Investigation into effects of tocilizumab and epoetin beta in rats with experimental sciatic nerve injury model.

OBJECTIVE: To investigate the effects of tocilizumab (TCZ), epoetin beta (EPO), and their combination on nerve regeneration in a sciatic nerve injury model. MATERIALS AND METHOD: Male Sprague-Dawley rats were divided into (-) negative control, sham, TCZ, EPO ((+) positive control), and TCZ+EPO groups. The TCZ group received TCZ (8 mg/kg intraperitoneal) immediately after surgery. On day 14th, the EPO group received EPO (5000 IU/kg, intraperitoneal); the TCZ+EPO group received TCZ (8 mg/kg, intraperitoneal), EPO (5000 IU/kg, intraperitoneal), and TCZ (8 mg/kg, intraperitoneal) post-surgery. Motor and sensory functions were assessed pre and post-surgery. Lipid peroxidation and oxidative stress parameters were evaluated biochemically in the serum, and sciatic nerve tissue was evaluated histopathologically using haematoxylin-Eosin and Masson trichrome staining. CONCLUSIONS: TCZ and EPO decreased nerve injury effects by increasing motor and sensory conduction velocities of the sciatic nerve. Biochemically, TCZ and EPO significantly increased Superoxide Dismutase, Catalase, and Glutathione peroxidase 4 levels while decreasing Lipid Peroxidation levels (p=0.001). Histopathologically, neuronal degeneration following nerve injury was decreased in the groups receiving TCZ and EPO (p=0.001). EPO and TCZ attenuate the adverse effects of nerve injury. However, the TCZ+EPO treatment favoured biochemical activities over tissue and functional activities. This has been confirmed functionally, biochemically, and histopathologically.

Comparison of irisin hormone expression between thyroid cancer tissues and oncocytic variant cells.

Objective: The incidence of thyroid cancer has been continuously increasing. The main objective of this study was to investigate irisin expression in various thyroid pathologies and to compare these expression patterns with irisin expression in healthy thyroid tissues. Methods: The study groups consisted of 20 cases each of control thyroid tissue, Hashimoto's thyroiditis, thyroid papillary carcinoma, oncocytic papillary carcinoma, follicular thyroid carcinoma, oncocytic follicular thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma. Irisin expression was evaluated using immunohistochemistry. Irisin levels in thyroid tissue supernatants were measured using ELISA. Results: Patients with HT showed increased irisin expression compared with controls (p<0.05). In addition, mild immunoreactivity was observed in the thyroid tissues of patients with papillary carcinoma while significantly increased irisin immunoreactivity was observed tissues of patients with oncocytic papillary carcinoma (p<0.05). There was no difference in irisin immunoreactivity in thyroid tissues between patients with follicular carcinoma and controls. However, irisin immunoreactivity was higher in tissues of patients with oncocytic follicular carcinoma than in tissues of patients with follicular carcinoma (p<0.05). No irisin immunoreactivity was observed in tissues of patients with medullary carcinoma, a malignant tumor the thyroid; however, irisin expression was significantly increased in tissues of patients with anaplastic carcinoma compared with that in tissues of controls (p<0.05). Furthermore, in all thyroid tissues with irisin expression, irisin immunoreactivity was observed in follicular cells, indicating that irisin is produced by these cells. Conclusion: Irisin is a novel potential immunohistochemical marker for differentiating oncocytic variants of papillary and FTCs from papillary and follicular thyroid cancers.

Effects of Copper, Zinc, and Vitamin Complex (Cernevit®) on Hepatic Healing in Rats Experimentally Subjected to Blunt Hepatic Trauma.

Solid organ injuries following blunt trauma are frequently encountered. The use of non-operative approach is gradually increasing. Thus, research on the methods that could enhance healing in solid organ injuries is in progress. Agents known to have antioxidant property were used after an experimentally induced blunt hepatic trauma. Thirty-two Wistar albino rats weighing 200 g were dropped from a height of 40 cm on to the right upper abdominal quadrant to produce a grade II-III hepatic injury. Rats were divided into control, Zn-administered, Cu-administered, and vitamin complex-administered groups, with eight rats in each. Aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were measured in the blood samples. The percentage of cells displaying Ki-67 nuclear staining was estimated. The sections were stained with hematoxylin and eosin and the degree of inflammation in the samples was semi-quantitatively assessed. Treatment with zinc, copper, and Cernevit® caused varying levels of decrease in AST, ALT, and LDH levels compared to the control group. Ki-67 positivity was significantly lower in group I compared with groups II and III (p = 0.002). Ki-67 positivity was significantly higher in group II compared to the other groups (p < 0.05). A marked improvement was observed in inflammation in group II. Copper and zinc treatment decreased inflammation as well as blood levels of AST and ALT, and enhanced the healing of traumatized hepatic tissue. However, Cernevit® reduced only the degree of inflammation.

Concentrations of preptin, salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus.

This study was undertaken to ascertain whether human milk contains preptin, salusin-alpha (salusin-α) and -beta (salusin-ß) and pro-hepcidin and hepcidin-25, and whether there are relationships between plasma and milk preptin, salusin-α and -ß and pro-hepcidin and hepcidin-25 concentrations in lactating mothers with and without gestational diabetes mellitus (GDM). Blood was obtained from non-lactating women (n = 12), non-diabetic lactating women (n = 12), and GDM lactating women (n = 12). Colostrum, transitional milk, and mature milk samples were collected just before suckling from healthy and GDM lactating women. Peptides concentrations were determined by ELISA and EIA. Mammary gland tissues were screened immunohistochemically for these peptides. Women with GDM had significantly higher plasma and colostum preptin concentrations than healthy lactating women during the colostral and transitional milk period. Salusin-alpha and -beta levels in milk and plasma were lower in women with GDM. Salusin-α and -ß were significantly lower in both plasma and colostrums of GDM than of healthy lactating women. Women with GDM had significantly higher colostum prohepcidin and hepcidin-25 concentrations than healthy lactating women during the colostral period. Plasma prohepcidin was also higher in women with GDM than in healthy lactating women during the colostral period, but plasma prohepcidin and hepcidin-25 levels decreased during mature milk period. Transitional milk pro-hepcidin and hepcidin-25 levels in women with GDM were higher than in healthy lactating women. All these results revealed that the mammary gland produces those peptides, which were present in milk at levels correlating with plasma concentrations.

The bioactive peptides salusins and apelin-36 are produced in human arterial and venous tissues and the changes of their levels during cardiopulmonary bypass.

This study aimed to examine the effects of CPB on salusin-α, salusin-ß and apelin-36 bioactive peptides in people who are planned to undergo coronary artery bypass graft (CABG) operation due to coronary artery disease and to explore whether these peptides are produced in human aortic, saphenous and arterial tissues. The study included age and BMI matched 15 patients who underwent CABG operation by CPB. In order to determine salusin-α, salusin-ß and apelin-36 levels, venous blood samples were collected before induction of anesthesia (T1), before CPB (T2), 5 min before the removal of cross-clamp (T3), 5 min after the removal of cross-clamp (T4), upon arrival in the intensive care (T5), at postoperative 24th hour (T6) and 72nd hour (T7). Salusin and apelin expressions of the tissues were shown by immunohistochemical method. Peptide amounts of sera and tissues were measured using ELISA. Salusins production by vessels occurs in fibroblast cells of the media in the aorta and smooth muscle cells of the media in the LIMA and saphena. Apelin is produced by endothelial cells of the intima and fibroblast cells of the media in the aorta and by smooth muscle cells of the media in the LIMA and saphena. Changes in the levels of salusin-ß and apelin-36 were significant during CPB. Salusin-α, salusin-ß and apelin-36 are locally synthesized in the arteries and veins. Salusins and apelin-36 might be important markers in the CPB, and also that salusin-ß was more specific in comparison to salusin-α.

Nadroparin sodium activates Nrf2/HO-1 pathway in acetic acid-induced colitis in rats.

Effects of nadroparin sodium, a low molecular weight heparin, in colitis was investigated by analyzing proteins implicated in nuclear factor E2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) and nuclear factor kappa B (NF-κB) pathways. Twenty-eight rats were used. Colitis was induced by acetic acid (AA). Nadroparin sodium was given to prevention and treatment groups in addition to AA. Colitis was assessed histologically and levels of proteins were analyzed with Western blot. Nadroparin not only prevented and ameliorated the AA-induced colitis histopathologically but also decreased expression of colon NF-κB, activator protein-1, cyclooxygenase-2, tumor necrosis factor-alpha, and IL-6, which were significantly increased in group AA compared to control. The accumulation of Nrf2 in nuclear fraction and HO-1 found low in group AA was increased with nadroparin (p < 0.05). The mean malondialdehyde level increased with AA and was decreased significantly with nadroparin prevention and treatment (p < 0.001). Nadroparin sodium has both protective and therapeutic effects against colonic inflammation via exerting anti-oxidative and anti-inflammatory effects by modulating Nrf2/HO-1 and NF-κB pathways.

Primary hepatic actinomycosis.

OBJECTIVES: To present a case of primary hepatic actinomycosis. CLINICAL PRESENTATION: A-40-year-old man was admitted to the general surgery clinic with a 1-month history of abdominal pain and weight loss. Liver transaminase, bilirubin levels and white blood cell counts were increased. Abdominal ultrasound and CT revealed cystic lesions with necrotic debris involving the posterior segment of the right lobe of the liver and the medial segment of the left lobe. INTERVENTION: The patient underwent surgery under general anesthesia. On exploration, three cavities were found within the liver containing necrotic material. Surgical debridement and drainage was performed. Histopathological examination revealed actinomycotic colonies with a surrounding suppurative granulomatous reaction. The patient was treated with penicillin for 3 months. CONCLUSION: This case showed that histological examination of biopsy or surgical material or anaerobic cultures was needed for definitive diagnosis and that hepatic actinomycosis should be included in the differential diagnosis of solitary or multiple hypodense liver lesions.

Preventive role of genistein in an experimental non-alcoholic steatohepatitis model.

BACKGROUND AND AIM: The aim of the present study was to evaluate the preventive role of genistein, a phytoestrogen with a wide variety of pharmacological effects, in an experimental non-alcoholic steatohepatitis (NASH) model. METHODS: Thirty-six Sprague-Dawley rats were divided into three groups. Group 1 (control) received only a standard rat diet, group 2 (placebo) was given a high fat diet (HFD) plus 0.5 mL/day saline subcutaneously, and group 3 (genistein group) a HFD plus subcutaneous genistein injection at dose of 0.2 mg/kg/day for 6 weeks. All rats were killed after 6 weeks. Serum aminotransferases, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and plasma and liver malondialdehyde (MDA) levels were measured. Additionally, steatosis, ballooning degeneration and inflammation of the liver were examined histopathologically. RESULTS: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.001 for each), plasma and liver tissue MDA and plasma TNF-alpha levels (P < 0.001, <0.001, <0.01, respectively) were found to be higher in the placebo group than in the control group. TGF-beta levels, however, were comparable in the placebo and control groups (P > 0.05). Histopathologically, steatosis, inflammatory cells per mm(2) and ballooning degeneration were significantly higher in the placebo group than in the control group (P < 0.001 for each). Nevertheless, AST and ALT (P < 0.05 for each), plasma and liver tissue MDA (P < 0.05 for each) and plasma TNF-alpha levels (P < 0.001) were significantly decreased in the genistein group compared to the placebo group. Histopathologically, steatosis (P < 0.05), inflammatory cells per mm(2) and ballooning degeneration (P < 0.01 for each) in the genistein group were also significantly lower than in the placebo group. CONCLUSIONS: Genistein, a strong antioxidant agent, significantly decreased the plasma TNF-alpha level and remarkably prevented the emergence of NASH by improving the biochemical and histopathological abnormalities via attenuating oxidative stress.

Ghrelin is present in teeth.

Ghrelin belongs to the family of a gut-brain hormone that promotes food intake and controls energy balance. Recently, it has also been shown to regulate bone formation directly. Dental tissue shares several functional, developmental and anatomical similarities with bone, and in the present study we have investigated the presence of ghrelin in 44 human teeth using immunocytochemistry and radioimmunoassay. Both methods showed that the hormone is present in canines and molars, mainly in the odontoblasts but also in the pulp. Ghrelin could potentially play interesting physiological roles in teeth.

The effect of Bosentan on healing of colonic anastomosis.

BACKGROUND: Ischemia is the most important factor compromises wound healing in colonic anastomosis. Mesenteric vessels are ligated at first while performing colonic resection and following anastomosis. Therefore blood supply of the related segments of colon temporarily interrupted and ischemia can easily occur. This study was carried out to explore whether Bosentan, an endothelin-receptor antagonist, can eliminate vasoconstruction, increase blood flow in the splanchnic area and anastomotic region and therefore possibly facilitate wound healing and prevent intra-abdominal adhesion formation. METHODS: Study is conducted on 30 female Wistar-Albino rats weighing 180-240 gr. Rats were allocated into three groups. Group 1 (n = 10) recevied full-thickness resection of the left colon and end-to-end anastomosis. In Groups 2 (n = 10) and 3 (n = 10), vessels of 2-3 cm segment of the left colon were ligated, indications of necrosis of that segment were expected, followed by resection and end-to-end anastomosis. Two milliliter of saline and 5 mg/kg Bosentan was given intraperitoneally in Group 2 and 3, respectively. On postoperativ day 6, intra-abdominal adhesions were scored. Healing of anastomosis, anastomotic bursting pressures, tissue hydroxyproline levels and histopatologically healing scores were assessed. RESULTS: Macroscopic adhesion score in Group 3 was lower than the remained groups (p < 0.05). Tissue hydroxyproline levels were significantly higher in Group 3 compared to the Groups 1 and 2 (p < 0.001). Mean anastomotic bursting pressures were 200 mmHg, 164 mmHg and 240 mmHg in Groups 1, 2 an 3, respectively (p < 0.05 between Groups 1 and 3; p < 0.001 between Groups 2 and 3). Histopathologically, healing scores of Group 1 were significantly higher than the other groups (p < 0.05 group 1-3, group 2-3). CONCLUSION: Bosentan increases anastomotic healing of ischemic colonic anastomosis and decreases intra-abdominal adhesion formation.