Investigation of Insulin-Like Growth Factor-1 (IGF-1), P53, and Wilms' Tumor 1 (WT1) Expression Levels in the Colon Polyp Subtypes in Colon Cancer.

BACKGROUND There is no study in the literature investigating the expression levels of WT1, p53, and IGF-1 in colon polyp subtypes. In this study, we aimed to investigate the expression levels of IGF-1, p53, and WT1 in colon polyp subtypes and to determine whether expression levels are correlated with each other. MATERIAL AND METHODS Tissue specimens were obtained from 105 patients (80 men, 25 women; age range, 30-91 years) who underwent surgical resection for colorectal cancer (CRC) at Ordu University School of Medicine, Department of Pathology between January 2015 and 2017. Parameters such as age, sex, region of origin, and pathological diagnosis type were determined. The preparations were immunohistochemically stained with corresponding markers. RESULTS The results of the study showed that there was a statistically significant relationship between WT1 expression (negative - positive) in polyps and the place where the sample was taken (P=0.011). There is a positive relationship between P53 staining score (0-3) and positive frequency of IGF-1 (60.9-85.7%). There was a statistically significant change in P53 scores and location (P=0.006, p=0.015, respectively). As the P53 score of the polyps increased (0 to 3), the rate of adenomatous (34.8-78.4%) increased, so a positive relationship was found. WT1 and IGF-1 gene expression was associated with tumor location, p53 staining score, and sex. CONCLUSIONS WT1 and IGF-1 are appropriate markers for CRC, and WT1 expression in CRC primary tumors especially could be a novel independent marker for prognosis and tumor progression.

Adipose Tissue-Derived Stromal Vascular Fraction Increases Osteogenesis in an Experimental Design Zygomatic Bone Defect Model.

INTRODUCTION: Facial bone defects are frequently encountered problems in clinical practice. Bone grafts, flaps, and alloplastic materials are often used in their treatment. This leads to donor site morbidity and prolongation of the operation. The authors have planned this study to examine whether adipose tissue derived stromal vascular fraction (SVF) has an osteogenic effect in the critical sized membranous bone defect of the zygomatic bone. MATERIALS AND METHODS: Twenty male Wistar Albino rats were used. Bilateral zygomatic arches were opened with lateral incisions. A standard 3-mm bone defect was created bilaterally on the zygomatic arches of the rats. In the experiment side, the stem cell-rich SVF that was obtained by applying centrifugal process to the adipose tissue derived from the inguinal fat pad was injected into the site of the right zygomatic arch bone defect. In the control side, left zygomatic arch was left for secondary bone healing without any treatment after a 3-mm critical bone defect was created. In the postoperative 10th (n:5) and 20th weeks (n:13), the healing areas of bone defects were assessed by a 3-dimensional tomography, and then, the rats were sacrificed and bone healing was examined histologically. RESULTS: There were no statistically significant differences on the 10th week results. At the 20th week new bone formation amount calculated from the 3-dimensional computed tomography results was significantly higher in the experiment side (P = 0.033). In the histological examination at the 20th week, there was significantly more callus formation in the experiment side (P = 0.0112). DISCUSSION: Stem cells can increase the rate of bone healing by differentiating into certain tissues. It is predicted that adipose tissue-derived SVF rich with mesenchymal stem cells can increase bone healing in facial bone defects and this application could replace the use of bone grafts and flaps in clinical practice. As a result, it is concluded that adipose tissue-derived stem cells can potentiate osteogenesis and reduce the possibility of developing necrosis on the bone ends.

The effect of smoking on placental pendrin expression.

Pendrin is important for transport of iodine across the placenta. Thiocyanate coming from cigarette is a competitive inhibitor of iodine transport. We aimed to evaluate the pendrin immunostaining intensity in placentas of smoker and non-smoker women. Placental tissues from 61 women, of which 28 were in smoking, and 33 were in non-smoking group were evaluated by immunohistochemical staining. Positive immunostaining was evaluated using a semiquantitative score: 0, negative; +, mild; ++, moderate; and +++, intense. Birth weight was significantly lower in the smoker group (p = 0.024). There was a negative correlation between birth weight and intensity of placental pendrin immunostaining in the smoker group (r = -0.44, p = 0.02). Placentas of the smoking women showed significantly higher immunostaining with pendrin than the control group (p = 0.006). Thiocyonate coming from cigarettes may competitively inhibit pendrin mediated iodine transport in the placenta and adversely affect foetal development by this mechanism.

Relationship of CD95 and COX-2 in renal cell carcinomas with survival and other prognostic parameters: A tissue microarray study.

OBJECTIVE: To investigate the expression of cyclooxygenase-2 and cluster of differentiation 95 in renal cell carcinomas having different clinico-pathological characteristics. METHODS: The study entailed histopathological diagnoses carried out on paraffin blocks at the Department of Pathology of the Medical Hospital of Duzce University, Turkey, between 2005 and 2011. Immunohistochemical staining for cyclooxygenase-2 and cluster of differentiation 95was performed on tissue microarray using standard procedures. Each patient's age and gender as well as the tumour's grade, stage, diameter, ureteral surgical margins, vascular invasion, capsule invasion and subtype were assessed. In order to determine if the cases were still alive, relatives were telephoned and identity registration records were checked. SPSS 18 was used for statistical analysis. RESULTS: There were 49 paraffin blocks in the study.Significant correlations were found between cyclooxygenase-2 and tumour subtype (p=0.044) as well as between cyclooxygenase-2 and tumour diameter (p=0.026). There was a significant correlation between cluster of differentiation 95and the Fuhrman grade (p=0.050). CONCLUSIONS: Expression of cluster of differentiation 95and cyclooxygenase-2 may be correlated with prognostic parameters in renal cell carcinoma and may also be associated with tumour progression.

Protective role of Proanthocyanidin in experimental ovarian torsion.

BACKGROUND: Proanthocyanidin is a potent bioactive antioxidant naturally occurring in grape seed and acts as reactive oxygen species (ROS) scavenger. The aim of this study was to investigate the effects of proanthocyanidinin in experimental ovarian torsion injury. METHODS: Twenty four rats were randomly divided into three groups (n=8). Group 1: the laparotomy group, group 2: ovarian torsion group, and group 3: intervention group administered proanthocyanidinin of 50 mg/kg before bilateral ovarian ischemia and reperfusion. Histologic examination and scoring was done at the end of the experiment. Statistical analyses were performed using the SPSS v. 19. RESULTS: Ovarian histopathologic findings of all three groups were significantly different in terms of hemorrhage (p<0.001), edema (p=0.001) and vascular dilatation (p< 0.001). Pathologic changes induced by I/R were reduced in ovaries of rats administered proanthocyanidin, in particular, hemorrhage, edema and vascular dilatation. CONCLUSION: Proanthocyanidin, known as free radical scavenger and antioxidant, is protective against tissue damage induced by ischemia and/or ischemia/reperfusion in rat ovaries.

Dermal absorption and toxicity of alpha amanitin in mice.

The fungus Amanita phalloides is known to contain two main groups of toxins: amanitins and phallotoxins. The amanitins group effectively blocks the RNA polymerase II enzyme found in eukaryotic cells. As alpha amanitin has a lethal effect on the majority of eukaryotic cells, it can be valuable as an antiparasitic or antifungal drug. It can be used externally against ectoparasites. It is critical that percutaneous applications of the alpha amanitin toxin are not harmful to the recipient. In this study, the absorption and the toxicity of percutaneous and intraperitoneal (ip) applications of 1 mg/kg alpha amanitin to mice were compared. Potential skin, liver and kidney toxicities were investigated through pathological examination. HPLC analysis was used to determine the amount of the toxin. No toxicity or toxin were found in the skin, liver, or kidneys of the mice in the control group. Interestingly, the percutaneous application group also showed no toxicity, and the toxin was not present in this group. After 24 h, Councilman-like bodies and pyknotic cells were observed in the mice in which alpha amanitin was applied intraperitoneally, demonstrating the presence of toxicity. Peak levels of alpha amanitin (µg/mL) in the liver, kidney, and blood in the ip application group were measured at 3.3 (6 h), 0.2 (6 h) and 1.2 (1 h), respectively. The results demonstrated that the toxin was not absorbed through the skin of the mice and that the percutaneous application of alpha amanitin did not have any toxic effects. Thus, alpha amanitin may be administered percutaneously for therapeutic purposes.

Two different treatment options for intramuscular plantar hemangioma: surgery versus percutaneous sclerotherapy.

Intramuscular hemangiomas are benign neoplasms usually seen in children and adolescents. They tend to occur in the deep fascia and muscle and more often in the lower extremity, although they are rarely encountered in the plantar musculature. Surgical excision, ultrasound- or fluoroscopic-guided percutaneous sclerotherapy, and angiographic embolization are all treatment options. Surgical excision is the most prevalent form of therapy, although this can be difficult in the hands and feet. For this reason, ultrasound- and fluoroscopic-guided percutaneous sclerotherapy is a useful treatment option for pedal intramuscular hemangioma. In the present report, we describe 2 cases of intramuscular hemangioma in children, 1 treated by excision and 1 by percutaneous sclerosis.

Expression of AEG-1 and p53 and their clinicopathological significance in malignant lesions of renal cell carcinomas: a microarray study.

The aim of this study was to investigate the relationship of AEG-1 and p53 with the prognostic parameters of renal cell carcinoma (RCC). In this study, 50 paraffin blocks were histopathologically diagnosed at the Department of Pathology of the Medical Hospital of Duzce University, between 2005 and 2011. The cases consisted of 24 clear cell (CC) and 26 non-clear cell (NCC) RCC subtypes as follows: 24 (48%) clear cell RCC, 12 (24%) papillary RCC, 4 (8%) multilocular cystic RCC and 10 (20%) chromophobe RCC; none had sarcomatoid changes. By immunohistochemical analysis we investigated AEG-1 and p53 expression in carcinomas of the kidney, and by statistical analysis determined their relationship with clinicopathological parameters. Significant relationships were found between increasing tumor diameter and the increase of p53 (p = 0.028). In addition, p53 was significantly related to renal sinus invasion (p = 0.05) and Fuhrman grade (p = 0.026). There was a significant relationship between increased AEG-1 staining scores and CC and NCC carcinoma subtypes (p = 0.032), tumor capsule invasion (p = 0.01) and lymphovascular invasion (p = 0.015). There was also a significant correlation between tumor size and capsule and lymphovascular invasion (p = 0.02). We concluded that high AEG-1 and p53 expression correlates with the prognostic parameters in RCC patients, and in addition may be associated with tumor progression.

Acute generalized exanthematous pustulosis associated with terbinafine: a case report.

A 27-year-old male patient who has used oral terbinafine for two weeks was admitted to our outpatient clinic for non-follicular millimetric pustules on erythematous and edematous different-sized plaques on his trunk and flexural areas. He was diagnosed with acute generalized exanthematous pustulosis (AGEP) because of terbinafine use in the light of history, clinical and histopathological findings. An AGEP is a rare and severe pustular reaction usually triggered by systemic drug intake. Approximately, 2.3% of the patients having oral terbinafine have been reported to develop cutaneous adverse effects. Although terbinafine is a commonly used medicine, it must be considered that it may cause severe adverse reactions.

Neutrophilic eccrine hidradenitis induced by cetuximab.

Cetuximab is an epidermal growth factor receptor inhibitor used in metastatic colorectal cancer, and head and neck cancers. Several cutaneous side effects due to cetuximab such as acne-like rash, pruritus, dry skin, desquamation, hypertrichosis, and paronychia have been reported so far. A 59-year-old male patient with metastatic colon cancer referred to our outpatient clinic for his lesions on the dorsal surfaces of his hands and wrists, and on thighs developing after the chemotherapy. He was diagnosed as neutrophilic eccrine hydradenitis related to cetuximab in the light of clinical and histopathological findings. According to our knowledge, this is the first reported case of neutrophilic ecrine hydradenitis due to cetuximab.

Correlation of E-cadherin, VEGF, COX-2 expression to prognostic parameters in papillary thyroid carcinoma.

Thyroid cancer represents approximately 1% of all human malignancies. papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland, accounting for 70-80% of all thyroid cancers. In the US, the incidence of thyroid cancer is 4 per 100,000 individuals. It is two to four times as frequent in women as in men. The development of PTC is influenced by many factors including genetic alterations, growth factors, and physical agents such as radiation. In order to recognize the prognosis for PTC, a lot of clinic and pathological parameters such as; age, tumor size, extra-thyroid tumor spread, lymph node, distant metastases, gender, tumor stage are used. As most of these parameters are subjective, more objective and useful prognostic factors are needed for determining biologic behavior, providing an initial assessment. In this study, we aimed to compare the expressions of COX-2, E-cadherin, VEGF to classical prognostic factors, and to investigate the correlation with prognosis. Operation records from 79 PTC cases were examined retrospectively. In the study, we aimed to investigate the whole tissue by means of stereology method, which is an impartial one, and we indicated the expression COX-2, VEGF, E-cadherin immunohistochemically in 79 resection diagnosed with PTC. We determined correlations between the expressions of COX-2 and VEGF, E-cadherin, and age, gender, and stage.

Superficial Acral Fibromyxoma: A case report.

INTRODUCTION: Superficial Acral Fibromixoma is a benign and rare tumor of the soft tissues, also it called digital fibromyxoma. It is a painful, slow growing solitary mass that is frequently observed in the fingers, toes and nail beds. Local recurrence is often associated with a positive margin. PRESENTATION OF CASE: A 54-year-old male patient had admitted to local state hospital with complaint of a two-lobed mass lesion in the 5th finger of the right hand. The lesion was closely adjacent to the 5th finger flexor tendon. The specimen of the patient undergoing excisional biopsy was sent to our pathology department. CONCLUSION: Superficial Acral Fibromyxoma is one of the rare benign myxoid neoplasms. Its treatment is surgical excision. We reported the case for its rarity and to keep in mind in the acral region neoplasms.

The role of N-acetylcysteine in preventing hepatic injury associated with systemic oxidative stress after extracorporeal shock wave treatment.

BACKGROUND: Systemic oxidative stress may cause detrimental consequences for the liver, leading to hepatic fibrogenesis. OBJECTIVES: To investigate histopathological changes in liver tissues due to the increased systemic oxidative stress associated with rat extracorporeal shock wave lithotripsy (SWL) model and to document the consequences of N-acetylcysteine (NAC) administration. MATERIAL AND METHODS: In this experimental SWL model, 18 Wistar albino rats were randomly assigned into 3 groups. The control group (group I) had no intervention. Group II underwent SWL treatment with intraperitoneal saline injection. Group III also had SWL with intraperitoneal NAC and was divided into short-term (group III-14 days) and long-term (group III-28 days) subgroup. Hepatectomy was performed for histopathological examinations. Histopathological alterations were evaluated with light microscopy. Immunohistological staining for p53 and myeloperoxidase was also performed. RESULTS: Blood samples revealed a significant increase in plasma oxidative stress index (OSI) after plasma total antioxidant status (TAS) and total oxidant status (TOS) had been measured. It was shown that this increased systemic oxidative stress adversely affected liver tissues. Predominantly, sinusoidal dilatation was remarkably observed in rats with significantly high OSI values (p = 0.043). Similarly, periportal necrosis significantly increased in rats with high OSI values (p = 0.033). p53 positivity was also remarkable in rats with systemic oxidative stress (p = 0.049). N-acetylcysteine administration provided a significant decrease in OSI. N-acetylcysteine also improved all these alterations, including p53 staining. Particularly, sinusoidal dilatation was significantly protected in the long-term NAC group (group III-28 days). CONCLUSIONS: We demonstrated that SWL-induced systemic oxidative stress causes histological alterations in liver tissues. Increased p53 and myeloperoxidase staining as markers of oxidative damage were also detected. N-acetylcysteine may protect from these histological and ultra-structural alterations related to oxidative stress.

Tranexamic acid has positive effect in early period of tendon healing by stimulating the tumor necrosis factor-alpha and matrix metalloproteinase-3 expression levels.

OBJECTIVES: This study aims to evaluate the effect of tranexamic acid (TXA) application in tendon healing by using its immunohistochemical effects on tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-3 (MMP-3), and transforming growth factor-beta (TGF-ß) expression; and to identify if TNF-α, MMP-3, and TGF-ß can be used to monitor and evaluate tendon healing or not in tenotomized rat Achilles tendons. MATERIALS AND METHODS: Twelve male Wistar-Albino rats (age 6-7-month-old; weighing 300-350 g) were used in this retrospective study conducted between November 2016 and May 2017. The rats were divided into two groups with similar weights. The right legs of the rats were determined as the study group (TXA), and the left legs as the control serum physiologic (SP) group. Under anesthesia, bilateral Achilles tenotomy was performed and surgically repaired. 1 mL of TXA was applied locally for the right side and 1 mL of SP was locally applied for the left side. Half of the rats were sacrificed at the third week (right leg-TXA3, left leg-SP3) and the other half at sixth week (right leg-TXA6, left leg-SP6) and tendon samples were taken from the extremities. Immunohistochemical findings of TNF-α, MMP-3, and TGF-ß were evaluated on the basis of the frequency and intensity of staining. RESULTS: In TNF-α and MMP-3 and TXA groups, there was a significant difference in staining compared to SP groups (p<0.05). Regarding TNF-α expression, the total index score in the TXA6 subgroup was higher than the TXA3, SP6, and SP3 subgroups (8, 7, 3, and 4, respectively). Overall scores of TNF-α showed that TXA groups had significantly higher scores when compared to SP groups (p<0.05). In addition, total MMP-3 expression scores were significantly higher in TXA groups than in SP groups, respectively; TXA3: 14, TXA6: 11, SP3: 10, and SP6: 9 (p<0.05). However, the degree of staining with TNF-α was found to be significantly lower than MMP-3 (p<0.05). Immunohistochemical reactivity was not observed with TGF-ß. CONCLUSION: Tranexamic acid has positive effect in early period of tendon healing by stimulating the TNF-α and MMP-3 expression levels. TNF-α and MMP-3 can be used to monitor and evaluate tendon healing.

Histologic evaluation of the effects of Er:YAG laser on bone ablation.

AIM: The aim of the present study was to compare the healing of bone defects created using an Er:YAG laser with those defects created using a surgical bone drill. METHODS AND MATERIALS: Fourteen Wistar rats were used for this study. Femurs were perforated with a surgical bone drill, coupled to a micromotor (bur group) to create a bone defect. Another defect was created using a 2940 nm wavelength Er:YAG laser on the same femur (Er:YAG Group). The Er:YAG laser was used with a energy density of 1.5 W in noncontact mode under a water coolant. Incisions were then sutured with polyglycolic acid sutures. Seven rats were sacrificed at day ten and the other seven at day 20 to compare the status of bone repair of each group at those post-surgical intervals. The femurs were fixed with 10% neutral buffered formalin and decalcified in 10% EDTA. The specimens were embedded in paraffin and sectioned at a 5 micron thickness and stained with hematoxylin and eosin (H&E) stain. The specimens were examined at a magnification of X100 and scored using a standardized histologic scoring system. RESULTS: Stages of bone healing including union, spongioza, cortex, and bone marrow development were evaluated and no significant difference between groups were found at days ten and 20 of healing. There was also no significant difference among the two groups in sum of histologic scores on day ten. CONCLUSION: Bone can be ablated effectively and precisely using a Er:YAG laser without the vibration associated with steel surgical burs, but it is a slower process than when burs are used. There was no significant difference between the two groups in terms of bone repair at ten and 20 day intervals of healing. CLINICAL SIGNIFICANCE: Within the limits of this study a 2940 nm Er:YAG laser at 1.5 W can be used with confidence in cases requiring effective bone ablation.

Comparison of incisional delay patterns on a rat random flap model.

One of the simplest form of surgical delay can be performed by placing an incision around the flap without undermining, prior to flap elevation. In this study, we have compared the efficiency of different patterns of skin incision to improve flap survival. Twenty-eight animals were used in four groups. Incisional delay was performed prior to flap elevation in the three experiment groups. Complete incision of the three flap edges was performed in the all experiment groups with the exception of an intact skin section on the middle 1/3rd of the bilateral edges in group 1 (bilateral skin edge preserved delay: BSEPD), of a unilateral edge in group 2 (unilateral skin edge preserved delay: USEPD) and of the superior edge in group 3 (superior skin edge preserved delay: SSEPD) without any undermining. Two weeks following the delay procedure, dorsal skin flaps were raised and reinserted back to their place. The results were evaluated with the measurement of necrotic flap area, microangiographic imaging and histological evaluation. The mean percentage of necrotic flap area to whole flap area was 16.94%, 7.54%, 23.34% and 50.6% in the BSEPD, USEPD, SSEPD and control groups, respectively. In selected microangiographic images, vessels were more prominent in the delay groups. The results of the study indicate that three sided incision with an intact skin on the superior edge is not effective in providing a sufficient delay and flap survival improvement when compared to incisions with intact skin on the unilateral and bilateral edges.

The beneficial effects of subcutaneous Allium cepa injection on random flap survival in rats.

Random flaps are frequently used in the practice of reconstructive surgery. The aim of this experimental study was to investigate the effects of Allium cepa on random flap survival in rats. Fourteen Wistar rats were used for this experimental study. The subjects were divided into experiment and control groups. Rats in the experiment group received daily injections of A. cepa extract for 7 d before the elevation of the flaps. Following the treatment period, elevation and reinsertion of the dorsal flaps were performed. Necrotic and total flaps areas were marked and calculated 7 d after the flap elevation. Histological examinations and microangiography were performed to evaluate the results. The mean value of the proportion of necrotic flap areas to the total flap area was 25.06 and 50.6% in the A. cepa and control group, respectively (p = .0079). In the histological examination, number of vessels identified in the dermis were 23.75 ± 0.7 and 33.75 ± 9 in the A. cepa and control group, respectively (p = .7457). In angiographic images, vessels formations were more noticeable in the A. cepa group. We conclude that preoperative subcutaneous A. cepa injection increases dorsal flap survival in rats.

The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced apoptosis of hippocampal neural cells.

This study investigated the frequency of apoptosis in rat hippocampal neural cells after intraperitoneal nicotine injection, examining the roles of the inflammatory markers myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha) in nicotine-induced brain damage and the protective effects of three known antioxidant agents, N-acetylcysteine (NAC), erdosteine, and vitamin E. Female Wistar rats were divided into seven groups, each composed of nine rats: 2 negative control groups, 2 positive control groups, one erdosteine-treated group (500 mg/kg), one NAC-treated group (500 mg/kg), and one vitamin E-treated group (500 mg/kg). Nicotine was intraperitoneally injected at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Apoptosis level in hippocampal neural cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling) method. Staining of cytoplasmic TNF-alpha in hippocampal neural cells and hippocampus MPO activity were evaluated by immunohistochemistry. Nicotine administration had no effect on local TNF-alpha production, or hippocampal MPO activity. The treatments with erdosteine, NAC and vitamin E significantly reduced the rate of nicotine-induced hippocampal neural cell apoptosis. This findings suggest that erdosteine and NAC can be as effective as vitamin E in protecting against nicotine-induced hippocampal neural cell apoptosis.

Epithelioid hemangioendothelioma of the submandibular gland.

Epithelioid hemangioendothelioma (EH) is a seldom tumor of vascular origin, which occurs at sites such as liver, lung or soft tissues, and has a highly unpredictable malignant potential and clinical course. We submitted a case with epithelioid hemangioendothelioma of submandibular gland. The patient was a 44-year-old woman who presented with left submandibular painly mass. Fine needle aspiration showed a mixed lymphoid population. Contrast enhanced Computerize Tomography (CT) scan revealed that to be a well-circumscribed and including microcalcification in centre 2.5 cm x 2.0 cm mass in diameter without evidence of bony invasion. Submandibular gland was excised. The pathological result was interpretated as epithelioid hemangioendothelioma of the submandibular gland. The patient was seen regularly for recurrence.

Local application of tranexamic acid affects tendon healing negatively in the late period.

OBJECTIVES: This study aims to evaluate the potential adverse effects of tranexamic acid (TA) on tendon healing. MATERIALS AND METHODS: Twelve male Wistar-Albino rats (weighing 300 g to 350 g) were used in the study. Rats were divided into two groups. Right legs of the rats were determined as the TA group and left legs as the serum physiologic (SP) group. Bilateral Achilles tenotomy was performed and surgically repaired. For the right side, 1 mL of TA and for the left side, 1 mL of SP were applied. Half of the rats were sacrificed at the third week and the other half at the sixth week and tendon samples were collected from the extremities. Histological analyses were performed according to the tendon scoring system (Bonar classification). RESULTS: Tenocyte cell morphology was better in the third week in TA group than in SP group. In terms of colloidal organization, SP groups gave superior results in all weeks. An analysis of total tendon healing scores revealed that the results of the third week TA groups were superior to the results of the sixth week TA groups. Tenocyte morphology and total tendon healing scores of rats in the sixth week TA group were statistically significantly lower compared to the third week TA group (tenocyte morphology p=0.009, total score p=0.041). CONCLUSION: In this study, we detected that locally administered TA has an adverse effect on tendon healing in late period. However, further immunohistochemical and biomechanical studies are needed to support these results.