC levels significantly lower in betaine-treated regressed rats than non-treated regressed group. Our results indicate that betaine treatment may accelerate regression of HFrD-induced hepatic TG accumulation and oxidative stress in rats.

Statin-induced calcific Achilles tendinopathy in rats: comparison of biomechanical and histopathological effects of simvastatin, atorvastatin and rosuvastatin.

PURPOSE: Accumulating clinical evidence indicates the risk of tendinopathy and spontaneous and/or simultaneous tendon ruptures associated with statin use. This experimental study was designed to evaluate and compare the biomechanical and histopathological effects of the three most commonly prescribed statins (simvastatin, atorvastatin and rosuvastatin) on the Achilles tendon in rats. METHODS: Statins were administered by gavage to rats at daily doses of 20 and 40 mg/kg for 3 weeks. One week later, the Achilles tendons were dissected and their biomechanical properties, including ultimate tensile force, yield force and elastic modulus, were determined. The samples were stained with haematoxylin-eosin and examined under a light microscope. The biomechanical properties of the tibia were tested by three-point bending test. Bone mineral density (BMD) and the lengths of tibias were measured by computed tomography. RESULTS: All the statins caused deterioration of the biomechanical parameters of the Achilles tendon. Histopathological analysis demonstrated foci of dystrophic calcification only in the statin-treated groups. However, the number and the total area of calcific deposits were similar between the statin groups. The biomechanical parameters of tibias were improved in all the statin groups. BMD in the statin-treated groups was not significantly different from the control group. CONCLUSION: All the statins tested are associated with calcific tendinopathy risk of which full awareness is required during everyday medical practice. However, statin-associated improvement of bone biomechanical properties is a favourable feature which may add to their beneficial effects in atherosclerotic cardiovascular disease, especially in the elderly.

Clinical, Histological, and Histomorphometric Evaluation of Demineralized Freeze-Dried Cortical Block Allografts for Alveolar Ridge Augmentation.

Autogenous bone-block grafts are the "gold standard" for block bone grafting, but have several disadvantages. Allografts have the potential to overcome these disadvantages. The purpose of this study was to evaluate the clinical and histomorphometric features of demineralized freeze-dried cortical block allografts (DCBA) used for ridge augmentation. Eleven patients who showed bone deficiencies of <5 mm in the horizontal plane were included in this study. The recipient sites were reconstructed with DCBA. The primary outcomes of interest were bone-width measurements, postoperative clinical evaluations, and histomorphometric analysis of the biopsy samples collected during the implant surgery. Clinical analysis showed that the mean gain in horizontal bone was 1.65 ±â€Š0.14 mm, and that the mean percentage of graft resorption was 5.39 ±â€Š2.18%. On postoperative day 7, edema, pain, and bruising were observed in 18.2%, 0%, and 9.1% of the patients, respectively. In the biopsy samples, the mean percentages of newly formed bone, residual block allograft, and marrow and connective tissue were 40.30 ±â€Š24.59%, 40.39 ±â€Š21.36%, and 19.30 ±â€Š15.07%, respectively. All of the block grafts were successfully integrated into the recipient sites. DCBA may be a viable alternative for treating both deficient maxillary and mandibular alveolar ridges.

Two Composite Bone Graft Substitutes for Maxillary Sinus Floor Augmentation: Histological, Histomorphometric, and Radiographic Analyses.

OBJECTIVE: To histologically, histomorphometrically, and radiographically compare clinical performance of 2 composite bone graft substitutes for maxillary sinus floor augmentation (MSFA). MATERIALS AND METHODS: Partially or totally edentulous patients requiring MSFA underwent grafting procedures using a 2:1 mixture of biphasic calcium sulfate (CS) and deproteinized bovine bone (group CB) or biphasic CS and alloplast (group CA). Grafts were allowed to heal for 5 months before placing the implants. During implant surgery, bone samples were collected from grafted areas for histology and histomorphometry. Graft height was analyzed using cone beam computed tomography. RESULTS: Sixteen patients completed the study. Mean percentages of new bone were 34.40% ± 18.91% and 36.71% ± 15.32% for the CA and CB groups, respectively; percentages of residual graft particles were 6.98% ± 5.09% and 5.52% ± 4.12%, respectively. The only significant finding was a greater graft height loss in the CA group (24.44% ± 6.52% vs 14.60% ± 4.58%). CONCLUSION: Both graft substitutes were integrated in bone, confirming their biocompatibility and effectiveness for MSFA. The CB group showed less bone height loss than the CA group.

Effect of the plant-based hemostatic agent Ankaferd Blood Stopper® on the biocompatibility of mineral trioxide aggregate.

BACKGROUND: Due to the detrimental effect of blood contamination on the physico-chemical properties of mineral trioxide aggregate (MTA), obtaining an effective hemostasis in the surgical crypt during apical surgery is of paramount importance. The purpose of this in vivo study was to analyze the effect of Ankaferd Blood Stopper® (ABS) contamination on the biocompatibility of MTA. METHODS: Forty of 56 Wistar-Albino rats were divided randomly and equally into two groups (MTA and MTA-ABS) according to whether or not a hemostatic agent was used. The remaining 16 rats were designated as the control group. Rats in the experimental groups received freshly mixed MTA-Angelus in polyethylene tubes, which were inserted into monocortical bore holes created in their tibias. In the MTA-ABS group only, 0.5 mL of ABS solution was administered topically on the defect sites followed by implantation of MTA tubes. Inflammation, foreign-body reaction (FBR), necrosis, fibrosis, and new bone formation (NBF) were studied 7, 30, 60, and 90 days after implantation. RESULTS: On day7, statistically significant differences were found in tissue reactions with regard to NBF and necrosis (p = 0.044 and p = 0.024, respectively), the latter being observed in 40 % of the samples only in the MTA-ABS group. Slight inflammation in all groups was confined to day-7 only. Mild necrosis was present in the MTA-ABS group only on day-7. Severity of the foreign body reaction and fibrosis was limited. New bone formation increased gradually over time in all groups, reaching a maximum on day-90. CONCLUSIONS: MTA and ABS-contaminated MTA are equally biocompatible. ABS does not impair the properties of MTA.

Effect of intraperitoneal cetuximab administration on colonic anastomosis and early postoperative adhesion formation in a rat model.

OBJECTIVE: We aimed to evaluate the effect of intraperitoneal cetuximab administration on the healing of anastomosis and development of early adhesion formation in a rat model. MATERIALS AND METHODS: Twenty-four female rats were used. A colon segment was resected and end-to-end anastomosis was performed. The rats were randomized into three groups after the performance of colonic anastomosis and received 10 mL of intraperitoneal solution including study drugs after closure of abdominal cavity: normal saline was administered to the normal saline group (n=8), cetuximab (400 mg/m(2)) was administered to the postoperative 1 group (n=8) 1 day after surgery, and cetuximab (400 mg/m(2)) was administered to the peroperative group (n=8) during surgery. RESULTS: The mean adhesion grade was 2.63±0.92, and 0.50±0.76 and 0.63±0.74 for control and test groups, respectively. Cetuximab reduced adhesion formation in test groups (p<0.05). When all groups were compared, it was found that vascular endothelial growth factor levels decreased significantly only in the abdomen (p<0.05). Hydroxyproline levels and anastomosis bursting pressure were examined, and a statistical difference was found between groups (hydroxyproline p<0.05, bursting pressure p<0.05). However, when postoperative 1 day group was compared with the control group, it was found that there was no difference between groups according to these parameters (p>0.05), but when peroperative group was compared with the control group a significant decrease was observed in both parameters. Histopathological healing score was also evaluated. No statistical difference between groups was found. CONCLUSION: Twenty-four hours later from the operation, intraperitoneal cetuximab therapy may be a safe and feasible treatment for metastatic colorectal patients.

Circulating levels of apelin, glucagon-like peptide and visfatin in hypercholesterolemic-hyperhomocysteinemic guinea-pigs: their relation with NO metabolism.

The aim of this study was to determine the levels of regulatory peptides apelin, glucagon-like peptide (GLP-1) and visfatin in hypercholesterolemic and hyperhomocysteinemic state and to examine their relation with nitric oxide (NO) metabolism. 32 Male guinea pigs were divided into four groups and each group was fed as follows: (a) commercial chow, (b) cholesterol (chol)-rich diet, (c) methionine (meth)-rich diet, and (d) chol + meth-rich diet. Blood samples were drawn at the end of 10 weeks, and abdominal aorta was dissected for histopathological examination. Serum insulin, GLP-1, apelin, visfatin, and nitrotyrosine concentrations were measured by the manufacturer's kits based on ELISA; asymmetric dimethylarginine (ADMA) and arginine levels were measured by the high performance liquid chromatography. Homocysteine level was measured by the chemiluminescence immunoassay; glucose, total chol and triglyceride levels were measured by the autoanalyzer. The microscopic examination of aorta indicated varying degrees of vascular disturbance in chol- and chol + meth-fed groups. High levels of chol and homocysteine, accompanied with significantly low levels of apelin and GLP-1 were detected in the plasma. Visfatin, ADMA, and nitrotyrosine levels both in chol- and chol + meth-fed groups were significantly higher than those in control animals, whereas arginine and arginine/ADMA ratio were lower. This study indicated that circulating levels of apelin, GLP-1, and visfatin are markedly altered during the development of atherosclerotic changes in close association with chol, homocysteine, NO, and ADMA levels. The measurements of these peptides in serum may help for the diagnosis and follow-up of vascular dysfunction.

Effect of olive leaf extract treatment on doxorubicin-induced cardiac, hepatic and renal toxicity in rats.

Doxorubicin (DOX) is known to increase in oxidative stress in several organs. Olive leaf extract (OLE) has potent antioxidant effects; therefore, we evaluated the ability of OLE to reduce DOX-induced toxicity in the heart, liver, and kidneys of rats. DOX (30mg/kg; i.p.) was administered to rats, which were sacrificed 4 days after DOX. The rats received OLE (6 and 12mL/L in drinking water) for 12 days. Serum cardiac troponin I (cTnI) levels, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities, urea and creatinine levels, as well as prooxidant and antioxidant status in organs were measured. DOX was found to increase serum markers that indicate tissue injury, malondialdehyde (MDA), diene conjugate (DC), and protein carbonyl (PC) levels, and to decrease glutathione (GSH) levels in organs. Histopathologic changes were also evaluated. OLE, especially OLE 1000, led to decreases in serum cTnI and urea levels, ALT and AST activities, and amelioration in histopathologic findings. Decreases in MDA, DC, and PC, and increases in GSH levels were observed in organs of DOX-treated rats due to OLE. We conclude that OLE treatment may be effective in decreasing DOX-induced cardiac, hepatic and renal oxidative stress and injury.

Effect of probiotic supplementation on bacterial translocation in common bile duct obstruction.

OBJECTIVE: To investigate the effects of probiotics on bacterial translocation in the obstructive common bile duct with comparison to an enteral product containing arginine and glutamine. MATERIAL AND METHOD: In our study, 40 Sprague-Dawley rats each weighing 250-300 g were used. Animals in Group 1 (sham) were laparatomized and fed standard chow supplemented with physiologic saline at daily doses of 2 ml through orogastric tube for 7 days. Common bile ducts of the animals in the other groups were ligated with 3/0 silk sutures. Group 2 (control group) was fed standard chow supplemented with daily doses of 2 ml physiologic saline. Group 3 (probiotic group) was fed standard chow supplemented with a probiotic solution (Acidophilus plus) containing strains of Lactobacillus acidophilus, Bifidobacterium bifidum and Lactobacillus bulgaricus at a daily doses of 2 × 10(9) colony forming units (CFU). Group 4 (formula group) was fed only an enteral solution (Stresson Multi Fiber) containing glutamine, arginine and a medium-chain fatty acid at daily doses of 2 g/kg. At the end of the 7th day, all animals were relaparatomized, and to determine bacterial translocation, aerobic, and anaerobic cultures were obtained from the specimens of mesenteric lymph nodes, intestinal mucosa, and blood samples. Smear cultures prepared from caecum were examined to determine the number of CFU. Finally, for histological examination specimens were excised from terminal ileum, and oxidative damage was assessed in liver tissues. Afterwards all animals were killed. RESULTS: Moderately lesser degrees of bacterial translocation, and mucosal damage were seen in Groups 3, and 4 relative to Group 2 (p < 0.05). In Group 4, any difference was not seen in the number of cecal bacteria relative to baseline values, while in Group 3, significant decrease in cecal colonization was seen. Among all groups, a significant difference between levels of malondialdehyde, and glutathione was not observed. CONCLUSION: At the end of our study, we have concluded that both probiotics, and enteral diets which contain immunomodulators such as glutamine, and arginine alleviate bacterial translocation, and impairment of intestinal mucosa.

Does dexamethasone therapy affect intimal hyperplasia after injury in rat abdominal aorta models?

BACKGROUND: Intimal hyperplasia is a normal adaptive feature of arteries in response to injuries, which include invasive vascular interventions. Its development limits the long-term success of bypass grafts. Various pharmacological agents have been successfully employed in experimental models to reduce the degree of intimal hyperplasia. In our study, we investigated the efficacy of dexamethasone in reducing intimal hyperplasia in rat abdominal aortas after partial transection and primary repair. METHODS: In this study, 20 Wistar Albino rats were randomly selected and divided into four groups to compare the effects of low- and high-dose dexamethasone on intima and media thickness compared to the control. Group A (n=5) was the control group, where only skin incision and laparotomy were performed. For Group B (n=5), a median laparotomy was performed, the abdominal aorta was partially transected, and repaired with an 8.0 prolene suture. Doses of 0.1 mg/kg and 0.2 mg/kg dexamethasone were administered in Group C (n=5) and Group D (n=5), respectively. After two weeks, all rats were euthanized, and the repaired abdominal aortas were excised and examined histopathologically. Intima and media thicknesses were measured using the 'Olympus AnalySIS 5' program (Olympus Corporation, Japan) after digital photos were taken. RESULTS: Based on the measurements, we demonstrated that after transection and repair of the abdominal aorta, the intima/media ratio was not significantly different between the low-dose dexamethasone and non-dexamethasone groups. The intima/media ratio was significantly lower in the high-dose dexamethasone group than in the non-dexamethasone and low-dose dexamethasone groups. CONCLUSION: After vascular interventions, dexamethasone treatment may reduce intimal hyperplasia and increase patency by providing vascular remodeling.

Effects of intraperitoneal bevacizumab administration on colonic anastomosis and early postoperative adhesion formation.

AIM: The purpose of this study is to investigate the effect of intraperitoneal (IP) bevacizumab on colonic anastomosis and evaluate the effects on early postoperative adhesion formation. MATERIALS AND METHODS: A total of 24 mature female Sprague-Dawley rats were used for this study. Rats were randomly assigned to a control group that received saline (n = 8) or to experimental groups (n = 8 each) that received bevacizumab at a dose of 2.5 mg/kg (group 1) or 5 mg/kg (group 2). Animals were killed humanely on the seventh day after operation, and measurements of anastomotic strength and biochemical variables were performed. RESULTS: The mean adhesion grade was 2.63 ± 0.92, and 1 ± 0.93 and 0.75 ± 0.71 for the control and test groups, respectively. Bevacizumab significantly reduced adhesion formation in both low-dose and high-dose IP applications (P < .05). When all groups were compared, it was found that VEGF levels decreased significantly only in the tissue (P = .001), whereas there was no significant difference in the blood and the IP fluid (P = .73 and .08, respectively). We evaluated hydroxyproline levels, anastomosis bursting pressure, and histopathological healing scores. When each of these parameters were examined, there was statistical difference between groups (P = .01, .004, and .01, respectively). It was found that these parameters significantly decreased depending on increasing drug dose. CONCLUSION: IP administration of bevacizumab effectively reduced the formation of adhesions and caused significant impairment of anastomotic wound healing when standard doses were administered (5 mg/kg), but the 2.5-mg/kg dosage did not affect the anastomotic wound healing and also effectively reduced the formation of adhesions.

Altered expression of MZB1 in periodontitis: A possible link to disease pathogenesis.

BACKGROUND: Our previous study explored the molecular signatures of generalized aggressive periodontitis (GAgP) using gingival tissues through omics-based-whole-genome transcriptomic analysis. This continuation study aimed to investigate the whole protein profiling of these gingival samples through liquid chromatography-mass spectroscopy/mass spectroscopy (LC-MS/MS) analysis and to validate the identified proteins through immunohistochemistry to provide further evidence for the quality of the results. METHODS: In previous study, gene expression patterns were identified in gingival tissues from 23 GAgP and 25 control individuals. In the current study, comparative proteomic analysis was performed on isolated proteins from the same study groups using LC-MS/MS analysis. The data from the transcriptomics study published before and the proteomics data were integrated to reveal any common genes and proteins. Additionally, immunohistochemical analysis was conducted to further investigate the findings. RESULTS: The most upregulated proteins in patients compared to controls were ITGAM, AZU1, MMP9, BPI, UGGG1, MZB1, TRFL, PDIA6, PRDX4, and PLG. The top six pathways associated with these proteins were involved in innate immune system, post-translational protein phosphorylation, interleukin-4 and -13 signaling, toll-like receptors cascades, and extracellular matrix organization. Based on the integration and validation analysis of transcriptomics and proteomics data, as well as immunohistochemical analysis, MZB1 was identified as a shared gene and protein that were upregulated in the patients. CONCLUSIONS: MZB1 is a protein that is involved in the development of B cells and the production of antibodies. Its upregulation in periodontitis suggests that there may be a dysregulation of the immune response in this condition, and MZB1 may be a potent biomarker for periodontitis.

The roles of matrix metalloproteinases-2, -7, -10 and tissue inhibitor of metalloproteinase-1 in the pathogenesis of oral lichen planus.

BACKGROUND: The aim of this study was to investigate the roles of Matrix Metalloproteinases (MMP)-2, Metalloproteinases-7, Metalloproteinases-10 and Tissue Inhibitors of Metalloproteinase-1 (TIMP-1) in the pathogenesis of oral lichen planus (OLP) disease in same tissue samples. METHODS: Thirty-nine individuals [29 patients with OLP (74%) and 10 healthy control subjects (25%)] were included in our study. The mean age was 48 ± 14.39 with a range of 20-75. RESULTS: MMP-2 and MMP-7 expression was significantly different in the patient and control groups in the epithelium and the connective tissue (P<0. 05). The ratio of MMP-2/TIMP-1 and MMP-7/TIMP-1 were higher in patient with OLP group than control group. CONCLUSIONS: Along with the exposure of the role of MMPs activity on diseases characterized by the tissue destruction, several studies were conducted on the pharmacological control of MMPs activity. However, understanding of the biological functions of MMPs is very important for the development and implementation of MMP inhibitors in the treatment of diseases. According to the results of this study, we suggest that MMP-2, MMP-7, and TIMP-1 may be involved in the formation of OLP lesions. Further studies on MMPs may be useful for understanding and treating the diseases such as OLP.

Oral and maxillofacial considerations in Gardner's Syndrome.

Gardner's Syndrome is a variant of familial adenomatosis polyposis (FAP) with a triad consisting of polyps of the colon, multiple osteomas and surface tumors of soft and hard tissue. The intestinal polyps have a %100 risk of undergoing malignant transformation, therefore early identification of this disease is very important. There are several symptoms of Gardner's syndrome in the oral and maxillofacial surgery, which can be discovered during routine dental examination. We report a case of a 25-year old male patient with Gardner's syndrome who has not any intestinal polyps but osteomas in the mandible and jaw deformalities.

Low Mmp 9 and VEGF levels predict good oncologic outcome in mid and low rectal cancer patients with neoadjuvant chemoradiation.

BACKGROUND: The aim of this study was to evaluate apoptotic (Bcl-2, Bax expression, caspase-3 activity, and cytochrome-c) and angiogenic (MMP-9 levels and VEGF expression) markers in operable rectal cancer patients who were treated with preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Understanding these factors will facilitate the identification of potential pathological responders before treatment, leading to better local control and survival rates. METHODS: Between March 2006 and March 2008, 29 patients withTNM Stage III (cT3 N+) mid or low rectal cancer were included in this study. Our sample consisted of 17 males (58.6%) and 12 females (41.4%). The median age was 60 years (range 24-88 years). Biopsy samples were taken from different portions of the tumors using flexible endoscopy before neoadjuvant CRT. Preoperatively, all patients received radiation (45-50.4 gray (Gy) in 25 cycles with concurrent 5-florouracil (5-FU) chemotherapy. RESULTS: A complete response was observed in 7 of 29 patients (24%). Bax staining was negative in 1 of the 7 patients (14%) in the pathological complete response (PCR) group and in 18 of the 22 patients (82%) in the no pathological complete response (noPCR) group (p = 0.001). MMP-9 and VEGF levels were higher in the noPCR group than the PCR group (p = 0.04, p = 0.05 respectively). No statistically significant differences were found between VEGF and MMP-9 levels in nodal downstaging. No statistically significant relationships were found between the other apoptotic factors (Bcl 2, cytochrome-c, and caspase-3 activity) and pathological response rate (p > 0.05). CONCLUSION: In neoadjuvant CRT patients, high levels of Bax expression and low levels of VEGF and MMP-9 expression on preoperative biopsies indicate that the patient will potentially be a good pathological responder.