Safak Ersoz

Jaw bone changes in rats after treatment with zoledronate and pamidronate

OBJECTIVE The aim of this study was to histopathologically evaluate the effects of pamidronate and zoledronate on the mandible in an animal model. STUDY DESIGN Sixty female Sprague-Dawley rats were used in this study. Animals were divided into 6 groups (10 per group): control-1 (C1), injected with saline solution for 6 weeks; zoledronate-1 (ZA1), injected with zoledronate for 6 weeks; pamidronate-1 (PA1), injected with pamidronate for 6 weeks; control-2 (C2), injected with saline solution for 8 weeks; zoledronate-2 (ZA2), injected with zoledronate for 8 weeks; and pamidronate-2 (PA2), injected with pamidronate for 8 weeks. No dental procedures were performed on the animals. Rats were killed 2 days after the end of drug therapy, and the posterior and anterior mandible and femur of each rat were evaluated histopathologically. RESULTS Histological examination revealed inflammation limited to the posterior mandible of the ZA2 and PA2 groups; the anterior mandible and femur were not affected. Soft tissue necrosis was evident in one rat in the ZA2 group. CONCLUSION Specific, bisphosphonate-associated inflammatory bony and soft tissue changes were observed in the mandible, suggesting that these drugs may set the stage for altered healing associated with the development of bisphosphonate-related osteonecrosis of the jaw.

Prognostic importance of Claudin-1 and Claudin-4 expression in colon carcinomas

In this study, we analyzed Claudin-1 and Claudin-4 expressions in colon carcinomas. We investigated the relationship between the expression of these tight junction proteins and clinicopathologic parameters. Claudin-1 and 4 expressions were determined by immunohistochemical methods, and the rate of cells expressing these tight junction proteins were calculated with stereologic methods. Fifty-nine colon cancer cases were enrolled in the study group. Claudin-1 and 4 expressions were found to be significantly lower in cases with lymph node metastasis. Mean staining rates of Claudin-1 and 4 in lymph node (+) cases were 36.1±20.1 and 58±28.9, while in lymph node (-) cases, these were 63.8±25.9 and 72.3±25.6, respectively (p=0.0005 for Claudin-1, p=0.049 for Claudin-4). The mean staining rate for Claudin-1 in adenomatous polyps was significantly higher than incarcinomas (77.13±23.4 and 50.6±26.93, respectively) (p=0.003), while it was quite similar for Claudin-4 (65.4±26.9 and 65.3±27.9, respectively). In this study, we demonstrated Claudin-1 and 4 expressions in colon cancer cases. Claudin-1 expression seems to be more prominent in adenomatous polyps as compared with cancer cases. Expression of Claudin-1 decreases significantly in the presence of lymph node metastasis and diminishes in mucinous carcinoma cases, indicating a negative correlation between Claudin-1 expression and neoplastic progression.

Protective Effect of the Grape Seed Proanthocyanidin Extract in a Rat Model of Contrast-Induced Nephropathy

Aim: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on preventing CIN. Materials and Methods: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index (AI) and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. Conclusion: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis.

Does an alkaline environment prevent the development of bisphosphonate-related osteonecrosis of the jaw? An experimental study in rats

OBJECTIVE To investigate the preventive effect of locally applied sodium bicarbonate on bisphosphonate-related osteonecrosis of the jaw (BRONJ). STUDY DESIGN Thirty-six Sprague-Dawley rats were divided into 4 groups. Animals in group I received 0.1 mg/kg sterile saline 3 times per week for 8 weeks. Groups II, III, and IV received intraperitoneal zoledronate injection in the same manner with the same frequency and duration. The right first molar tooth was extracted in groups III and IV. One mL 8.4% sodium bicarbonate (SB) was applied to the extraction socket at the time of extraction in group IV. The effect of locally applied SB as an alkalizing agent was evaluated by histomorphometric analysis. RESULTS BRONJ was observed in none of the animals in the control groups, 67% of the animals in the tooth extraction group, and none of the animals in the local SB application group (P < .01). CONCLUSIONS Administration of locally applied SB had positive effects on the prevention of BRONJ in animals, but further studies are required to verify the effectiveness of this form of treatment before its use in humans.

The effects of adjunctive parathyroid hormone injection on bisphosphonate-related osteonecrosis of the jaws: an animal study

Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) is a serious and challenging complication of chronic BP uptake in patients with osteoporosis who require management of skeletal-related events. The efficiency of adjunctive parathyroid hormone (PTH) injection was evaluated after chronic BP administration that was followed by tooth extraction. BRONJ was not observed in any of the subjects in the control groups, while BRONJ was observed in 66% and 22% of the subjects in the tooth extraction group and the tooth extraction with PTH injection group, respectively. In addition the presence and severity of inflammation was lower in the PTH injected group than in the tooth extraction group, but the difference was not statistically significant (P>0.01). In conclusion, the administration of 30μg/kg/day PTH during a period of 8 weeks had positive effects on the resolution of BRONJ, but further studies are required to verify the effectiveness of PTH in the treatment of BRONJ.

A Case of Acute Colitis with Severe Rectal Bleeding in a Patient with Chronic Myeloid Leukemia after Dasatinib Use

matologic remission. Ten weeks after starting dasatinib treatment, the patient was admitted to our hospital with abdominal pain and rectal bleeding. Laboratory results were as follows: hemoglobin 10.3 g/dl, white blood cells 6 ! 10 9 /l, platelets 185 ! 10 9 /l, prothrombin time 14 s, active partial thromboplastin time 33.3 s, international normalized ratio 1.25. Stool examination was negative for parasites and other pathogenic bacteria. Sigmoidoscopic examination was performed with only rectal osmotic laxative without entire colon cleansing. There was no active bleeding, but multiple milimetric nodular hyperemic lesions on the mucosa were seen in the left side of colon and biopsies were taken during sigmoidoscopic examination ( fig. 1 ). Histopathological findings revealed nonspecific active colitis ( fig. 2 ). The patient was hospitalized and dasatinib treatment was stopped. No bleeding was observed during follow-up and colonoscopy was performed 2 weeks later. Endoscopic and histopathological findings were all normal, and dasatinib treatment was restarted. The patient was admitted to the hospital again with hematochezia 1 month after dasatinib administration. Colonoscopy repeated and findings were consistent with acute colitis. Again dasatinib treatment was stopped and patient was observed for 5 days in hospital without any bleeding. Repeated colonoscopy was normal after dasatinib treatment discontinuation. Nilotinib (400 mg/day) was started as an alternative to dasatinib for CML treatment. The patient remained in hematological remission during 6 months of follow-up without any further complication. Dasatinib is a second-line tyrosine kinase inhibitor used in imatinib resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia. It inhibits several critical oncogenic proteins, including bcr-abl, Src familial kinase, Kit, platelet-derived growth factor receptor and ephrin A receptor kinase. Dasatinib, which binds both active and inactive conformation of bcr-abl oncoprotein, has greater potency than imatinib for both wild-type and mutant BCR-ABL, except the T315I mutation [1, 2] . Mild to moderate thrombocytopenia and neutropenia occurred in approximately 50% of patients, but it is generally well tolerated. Other side effects are diarrhea, headache, weakness, pleural effusion, nausea and peripheral edema. Gastrointestinal bleeding may occur in up to 7% of patients using dasatinib [3] . Current literature suggests severe rectal bleeding due to acute colitis during dasatinib treatment has been reported only in 1 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia patient [4] . Here, we report an adult case with acute colitis with severe rectal bleeding after dasatinib use. This complication has not been previously reported in an adult population. A 55-year-old patient had been diagnosed with blastic phase of CML 2 years ago. After remission induction treatment including cytosine arabinoside, idarubicin and imatinib (400 mg/day), maintenance treatment was continued with imatinib. During the follow-up, dasatinib (100 mg/day) was started because of disappearance of heReceived: December 14, 2009 Accepted after revision: January 28, 2010 Published online: April 8, 2010

Antiapoptotic and Antioxidant Effects of GSPE in Preventing Cyclosporine A-Induced Cardiotoxicity

Objectives: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. Materials and methods: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. Conclusion: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities

Amikacin-Induced Nephropathy: Is There Any Protective Way?

Amikacin is a commonly used antibacterial drug that can cause significant nephrotoxic effects in both humans and experimental animals. It has been reported that one mechanism of the toxic effects of aminoglycoside antibiotics are the result of oxidative reactions. The aim of this study is to examine the effects of N-acetylcysteine, a thiol-containing antioxidant, on renal function (serum creatinine) and morphology (renal tubular damage) in mice subjected to amikacin-induced nephrotoxicity. A total of 32 mice were equally divided into four groups that were injected with either saline, amikacin (1.2g/kg intraperitoneally), N-acetylcysteine (150mg/kg intraperitoneally for three days) plus amikacin (1.2 g/kg intraperitoneally on the third day as a single dose), or N-acetylcysteine (150mg/kg intraperitoneally). Amikacin administration led to granulovacuolar tubular degeneration in light microscopic examination and myeloid bodies, mitochondrial electron-dense material deposition, and mitochondrial swelling in the proximal tubule epithelium in the electron microscopic evaluation. N-acetylcysteine administration before amikacin injection caused significant decreases in myeloid body and mitochondrial swelling and granulovacuolar tubular degeneration formation. Serum creatinine levels did not change as a result of any treatment. The results show that N-acetylcysteine has a protective effect on nephrotoxicity induced by amikacin. Higher doses of amikacin should be tried to observe biochemical effects.

The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy.

Background/Aims: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. Methods: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. Results: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. Conclusion: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

The Significance Of Galectin-3 Expression in the Immunocytochemical Evaluation of Thyroid Fine Needle Aspiration Cytology

The aim of this study is to evaluate the significance of immunohistochemical expression of Galectin-3 in the differential diagnosis of benign and malignant thyroid nodules. We studied the fine needle aspiration specimens of 38 patients who had evaluated for nodular goiter and undergone a thyroid surgery between 2004–2005. Slides had been stained immunocytochemically with Galectin-3. The cytoplasmic staining of Galectin-3 was analyzed. Three cases of five follicular carcinomas had positive staining for Galectin-3, while two had not. Two cases with follicular adenomas were negative for Galectin-3. Five cases of six papillary carcinomas had positive staining for Galectin-3, while one case (the case with a papillary microcarcinoma) had not. The single cases with medullary and anaplastic carcinomas were negative for Galectin-3. None of the cases with a benign thyroid pathology had positive staining for Galectin-3. Galectin-3 immunocytochemical staining, had a sensitivity of 61.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 83.3% for thyroid malignancies. For the evaluation of follicular neoplasm, Galectin-3 immunocytochemical staining had a sensitivity of 60%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 50%. Galectin-3 expression in thyrocytes is a strong indicator of a malignant proliferative lesion especially for papillary and to an extent in follicular thyroid neoplasms. Galectin-3 could be used as a supplementary marker for cytological diagnosis.