Protective role of S-adenosylmethionine on high fat/high cholesterol diet-induced hepatic and aortic lesions and oxidative stress in guinea pigs.

S-adenosylmethionine (SAM) is the main methyl group donor and has antioxidant potential. In this study, preventive and regressive potential of SAM were investigated in high fat/high cholesterol (HFHC) diet-induced non-alcoholic fatty liver disease (NAFLD) in guinea pigs. They were injected with SAM (50 mg/kg, i.p.) for 6 weeks along with HFHC diet or 4 weeks after HFHC diet. Serum transaminase activities, total cholesterol (TC), triglyceride (TG), cytochrome p450-2E1 (CYP2E1) and hydroxyproline (Hyp) levels, prooxidative and antioxidative parameters, protein expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1) together with histopathological changes were examined in the liver. SAM treatment diminished HFHC diet-induced increases in serum transaminase activities and hepatic TC, TG, CYP2E1, Hyp, α-SMA and TGF-ß1 expressions and ameliorated prooxidant-antioxidant balance. Histopathological scores for hepatic steatosis, inflammation, and fibrosis were decreased by SAM treatment. Increases in TC, diene conjugate levels, and lipid vacuoles within the tunica media of the aorta were reduced in HFHC-fed animals treated with SAM. These protective effects were also detected in the regression period of HFHC-guinea pigs due to SAM. In conclusion, SAM treatment was found to be effective in prevention and regression of HFHC-induced hepatic and aortic lesions together with decreases in oxidative stress in guinea pigs with NAFLD.

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.

Investigation of the protective effect of gel incorporating Eugenia jambolana leaf extract on 5-fluorouracil-induced oral mucositis: an animal study.

PURPOSE: The study aimed to evaluate the possible preventive effect of two concentrations (3 and 5% w/w) of Eugenia jambolana (EJ) extract against 5-FU-induced mucositis. METHOD: Sixteen adult rats were separated into four groups: two control and two preventive groups. Animals in Groups 1, 2, and 3 were injected intraperitoneally with 60 mg/kg/day of 5-FU on Day 1 followed by 150 mg/kg/day on Day 5. The rats in Group 4 (negative control) were given physiological saline at the same times and doses. Furthermore, on the fifth day of the study, the cheek and sublingual mucosa were irritated by external superficial scratches using the tip of an 18-G needle, followed by the application 15 µL of 20% acetic acid, after which 3 and 5% EJ w/w gels were applied topically for animals in Groups 2 and 3, respectively. RESULTS: The weight and the mucositis scores were recorded. Antioxidant and anti-inflammatory markers and biochemical tests were analyzed. Significant differences were found between the study groups in weight loss, clinical mucositis scores, mortality rates, and antioxidant and anti-inflammatory parameters. CONCLUSION: The preventive effect of 3% gel was significant, with no mortality rate, making it an option for preventive strategies.

Melatonin pretreatment modulates anti-inflammatory, antioxidant, YKL-40, and matrix metalloproteinases in endotoxemic rat lung tissue.

We aimed to investigate the effects of melatonin administered before and during endotoxemia on the lung tissue of rats, cytokine, YKL-40, matrix metalloproteinase (MMP) and inhibitor levels, oxidative stress parameters, and energy balance. Sepsis was induced with lipopolysaccharide (LPS), the cell wall molecule of gram negative bacteria. Rats were divided into four groups, Control, LPS (Escherichia coli O127:B8, 20 mg/kg), melatonin (10 mg/kg), and melatonin+LPS (M+LPS). After injections, lung tissues samples were taken for experimental analyses. YKL-40, thiobarbituric acid reactive substances (TBARS), glutathione reductase (GR), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) enzymes levels were measured, high-energy components were analyzed; tumor necrosis factor-alpha (TNF-α), MMP-2, YKL-40, MMP-9, myeloperoxidase (MPO), tissue inhibitors of matrix metalloproteinase (TIMP)-1, and interleukin (IL)-10 immunoreactivities were investigated. In LPS group, YKL-40, creatine phosphate (both, p < 0.05), SOD, GR, adenosine mono-phophate (AMP), adenosine tri-phosphate (ATP) (for all, p < 0.01) were significantly decreased, while TBARS and adenosine di-phosphate (ADP) levels were increased (p < 0.01, p < 0.05; respectively) compared to other groups. MMP-2 and -9, TIMP-1, TNF-α, IL-10, and MPO immunoreactivity were investigated in LPS group. On the contrary, in M+LPS group, MMP-9, TIMP-1 immunoreactivities were not found and IL-10 and MMP-2 immunoreactivities were found with little involvement. In M+LPS group, YKL-40, GR, AMP, ATP, creatine phosphate (for all, p < 0.05), and SOD (p < 0.01) levels were significantly increased and TBARS levels were decreased (p < 0.05). In our study, we suggest that melatonin exerts a protective and curative effect by reducing the matrix metalloproteinase levels responsible for tissue damage balance, stimulating the release of antioxidant enzymes, regulating cytokines and energy balance during endotoxemia.

Effects of systemic androgens on late-stage urethral wound healing: An animal study.

BACKGROUND: There are limited data regarding the effects of systemic androgens on late-stage urethral wound healing. OBJECTIVE: To evaluate the effects of systemic androgens on fibrosis and scar formation in late-stage urethral wound healing. MATERIALS AND METHODS: Forty-five male Sprague Dawley rats were divided into three groups. First group consisted of 15 rats that were castrated on 23 days of age and were given 5 mg/kg testosterone undecanoate with 1/25 ml cottonseed oil intraperitoneally at weekly intervals for 3 weeks (castrated and replaced with testosterone rats [CAS+T] group). The castrated rats (CAS) group included 15 castrated rats. The remaining 15 rats underwent sham surgery. CAS and sham groups also received 1/25 ml cottonseed oil intraperitoneally at weekly intervals for 3 weeks. Furthermore, all groups were divided into three subgroups after testosterone/placebo administration (urethroplasty performed after first, second, and third weeks) in accordance with the urethroplasty timing. All animals were sacrificed 6 weeks after urethroplasty. Serum testosterone level was measured, tissue samples were investigated using hematoxylin and eosin and Masson's trichrome. Alpha-SMA, Coll 1 and Coll 3 primary antibodies were applied for immunohistochemical examination. Expression of cytokines and growth factors, such as Bax, Bcl2, IL-10, IP-10, TNF-alpha, TGFb1, MMP9, Col-I, Col-III, TIMP-1, fibronectin, fibroblast growth factor 10, platelet-derived growth factor, alpha-SMA, were also evaluated in the tissues. RESULTS: The blood testosterone levels were significantly higher in CAS+T group at the time of urethroplasty compared with the levels in CAS group; however, this difference was not observed at the time of sacrification (p < 0.001 and 0.97, respectively). Histological analysis with hematoxylin and eosin and Masson's trichrome staining revealed a significantly higher fibrosis in the sham group compared with the others. Significantly lower fibrosis was detected in the CAS group in the pairwise comparison of the pathological fibrosis area between the CAS and CAS+T groups (p < 0.001). Furthermore, tissue collagen-1, collagen-3, and alpha-SMA expression levels were statistically different between CAS and CAS+T groups (p < 0.001, <0.05, and <0.001, respectively). The tissue levels of BAX, TIM-1, MMP-9, Coll-I, Coll-III, TGF-beta, TNF-alpha, and IL-10 mRNA expressions in the CAS+T group were different than the levels in CAS group (as <0.5-fold and >1.5-fold changes, respectively). The expressions of all these markers were significantly higher in the sham group. The subgroup analysis of CAS+T group (urethroplasty performed after first, second, and third weeks) revealed similar histopathological wound healing findings. DISCUSSION: Debate continues on the effects and benefits of androgen use regarding urethral healing. There are two main routes for administration as systemic or local. This study focuses on the late-stage histologic and biochemical effects of systemic androgens. CONCLUSION: Systemic androgens adversely affect wound healing and cause abnormal extracellular matrix as well as scar formation.

Histologic, Histomorphometric, and Clinical Analysis of the Effects of Growth Factors in a Fibrin Network Used in Maxillary Sinus Augmentation.

This randomized controlled clinical trial evaluated the effect of mineralized plasmatic matrix (MPM), comprised of synthetic graft and platelet concentrates, on new bone formation and volume stability over time in maxillary sinus lifting (MSL). Unilateral MSL was performed in 20 patients with either beta-tricalcium phosphate (ß-TCP) or MPM grafts (10 sinuses each). Six months postsurgery, specimens were obtained with a trephine bur prior to implant placement in 39 cases. Volumetric changes in sinus augmentation were analyzed between 1 week (T-I) and 6 months (T-II) postsurgery. Histomorphometric and histological analyses of biopsy samples revealed mean new bone percentages of 35.40% ± 9.09% and 26.92% ± 7.26% and residual graft particle areas of 23.13% ± 6.16% and 32.25% ± 8.48% in the MPM and ß-TCP groups, respectively (p < 0.05). The mean soft-tissue areas in the MPM and ß-TCP groups were 41.48% ± 8.41% and 40.83% ± 8.86%, respectively (p > 0.05). Graft reductions between baseline and 6-months postprocedure in the ß-TCP and MPM groups were 17.12% ± 13.55% and 14.41% ± 12.87%, respectively, with significant graft volume reduction observed in both groups (p < 0.05) while there is no significant difference between MPM and ß-TCP groups (p > 0.05). Thus, MPM, representing growth factors in a fibrin network, increases new bone formation and has acceptable volume stability in MSL procedures.

Comparative Analysis of Using Bone Graft, Hydroxyapatite Coralline (Biocoral®) and Porous Polyethylene (Medpor®) Implants for Cranioplasty in a Rat Model of Cranial Bone Defect.

AIM: To compare the efficacy of bone graft, hydroxyapatite coralline (Biocoral®), and porous polyethylene (Medpor®) implants for cranioplasty in a rat model of cranial bone defects. MATERIAL AND METHODS: Two parietal bone defects were created in each of 16 male Sprague-Dawley rats. One was repaired with a bone graft using bone removed from the contralateral defect, and the other was filled with either Medpor® or Biocoral® (each n=8, with the repair on the left in four and the right in the other four). The rats were sacrificed at either 4 or 8 weeks, and implant stability, volumetric changes, and histological parameters were compared between the three materials. RESULTS: At 8 weeks, scores for bone formation (p=0.003), healing of the defects (p=0.008), and material resorption (p=0.010) were higher for the bone grafts than for Biocoral® and Medpor®, whereas the fibrosis scores were significantly higher for Medpor® and Biocoral® than for the bone grafts (p=0.004). The other parameters were similar between the three materials at 8 weeks, except for significantly higher inflammatory cell infiltration with Medpor® than with Biocoral® and bone grafts (p=0.005). CONCLUSION: Implant stability scores were similar for the three implant materials. However, there was better bone formation and healing of the defects with bone grafts, a lower risk of resorption and greater fibrosis induction with Medpor® and Biocoral®, and less volumetric reduction with Medpor®.

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.

Use of Muscle Graft Versus Fascia Flap as Interpositional Material in Prevention of Reossification in a Rat Model of Skull Bone Defect.

AIM: To investigate the utility of two different interpositional materials (muscle graft vs. fascia flap) for preventing the osseous reunion of skull bone defect including the coronal suture line in rats. MATERIAL AND METHODS: A total of 32 male Sprague-Dawley rats were divided into 2 groups (n=16 for each) after the formation of bilateral coronal bone defect, based on the interpositional materials used to prevent re-ossification; the rats were divided into the muscle graft (MG) group and the fascial flap (FF) group. In each group, the other side of the coronal suture served as the control. The rats were sacrificed at postoperative 4 weeks or 8 weeks for histopathological, radiological, and microbiologic investigations. RESULTS: At postoperative 8 weeks, there was partial reunion in the defects with bony tissue in both the groups; no obvious differences were noted between the groups on radiological examination.The defect content involved bone and fibrous tissue in the MG group and bony bridges and loose connective tissue in the FF group. New bone formation was moderate, marked, and extreme and the reduction in defect size was marked, moderate, and extreme in the MG, FF, and control groups, respectively. CONCLUSION: Our findings revealed that neither the temporal MG nor the temporal FF were able to achieve complete prevention of re-ossification of the skull bone defects including the coronal suture line; further, neither material was superior to the other.

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.

The efficacy of sustained-release chitosan microspheres containing recombinant human parathyroid hormone on MRONJ

Abstract Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.

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.

Elevated levels of 8-OHdG and PARK7/DJ-1 in peri-implantitis mucosa.

BACKGROUND: Reactive oxygen species contribute to periodontal tissue homeostasis under control of anti-oxidative responses. Disruption in this balance induces severe inflammation and extended tissue degradation. PURPOSE: Aim of this study was to identify the expression levels of nuclear factor, erythroid 2 like 2 (NFE2L2/NRF2), Parkinsonism associated deglycase (PARK7/DJ-1), kelch-like ECH associated protein 1 (KEAP1), and 8-hydroxy-deoxyguanosine (8-OHdG) in peri-implant mucosal tissues affected by peri-implantitis, and to compare the levels to those of periodontally diseased and healthy tissue samples. METHODS: Tissue biopsies were collected from systemically healthy, non-smoking 12 peri-implantitis patients, 13 periodontitis patients, and 13 periodontally healthy controls. Expression levels of NFE2L2/NRF2, PARK7/DJ-1, KEAP1, and 8-OHdG in tissue samples were analyzed immunohistochemically. Statistical analysis was performed by one-way ANOVA with Tukey's HSD test. RESULTS: Inflammatory cell infiltration in the connective tissue and loss of architecture in the spinous layer of the epithelium were prominent in peri-implantitis. Proportions of 8-OHdG and PARK7/DJ-1 expressing cells were elevated in both peri-implantitis (P = .025 for 8-OHdG and P = .014 for PARK7/DJ-1) and periodontitis (P = .038 for 8-OHdG and P = .012 for PARK7/DJ-1) groups in comparison with controls. Staining intensities of 8-OHdG and PARK7/DJ-1 were higher in the periodontitis and peri-implantitis groups than in the control (P < .01) groups. There was no difference in the expression levels of NFE2L2/NRF2 between the groups. KEAP1 was not observed in any tissue sample. CONCLUSIONS: Peri-implantitis is characterized by severe inflammation and architectural changes in the epithelium and connective tissue. The expressions of 8-OHdG and PARK7/DJ-1 are elevated in both peri-implantitis and periodontitis.

Effects of betaine supplementation on nitric oxide metabolism, atherosclerotic parameters, and fatty liver in guinea pigs fed a high cholesterol plus methionine diet.

OBJECTIVE: The aim of this study was to investigate the effect of high cholesterol (CHOL) and CHOL + methionine (MET) diets on atherogenic and oxidative index parameters and on the factors that influence nitric oxide (NO) bioavailability. Also, attempts were made to determine whether dietary betaine (BET) resulted in any improvement in the changes that occurred after CHOL + MET administration. METHODS: Guinea pigs were fed chow containing 1.5% CHOL with or without 2% MET for 10 wk. A third group received the CHOL + MET + BET diet. Control groups were given standard chow or standard chow + BET. Arginine, NO, nitrotyrosine (NT), and asymmetric dimethylarginine (ADMA) levels; lipid profile; and dimethylarginine dimethylaminohydrolase (DDAH) activity were measured. The liver and aorta were subjected to histopathologic analysis. RESULTS: The CHOL + MET diet caused higher serum CHOL and homocysteine levels, but no further increases were seen in aortic CHOL and diene conjugate (DC) levels and histopathologic lesions as compared with the CHOL group. Hepatic lipids and DC levels were also higher, and histopathologic lesions were more severe. CHOL + MET feeding increased ADMA and NT levels as compared with those of the CHOL-fed group. When BET (1 g/kg body weight/d) was added to the CHOL + MET diet, homocysteine and lipid levels decreased and histopathologic changes were reversed. BET diet decreased serum ADMA and hepatic and aortic DC levels and partly restored DDAH activity. CONCLUSIONS: BET supplementation may be effective in preventing hyperlipidemia, disturbed NO availability, oxidative stress, and the development of fatty liver and atherosclerotic lesions that might result from excess amounts of cholesterol and methionine in the diet.

Effects of pamidronate administration on tooth eruption and mandibular growth in new born rats.

PURPOSE: Bisphosphonates are commonly used drugs in pediatric patients in the treatment of osteoporotic diseases and various types of cancers. The purpose of this study was to evaluate the effects of pamidronate administration on mandibular growth and tooth eruption in new born rats. MATERIALS AND METHODS: Forty Sprague Dawley rats were included in the study and divided into four groups as; 14th day pamidronate group, 30th day pamidronate group, 14th day control group and 30th day control group. Pamidronate groups were daily injected with 1.25 µg/g pamidronate disodium subcutaneously whereas control groups were injected with sterile saline. Eruption levels of lower incisor and molar teeth were assessed macroscopically. Mandibular growth was assessed by measuring reference points in cone beam tomography. Histological and histomorphometric examinations were performed under light microscope to evaluate tooth morphology and number of osteoclasts. RESULTS: Retardation in mandibular growth, decrease in number of osteoclasts, delay in tooth eruption, degeneration in both tooth morphology and structure were observed in the pamidronate groups compared to control groups. CONCLUSION: Pamidronate administration during growth and development stage may adversely affect tooth eruption and mandibular growth in new born 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.

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.

Impact of Superoxide Dismutase-Gliadin on Radiation-induced Fibrosis: An Experimental Study.

AIM: Radiation-induced fibrosis (RIF) has since long been considered as irreversible. Further understanding of its mechanisms has led to trials investigating RIF treatment and prevention. The effect of superoxide dismutase (SOD)-gliadin, an oral form of SOD that resists gastrointestinal inactivation, on RIF treatment was evaluated in this experimental study. MATERIALS AND METHODS: A total of 36 Wistar albino mice were randomly distributed into four groups. According to group, 25 Gy radiation or sham-radiation were performed on day 0. Acute and late reactions were recorded. After 6 months, mice were treated with SOD-gliadin, 10,000 units per kg per day, or placebo. SOD-gliadin and placebo treatments were administered daily for 8 days by oral gavage. Later the mice were sacrificed, dissected and histopathologically analyzed. Accumulated hyaline and collagen at the dermis is an indicator of fibrosis. Therefore measurements of the dermal thickness were used to quantify the degree of RIF. Additionally, the morphological changes were analyzed, and the differences reported. RESULTS: The mean and standard deviation for dermal thickness were 0.45±0.09 mm in the sham-irradiated placebo-treated group, 0.51 mm±0.16 mm in the sham-irradiated SOD-gliadin-treated group, 0.92 mm±0.23 mm in the irradiated placebo-treated group and 0.71 mm±0.17 mm in the irradiated SOD-gliadin-treated group. The difference in mean dermal thickness between irradiated placebo-treated and irradiated SOD-gliadin-treated mice was statistically significant (p=0.002). CONCLUSION: Quality of life while prolonging survival has an increasing importance in patients with cancer. RIF can be a crucial problem after all radiotherapy modalities. SOD-gliadin has advantageous effects on conditions that call for an increased expression of antioxidant enzymes. The results of our study suggest that oral SOD-gliadin may prevent or ameliorate RIF and patients can benefit from the positive effects of SOD.