Myelomatous pleural effusion developing after autologous stem cell transplantation in a patient with multiple myeloma: A rare case.

Myelomatous pleural effusion (MPE) is a very rare condition with a poor prognosis. In our case of multiple myeloma (MM) with early recurrence presenting with a MPE, management of the treatment is discussed together with the case presentation. A 35 year old female patient with a diagnosis of lambda light chain MM presented with complaints of dyspnea and pain in the left shoulder 2 months after autologous transplantation. On physical examination, respiratory sounds were decreased in the lower lobe of the left lung and there was dullness. Pleural effusion and plasmacytoma, more prominent on the left, were detected on chest X ray and thorax computed tomography (CT). The pleural fluid collected during therapeutic thoracentesis was examined by flow cytometry, cytology, and peripheral smear examination and as a result, the patient was considered to have early recurrence after autologous transplantation, DRd chemotherapy was immediately started, and clinical and radiological improvement was observed. Pleural effusion developing in patients with MM should be evaluated in terms of MPE. In the presence of MPE, the duration of response to treatment is short, thus effective and dynamic treatment methods for bridging should be used before referral of the patients to clinical trials and hematopoietic stem cell transplantation.

The Structural Profile of HPV 18 in Terms of Chromosomal and Nuclear Degenerative Changes and the Ratio of Nucleus/Cytoplasm on Liquid based Cervical Cells.

Background: HPV 18 is one of the important oncogenic types. HPV 18 is generally evaluated together with HPV 16 and/or high-risk HPV types in light microscopic studies. The purpose of this study was to evaluate the impact of only HPV 18 on the nucleus/cytoplasm ratio, and chromosomal and nuclear degenerative changes in liquid-based samples. Materials and Methods: Eighty liquid-based cervical samples were used in this retrospective study. These smears were prepared by HPV Deoxyribonucleic Acid (DNA) detection and genotyping with the Cobas 4800 HPV system. Forty HPV 18 infected and forty smears with no infection agent were evaluated for chromosomal (nuclear budding, micronuclei), nuclear degenerative changes (membrane irregularity, nuclear enlargement, hyperchromasia, abnormal chromatin distribution, binucleation (BN), karyorrhexis (KR), karyolysis (KL), karyopyknosis (KP)), and cytologic findings (koilocyte (KC), cells with perinuclear PR) using light microscopy. Cellular diameters were evaluated using image analysis software. Statistical analysis was performed with Statistical Package for Social Sciences (SPSS) 19.0. p values < .05 were considered significant. Results: The statistically significant difference between the presence of HPV 18 and karyorrectic cell, KC, nuclear membrane irregularity, enlargement, the mean nuclear width and height (p < 0.05). No cellular changes other than those mentioned were observed. Conclusions: The present study is significant in that, it reveals the relationship between only and particularly HPV 18 and nucleus/cytoplasm ratio, and chromosomal and nuclear degenerative changes in liquid-based cytology. HPV 18 affects KR, koilocytosis, nuclear membrane irregularity, enlargement, and nuclear diameters. Light microscopic analysis of these abnormalities increases the sensitivity and specificity of cytology in the evaluation of cellular pictures due to HPV 18.

Investigation of CD56, ADAM17 and FGF21 Expressions in the Placentas of Preeclampsia Cases.

Objective: In the present study, we investigated the expression of CD56, ADAM17 and FGF21 antibodies (Ab), which we think have an effect on the pathophysiology of preeclampsia (PE), in pregnant patients with healthy placentas and placentas with PE. The expression of these antibodies has been investigated in a limited amount of former research, but their role in PE has not yet been clarified. With this study, we aimed to contribute to the elucidation of the pathophysiology of PE and the detection of new target molecules for treatment. Materials and Methods: Parturients with singleton pregnancy at 32 weeks or above without any maternal or fetal pathology who were admitted to the Department of Obstetrics and Gynecology, Zonguldak Bülent Ecevit University Practice and Research Hospital between 11 January 2020 and 7 January 2022 were included in the present study. Pregnant women with coexisting disease or a pathology related to the placenta (ablation placenta, vasa previa, hemangioma, etc.) were excluded. CD56, ADAM17 and FGF21 antibodies were histopathologically and immunohistochemically detected in 60 placentas with PE (study group) and 43 healthy placentas (control group). Results: CD56, ADAM17 and FGF21 proteins were all more intensely expressed in preeclamptic placentas and a statistically significant difference was found between the two groups for all three antibodies (p < 0.001). Deciduitis, perivillous fibrin deposition, intervillous fibrin, intervillous hemorrhage, infarct, calcification, laminar necrosis and syncytial node were found to be significantly more common in the study group (p < 0.001). Conclusions: We observed that CD56, ADAM17 and FGF21 expressions increased in preeclamptic placentas. These Ab may be responsible for the pathogenesis of PE, which can be illuminated with further studies.

The Investigation of Therapeutic Implications of Mast Cell Stabilizer Cromolyn Sodium on Cholestasis and Cholestatic Pruritus in Experimental Cholestasis.

BACKGROUND: Relevant studies have indicated that hepatic mast cells may have potential roles in the progression of cholestasis and cholestasis-induced itch. We aimed to compare the effects of cromolyn sodium and other medications on cholestatic pruritus, serum biochemistry, histamine, total bile acids, autotaxin, liver histopathology, and mast cell distribution in tissues in an experimental cholestasis model conducted by bile duct ligation. METHODS: Rats received the determined treatment consecutively for 10 days in addition to bile duct ligation. On the 5th and 10th days of the experiment, the rats' itching behaviors were observed for 5 minutes. After 10 days, blood and tissue samples were taken. RESULTS: Significant decreases in serum histamine and autotaxin levels, plasma total bile acids, total bilirubin, and biliary enzymes were reported only in cromolyn sodium-treated rats compared to the control group. In immunohistochemistry of the liver samples, the peribiliary mast cells stained positive for autotaxin. Except for bile duct infarctus, all histopathological findings of cholestasis significantly improved only in cromolyn sodium-treated and sertraline-treated rats. The liver and peritoneal mast cells significantly decreased only in cromolyn sodium-treated rats compared to the control group. On the 10th day of the experiment, the mean duration of itching was significantly lower in all groups, except for naloxone- and ondansetron-treated rats. CONCLUSION: Cromolyn sodium has promising antipruritic efficacy and provides biochemical and histopathological recovery of the relevant parameters of cholestasis induced by bile duct ligation. For the first time in the literature, we showed that peribiliary mast cells can produce autotaxin, which is a very important pruritogenic signal in the setting of cholestasis.

The Relationship of Clinicopathological Findings and PDGFR-ß Expression With Tumor Recurrence in Gastrointestinal Stromal Tumors.

BACKGROUND: Considering the difficulty in predicting the biological behavior of gastrointestinal stromal tumors (GISTs) based on histological findings alone, genetic abnormalities have recently become an area of focus. Platelet-derived growth factor receptor (PDGFR), with 2 isoforms (α and ß) is one of the mutations that play a role in the development of GIST. There are very little data determining the relationship of GIST with PDGFRß which is associated with poor prognosis in other mesenchymal and epithelial tumors. In this study, we aimed to show the relationship between clinicopathological criteria and recurrence. We also wanted to evaluate the effect of PDGFRß expression on recurrence and clinicopathological findings. METHODS: We evaluated 40 GIST patients retrospectively for detailed clinicopathological findings, postoperative immunohistochemical tumor markers (CD117, Ki67), and also for tumor recurrence. Immunohistochemical examination for PDGFRß was performed for the all GIST cases. RESULTS: Tumor recurrence was related to male gender (P = .003), serosal localization (P = .004), surgical margins positivity (P = .001), risk group (P = .011), mitotic activity (P = .000), and Ki67 proliferation index (P = .000). PDGFRß was not significantly associated with tumor recurrence (P = .277). CONCLUSION: We can say that the most important parameters related with recurrence of GISTs are mitotic activity and the Ki67 proliferation index. The determination of the cut-off value of the Ki67 proliferation index as 13% instead of 10% would be much more specific and sensitive. Although PDGFRß may be used for the diagnosis of GIST as an alternative for PDGFRα in cases with cKIT negativity, it is not an indicator of tumor recurrence as in other tumors.

Biological importance of podoplanin expression in chorionic villous stromal cells and its relationship to placental pathologies.

Podoplanin, a reliable marker of lymphatic endothelium, is a mucin-type transmembrane protein. Although the human placenta is devoid of a lymphatic system, chorionic villous stromal (CVS) cells express podoplanin. In this study, the pattern of podoplanin expression in normal and pathological placental tissues and the biological role of podoplanin were investigated. In total, 198 placental tissues belonging to 184 patients, seen at the Department of Pathology of Bulent Ecevit University Education and Research Hospital, Zonguldak, Turkey, were evaluated histopathologically and determined to meet the study criteria. The tissues were assigned to control, cisternal placental disorders, inflammation and hypoxic-ischemic pathology groups. Podoplanin expression in CVS cells was graded from 0 to 3 depending on the staining intensity, as determined by an immunohistochemical evaluation of chorionic villi in the most intensively stained tissue region. Podoplanin levels in control CVS cells increased in parallel with placental maturation, whereas in molar pregnancies podoplanin expression was lower than in control tissues. In the acute placental inflammation group, podoplanin immunoreactivity was similar to that in the control group, whereas in the preeclampsia group, podoplanin expression was higher than in all other groups. Our study showed an increase in podoplanin expression in CVS cells during pregnancy. In preeclamptic patients, the increase in podoplanin expression may be a response to hypoxic-ischemic conditions, whereas in molar pregnancies the decrease in podoplanin levels may cause villous swelling by disrupting intercellular fluid homeostasis.

Correlation of vascular endothelial growth factor and vascular endothelial growth factor receptor-1 levels in serum and thyroid nodules with histopathological and radiological variables.

BACKGROUND/AIM: Vascular endothelial growth factor (VEGF) is a major cytokine in angiogenesis and has a role on aggressivity of various tumors. The expression of VEGF has been shown to increase in differential thyroid cancer. The aim of the study was to evaluate serum and intranodular VEGF (nVEGF) and VEGF receptor-1 (VEGFR-1) levels in patients with thyroid nodules and their relevance to ultrasonographic and pathological results. MATERIALS AND METHODS: A total of eighty patients were included in the study. Thyroid fine-needle aspiration biopsies were performed, and the levels of serum and nVEGF and VEGFR-1 were measured. Any possible correlations between serum and nVEGF, VEGFR-1, and biochemical/radiological variables were investigated. RESULTS: There were no significant differences between serum VEGF (sVEGF), nVEGF, sVEGFR-1, nVEGFR-1 levels, number of nodules, size of nodules, and benign and malignant ultrasonographic features. sVEGF and nVEGF were higher in malignant or suspicious nodules than that in benign nodules, but did not reach statistical significance (P > 0.05). sVEGFR-1 and nVEGFR-1 levels were higher in hyperthyroid patients than that in euthyroid patients (P < 0.05 and P = 0.003, respectively). nVEGFR-1 level was higher in hypothyroid patients than that in euthyroid patients (P = 0.016). sVEGF level was found to be higher in hyperactive nodules than that in others. Both sVEGFR-1 (P = 0.008) and nVEGF levels (P = 0.01) significantly increased with increasing age. nVEGFR-1 decreased with increasing body mass index (BMI) (P = 0.004). CONCLUSIONS: Our study showed the relationships of sVEGF, nVEGF, sVEGFR-1, and nVEGFR-1 levels with age, gender, BMI, and hyperthyroidism. To determine the role of VEGF/VEGFR-1 in thyroid nodules, further studies are required with a large number of patients.

The effect of generalized seizure activity on ischemia-induced cardiac arrhythmias and myocardial injury with histopathological evaluation in anesthetized rats

Background/aim: Epileptic seizure leads to sudden unexpected death in epilepsy (SUDEP) among affected patients. The causes of SUDEP are still unclear. The aim of this study was to research the effect of epilepsy on myocardial injury and arrhythmias during experimentally induced acute myocardial ischemia. Materials and methods: Wistar albino rats were divided into four groups: sham, pentylentetrazole (PTZ) + sham, ischemia, and PTZ + ischemia groups. PTZ (65 mg/kg, ip) was given 2 h before ischemia. Seizure scoring was conducted by evaluating the PTZ-induced behavioral changes in the rats. The left main coronary artery was ligated in anesthetized rats for 30 min. The incidence and the number of ventricular arrhythmias were determined. Histopathological scoring was performed for tissue injury by using a microscope. Results: Seizure scores were not different among the groups (P > 0.05). The incidence and number of ventricular tachycardia (VT) episodes were significantly higher in the PTZ + ischemia group than in the ischemia group (P ˂ 0.05). More prominent myocardial damage was observed in the PTZ + ischemia group than in the other groups (histopathological scores: PTZ + ischemia; 2.5 ± 0.5 versus ischemia; 1.2 ± 0.4, P ˂ 0.05). Conclusion: PTZ-induced seizure in rats increased myocardial injury and the incidence and number of VT episodes in myocardial ischemia. These results reveal that seizure in epilepsy patients may increase ventricular arrhythmia and myocardial injury during heart attack.

The effects of S-nitrosoglutathione on intestinal ischemia reperfusion injury and acute lung injury in rats: Roles of oxidative stress and NF-κB.

BACKGROUND: Intestinal ischemia and reperfusion (I/R) induces oxidative stress, inflammatory response, and acute lung injury. S-nitrosoglutathione (GSNO), a nitric oxide donor, has been documented to have protective effects on experimental ischemia models. AIM: The aim of this study was to examine the effect of GSNO on I/R-induced intestine and lung damage and detect the potential mechanisms emphasizing the protective role of GSNO. METHODS: Intestinal I/R was induced by occluding the superior mesenteric artery for 30 min followed by reperfusion for 180 min. GSNO was administered intravenously before reperfusion period (0.25 mg/kg). The levels of lipid peroxidation, reduced glutathione, and myeloperoxidase (MPO), histopathological evaluation and immunohistochemical expressions of both nuclear factor KappaB (NF-κB) and inducible nitric oxide (iNOS) in intestine and lung tissues were assessed. RESULTS: Histolopathologic evaluation demonstrated that intestinal I/R induced severe damages in the intestine and the lung tissues. Histopathological scores decreased with GSNO treatment. GSNO treatment reduced lipid peroxidation and MPO levels and inhibited expression of NF-κB and iNOS in the intestine. CONCLUSION: Our results suggest that GSNO treatment may ameliorate the intestinal and lung injury in rats, at least in part, by inhibiting inflammatory response and oxidative stress.

The Clinical Values of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Levels in Blood and Thyroid Nodules.

AIM: Insulin-like growth factor-1 (IGF-1) is a potent mitogen for many cells. IGF-1 plays a role in the pathogenesis of various tumors with its mutagenic and antiapoptotic properties. The aim of this study was to determine both the serum and intranodular levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with nodular thyroid diseases. MATERIALS AND METHODS: In this study, 80 subjects who performed fine-needle aspiration biopsy (FNAB) were required in order to investigate the effects of serum and intranodular IGF-1 and IGFBP-3 in the pathogenesis of nodules. After performing FNAB, IGF-1 and IGFBP-3 levels were determined in blood and aspiration samples. RESULTS: The serum levels of IGF-1 (232.8 ± 12.9 ng/ml) and IGFBP-3 (4.8 µg/ml) were found significantly higher than that of the intranodular IGF-1 (39.1 ng/ml) and intranodular IGFBP-3 levels (0.173 µg/ml) (p < 0.01). Intranodular levels of IGF-1 and IGFBP-3 were higher in subjects with multinodular thyroid gland than those of subjects with solitary nodules (p = 0.043). A positive correlation between the nodule size and the serum IGFBP-3 levels was detected (p = 0.042, r = 0.23). CONCLUSION: This study demonstrated the possible role of both IGF-1 and IGFBP-3 in the growth and the formation of multinodularity of thyroid nodules.

Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats.

AIMS: Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. MAIN METHODS: Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. KEY FINDINGS: The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well. SIGNIFICANCE: Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress.

Effects of humanin on experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid in rats.

BACKGROUND/AIM: The excessive apoptosis of intestinal epithelial cells (IECs) partly accounts for the development of colonic inflammation and eventually results in ulcerative colitis (UC). Humanin, an endogenous anti-apoptotic peptide, has previously been shown to protect against Alzheimer's disease and a variety of cellular insults. The present study aimed to investigate the effects of glysin variant of humanin (HNG) on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. MATERIALS AND METHODS: Rats were divided into four groups as follows: Group 1 (n = 8): control; isotonic saline solution 0.1 ml/rat rectally, Group 2 (n = 8): TNBS colitis; 0.1 ml of a 2.5% (w/v) TNBS solution in 50% ethanol rectally, Group 3 (n = 8): 10 µM HNG, and Group 4 (n = 8): 20 µM HNG intraperitoneal (ip) on day 2 and 6 after rectal TNBS administration. Rats were sacrificed 7 days after the induction of colitis. Blood and tissue samples were harvested for biochemical and histopathological analysis. RESULTS: HNG treatment significantly ameliorated weight loss and macroscopic and microscopic scores. TNBS-induced colitis significantly increased the colonic mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and caspase-3 activities in group II in comparison to the group I. HNG treatment was associated with an inhibition of mRNA expression of TNF-α and IL-1ß, and a decrease in caspase-3 activities in colon tissues in group III and IV when compared to group II. CONCLUSION: The results of this study indicate that HNG treatment may exert beneficial effects in UC by decreasing inflammatory reactions and apoptosis.

Relationship of mast cell density with lymphangiogenesis and prognostic parameters in breast carcinoma.

In many cancers, mast cell density (MCD) in the tumor microenvironment is associated with tumor progression and, to a greater extent, angiogenesis. Our study was designed to investigate the correlation between MCD, tumor lymphangiogenesis, and several well-established prognostic parameters in breast cancer. One hundred and four cases of invasive breast carcinoma diagnosed in our clinic between 2007 and 2011 were included. Mast cells and lymphatic vessels were stained with toluidine blue and D2-40, respectively, and their densities were calculated in various areas of tumors and lymph nodes. The variables of MCD and lymphatic vessel density (LVD) were compared using prognostic parameters as well as with each other. As tumor size and volume increased, MCD increased comparably in metastatic lymph nodes; intratumoral and peritumoral LVD also increased. Lymphovascular invasion, lymphatic invasion, perineural invasion, and estrogen receptor positivity were positively related to intratumoral MCD. The relationship between peritumoral MCD and nontumoral breast tissue MCD was statistically significant. Stage was correlated with MCD in metastatic lymph nodes. Metastatic lymph node MCD and intratumoral MCD were also significantly related. Stage, lymphatic invasion, perineural invasion, lymphovascular invasion, and metastatic lymph node MCD were all correlated with intratumoral and/or peritumoral LVD. As nuclear grade increased, intratumoral LVD became higher. In breast carcinoma, MCD, depending on its location, was related to several prognostic parameters. Notably, mast cells may have at least some effect on lymphangiogenesis, which appears to be a predictor of tumor progression.

Clinicopathological features and pituitary homeobox 1 gene expression in the progression and prognosis of cutaneous malignant melanoma.

The evidence that PITX1 (pituitary homeobox 1) is a significant tumor suppressor in human cancer remains largely circumstantial, but it clearly warrants further study as little is known about the tumor-inhibitory roles of PITX1 in cutaneous malignant melanoma. The aims of this study were to investigate PITX1 gene expression in patients with cutaneous malignant melanoma and to evaluate its potential relevance to clinicopathological characteristics and tumor cell proliferation. Clinicopathological findings of patients with cutaneous malignant melanoma were analyzed retrospectively. PITX1 and Ki-67 expression were detected by immunohistochemistry in malignant melanoma and healthy tissue samples from each patient. Labeling indices were calculated based on PITX1 gene and Ki-67 expression. The correlation between PITX1and Ki-67 expressions was analyzed in cutaneous malignant melanoma cases. The relationship between PITX1 expression intensity and clinicopathological characteristics was also analyzed. PITX1 expression was observed in all (100%) normal healthy skin tissue samples. In addition, PITX1 expression was found in 56 (80%) and was absent in 14 (20%) of the 70 cutaneous malignant melanoma cases. Ki-67 positive expression was only detected in the 14 (20%) PITX1-negative cases. PITX1-positive tumor cells were observed on the surface, but Ki-67 positive tumor cells were observed in deeper zones of the tumor nests. PITX1 expression was downregulated in human cutaneous malignant melanoma lesions compared with healthy skin tissue, but Ki-67 expression was upregulated in concordance with the progression of cutaneous malignant melanoma. PITX1 expression may be involved in tumor progression and is a potential tumor suppressor gene and prognostic marker for cutaneous malignant melanoma.

T-cell/histiocyte-rich large B-cell lymphoma of stomach.

T-cell/histiocyte-rich large B-cell lymphoma is an unusually encountered lymphoid neoplasm of stomach with aggressive course, and is an uncommon morphologic variant of diffuse large B-cell lymphoma. An ulcerated mass, 7x5x1 cm in size was observed within the gastrectomy specimen of a 76-year-old female patient. In cross sections, besides mature lymphoid cells displaying T-cell phenotype, a neoplastic formation composed of large, pleomorphic atypical lymphoid cells with, prominent nucleoli, vesicular nuclei and abundant eosinophilic cytoplasm displaying B-cell phenotype were observed. Meanwhile, histiocyte-like mononuclear cells and Reed-Sternberg-like multinuclear cells expressing CD68 and Mac387 were also observed. The diagnosis of the case was T cell/histiocyte-rich large B-cell lymphoma. This rarely encountered neoplasm should be kept in mind in the differential diagnosis of primary gastric lymphomas.

Midkine: A Novel Biomarker to Predict Malignancy in Patients with Nodular Thyroid Disease.

Background. Midkine (MK), a new heparin-binding growth factor, plays important roles in a variety of biological phenomena such as carcinogenesis, inflammation, and angiogenesis. In this study, we aimed to evaluate serum midkine (SMK) and nodular midkine (NMK) levels in patients with thyroid nodules to predict malignancy and whether there was any association between. Methods. A total of 105 patients (74 women, 31 men) with thyroid nodules were enrolled. The levels of SMK and NMK were measured. Any possible correlation between SMK, NMK, and biochemical, cytopathological, or radiological variables was investigated. Results. Both SMK and NMK were found to be higher in hypoechoic nodules with an irregular border and without a halo (p < 0.05). Serum MK levels were significantly higher in nodules with microcalcifications than nodules with macrocalcification or without calcification (p = 0.001). SMK levels were found to be correlated with NMK levels (SMK 0.63 ng/ml versus 1.04 ng/mL and NMK 0.55 ng/mL versus 0.55 ng/mL, r (2) = 0.54, p < 0.001). Conclusion. Both SMK and NMK can predict tumorigenesis of highly malignant/suspicious thyroid cytopathology and also well correlated with sonographic features of thyroid nodules. We suggest that MK levels may serve as an alternative biomarker, in conjunction with the cytopathological results in preoperative assessment of thyroid nodules.

Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats.

PURPOSE: Multiple organ failure, including acute lung injury, is a common complication of intestinal ischemia and reperfusion (I/R) injury and contributes to its high mortality rate. Activated polymorphonuclear neutrophils and reactive oxygen species contribute to the lung injury caused by intestinal I/R. Mineralocorticoid receptor antagonist spironolactone has a protective effect against I/R injury in animal models of retina, kidney, heart, and brain. The aim of the present study is to investigate the effect of aldosterone receptor blocker spironolactone on lung injury induced by intestinal I/R. METHODS: Wistar albino rats were divided into four groups: (1) sham control; (2) intestinal I/R (30 min of ischemia by superior mesenteric artery occlusion followed by 3 h of reperfusion); (3) spironolactone pretreatment (20 mg/kg) + I/R; and, (4) spironolactone pretreatment without I/R. Spironolactone was given orally 3 days prior to intestinal I/R. A marker for lipid peroxidation (malondialdehyde; MDA), an indicator or oxidation state (reduced glutathione; GSH), an index of polymorphonuclear neutrophil sequestration (myeloperoxidase; MPO), inducible nitric oxide synthase (iNOS) immunoreactivity, and the histopathology of the lung tissue were analyzed. RESULTS: Spironolactone pretreatment markedly reduced intestinal I/R-induced lung injury as indicated by histology and MDA and MPO levels. Moreover, the pretreatment decreased the iNOS immunoreactivity. CONCLUSION: The present study strongly suggests that spironolactone pretreatment decreased neutrophil infiltration, iNOS induction, oxidative stress, and histopathological injury in an experimental model of intestinal I/R induced-lung injury of rats.

Chronic treatment with resveratrol, a natural polyphenol found in grapes, alleviates oxidative stress and apoptotic cell death in ovariectomized female rats subjected to chronic cerebral hypoperfusion.

OBJECTIVES: Resveratrol appears to have neuroprotective potential in various animal models of brain disorders including cerebral ischemia and neurodegenerative diseases. Chronic cerebral hypoperfusion is a well-known pathological condition contributing to the neurodegenerative diseases such as vascular dementia. Purpose of the present study is to evaluate the possible therapeutic potential of resveratrol in a model of vascular dementia of ovariectomized female rats. Assessment of the potential was based on the determination of brain oxidative status, caspase-3 level, glial fibrillary acidic protein (GFAP), and neuronal damage on hippocampus and cerebral cortex. METHODS: For creating the model of chronic cerebral hypoperfusion, ovariectomized female Wistar rats were subjected to the modified two vessel occlusion method, with the right common carotid artery being occluded first and the left one a week later. RESULTS: At the 15th day following the ligation, neuronal damage was accompanied by the increased immunoreactivities of both GFAP and caspase-3, and significant neurodegeneration was evident in the hippocampus and cortex, all of which were significantly alleviated with resveratrol treatment (10 mg/kg). Biochemical analysis revealed that the resveratrol treatment decreased lipid peroxidation and restored reduced glutathione level as well. DISCUSSION: The collected data of the present study suggest that the administration of resveratrol may provide a remarkable therapeutic benefit for vascular dementia, which is most likely related to the prevention of both apoptotic cell death and oxidative stress. We believe that therapeutic efficacy of resveratrol deserves to be tested for potential clinical application in postmenopausal elderly women suffering from vascular dementia.

Pretreatment with remifentanil protects against the reduced-intestinal contractility related to the ischemia and reperfusion injury in rat / Pré-tratamento com remifentanil protege contra a redução da contratilidade intestinal relacionada à lesão de isquemia e reperfusão em ratos

BACKGROUND AND OBJECTIVES: Serious functional and structural alterations of gastrointestinal tract are observed in failure of blood supply, leading to gastrointestinal dismotility. Activation of opioid receptors provides cardioprotective effect against ischemia-reperfusion (I/R) injury. The aim of the present study was to determine whether or not remifentanil could reduce I/R injury of small intestine. METHODS: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (3 h). Four groups were designed: sham control; remifentanil alone; I/R control; and remifentanil + I/R. Animals in remifentanil + I/R group were subjected to infusion of remifentanil (2 ug kg-1 min-1) for 60 min, half of which started before inducing ischemia. Collecting the ileum tissues, evaluation of damage was based on contractile responses to carbachol, levels of lipid peroxidation and neutrophil infiltration, and observation of histopathological features in intestinal tissue. RESULTS: Following reperfusion, a significant decrease in carbachol-induced contractile response, a remarkable increase in both lipid peroxidation and neutrophil infiltration, and a significant injury in mucosa were observed. An average contractile response of remifentanil + I/R group was significantly different from that of the I/R group. Lipid peroxidation and neutrophil infiltration were also significantly suppressed by the treatment. The tissue samples of the I/R group were grade 4 in histopathological evaluation. In remifentanil + I/R group, on the other hand, the mucosal damage was moderate, staging as grade 1. CONCLUSIONS: The pretreatment with remifentanil can attenuate the intestinal I/R injury at a remarkable degree possibly by lowering lipid peroxidation and leukocyte infiltration.

JUSTIFICATIVA E OBJETIVOS: Alterações funcionais e estruturais sérias do trato gastrointestinal são observadas na insuficiência de irrigação sanguínea, levando a alterações da motilidade gastrointestinal. A ativação dos receptores opioides proporciona um efeito cardioprotetor contra a lesão de isquemia/reperfusão (I/R). O objetivo do presente estudo foi determinar se remifentanil pode ou não reduzir a lesão de I/R do intestino delgado. MÉTODOS: Ratos machos albinos, da linhagem Wistar, foram submetidos à isquemia mesentérica (30 minutos) seguida de reperfusão (3 horas). Quatro grupos foram designados: sham controle; remifentanil isolado; controle I/R; remifentanil + I/R. Os animais do grupo remifentanil + I/R foram submetidos à infusão de remifentanil (2 µg kg-1 min-1) por 60 min, metade dos quais iniciou antes da indução da isquemia. Coletando os tecidos do íleo, a avaliação dos danos foi baseada nas respostas contráteis ao carbacol, nos níveis de peroxidação lipídica e infiltração de neutrófilos e na observação das características histopatológicas no tecido intestinal. RESULTADOS: Após a reperfusão, uma diminuição significativa da resposta contrátil induzida por carbacol, um notável aumento tanto da peroxidação lipídica quanto da infiltração de neutrófilos e uma lesão significativa da mucosa foram observados. A média da resposta contrátil no grupo remifentanil + I/R foi significativamente diferente daquela do grupo I/R. A peroxidação lipídica e a infiltração de neutrófilos também foram significativamente suprimidas pelo tratamento. As amostras de tecido do grupo I/R apresentaram grau 4 na avaliação histopatológica. No grupo remifentanil + I/R, por outro lado, a lesão da mucosa foi moderada, apresentando estadiamento de grau 1. CONCLUSÕES: O pré-tratamento com remifentanil pode atenuar a lesão intestinal de I/R em um grau notável, possivelmente pela redução da peroxidação lipídica e da infiltração leucocitária.