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Aim: Small intestine (SI) transit in the streptozotocin (STZ) induced diabetic rats were examined by using 99mTcmebrofenin scintigraphy. Materials and methods: Wistar albino rats (mean body weight: 220±12 g) were studied for both control (n=10) and diabetes mellitus (DM) (n=10) groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg kg(-1) body weight. SI transit time was assessed by measuring arrival times of 99mTc-mebrofenin from duodenum to caecum. Results: The mean transit time of 99mTc- mebrofenin was 67.8±11 min in control group. The mean transit time of SI was prolonged in STZ induced diabetic animals with (111.9±12.5, p=0.01). There was significant correlation between small intestinal transit time and blood glucose level (r: 0.73, p=0.01). Conclusion: We observed that SI transit was prolonged in diabetic animals using 99mTc- mebrofenin, and additionally this technique is a readily available method for the detection of transit abnormalities in animal experiment. [ABSTRACT FROM AUTHOR]

Primary lung tumors mimicking the salivary gland-type neoplasms are extremely rare. These types of tumors originate from submucosal bronchial glands. Epithelial-myoepithelial carcinoma is an uncommon tumor in this group, and only 7 cases have been reported. It is considered to be a low-grade malignant neoplasm. We report a case of epithelial-myoepithelial carcinoma of bronchial gland origin in a 73-year-old man who presented with coughing and dyspnea. The bronchus of the left lower lobe contained a tumor mass that had a polypoid growth pattern. The tumor also extended into the pulmonary parenchyma, forming a well-circumscribed mass with a pushing margin. The tumor consisted of epithelial and myoepithelial cells. The epithelial cells were positive for cytokeratins and epithelial membrane antigen, while the myoepithelial cells were positive for S100 protein and muscle-specific actin. According to these findings, we diagnosed epithelial-myoepithelial carcinoma. After undergoing pneumonectomy, the patient has been disease free for 34 months. [ABSTRACT FROM AUTHOR]

Microcystins (MC) are a group of structurally similar cyanotoxins with currently 279 described structural variants. Human exposure is frequent by consumption of contaminated water, food or food supplements. MC can result in serious intoxications, commensurate with ensuing pathology in various organs or in rare cases even mortality. The current WHO risk assessment primarily considers MC-LR, while all other structural variants are treated as equivalent to MC-LR, despite that current data strongly suggest that MC-LR is not the most toxic MC, and toxicity can be very different for MC congeners. To investigate and analyse binding and conformation of different MC congeners, we applied for the first time Molecular Dynamics (MD) simulation to four MC congeners (MC-LR, MC-LF, [Enantio-Adda5]MC-LF, [β-D-Asp3,Dhb7]MC-RR). We could show that ser/thr protein phosphatase 1 is stable in all MD simulations and that MC-LR backbone adopts to a second conformation in solvent MD simulation, which was previously unknown. We could also show that MC congeners can adopt to different backbone conformation when simulated in solvent or in complex with ser/thr protein phosphatase 1 and differ in their binding behaviour. Our findings suggest that MD Simulation of different MC congeners aid in understanding structural differences and binding of this group of structurally similar cyanotoxins., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this manuscript, which appeared in ALTEX (2020), 37(1), 24-36, doi:10.14573/altex.1904031 , there were errors in Tables 1 and 3.

Microcystins (MC) represent a family of cyclic peptides with approx. 250 congeners presumed harmful to human health due to their ability to inhibit ser/thr-proteinphosphatases (PPP), albeit all hazard and risk assessments (RA) are based on data of one MC-congener (MC-LR) only. MC congener structural diversity is a challenge for the risk assessment of these toxins, especially as several different PPPs have to be included in the RA. Consequently, the inhibition of PPP1, PPP2A and PPP5 was determined with 18 structurally different MC and demonstrated MC congener dependent inhibition activity and a lower susceptibility of PPP5 to inhibition than PPP1 and PPP2A. The latter data were employed to train a machine learning algorithm that should allow prediction of PPP inhibition (toxicity) based on MCs 2D chemical structure. IC50 values were classified in toxicity classes and three machine learning models were used to predict the toxicity class, resulting in 80-90% correct predictions.

Cyanobacterial microcystins (MCs), potent serine/threonine-phosphatase inhibitors, pose an increasing threat to humans. Current detection methods are optimised for water matrices with only a few MC congeners simultaneously detected. However, as MC congeners are known to differ in their toxicity, methods are needed that simultaneously quantify the congeners present, thus allowing for summary hazard and risk assessment. Moreover, detection of MCs should be expanded to complex matrices, e.g., blood and tissue samples, to verify in situ MC concentrations, thus providing for improved exposure assessment and hazard interpretation. To achieve this, we applied two synthetic deuterated MC standards and optimised the tissue extraction protocol for the simultaneous detection of 14 MC congeners in a single ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) run. This procedure was validated using plasma and liver homogenates of mice (male and female) spiked with deuterated MC standards. For proof of concept, tissue and plasma samples from mice i.p. injected with MC-LR and MC-LF were analysed. While MC-LF was detected in all tissue samples of both sexes, detection of MC-LR was restricted to liver samples of male mice, suggesting different toxicokinetics in males, e.g., transport, conjugation or protein binding. Thus, deconjugation/-proteinisation steps should be employed to improve detection of bound MC.

Microcystins (MCs) are highly toxic natural products which are produced by cyanobacteria. They can be released to the water during harmful algal blooms and are a serious threat to animals and humans. Described is the total synthesis of the cyanotoxin microcystin-LF (MC-LF, 1a) and two derivatives thereof. Deuterated derivative 1b is of interest as an internal standard during MC quantification in biological samples by mass spectrometry and alkyne-labeled 1c can be employed for toxin derivatization by click chemistry with an azide-containing reporter molecule or as an activity-based probe to identify interaction partners. Application of tert-butyl ester protecting groups for erythro-β-d-methylaspartic acid and γ-d-glutamic acid were key for an isomerization-free synthesis. The analytical data of synthetic MC-LF were identical to those of an authentic sample of the natural product. All derivatives 1a-c were determined to be potent inhibitors of protein phosphatase-1 with similar activity.

Cyanobacteria can produce heptapetides called microcystins (MC) which are harmful to humans due to their ability to inhibit cellular protein phosphatases. Quantitation of these toxins can be hampered by their adsorption to common laboratory-ware during sample processing and analysis. Because of their structural diversity (>100 congeners) and different physico-chemical properties, they vary in their adsorption to surfaces. In this study, the adsorption of ten different MC congeners (encompassing non-arginated to doubly-arginated congeners) to common laboratory-ware was assessed using different solvent combinations. Sample handling steps were mimicked with glass and polypropylene pipettes and vials with increasing methanol concentrations at two pH levels, before analysis by liquid chromatography-tandem mass spectrometry. We demonstrated that MC adsorb to polypropylene surfaces irrespective of pH. After eight successive pipet actions using polypropylene tips ca. 20% of the MC were lost to the surface material, which increased to 25%-40% when solutions were acidified. The observed loss was alleviated by changing the methanol (MeOH) concentration in the final solvent. The required MeOH concentration varied depending on which congener was present. Microcystins only adsorbed to glass pipettes (loss up to 30% after eight pipet actions) when in acidified aqueous solutions. The latter appeared largely dependent on the presence of ionizable groups, such as arginine residues.

Background: Microcystins (MCs) contaminate water bodies due to cyanobacterial blooms all over the world, leading to frequent exposure of humans to MCs through consumption of meat, fish, seafood, blue-green algal products and water, accidental ingestion of contaminated water and scum during recreational activities and inhalation of cyanobacterial aerosols. For monitoring of human exposure, sensitive screening methods are needed. However, during the analytical process of various matrices, such as human serum, some problems appear to regularly occur during sample preparation and storage, leading to MC loss and thus to underestimation of the true MC concentration. The aim of the current study was therefore to assess the pitfalls of the MC-extraction method from human serum with more detail., Methods: Six MC congeners (MC-LR, -YR, -RR, -LA, -LW, -LF) and defined equimolar MC mixtures thereof were spiked into human serum, and quantified using the commercially available Adda-ELISA subsequent to standard extraction (methanol extraction with subsequent SPE). To detect the potential influence of sample storage and preparation/storage materials, different types of material such as glass, standard polypropylene and surface-treated polypropylene were compared., Results: Loss of MC during preparation and storage is largely dependent on (1) the handling of the stored material, (2) the 'surface' of the storage material and (3) the hydrophobicity of the MCs., Conclusions: The pitfalls described for MC analysis with the ELISA are primarily associated with sample preparation and clean-up and thus also apply to other analytical techniques for MC detection beyond the ELISA used. It can be concluded that ELISA-based methods are suitable tools for the detection of MCs in human sera and other samples., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Microcystins (MCs) are cyanobacterial toxins which place the public at risk via exposure to MC contaminated water, food or algal food supplements. Subsequent to the fatal intravenous exposure of dialysis patients in Caruaru, Brazil, several techniques (LC-MS, GC-MS and ELISA) were adapted to detect MCs in human serum. As patients chronically exposed to low concentrations of MCs also present with very low MC serum levels, only LC-MS methodology would appear to allow detection of these MC levels. However, LC-MS detection depends on the availability of respective MC congener standards and the levels of non-covalently bound MC in the sample. In contrast, immunological techniques, e.g. MC-ELISA potentially could detect even covalently bound MC, provided the MC-antibody was raised against an epitope found in nearly all of the MC congeners. As the Adda-side-chain moiety is present in nearly all of the MC congeners known to date, the anti-Adda antibodies, when applied in Adda-ELISAs, could represent a relatively simple and robust technique for the qualitative and quantitative determination of MC in human serum. The aim of the current study was to determine whether commercially available Adda-ELISAs and their respective sample preparation methods would allow MC quantification in human serum. The Adda-ELISA (polyclonal antibody) and the Adda-ELISA (monoclonal antibody) kit for serum (Serum-ELISA) were used for determination of the concentration-dependent recovery of MCs in MC-spiked serum. Human serum samples were spiked with varying concentrations of MCs (MC-LR, -YR, -RR, -LA, -LW, -LF and defined MC mixtures) and extracted using two different methods. MC-spiked bovine serum and standard cell culture medium containing 10% FBS served to investigate potential matrix effects. Inter-laboratory comparison was performed allowing identification of potential sources of error. The results suggest that both ELISAs are suitable tools for the analysis of MCs in human blood serum although both also displayed some weaknesses notably the time needed for sample preparation or the overestimation of some specific MC congener concentrations. Based on the ELISA detection ranges, sample concentration and/or MC spiking may be required for detection of low levels of MCs in human blood., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Introduction. The role of chronic cholestasis (CC) in liver injury and fibrosis remains unclear. The aims of this study were to define the role of endothelial nitric oxide synthase (e-NOS) in CC and the protective effect of N-acetyl-L-cysteine (NAC) in liver and kidney injury. Materials and Methods. Group A (sham group); Group B (CBDL); and Group C (CBDL + NAC). Group C received daily dosage of NAC (100 mg/kg) intraperitoneally for up to 4 weeks. Results. The rate of bridging fibrosis was higher (100% versus 20%, P = .025), but the intensity of e-NOS in liver was lower in rats that received NAC (1.3 versus 2.7, P = .046). The necrotic area in the kidneys among rats that received NAC was lower at week 4 (48% versus 57%; P < .001). The numbers of e-NOS stained cells in kidney were similar in sham group and the two groups with CBDL. Discussion. NAC reduced the stimulus for liver fibrosis in this rat model of CC and attenuated liver and kidney injury. Our study showed that e-NOS expression increased in liver tissue of rats with CC and that this was reversed by NAC. Treatment with NAC might restore e-NOS protein expression and prevent liver injury in CC.

This study aimed to compare the efficacy of topical dimethyl sulfoxide (DMSO), intralesional and systemic carnitine as monotherapy and in combination against ulceration in rats induced by intradermal doxorubicin extravasation. Sixty-nine 3-month-old male Wistar albino rats, weighing between 200-225 g, were used in this study. Rats were applied monotherapy or a combination of topical DMSO, intraperitoneal or intralesional carnitine. Control groups received saline or no drug. The necrotic area was measured and extravasated neutrophil leukocytes were counted in healthy tissue adjacent to necrotic areas. Monotherapy with topical and systemic carnitine did not significantly reduce the size of necrotic areas. However, topical DMSO had reduced necrotic areas and inflammatory cells significantly and the addition of systemic carnitine to topical DMSO had increased the efficacy. DMSO is an effective, safe, and easy-to-apply treatment for doxorubicin-induced extravasation. Further clinical studies are needed to evaluate the use of carnitine in combination with DMSO.

Introduction: Gastric cancers are the second cause of cancer related deaths all around the world but gastric carcinogenesis remains a mystery. Intestinal metaplasia (IM) and spasmolytic polypeptide expressing metaplasia (SPEM) are the two types of preneoplastic metaplasias. In this study, we aimed to investigate expression of Pancreatic duodenal homeobox 1 (PDX1), mucins (MUCs), trefoil factors (TFFs) in SPEM and IM surrounding gastric carcinomas., Material and Methods: Tissue samples of tumor adjacent gastric mucosa including IM (n = 61) and SPEM (n = 36) from 70 gastrectomy specimens were used for immunohistochemical analysis of PDX1, mucins (MUC5AC, MUC6) and trefoil factors (TFF2, TFF3)., Results: Nuclear expression of PDX1 was present in both SPEM (32/36) and IM (60/61) and there was no significant difference in expression of PDX1 between the two types of metaplasias. While TFF3 and MUC5AC were abundant in IM, SPEM showed 100% expression of TFF2 and MUC6 and also lower positivity with TFF3 and MUC5AC. PDX1 positivity was related to expression of MUC5AC (60/61, p < 0.001) and TFF3 (60/61, p < 0.001) in IM and also associated with expression of MUC5AC (14/32, p < 0.05), MUC6 (32/32, p < 0.001), TFF2 (32/32, p < 0.001) and TFF3 (9/32, p < 0.05) in SPEM. Coexpression of TFF3 and TFF2 was present in 10 of 36 (27.7%) samples of SPEM and also 29 of 61 (47.5%) samples of IM exhibited dual expression of trefoil peptides., Conclusions: PDX1 may affect the development of SPEM and IM. Expression patterns of TFFs and MUCs may indicate that IM evolves from SPEM., (Copyright: © 2013 Termedia & Banach.)

In the current study, amifostine is evaluated for its radioprotective role in serum and kidney tissue by oxidative (malondialdehyde-MDA, advanced oxidation protein product-AOPP) and antioxidative markers (catalase, glutathione-GSH, free-thiols-F-SH). Thirty Wistar albino 3-4 months old, female rats, were randomly divided into Group I (n = 10): Control, Group II (n = 10): Irradiation-alone, Group III (n = 10): Amifostine before irradiation. In Group II and III, right kidneys of the rats were irradiated with a single dose of 6 Gy using a 60Co treatment unit. Rats in Group III received 200 mg/kg amifostine intraperitoneally, 30 min prior to irradiation. Following sacrification at 24th week, blood and kidney tissue samples were collected. Statistical analysis was done by One-way ANOVA, Post hoc Bonferroni, Dunnett T3, and Mann-Whitney U tests. Administration of amifostine significantly decreased the serum AOPP and MDA levels when compared to the irradiation-only group (P = 0.004, P = 0.006; respectively). Also amifostine significantly increased serum catalase activities and GSH levels, when given 30 min prior to irradiation (P = 00.02, P = 0.000; respectively). In the kidney tissue, administration of amifostine significantly decreased AOPP and MDA levels (P = 0.002, P = 0.016; respectively). Tissue GSH activity was increased following amifostine administration (P = 0.001). There was no statistically significant result on histopathological evaluation. Amifostine may reduce radiation-induced nephropathy by inhibiting chronic oxidative stress. Biomarkers of oxidative stress in serum and kidney tissue may be used for evaluation of the radiation-induced nephropathy.

Purpose: The aim of the study is to assess the predictive power of DCE-MRI semi-quantitative parameters during treatment of breast cancer, for disease-free (DFS) and overall survival (OS)., Materials and Methods: Forty-nine women (age range, 28-84 years; mean, 50.6 years) with breast cancer underwent dynamic contrast enhancement MRI at 1.0T imaging, using 2D FLASH sequences. Time intensity curves (TICs) were obtained from the regions showing maximal enhancement in subtraction images. Semi-quantitative parameters (TICs; maximal relative enhancement within the first minute, E (max/1); maximal relative enhancement of the entire study, E(max); steepest slope of the contrast enhancement curve; and time to peak enhancement) derived from the DCE-MRI data. These parameters were then compared with presence of recurrence or metastasis, DFS and OS by using Cox regression (proportional hazards model) analysis, linear discriminant analysis., Results: The results from of the 49 patients enrolled into the survival analysis demonstrated that traditional prognostic parameters (tumor size and nodal metastasis) and semi-quantitative parameters (E(max/1), and steepest slope) demonstrated significant differences in survival intervals (p<0.05). Further Cox regression (proportional hazards model) survival analysis revealed that semi-quantitative parameters contributed the greatest prediction of both DFS, OS in the resulting models (for E(max/1): p=0.013, hazard ratio 1.022; for stepest slope: p=0.004, hazard ratio 1.584)., Conclusion: This study shows that DCE-MRI has utility predicting survival analysis with breast cancer patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Hypoxia inducible factor 1 alpha (HIF-1α) is a nuclear protein upregulated in response to reduced cellular oxygen concentration which therefore acts as a marker for hypoxia. The aim of this study was to determine tumoral angiogenesis with immunohistochemical markers in endometrium cancer and its relation with stage, grade, survival rates and other prognostic factors., Material and Methods: Using the database in our Gynecologic Oncology clinic, we selected 94 patients who were diagnosed with endometrial cancer and underwent primary surgery at our institution between 2001 and 2010. Tissue microarrays believed to demonstrate the optimum part of the tumor were reprepared from the paraffin blocks. Angiogenesis and microvessel density (MVD) were investigated with the aid of HIF-1α and CD34 antibodies., Results: High expression of HIF-1α was significantly more frequent in advanced grade endometrial cancers (p=0.044). HIF-1α expression was highly correlated with CD34 expression in the tumor cells (p<0.001). However lack of relation among stage, overall survival rates and histological types were analyzed with HIF-1α. When we compared HIF-1α positive and negative cases with cervical, adnexial, lymphovascular and myometrial invasion, there was no difference between these groups. MVD was evaluated with CD34 and it was remarkable and significantly different on advanced grade tumors (r=0.268; p=0.009). A similar significant difference was observed between the high expression of CD34 and type II endometrial cancer histology (p<0.001). However, there was no relationship between the MVD and stage or survival rates., Conclusion: High expression of HIF-1α is associated with tumoral angiogenesis in endometrial adenocarcinomas. Further studies targeting HIF-1α for disrupting mechanisms essential for tumor growth in endometrium cancer will be significant investigations in the future.

Purpose: Several studies performed on pancreatic-duodenal homeobox 1 (PDX1) have demonstrated a loss of expression and negative tumor modulator effect in gastric carcinoma. Relations between PDX1 and gastric metaplasia, differentiated type of gastric carcinoma, and the early stage of the disease have been exhibited in previous reports. The aim of this study was to examine expressions of PDX1, caudal type homeobox 2 (CDX2) and mucin (MUC) profiles to address the role of PDX1 in gastric carcinogenesis and its relationship with CDX2., Methods: Seventy gastrectomy specimens were analyzed immunohistochemically for PDX1, CDX2, MUC2, MUC5AC, and MUC6 expressions. The sum of cytoplasmic and nuclear PDX1 immunostaining and PDX1 positivity were assessed. All of the antibodies were examined for a correlation with tumor type, clinicopathologic parameters, and metaplasias. The relation of Ki-67 proliferation index with the expression profiles was also investigated., Results: Neither PDX1 (66/70) nor CDX2 (37/70) and the mucin profiles (MUC2:11/70, MUC5AC:48/70, MUC6:41/70) showed a significant difference between differentiated and undifferentiated types of gastric carcinoma and clinicopathologic parameters. The PDX1 expression frequency was 94.3%, with an average PDX1 score of 8.8 ± 4.2. PDX1 and CDX2 expression showed a significant difference (P = 0.026 and P = 0.002, respectively) among the phenotypic classification of gastric carcinomas. All of the gastric and intestinal mixed-phenotype gastric carcinomas (GI-type) showed both PDX1 and CDX2 immunopositivity. Except for the relation of PDX1 score with MUC6 expression, no significant difference was detected between PDX1 and CDX2, MUC2, and MUC5AC expressions. A relationship between CDX2 and MUC2 and also between MUC5AC and MUC6 was found statistically. The Ki-67 proliferation index revealed a significant positive correlation with PDX1, CDX2, and MUC2 positivity., Conclusions: PDX1 expression revealed a higher positivity in gastric carcinomas than the previous studies and showed no relation with tumor type, clinicopathologic parameters, CDX2 expression, or mucin profiles. However, a significant relation of PDX1 and CDX2 expressions among phenotypic classification of gastric carcinomas reveals an idea about similar functions for PDX1 and CDX2 in the evolution of gastric carcinoma.

Breast cancer is the leading cause of death among women, and morphine is used to relieve the pain of patients with cancer. The data on the effects of morphine on tumour growth and angiogenesis are contradictory. We determined in mouse breast cancer model whether analgesic doses of morphine would affect tumour angiogenesis, and then the correlation between microvessel density (MVD), Doppler sonography (DS) and 99mTc-Tetrofosmin (TF) uptake. Ehrlich ascites tumour cell xenografts, Pgp-negative tumour were divided into two groups: (a) Morphine sulphate [0.714 mg/kg/day (equivalent to 50 mg per day for a 70 kg human)], (b) no-morphine. For the determination of angiogenesis in mice tumour tissue, TF scintigraphy, microvessel density and DS were done. MVD was significantly different between groups (49.4±1.8 vs. 41.8±1.9, morphine and no-morphine groups, respectively, P<0.001). A strong correlation was found between late uptakes of mass at scintigraphy and degree of angiogenesis in histopathologic examination (r=0.52, P<0.01). There was statistically significant inverse correlation between degree of angiogenesis in histopathologic examination and washout ratio of TF (r=0.40, P<0.05). The higher values for angiogenesis are related to higher TF reuptake. There was no statistically significant correlation between DS and TF. A strong correlation was found between MVD and grade of DS (r=0.51, P<0.01). Our preclinical mice study indicates that morphine at clinically relevant doses stimulates angiogenesis, and angiogenesis triggered of morphine is demonstrated with MVD and DS, but not TF. However, uptake and washout of TF are compared with immunohistochemically assessed morphine-stimulated angiogenesis in tumour tissue.

Background: Mesenteric ischemia and reperfusion (I/R) syndrome (MIRS) has been considered a clinicopathologic entity associated with a variety of clinically severe conditions with decreased intestinal blood flow and has been known to induce I/R damage in various organs. Sirolimus (SRL), a macrolide antibiotic isolated from a strain of Streptomyces hygroscopicus, is a potent and nonnephrotoxic immunosuppressant., Objective: This study was designed to investigate the potential impact of sirolimus on MIRS-induced I/R damage in renal, intestinal, pulmonary, and hepatic tissues in an experimental rat model., Methods: Twenty-four male Sprague-Dawley rats, aged 6 to 8 weeks and weighing 280 (±20 g), were studied. Using computer-generated random numbers, rats were assigned to 1 of the following 3 groups: group 1 (I/R group, n = 8), group 2 (I/R + sirolimus group, n = 8), and group 3 (control group, n = 8). Sirolimus, in a 1 mg/mL (60 mL) solution, was administered intraperitoneally in a dose of 1.5 mg/kg/d to the rats assigned to group 2 starting from 3 days before the surgical procedure. In surgery, a laparotomy was performed to clamp the superior mesenteric artery and, thus, induce bowel ischemia in groups 1 and 2. After 60 minutes of ischemia, the microvascular clamp on the superior mesenteric artery was removed for 3 hours of reperfusion. Soon after experimental induction of MIRS, bowel, lung, kidney, and liver specimens from each animal were harvested for both biochemical and histopathologic analysis., Results: There were statistically significant differences between groups 1 and 3 with regard to degrees of intestinal (P < 0.001), hepatic (P = 0.001), renal (P < 0.001), and pulmonary (P = 0.01) I/R damage. The lung specimens from group 2 had less inflammation and perivascular edema formation compared with specimens from group 1, but no statistical significance was observed between the groups (P < 0.33). There were statistically significant differences between groups 1 and 2 with regard to degrees of intestinal, hepatic, and renal I/R damage (P = 0.001 for all)., Conclusion: The findings of the present study demonstrate the attenuating effects of sirolimus on I/R damage in the intestine and remote organs, including the liver and kidney in the setting of MIRS in an experimental rat model. As a therapeutic implication, the utility of sirolimus may be of clinical value in procedures associated with a high likelihood of I/R damage, including major abdominal operations and renal transplantation. However, whether these results apply to humans is unclear. Additional experimental and clinical studies are warranted to confirm the clinical utility of sirolimus in conditions potentially associated with I/R damage.

Purpose: The aim of the present study was to evaluate the radiation-induced cognitive dysfunction and the radioprotective effect of amifostine (AMI) in the brain of infantile rats., Methods: Thirty 2-week-old rats were randomly assigned into 3 groups of 10 rats each. Group 1: control (CONT), group 2: radiation alone (RT), and group 3: AMI before radiation (AMI+RT). The rats in the RT and AMI+RT groups were irradiated individually with a single dose of 20 Gy. All animals were evaluated by using the Morris water maze test to evaluate of their cognitive functions. Histopathological analyses of the hippocampus were also carried out after euthanasia., Results: The study showed that the place navigational function and the spatial probe test were not significantly different between the groups., Conclusion: It can be said that it is very important to determine when the radiation-induced brain injury is formed. From a clinical perspective, the patients can be intervened before irreversible functional deficits are formed and may be amenable to treatment.

Nontraumatic rapid growing giant fat necrosis of the breast mimicking breast tumors is a rare clinical manifestation. The imaging features of the fat necrosis which range from benign to malign findings may be better explained with associated aetiology. The present paper reports a 54-year old woman with a rapid growing, fibrous, and hard giant mass originating in the subareolar region of the left breast. Mammography and magnetic resonance imaging demonstrated a heterogeneous, well circumscribed mass in 12 × 12 cm size in the left breast. The lesion was suspected as a malignant tumor and underwent core biopsy. The histopathology examination of the biopsy revealed mononuclear cells, foamy, vacuolated, and bubbly cells containing fat. Excision biopsy of the mass was performed and the final pathological diagnosis was confirmed as fat necrosis. The wide clinical and radiologic manifestations of fat necrosis are still difficult to diagnose even with the new diagnostic modalities and a great proportion of these lesions need a biopsy to diagnose.