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.

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.

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 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.

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.

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 diagnostic role of testicular fatty acid-binding protein in testicular ischemia: A randomized controlled experimental study. / El papel de la proteína testicular acido graso en la isquemia testicular: estudio experimental randomizado.

OBJECTIVE: To investigate the diagnostic value of testicular fatty acid-binding protein (T-FABP) in acute testicular ischemia and prolonged ischemia. METHODS: The study included a total of 28 prepubertal male Wistar-Hannover rats. The animals were randomly divided into 4 groups as torsion groups (group I; min 30; 7 rats, group II; min 120; 7 rats, group III; min 240; 7 rats) and control group (group IV; 7 rats). In each group, the left testis was separated from the gubernaculum by blunt dissection together with the tunica vaginalis and spermatic cord, and then exposed. In the control group, the blood samples and left testicular tissues were collected at min 240 after extraction. In torsion groups, the left testis was rotated together with its cord elements,720° in a clockwise direction for the induction of an extravaginal TT model. The blood samples were obtained at min 30, 120, and 240 in the torsion groups. Bilateral testicular tissues were collected via orchiectomy for histopathological examination in all groups. RESULTS: The mean plasma T-FABP level in group III (torsion, min 240) was significantly higher than those of other groups. The T-FABP level at min 240 had a sensitivity and specificity of 100% and 85%, respectively, at a cut-off value of 1.059. A significant difference was found between the torsion groups and the control group with regard to histopathological scores. CONCLUSIONS: The increased T-FABP levels in testicular ischemia seem to be correlated with testicular necrosis rather than acute ischemia.

OBJETIVO: Investigar el valor diagnostico de la proteína testicular acido graso (PTAG) en la isquemia testicular aguda y prolongada. MÉTODOS: El estudio involucró 28 ratas Wastar-Hannover varones prepuberales. Los animales fueron randomizados y divididos en 4 grupos: grupo torsión (grupo I; min 30; 7 ratas, grupo II; min 120; 7 ratas, grupo III; min 240; 7 ratas), grupo control (grupo IV; 7 ratas). En cada grupo, el testículo izquierdo fue separado del gubernáculo con disección, junto con la túnica vaginalis y el cordón espermático, y después fueron expuestos. En el grupo control, la extracción de sangre y tejido testicular izquierdo fueron recolectados a los 240 minutosde la extracción. En el grupo de torsión, el testículo izquierdo se rotó junto con los elementos del cordón espermático, 720 grados en la dirección de las agujas del reloj para la inducción de un modelo TT extravaginal. Las muestras de sangre fueron obtenidas a los 30 minutos, 120 y 240 minutos en los grupos torsión. Tejido testicular bilateral fue recogido vía orquiectomia para examen anatomopatológico en todos los grupos. RESULTADOS: El nivel medio de PTAG en el grupo III (torsión 240 min) fue significativamente superior a los demás grupos. El nivel de PTAG a los 240 minutos tuvo una sensibilidad y especificidad del 100% y 85%, respectivamente a un valor de corte de 1.059. Se encontró una diferencia significativa entre los grupos de torsión y control en relación a los "scores" anatomopatológicos. CONCLUSIONES: Los niveles elevados de PTAG en la isquemia testicular parecen correlacionados con la necrosis testicular más que con la isquemia aguda.

The diagnostic role of testicular fatty acid-binding protein in testicular ischemia: a randomized controlled experimental study / El papel diagnóstico de la proteína fijadora de ácidos grasos testiculares en la isquemia testicular: un estudio experimental controlado aleatorizado

Objetive: To investigate the diagnosticvalue of testicular fatty acid-binding protein (T-FABP) inacute testicular ischemia and prolonged ischemia.Methods: The study included a total of 28 prepubertal male Wistar-Hannover rats. The animals were randomly divided into 4 groups as torsion groups (group I;min 30; 7 rats, group II; min 120; 7 rats, group III; min240; 7 rats) and control group (group IV; 7 rats). In eachgroup, the left testis was separated from the gubernaculum by blunt dissection together with the tunica vaginalisand spermatic cord, and then exposed. In the controlgroup, the blood samples and left testicular tissues were collected at min 240 after extraction. In torsion groups,the left testis was rotated together with its cord elements,720° in a clockwise direction for the induction of an extravaginal TT model. The blood samples were obtainedat min 30, 120, and 240 in the torsion groups. Bilateraltesticular tissues were collected via orchiectomy for histopathological examination in all groups.Results: The mean plasma T-FABP level in group III (torsion, min 240) was significantly higher than those ofother groups. The T-FABP level at min 240 had a sensitivity and specificity of 100% and 85%, respectively, ata cut-off value of 1.059. A significant difference wasfound between the torsion groups and the control groupwith regard to histopathological scores.Conclusions: The increased T-FABP levels in testicular ischemia seem to be correlated with testicular necrosis rather than acute ischemia.(AU)

Objetivo: Investigar el valor diagnosticode la proteína testicular acido graso (PTAG) en la isquemia testicular aguda y prolongada.Métodos: El estudio involucro 28 ratas Wastar-Hannover varones prepuberales. Los animales fueron randomizados y divididos en 4 grupos: grupo torsión (grupoI; min 30; 7 ratas, grupo II; min 120; 7 ratas, grupoIII; min 240; 7 ratas), grupo control (grupo IV; 7 ratas).En cada grupo, el testículo izquierdo fue separado delgubernáculo con disección, junto con la túnica vaginalisy el cordón espermático, y después fueron expuestos.En el grupo control, la extracción de sangre y tejidotesticular izquierdo fueron recolectados a los 240 minutos de la extracción. En el grupo de torsión, el testículoizquierdo se rotó junto con los elementos del cordónespermático, 720 grados en la dirección de las agujasdel reloj para la inducción de un modelo TT extravaginal. Las muestras de sangre fueron obtenidas a los30 minutos, 120 y 240 minutos en los grupos torsión.Tejido testicular bilateral fue recogido vía orquiectomiapara examen anatomopatológico en todos los grupos.Resultados: El nivel medio de PTAG en el grupo III(torsión 240 min) fue significativamente superior a losdemás grupos. El nivel de PTAG a los 240 minutos tuvouna sensibilidad y especificidad del 100% y 85%, respectivamente a un valor de corte de 1.059. Se encontróuna diferencia significativa entre los grupos de torsión ycontrol en relación a los “scores” anatomopatológicos.Conclusiones: Los niveles elevados de PTAG enla isquemia testicular parecen correlacionados con lanecrosis testicular más que con la isquemia aguda.(AU)

The protective effect of resveratrol against cyclosporine A-induced oxidative stress and hepatotoxicity.

The immunosuppressive agent cyclosporine A (CsA) has hepatotoxic potential. Increased reactive oxygen species (ROS) formation is among the causes leading to hepatotoxicity. This study aimed to investigate the effect of resveratrol (RES) on CsA-induced oxidative stress and hepatotoxicity in rats. Rats were treated with RES (10 mg/kg/day; i.p.) for 14 days. CsA (25 mg/kg/day; s.c.) was given during the last seven days together with RES. Serum alanine aminotransferase and aspartate aminotransferase activities together with hepatic histopathological examinations were performed. ROS, thiobarbituric acid reactive substances (TBARS), advanced oxidation protein products (AOPPs), ferric reducing antioxidant power, and glutathione levels as well as superoxide dismutase, and glutathione peroxidase activities were measured in the liver tissue. RES ameliorated histopathological changes and decreased hepatic ROS, TBARS, and AOPP levels significantly. However, antioxidant parameters did not change in CsA-treated rats. Our results indicate that RES treatment may be effective in decreasing CsA-induced oxidative stress and hepatotoxicity.

The preventive effect of medicinal herbal extract and gelatin sponge on alveolar osteitis: An in vivo micro-computed tomography and immunohistochemical analysis in rats.

OBJECTIVE: The purpose of this study was to evaluate the preventive effect of medicinal herbal extract (MHE) and gelatin sponge on alveolar osteitis (AO) in an experimental rat model. DESIGN: Twenty-one Sprague-Dawley male rats with a mean age of 12 weeks were used. After extraction of the maxillary right first molar, an AO model was created for each animal. The animals were randomly separated to three equal groups. Group I served as a control, Group II was subjected to an intra-alveolar MHE application, and gelatin sponge was left in the sockets of Group III. On the 7th post-extraction day, the animals were sacrificed. The specimens were analyzed by micro-computed tomography (micro-CT), histopathologically and immunohistochemically. RESULTS: Macroscopic evaluation revealed mild to intense signs of AO in all groups, but the difference was not significant (p < 0.05). Micro-CT analysis showed that bone formation was the highest in Group III (bone volume/total volume; 10.63 ± 4.9 %), whereas bone mineral density was the highest in Group I (2.05 ± 0.2 g/cm3). The difference was not significant (p > 0.05). In Group III, only 16.7 % of specimens showed no signal of inflammatory response (p < 0.01). The difference was not significant between the positive labeling for receptor activator of nuclear kappa-ß (RANK), receptor activator of nuclear kappa-ß ligand (RANKL), osteoprotegerin and osteopontin, but the intensity of Groups II and III was higher than the Group I for osteopontin (p < 0.01). CONCLUSIONS: MHE and gelatin sponge were not effective enough to prevent alveolar osteitis, but positive results were obtained in bone healing.

α-Lipoic Acid Ameliorates The Changes in Prooxidant-Antioxidant Balance in Liver and Brain Tissues of Propylthiouracil-Induced Hypothyroid Rats.

OBJECTIVE: There are controversial data about the prooxidant-antioxidant balance in hypothyroidism. We aimed to investigate the effect of α-lipoic acid (ALA) on oxidative stress parameters in the liver and brain of propylthiouracil (PTU)-induced hypothyroid rats. MATERIALS AND METHODS: In this experimental study, PTU (500 mg/L) was given to rats in drinking water for 10 weeks. ALA (0.2% in diet) alone and together with thyroxine (T4, 20 µg/kg body weight, s.c) were given to hypothyroid rats in the last 5 weeks of the experimental period. The levels of reactive oxygen species, malondialdehyde, protein carbonyl, ferric reducing antioxidant power (FRAP) and glutathione (GSH) levels, superoxide dismutase, and GSH peroxidase activities were determined in the liver and brain of rats. Histopathological examinations were also performed. RESULTS: Prooxidant parameters were increased in the brain but not liver in hypothyroid rats. ALA treatment alone lowered enhanced brain oxidative stress in hypothyroid rats. Also, ALA was found to ameliorate the changes as a result of oxidative stress arising from T4 replacement therapy. CONCLUSION: Our results indicate that ALA alone and together with T4 may be useful in reducing oxidative stress in thyroid dysfunctions.

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.

Pretreatment of simvastatin on liver trace element levels during endotoxemia.

There are a number of studies investigating anti-inflammatory effects of simvastatin in patients with sepsis and animal models. There are a few studies which investigated effect of simvastatin on elements in sepsis. In the present study, the impact of pretreatment with simvastatin on element levels was evaluated in liver during endotoxemia. Rats were divided into control, LPS, simvastatin, and simvastatin + LPS. The histopathologic examination of the liver was performed using hematoxylin and eosin. Selenium, zinc, iron, manganese, magnesium, and copper were analyzed using inductively coupled plasma - optical emission spectroscopy. In the LPS, the hepatocyte cell structure was damaged. In the simvastatin + LPS, hepatocyte, and sinusoidal cord damage were partially smaller than LPS. Levels of selenium, and copper significantly decreased in both of LPS and simvastatin + LPS. In the LPS group, iron was found to increase. In the simvastatin + LPS, zinc was increased. Simvastatin partially smaller liver damage by increasing zinc levels during endotoxemia.

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.

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.