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Biomedical subjects

Petek Korkusuz

Publications and source records attributed to Petek Korkusuz.

14 recordsLinked to original sources

Effects of ischemic preconditioning on rat lung: role of nitric oxide.

Recent studies suggest that ischemic preconditioning (IP) of the lung may have a protective effect in ischemia-reperfusion (I/R) injury. The purpose of the present study was to investigate the preconditioning hypothesis in rat pulmonary vascular bed and to examine the role of nitric oxide (NO) in IP. Isolated rat lung was perfused with Krebs-Henseleit solution containing indomethacin at a constant flow rate and perfusion pressure changes was recorded by a pressure transducer. In rat pulmonary vascular bed, 2 hours of hypothermic ischemia significantly attenuated histamine-induced vasodilator responses without affecting sodium nitroprusside (SNP) vasodilation when compared to sham values. However, 2 cycles of 5 minutes of ischemia and reperfusion that were applied prior to 2 hours of ischemia (IP protocol) prevented the attenuation of histamine-induced vasodilation. On the other hand, IP failed to prevent pulmonary edema after ischemia. Histopathological examination of rat lungs demonstrated that IP was able to protect endothelial cells and type II pneumocytes in lung. Moreover, in IP group, malondialdehyde (MDA) contents of the lung tissue were significantly lower and tissue glutathione (GSH) contents were significantly higher than those in I/R group. Administration of NO synthase inhibitor, N(G)-nitro-L-arginine-methyl ester (L-NAME) prior to the IP protocol abolished the protective effects of IP, but not affected the tissue malondialdehyde and glutathione levels. These results suggest that I/R impaired endothelium-dependent vasodilatory response, whereas endothelium-independent SNP-induced responses were preserved in rat pulmonary vascular bed. IP prevented the impairment of pulmonary vascular endothelium-dependent responses, and these effects may be partially mediated by NO.

Animals↗

Correlation of tissue selectin expression and hemodynamic parameters in rheumatic mitral valve disease.

BACKGROUND AND AIM OF THE STUDY: The study aim was to examine tissue expression of the adhesion molecules E-selectin and P-selectin on atrial, valvular and atrial myocardial blood vessel endothelium in patients with rheumatic mitral stenosis, and to investigate whether such expression was correlated with hemodynamics. METHODS: Thirteen patients (eight women, five men; mean age 51 +/- 10 years) with severe rheumatic mitral stenosis who underwent mitral valve replacement surgery were examined on preoperative day 1, using cardiac catheterization and echocardiography. Specimens from the mitral valve and left atrium of each patient were evaluated for CD 62E and CD 62P expression using indirect immunoperoxidase and immunofluorescence techniques RESULTS: A great majority of patients presented E and/or P selectin expression of variable intensity on atrial, valvular and atrial myocardial blood vessel endothelium. A more diffuse and stronger reaction for CD 62P was noted compared to that for CD 62E. The left ventricular end-diastolic diameter and left atrial diameter were positively correlated with endocardial CD 62P and CD 62E expression. Right atrial pressure was also strongly and positively correlated with endocardial expression of CD 62E (r = 0.80, p 0.03) and CD 62P (r = 0.8, p = 0.02). CONCLUSION: Marked tissue expression of CD 62E and CD 62P was identified on atrial, valvular and atrial myocardial blood vessel endothelium. Moreover, the degree of expression of adhesion molecules was significantly correlated with the left atrial and left ventricular chamber diameters, as well as right atrial pressure.

Adult↗

Focal segmental glomerulosclerosis associated with mitochondrial cytopathy: report of two cases with special emphasis on podocytes.

We report two children with focal segmental glomerulosclerosis (FSGS) associated with mitochondrial cytopathy (MC). Case 1 was diagnosed as MC with the findings of ptosis, ophthalmoplegia, failure to thrive, high serum lactate and pyruvate levels, ragged red fibers in muscle biopsy and the common 4.9 kb deletion in mtDNA when she was four years old. She subsequently developed FSGS four years later. Case 2 was a four month-old girl presenting with feeding difficulty from birth, with vomiting, seizures and nystagmoid eye movements, nephrotic proteinuria and hematuria. Renal biopsy revealed FSGS. Ultrastructural study demonstrated markedly pleomorphic mitochondria in podocytes with a severe effacement of foot processes. The analyses of muscle biopsy and skin fibroblasts for respiratory chain enzymes were found to be normal, while mitochondrial DNA analysis revealed the population of a single deleted mtDNA in the heteroplasmic state. The present cases illustrate FSGS as a rare renal complication of mitochondrial disease and provide further evidence of podocytes possessing abnormal mitochondria which may cause glomerular epithelial cell damage leading to glomerulosclerosis.

Child↗

Decrease in the numbers of mechanoreceptors in rabbit ACL: the effects of ageing.

It is proposed that there is a positive correlation between the numbers of mechanoreceptors and proprioceptive function. On the other hand, normal aging process is associated with deficits in proprioception. This study is designed to test the hypothesis that aging resulted in decreased numbers of mechanoreceptors. Anterior cruciate ligaments of 14 male rabbits (2 months, n=5; 12 months, n=4 and 60 months, n=5) were extracted and the total numbers of Ruffini, Pacini and Golgi tendon-like receptors were accounted. As a result, the numbers of mechanoreceptors, especially Ruffini receptors, decreased with aging (p<0.05). Increased age was associated with changes in the morphology of mechanoreceptors. In conclusion, aging results in both diminished numbers and changed morphology of mechanoreceptors.

Aging↗

Collagen-chondroitin sulfate-based PLLA-SAIB-coated rhBMP-2 delivery system for bone repair.

Bone morphogenetic proteins (BMPs) are osteoinductive proteins used intensively in clinical investigations involving various bone-related treatments. Owing to their high potential in new bone formation they require local application at the treatment site. For this purpose various controlled delivery systems with BMPs as the excipients have been prepared in recent years. Focusing on this clinical need a disc-shaped BMP carrier was designed as a local delivery system using soluble collagen and chondroitin sulfate. In situ release studies carried out with a model protein (FITC-labeled Protein A) presented a very high rate of release; with most of the protein content being released within 24 h. This rate could be decreased by providing a poly(L-lactide) (PLLA) and sucrose acetate isobutyrate-based (SAIB-based) coat around the release system, applied after BMP loading. In this way, it was possible to extend the release period from 24 h to about 12 days. In situ release of BMP from the same carriers, as quantitated using an ELISA kit, was even slower, with 50% of the protein being released in 15 days. In order to be able to secure the BMP delivery system at the bone defect site and to provide support a mesh knitted using Vicryl sutures and bonded with poly(L-lactide-co-glycolide) (PLGA) was tested in in vivo. Two time periods, 1 and 3 weeks, were used to evaluate the healing process. Osteoinduction by the BMP carrier system was assessed by histology-based bone scoring and X-ray examinations. PLLA-SAIB-coated collagen discs containing BMP presented good biocompatibility and optimum osteogenic stimulation. Structural changes in histological micrographs at week 1 indicated dose-dependent periosteal ossification. At the end of week 3 histological findings with both BMP (1 and 2 microg) doses were almost the same.

Animals↗

Immunohistological analysis of normal and osteoarthritic human synovial tissue.

Intercellular communication mediated by cell surface antigens is important in the maintenance of synovial tissue (ST) integrity. Chronic inflammation is a common feature of osteoarthritis (OA). Cellular attachment to and migration into ST is one of the critical aspects of chronic inflammation. This study was undertaken to examine the tissue distribution of a broad spectrum of monoclonal antibodies (mAbs) containing tetraspan antigens (CD9, CD63, CD151), endothelial cell antigens (CD31, CD36, CD105, CD106, CD146), integrins (CD49a-f, CD29, CD41, CD51, CD61), CD39, CD98, CD99, CD143 and, CD147 supplied from fifth and sixth international workshops and conferences on human leukocyte differentiation antigens in a comparative manner in human OA and normal synovium. Ten primary OA patients and six normal individuals were included in this study. The average age of the patients was 65.0 +/- 8.3 years and the average age of the controls was 31.8 +/- 5.3 years. Sections were screened using an indirect immunoperoxidase method. Tetraspan antigens and CD98 presented rather unique staining pattern in OA synovium suggesting special roles for each antigen on the synovial lining layer (SLL). Endothelial cells and type A synoviocytes expressed CD31 and CD36 in OA, but only endothelium in normal subjects. Integrins presented a uniform staining pattern in both groups. There was a positive reaction in some of the ST stromal elements for CD143 in all specimens. In conclusion, human normal and OA synovium were comparatively reviewed by a broad spectrum of mAbs with special attention being given to their functional aspects. This data suggests a significant difference in antigenic phenotype of SLL cells in OA and ST not to be considered at a normal-like state in OA. The fact that their activation was independent of the degree of lymphocyte infiltration further emphasizes the possible central importance of SLL.

Aged↗

Lack of correlation between Tc-99m-sestaMIBI uptake and cadherin expression in infiltrating ductal breast carcinoma as prognostic indicators.

Despite using various kinds of prognostic indicators, it is still not possible to predict the biological behavior of breast cancer in all patients. Tc-99m-sestaMIBI (MIBI) uptake determined by breast scintigraphy and cadherin expression of tumor tissue revealed by immunohistochemistry are suggested as potential agents for this purpose. We hypothesize that there can be a correlation between MIBI whose cellular mitochondrial content is claimed to play a significant role in its tumor uptake and cadherin whose downregulation causes an increase in mitochondrial activity in human mammary carcinoma cell lines. The aim of this study was to assess the relationship between the degree of MIBI tumor uptake and cadherin expression in infiltrating ductal breast carcinoma. Correlation with response to chemotherapy and some known prognostic factors of breast cancer such as tumor size, number of metastatic axillary lymph nodes and microscopic grading was also done. Fourteen patients who underwent scintimammography and subsequent surgical excisional biopsy that revealed infiltrating ductal carcinoma were enrolled in this study. Statistical analysis did not show any correlation between MIBI uptake and cadherin expression (p > 0.05). Also, no statistically significant correlation was noted between MIBI uptake and tumor size, number of metastatic lymph nodes, microscopic grade, stage of the disease or response to chemotherapy. Similarly, there was no statistically significant correlation between cadherin expression and tumor size, number of metastatic lymph nodes, microscopic grade, stage of the disease or chemotherapy response. The results of this study imply that there is no correlation between MIBI tumor uptake and cadherin expression with neither of them good enough to be used as prognostic indicators for breast cancer.

Adult↗

Three-dimensional structure of the modiolus. A computerized reconstruction study.

OBJECTIVE: Modiolus is a dense, compact, mobile fibromuscular structure, reachable by the dissection of buccolabial musculature. We undertook this study to provide detailed information about the macroscopic and microscopic anatomy of modiolus and its 3-dimensional (3-D) shape. METHODS: Fifteen micrometer thick serial sections were taken from the fixed cadaveric tissue samples and then stained with hematoxylin and eosin, and Massons' trichrome stain. Stained sections were photographed digitally and images were transferred to computer medium to perform 3-D reconstruction. The study was carried out in the dissection lab of the Anatomy Department of Hacettepe University, Ankara, Turkey between 2002 and 2003. RESULTS: The modiolus appears to be a tortuous, blunt conelike structure, extending vertically from the buccal mucosa to the dermis of the skin. The base of the cone is adjacent to the mucosa. CONCLUSION: As the structure has great clinical importance, and satisfactory complete 3-D analysis of the subject is not yet available; we believe that our study presenting the histological and 3-D description of the modiolus will be of great help to surgeons for satisfactory esthetic and functional results during surgical operations related to the oral commissure.

Adult↗

Immunophenotypic analysis of human spleen compartments.

Microanatomical compartments of the human spleen are yet under evaluation as most of the present information comes from experiments on animals with different anatomical structures. Immune staining of stromal and blood-born cells by cell surface antigens facilitates the differentiation of functional microanatomical compartmentalization of immune organs, including the spleen. Twenty-two specimens from healthy adult subjects with the average age of 35.6 +/- 13.8 (Range 17 to 58) years were included in this study. Monoclonal antibodies used in this study were supplied from the 5th, 6th and 7th International Workshops and Conferences on Human Leukocyte Differentiation Antigens. Tetraspan antigens presented a rather unique staining pattern in the human spleen, suggesting special roles for each (CD9, CD53, CD63, CD151 and CD231) in certain locations. Sinus lining cells presented a distinctive antigenic profile, sharing both endothelial cell (CD31, CD36, CD54, CD62P, CD102, CD105, CD106 and CD146) and macrophage lineage characteristics. The sheathed capillaries were not restricted to the perifollicular zone alone. Extracellular matrix receptors (CD49 a, CD49 b, CD49 c, CD49 e, CD49f, CD29 and CD44) stained the penicillary arterioles and vascular smooth muscle. These molecules were also found on the vascular endothelium. Leukocyte antigens (CD11a, CD11b, CD22, CD43, CD45, CD45RB, CD45RO and CD50) were mainly expressed in the white and red pulp of the spleen at different intensities, excluding the penicillary arterioles. Activation antigens (CD26, CD71 and CD98) presented a diffuse and broad staining pattern. In conclusion, microanatomical compartmentalization, microcirculation and function of the human spleen were evaluated using a wide panel of monoclonal antibodies.

Antigens, CD↗

Chondroitin sulfate-coated polyhydroxyethyl methacrylate membrane prevents adhesion in full-thickness tendon tears of rabbits.

Polyhydroxyethyl methacrylate (pHEMA) membranes coated on one side with chondroitin sulfate (CS) were used to block adhesion physically and to reduce friction between healing flexor tendons and the surrounding tissue in rabbit forepaws after surgical repair. Digits with pHEMA-only, standard tendon sheath repair, and with no sheath repair were the controls. Over 12 weeks the CS-coated membranes were evaluated for joint flexion, adhesion limitation, and tendon healing progress. The membranes initially allowed for better flexion (ie, for 6 weeks), but their relative superior effectiveness faded afterward. Histology showed that adhesions were less severe and healing was better in the CS-pHEMA membranes at 3 and 6 weeks. If further studies determine precise amounts or thicknesses of CS coats that will maximize its healing properties, CS-pHEMA should prove useful in clinical settings in which restoration of tendon sheath integrity with a minimum of adhesions is not possible.

Animals↗

Effects of probucol in hyperlipidemic rabbit liver: a preliminary ultrastructural study.

Probucol is a lipid-lowering agent with an antioxidant effect; however, its influence on the liver remains unclear. The effects of probucol on hyperlipidemic rabbit liver are investigated to add a structural data on its therapeutical profile. Local albino rabbits were divided into three groups. 1) Hyperlipidemic group: fed with 1% cholesterol (150 g/kg/day) enriched chow for 2 months. 2) Probucol treated group: group 1 + intraperitoneal probucol (10 mg/kg/day) administration for 15 days. 3) Control group fed with normal chow. The blood lipid profile was investigated biochemically. Liver samples were examined electronmicroscopically. Within the parenchymal cells of group 1, the amount of rough surfaced endoplasmic reticulum was increased, its cisterna was dilated displaying a moderately electron dense substance in it and showed close apposition with the condensed mitochondria. In group 2, smooth surfaced endoplasmic reticulum was in extensive amounts filling almost all of the cytoplasm, displayed a reticular, degenerated appearance and was in close relation with the condensed, degenerated mitochondria. Probucol may cause degenerative changes on the liver parenchyme at the subcellular level. It alters the structure of these cells mainly acting on the smooth surfaced endoplasmic reticulum and the mitochondria that are known to be involved in cellular detoxification.

Animals↗

In vivo tissue engineering of bone using poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) and collagen scaffolds.

Porous poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) and calcium phosphate-loaded collagen (CaP-Gelfix) foams were seeded with rat bone marrow stromal cells and implanted into defects created in rat femurs to study in vivo bone formation and to test their suitability for use in bone tissue engineering. At 3 and 6 weeks, new bone formation was evaluated by macroscopy, radiography, dual-energy X-ray absorptiometry (DEXA), and quantitative computerized tomography (QCT). Atomic contents of the implants were further assessed by QCT. Some initial inflammation that significantly decreased with time was observed in the CaP-Gelfix group. PHBV inflammation was minimal at all stages. Fibrous tissue formation in the CaP-Gelfix group was more than in the PHBV group. Both cell-loaded and cell-free PHBV matrices elicited minimal fibrous tissue formation during the 6-week implantation duration. Macroscopic and radiological studies demonstrated better healing with PHBV matrices than with CaP-Gelfix in 3 weeks. Histologically, fibrous connective tissue establishment and inflammation scores were significantly higher in the CaP-Gelfix group when compared with the PHBV group at both time intervals. At 6 weeks, however, the extent of healing was almost the same with both implants. DEXA and QCT results indicated that there was an increase in bone mineral density in both PHBV and CaP-Gelfix implants at the end of 6 weeks. This study suggests that even though PHBV and CaP-Gelfix have different bulk and surface chemistries they both are promising cell carriers that may be suitable for use in bone tissue engineering.

Animals↗

Free oxygen radical-induced acute pancreatitis. A light and electron microscopic study.

BACKGROUND/AIMS: To date direct toxic effects of free oxygen radicals in vivo on pancreatic parenchyma have not been studied thoroughly. We aimed to study: 1) the detailed histopathological changes induced by free oxygen radicals in pancreas; and 2) the preventive effect of intraductal catalase in H2O2-induced acute pancreatitis. METHODOLOGY: Wistar Albine rats were randomized into six groups. 1) First experiment: Bile-pancreatic duct was cannulated close to the liver and perfused through the duodenum with (i) normal saline solution, (ii) iron sulfate (FeSO4), (iii) hydrogen peroxide (H2O2), (iv) hydrogen peroxide and iron sulfate simultaneously. 2) Second experiment: Bile pancreatic duct was perfused either with H2O2 or H2O2 + catalase. Serum amylase and pancreas malondialdehyde levels were measured in both experiments after 3 hours of perfusion period. Tissue samples were obtained for histopathological examinations. RESULTS: 1) First experiment: Intraductal perfusion of FeSO4 or H2O2 or H2O2 + FeSO4 induced acute edematous pancreatitis with focal parenchymal necrosis. At the ultrastructural level, intracytoplasmic formation of vacuoles. fusion of the vacuoles and zymogen granules, and autophagosomes containing cellular organelles were found. Serum amylase and pancreas malondialdehyde levels, and morphological score were significantly higher in these groups than control group (p < 0.001). 2) Second experiment: Catalase perfusion simultaneously with H2O2 decreased the serum amylase and pancreas malondialdehyde levels, and morphological score significantly (p < 0.001) and prevented the desquamation of the columnar epithelium and development of gross edema but not parenchymal necrosis. CONCLUSIONS: Intraductal perfusion of FeSO4 or H2O2 or H2O2 + FeSO4-induced acute pancreatitis with marked light and electronmicroscopic changes. Intraductal perfusion of catalase and H2O2 simultaneously did not prevent or lessen the parenchymal necrosis. These findings have suggested that another mechanism of injury may also play a role in parenchymal injury in oxygen radical-induced acute pancreatitis.

Acute Disease↗