The Status of Spermatogenesis in Germ Cell Tumor Bearing Testis and Its Association with Metastatic Disease.

INTRODUCTION: We aimed to evaluate the status of spermatogenesis detected by histological examination of non-tumoral testicular tissues in tumor bearing testis and its association with advanced stage disease. PATIENTS AND METHODS: We retrospectively reviewed patients with testicular germ cell tumors (TGCTs) that undergone radical orchiectomy. All non-tumoral areas of the orchiectomy specimens were examined for the status of spermatogenesis. Patients were divided into two groups as localized (stage I) and metastatic (stage II-III) disease and analyzed separately for seminomatous (SGCT) and nonseminomatous germ cell tumors (NSGCT). RESULTS: Four hundred fifty-four patients were included in our final analysis. Of those, 195 patients had SGCT, and 259 patients had NSGCT. Three hundred and six patients had localized disease at the time of diagnosis. Median (Q1-Q3) age was 31 (26 - 38) years and 102 (22.5%) patients had normal spermatogenesis, 177 (39.0%) patients had hypospermatogenesis and 175 (38.5%) patients had no mature spermatozoa. On multivariate logistic regression analysis, embryonal carcinoma >50% (1.944, 95 %CI 1.054-3.585, P = .033) and spermatogenesis status (2.796 95% CI 1.251-6.250, P = .012 for hypospermatogenesis, and 3.907, 95% CI 1.692-9.021, P = .001 for absence of mature spermatozoa) were independently associated with metastatic NSGCT. However, there was not any variables significantly associated with metastatic SGCT on multivariate logistic regression analysis. CONCLUSION: Our study demonstrated that only 22.5% of patients with TGCTs had normal spermatogenesis in tumor bearing testis. Impaired spermatogenesis (hypospermatogenesis or no mature spermatozoa) and predominant embryonal carcinoma are associated with advanced stage NSGCT.

Peritumoral Adipose Tissue Density Predicts the Malignancy in cT1 Renal Masses.

OBJECTIVE: Not only the frequency of surgery for small renal masses has increased secondary to the improvements and frequent use of imaging techniques but also the frequency of detection of benign lesions in nephrectomy specimens has increased as well. We aimed to assess the predictive value of computed tomography density of perirenal adipose tissue and peritumoral adipose tissue in distinguishing between benign and malignant renal masses. MATERIALS AND METHODS: The current study included 116 patients who underwent nephrectomy for renal masses between January 2015 and December 2020. Clinicodemographic and preoperative computed tomography features and final pathological findings of the patients were recorded. According to the final pathological results, the patients were divided into 2 groups benign (n = 32) and malignant (n = 84). Groups were compared statistically in terms of perirenal adipose tissue and peritumoral adipose tissue density. RESULTS: The median tumor size was 5.00 cm. The rate of benign tumors was higher in female patients (P = .005). The median peritumoral adipose tissue density among cT1 and cT1a tumors was higher in the malignant group (P < .001, for each). At a cutoff value of 97.50 Hounsfield Units, the peritumoral adipose tissue density had a sensitivity of 83.0% and a specificity of 79.2% for predicting the presence of malignant tumors in ≤7 cm renal masses. Using a cutoff value of -97.50 Hounsfield Units, the peritumoral adipose tissue density had a sensitivity of 88.9% and a specificity of 83.3% for predicting the presence of malignant tumors in ≤4 cm renal masses. CONCLUSION: The peritumoral adipose tissue density in the preoperative computed tomography images predicts the malignancy in cT1 renal masses.

Carbon monoxide (CO) derived from the CO-releasing molecule CORM-2 reduces peritoneal adhesion formation in a rat model.

BACKGROUND: Although low-dose carbon monoxide (CO) administration has been shown to have an anti-fibrotic effect in various fibrotic diseases, its effects on peritoneal adhesion (PA), one of the postoperative complications, are not elucidated. In this study, the effect of CO-releasing tricarbonyldichlororuthenium (II) dimer (CORM-2) administration on the formation of PA and the underlying factors of its potential effect were investigated. METHODS AND RESULTS: After the induction of PA, rats were divided into four groups with 8 rats in each group. The rats received either (i) dimethyl sulfoxide:saline solution (1:10) as a vehicle, (ii) 2.5 mg/kg CORM-2, (iii) 5 mg/kg CORM-2, or (iv) inactive (i) CORM (iCORM) intragastrically every day for a duration of 7 days. PA was not induced in rats (n = 8) designated as sham controls. Gross, histological, immunohistochemical and quantitative real-time polymerase chain reaction analyses were performed to evaluate the effectiveness of CORM-2 administration. Gross analysis showed that CORM-2 administration reduced PA formation compared to rats treated with vehicle. Histological and immunohistochemical examinations showed that increased collagen deposition, myofibroblast accumulation, microvessel density, and M1 macrophage count in the peritoneal fibrosis area of vehicle-treated rats decreased following CORM-2 treatments. PCR analyses showed that CORM-2 treatments decreased hypoxia-induced Hif1a, profibrotic Tgfb1, ECM components Col1a1 and Col3a1, collagen degradation suppressor Timp1, fibrinolysis inhibitor Serpine1, and pro-inflammatory Tnf mRNA expressions, while increasing the M2 macrophage marker Arg1 mRNA expression. CONCLUSIONS: These results suggested that CORM-2 administration reduces PA formation by affecting adhesiogenic processes such as pro-inflammatory response, fibrinolytic system, angiogenesis and fibrogenesis.

Evaluation of Acetic Acid-Induced Chronic Gastric Ulcer Healing by Propionyl-L-Carnitine Administration.

The aim of our study was to investigate the healing effect of propionyl-L-carnitine (PLC) on chronic gastric ulcers and its underlying mechanisms. This study included rats with gastric ulcers induced by applying serosal glacial acetic acid. These rats were then given either saline (vehicle) or PLC at doses of 60 and 120 mg/kg, administered orally 3 days after ulcer induction for 14 consecutive days. Our study found that treatment with PLC resulted in a reduction of the gastric ulcer area, a faster rate of ulcer healing, and stimulated mucosal restoration. Additionally, the treatment with PLC reduced the number of Iba-1+ M1 macrophages while increasing the number of galectin-3+ M2 macrophages, as well as desmin+ microvessels, and α-SMA+ myofibroblasts in the gastric ulcer bed. The mRNA expression of COX-2, eNOS, TGF-ß1, VEGFA, and EGF in the ulcerated gastric mucosa was greater in the PLC-treated groups compared with the vehicle-treated rats. In conclusion, these findings suggest that PLC treatment may accelerate gastric ulcer healing by stimulating mucosal reconstruction, macrophage polarization, angiogenesis, and fibroblast proliferation, as well as fibroblast-myofibroblast transition. This process is associated with the upregulation of TGF-ß1, VEGFA, and EGF, as well as modulation of the cyclooxygenase/nitric oxide synthase systems.

Immunolabelling of SCF and c-KIT in canine perianal gland tumours.

c-KIT and its ligand stem cell factor (SCF) play a direct role in the oncogenesis of various cancers by regulating the cell fate. Recent evidence indicates that an increased expression of c-KIT/SCF, driven by hormonal imbalances, is an important step in the development of hormone-dependent cancers. We investigated the possible role of the c-KIT/SCF system in the carcinogenesis in 44 perianal gland tumours (16 adenomas, 15 epitheliomas and 13 carcinomas) and 10 normal perianal gland tissues by assessing the percentage and type of cells that expressed c-KIT and SCF as well as the cellular localization of immunoreactivity. No differences in immunolabelling of SCF were found between normal glands and neoplastic cells of any histotype. The highest expression of c-KIT was seen in carcinomas and a positive correlation was found between c-KIT labelling score and mitotic index (R = 0.876; P <0.01). c-KIT labelling patterns in hepatoid cells varied among the tumour histotypes with adenomas having only membranous labelling. Three labelling patterns (membranous only, membranous and cytosolic, and cytosolic only) were seen in the other tumour histotypes. Cytosolic labelling was statistically more frequent in carcinomas than in adenomas (P <0.001). These findings suggest that c-KIT expression and its cellular localization may play a role in the development and progression of perianal gland tumours by influencing cell proliferation.

Intermittent dilution of dietary digestible lysine lowers the incidence of white striping by suppressing the growth, lipid synthesis, and muscle damage in broiler chickens.

BACKGROUND: White striping (WS) is a myopathy of breast muscle (Pectoralis major) that affects the quality and consumer acceptance of breast fillets of broiler chickens. Previous studies have shown that intermittent dilution of dietary nutrients suppresses the development of WS on the breast muscle of broiler chickens. However, the mechanism by which these interventions reduce the occurrence of WS remains inconclusive. In this study, we adopted intermittent reduction of dietary digestible lysine (dLys) density or metabolizable energy (ME) and amino acid (AA) density using chemical and fatty acid composition of breast fillets, and blood metabolites to understand the mechanism while histopathology and immunohistochemistry of breast muscles were used for confirmation. RESULTS: Occurrence of WS was lower in broiler chickens fed 85% dLys diets in comparison with other groups. Crude protein and ether extract in breast meat of 85% dLys groups were greater (P < 0.001) and lower (P = 0.010), respectively. Serum concentrations of lipid metabolites and enzymes were lower in broiler chickens fed 85% dLys diets than control group (P < 0.05). Feeding 85% dLys diets had low degree of myodegeneration and necrosis, inflammation, lipid deposition, infiltration of T-lymphocyte (CD3+) and macrophages (Iba-1+), and low expression of heat-shock protein 70 (HSP70) than other groups (P < 0.001). CONCLUSION: Dilution of dietary dLys to 85% of the required quantities reduces the development of WS in broiler chickens by slowing the growth, lipid synthesis, and muscle damage confirmed by lower extent of histopathological lesions. © 2022 Society of Chemical Industry.

Prognostic Role of Long-Chain Acyl-Coenzyme A Synthetase Family Genes in Patients with Clear Cell Renal Cell Carcinoma: A Comprehensive Bioinformatics Analysis Confirmed with External Validation Cohorts.

INTRODUCTION: We aimed to determine the prognostic role of long-chain acyl-CoA synthetases (ACSLs) as a disease marker for kidney clear cell carcinoma (KIRC). PATIENTS AND METHODS: The Cancer Genome Atlas (TCGA) data were accessed via open access LinkedOmics database for KIRC. Provisional datasets were used for analysis as previously described and gene expression quantification data were downloaded. The corresponding clinical information of patients also were obtained from the database. Five ACSL family members, ACSL1, ACSL3, ACSL4, ACSL5, and ACSL6, were investigated in the TCGA-KIRC cohort. Xena browser, cBioPortal and UALCAN, and Cancer Cell Line Encyclopedia (CCLE) databases were also used to confirm the results. External validation was performed using patient cohorts from the Gene Expression Omnibus (GEO-NCBI) database. Finally, the protein-protein interaction (PPI) was constructed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape software. RESULTS: Pathological T3-T4 stage tumors had significantly lower ACSL1 mRNA expression (P = .009). Patients with pathologically confirmed metastasis exhibited significantly lower expression, as well (P = .02). ACSL1 mRNA expression was associated with overall survival (OS) and negatively correlated with OS time. Univariate and multivariate analyses showed that lower ACSL1 mRNA expression level was associated with mortality. Moreover, ACSL1 mRNA expression was exhibited significant difference in some VHL gene region mutations and PBRM1_p.R1010 mutation, and negatively correlated with HIF1-alpha mRNA expression (P < .001). Confirmatory analyses and external validation also revealed similar findings. CONCLUSION: Lowered ACSL1 mRNA expression is associated with worse tumor histopathology and poor overall survival in KIRC. It may be used for prognostic marker for KIRC.

Traditional Serrated Adenoma of the Urinary Bladder: The First Report.

A 71-year-old woman was hospitalized with hematuria and underwent cystourethroscopy. Cystourethroscopy revealed a polypoid bladder tumor. Histopathologic examination showed complex villiform growth pattern, slit-like serrations, and ectopic crypts lined by epithelium with eosinophilic cytoplasm, pseudostratified elongated nuclei, consistent with traditional serrated adenoma. Nephrogenic and intestinal metaplasia with severe inflammation were present in adjacent bladder mucosa. Molecular study of the polyp revealed mutation (p.G12V) in codon 12 of exon 2 of the KRAS gene. Traditional serrated adenoma is a rare type of colonic serrated polyp, making up less than 1% of the colonic polyps with a predilection to distal colon. In the literature, there is no traditional serrated adenoma reported outside the gastrointestinal tract. Here in we report the first extra-gastrointestinal traditional serrated adenoma within the bladder and bladder diverticulum, arising from intestinal metaplasia. The present study reports an additional information on molecular background of this unusual bladder polyp.

Tissue neutrophil elastase contributes to extracorporeal shock wave lithotripsy-induced kidney damage and the neutrophil elastase inhibitor, sivelestat, attenuates kidney damage with gratifying immunohistopathological and biochemical findings: an experimental study.

Although the efficacy of extracorporeal shock wave lithotripsy (ESWL) has been well established within the literature, debate continues on the safety of the procedure while focusing on cellular injury and its long-term consequences. Here, we describe the role of neutrophil elastase (NE) in ESWL-related rat kidney damage and investigate the protective effects of sivelestat, an inhibitor of NE, during the early and late phases. Four groups including control, ESWL alone, ESWL with sivelestat 50 mg/kg and ESWL with treatment of 100 mg/kg, each consisting of ten rats were created. Biochemical parameters of kidney function and damage and immunohistopathological findings were compared in the early (72 h after ESWL) and late (1 week after ESWL) periods between the groups. During the early period, serum and urine creatinine levels and urine kidney injury molecule-1 (KIM-1) levels and the KIM-1/creatinine ratio increased in rats treated with ESWL compared to the control group. Furthermore, increased tissue inflammation, ductal dilatation and hemorrhage, and glomerular, tubular, and interstitial damage with increased NE staining were also detected in the ESWL treatment group. During the late phase, although urine KIM-1 levels remained stable at high levels, other parameters showed significant improvements. On the other hand, the administration of sivelestat 50 mg/kg decreased serum creatinine and urine KIM-1 and KIM-1/creatinine levels significantly in rats treated with ESWL, during the early and late periods. Significant decreases in tissue inflammation, tubular, and interstitial tissue damage were also observed during the early period. In conclusion, ESWL-related kidney tissue damage occurs primarily during the early period, and NE is involved in this process. On the other hand, the NE inhibitor sivelestat attenuated this ESWL-induced kidney damage.

Effects of incubator oxygen and carbon dioxide concentrations on hatchability of fertile eggs, some blood parameters, and histopathological changes of broilers with different parental stock ages in high altitude.

The effects of incubator carbon dioxide (CO2) and oxygen (O2) concentrations with parental stock age (PSA) on embryonic deaths (ED), hatchability of fertile eggs (HFE), some blood parameters, and the tissue development of broilers were investigated. Four consecutive repetitions following the similar materials and methods were carried. From 3 different aged ROSS 308 broiler parental flocks 7,680 hatching eggs were obtained and classified as young (Y; 29 wk), middle (M; 37 wk) and old (O; 55 wk) as regards PSA, and randomly distributed. Four different incubator ventilation programs (IVP) as control (C; 0.67% CO2 and 20.33% O2), high CO2 (HC; 1.57% CO2 and 20.26% O2), high O2 (HO; 0.50% CO2 and 21.16% O2), and high CO2 + O2 (HCO; 1.17% CO2 21.03% O2) were applied with oxygen concentrator, and ED and HFE were investigated. Lung and heart tissues, hemoglobin value, packed cell volume, and red blood cell count, triiodothyronine, thyroxine, adrenocorticotropic hormone (ACTH) values of the chicks were analyzed. It was found that IVP affected ED and HFE. Higher rate of early ED (EED) was obtained from the HC than HCO, and higher middle+late stage+pipped but unhatched ED (MLPED) with a lower rate of HFE was observed in the C group than HO and HCO (P < 0.05). Association was found between PSA and IVP (P < 0.05), being more evident in EED for young PSA, in MLPED with HFE for Y and O PSA. From hematological values, no statistical difference in RBC, PCV, and Hb values were found among the treatment groups, ACTH concentration known as a response to stress was found to be higher than C in all groups, triiodothyronine concentration was higher in the HO group than C. In the histopathological examination, used IVPs were found to have negative effects on the lung and heart such as vacuolization, hemorrhage in all PSA groups except for C. Conclusively, PSA and IVP affected some hatching, blood and tissue development parameters of the broiler chicks.

Effects of ozone treatment on penile erection capacity and nitric oxide synthase levels in diabetic rats.

We aimed to determine the effects of ozone treatment on functional and biochemical changes in corpus cavernosum of diabetic rats. A total of 18 rats were included in the study. The rats were divided into the three groups as control, diabetes mellitus, and diabetes mellitus + ozone therapy groups. In the latter, ozone gas mixture was administered intraperitoneally for 2 weeks after the induction of experimental diabetes model. Erectile response was evaluated by determining mean intracavernosal pressure. Tissue neuronal, inducible and endothelial nitric oxide synthase levels were evaluated with commercial ELISA kits. Immunohistochemical evaluation was also performed to determine the expression levels of nitric oxide synthases semiquantatively. Mean intracavernosal pressure and intracavernosal pressure/systemic arterial blood pressure ratio were significantly higher in the diabetes mellitus + ozone therapy group than those of diabetes mellitus group (24.57 ± 6.36 mmHg vs. 5.98 ± 2.04 mmHg, p = 0.005 and 0.81 ± 0.16 vs. 0.26 ± 0.11, p = 0.0001, respectively). The level of penile tissue endothelial nitric oxide synthase was significantly higher in diabetes mellitus + ozone therapy group compared with others (19.28 ± 3.40 ng/mL vs. 13.47 ± 2.06 ng/mL and 13.28 ± 1.48 ng/mL, P = 0.01). Endothelial nitric oxide synthase expression increased significantly with ozone therapy. Our results suggest that ozone therapy may be beneficial in reducing the negative effects of diabetes on erectile dysfunction as a result of enhanced enzymatic activity in endothelial nitric oxide synthase levels.

Effect of essential oil supplementation to diet on meat quality, fatty acid composition, performance parameters and intestinal microbiota of Japanese quails.

The effect of essential oil (EO) supplementation on carcass characteristics of Japanese quails and interactions between ingredients and intestinal morphology were investigated in this study. A total of 250 quails were fed different diet: D1, basal diet (BD); D2, BD plus palmarosa oil (PO; 100 µg/kg diet); D3, BD plus lemon myrtle oil (LMO; 100 µg/kg diet); D4, BD plus α-Tops (mixture of α-terpineol, cineole and terpinene-4-ol; 100 µg/kg diet); and D5, BD plus cyclodextrin. Overall growth performance was determined at multiple time points during 35 days of experiment. Carcass characteristics (fatty acid, pH and colour), intestinal morphology and the expression levels of meat quality-related genes including the insulin-like growth factor (IGF-1), myogenin and avian uncoupling protein (avUCP) were examined at the end of the trial. Additionally, intestinal microbiome of quails was studied by next-generation sequencing-based culture-independent analysis. Although the inclusion of EOs into the diet had no effect on the growth performance of quails and the microbial profile, the significant changes in pH24 and colour (a*) of the quail's breast muscle (p < .05) in the group receiving PO were observed. Additionally, oleic acid content in the breast muscle was significantly higher in the EOs supplemented groups (p < .01). Quails fed the PO supplemented diet had higher villus and relatively rich in oleic acid. The expression levels of IGF-1 and myogenin genes in quail's muscle were not affected, but the expression of avUCP gene was significantly lower in quails fed with LMO and α-Tops (p < .05). The results demonstrated variable effects of these treatments on intestinal morphology. Taken together, dietary inclusion of EOs is found to be beneficial and hence can be recommended for improving the quality of poultry meat.

Protective effect of oleuropein on ketamine-induced cardiotoxicity in rats.

The antioxidant and cardioprotective effects of oleuropein have been reported in several studies; however, its effect on ketamine cardiotoxicity has not been known yet. The aim of this study was to investigate the effects of oleuropein in ketamine-induced cardiotoxicity model in rats. A total of 28 male Wistar Albino rats were included in the study and they were randomly divided into four groups, each having seven rats. Group 1 (control): rats were given 1 mL of DMSO by oral gavage method for 7 days. Group 2 (ketamine): on the seventh day of the study, 60 mg/kg ketamine was administered intraperitoneally. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Group 3 (oleuropein): rats were given 200 mg/kg/day oleuropein by oral gavage method for 7 days. Group 4 (oleuropein + ketamine): rats were given 1 × 200 mg/kg oleuropein by oral gavage method for 7 days. Furthermore, 60 mg/kg ketamine was administered intraperitoneally on the seventh day of the experiment. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Serum cardiac marker (TnI, CK-MB and CK) levels were measured. Histopathological analysis was performed on a portion of the cardiac tissue. Cardiac tissue oxidative stress and antioxidant markers (MDA, GSH, GSH.Px and CAT), TNF-α, IL-6, NF-κB, COX-2 and Nrf-2 gene expressions, and protein conversion levels of related genes were determined. Data obtained showed that ketamine administration increased MDA (p < 0.001), TNF-α (p < 0.01), IL-6 (p < 0.01), COX-2 (p < 0.001) and NF-κB (p < 0.001) levels, as well as serum TnI (p < 0.001), CK-MB (p < 0.001) and CK (p < 0.01) levels whereas decreased GSH (p < 0.05) and Nrf-2 (p < 0.05) levels, as well as GSH-Px (p < 0.001) and CAT (p < 0.05) enzyme activities. Oleuropein administration was observed to decrease MDA, TNF-α, IL-6, COX-2, NF-κB, TnI, CK-MB and CK levels close to the control group and to increase GSH levels and GSH-Px and CAT enzyme activities close to the control group. This study showed that oleuropein administration reversed the increased oxidative stress and inflammation as a result of the use of ketamine and had protective effects on the heart.

Impact of dutasteride on spermatogenesis and oxidative status in rats. / Impacto de dutasteride en la espematogénesis y el estrés oxidativo en ratas.

OBJECTIVES: Although the association between 5 alpha reductase inhibitors used for the treatment of both androgenetic alopecia and benign prostatichy perplasia and their side effects is well established, the impact of dutasteride on testicular structure is not clear. To evaluate the alterations in spermatogenesis and serum FSH, LH, testosterone and dihydrotestosterone concentrations along with the oxidative status in testes and blood of the rats treated with daily dutasteride. METHODS: A total of 18 male Sprague-Dawley rats have been divided into 2 groups as control (n=8) and dutasteride (n=10). After chronically administered, rats were sacrificed and their testes were harvested for histopathologica land biochemical evaluation.  Johnsen's criteria were used to assess spermatogenesis. Serum hormone concentrations and levels of reactive oxygenspecies (ROS) in both testicular tissue and serum were measured by ECLIA and ELISA, respectively. Results were compared with Mann- Whitney U test. RESULTS: DHT (7.35 ± 0.35 vs. 10.54 ± 0.95,p<0.001) and LH levels (0.32 ±  0.009vs. 0.43 ±  0.01,<0.001) were significantly lower in treatment group compared with controls where as testosterone levels were higher in dutasteride arm (3.41 ± 1.12 vs.1.52 ± 0.34, p<0.001). Johnsen score, serum FSH levels, serum and tissue ROS levels were similar betweenthe two groups. CONCLUSIONS: According to our results, administration of dutasteride does not appear to modify spermatogenesis and oxidative burden in rats. Further investigations are required to confirm our findings.

OBJETIVOS: Aunque la asociación entre los inhibidores de la 5'alfa reductasa y el tratamiento de la alopecia y de la hiperplasia benigna de próstata esta bien establecido, el impacto de dutasteride en la estructura testicular no esta claro. El objetivo de este trabajo es evaluar las alteraciones en la espermatogénesis y concentraciones de FSH, LH, testosterona y dihidrotestosterona junto con el estado oxidativo del testículo y en sangre de ratas con la administración diaria dedutasteride. MÉTODOS: Un total de 18 ratas Sprague Dawle fueron divididas en 2 grupos: control (n=8) y dutasteride (n=10). Después de una administración crónica de dutasteride, las ratas fueron sacrificadas y los testículos se analizaron del punto de vista anatomopatológico y bioquímico. Los criterios de Johnsen fueron utilizados para valorar la espermatogénesis. Los niveles séricos hormonales y de especias reactivas del oxigeno en el tejido testicular y serum fueron medidos con ECLIA y ELISA respectivamente. Los resultados se compararon con Test Mann-Whitney. RESULTADOS: Los niveles de DHT (7,35 ± 0,35 vs.10,54 ± 0,95, p<0,001) y LH ( ,32± 0,009 vs. 0,43 ± 0,01, <0,001) fueron significativamente menores en el grupo tratamiento en comparación con los controles, mientras que los niveles de testosterona fueron mas elevados en el brazo de dutasteride (3,41 ± 1,12 vs. 1,52 ± 0,34, p<0,001). El score de Johansen los niveles séricos de FSH y de ROS fueron similares entre ambos grupos. CONCLUSIONES: De acuerdo con nuestros resultados, la administración de dutasterida no parece modificar la espermatogénesis y la carga oxidativa en ratas. Mas investigaciones son necesarias para confirmar nuestros hallazgos.

Impact of dutasteride on spermatogenesis and oxidative status in rats / Impacto de dutasteride en la espematogénesis y el estrés oxidativo en ratas

OBJECTIVES: Although the association between 5 alpha reductase inhibitors used for the treatment of both androgenetic alopecia and benign prostatic hyperplasia and their side effects is well established, the impact of dutasteride on testicular structure is not clear. To evaluate the alterations in spermatogenesis and serum FSH, LH, testosterone and dihydrotestosterone concentrations along with the oxidative status in testes and blood of the rats treated with daily dutasteride. METHODS: A total of 18 male Sprague-Dawley rats have been divided into 2 groups as control (n=8) and dutasteride (n=10). After chronically administered, rats were sacrificed and their testes were harvested for histopathological and biochemical evaluation. Johnsen's criteria were used to assess spermatogenesis. Serum hormone concentrations and levels of reactive oxygen species (ROS) in both testicular tissue and serum were measured by ECLIA and ELISA, respectively. Results were compared with Mann- Whitney U test. RESULTS: DHT (7.35 ± 0.35 vs. 10.54 ± 0.95, p < 0.001) and LH levels (0.32 ± 0.009 vs. 0.43 ± 0.01, <0.001) were significantly lower in treatment group compared with controls whereas testosterone levels were higher in dutasteride arm (3.41 ± 1.12 vs. 1.52 ± 0.34, p < 0.001). Johnsen score, serum FSH levels, serum and tissue ROS levels were similar between the two groups. CONCLUSIONS: According to our results, administration of dutasteride does not appear to modify spermatogenesis and oxidative burden in rats. Further investigations are required to confirm our findings

OBJETIVOS: Aunque la asociación entre los inhibidores de la 5'alfa reductasa y el tratamiento de la alopecia y de la hiperplasia benigna de próstata esta bien establecido, el impacto de dutasteride en la estructura testicular no esta claro. El objetivo de este trabajo es evaluar las alteraciones en la espermatogénesis y concentraciones de FSH, LH, testosterona y dihidrotestosterona junto con el estado oxidativo del testículo y en sangre de ratas con la administración diaria dedutasteride. MÉTODOS: Un total de 18 ratas Sprague Dawle fueron divididas en 2 grupos: control (n = 8) y dutasteride (n = 10). Después de una administración crónica de dutasteride, las ratas fueron sacrificadas y los testículos se analizaron del punto de vista anatomopatológico y bioquímico. Los criterios de Johnsen fueron utilizados para valorar la espermatogénesis. Los niveles séricos hormonales y de especias reactivas del oxigeno en el tejido testicular y serum fueron medidos con ECLIA y ELISA respectivamente. Los resultados se compararon con Test Mann-Whitney. RESULTADOS: Los niveles de DHT (7,35 ± 0,35 vs. 10,54 ± 0,95, p < 0,001) y LH (0,32 ± 0,009 vs. 0,43 ± 0,01, < 0,001) fueron significativamente menores en el grupo tratamiento en comparación con los controles, mientras que los niveles de testosterona fueron mas elevados en el brazo de dutasteride (3,41 ± 1,12 vs. 1,52 ± 0,34, p < 0,001). El score de Johansen los niveles séricos de FSH y de ROS fueron similares entre ambos grupos. CONCLUSIONES: De acuerdo con nuestros resultados, la administración de dutasterida no parece modificar la espermatogénesis y la carga oxidativa en ratas. Mas investigaciones son necesarias para confirmar nuestros hallazgos

Hepatoprotective Activity of Linalool in Rats Against Liver Injury Induced by Carbon Tetrachloride.

This study aimed to investigate and compare hepatoprotective activity of Coriandrum sativum (Cs) and it is major component linalool (Ln) against experimentally induced hepatotoxicity in rats. Essential oil of Cs was isolated by hydrodistillation method and chemical composition was determined by GS-MS analysis. 42 male Wistar Albino rats were divited into 7 groups each containing 6. The experimental groups were designed as: Normal control group, 1 ml/kg CCl4 administirated group, 25 mg/kg Silymarin and CCl4 administirated group, 100 and 200 mg/kg Cs and CCl4 administirated groups, 100 and 200 mg/kg Ln and CCl4 administered groups. The protective activities were determined according to the results of liver biomarkers (AST, ALT, ALP), antioxidant parameters (GSH, GPx, CAT), lipid peroxidation (MDA) and histopathological examination. Linalool percentage of Cs was 81.6%. The groups treated with linalool (100 and 200 mg/kg) (p < 0.01) and coriander (200 mg/kg) (p < 0.05) had significantly reduced AST (262-375) and ALT (101-290) levels (U/L) compared to the CCl4 (600-622) group. The levels (nmol/g protein) of MDA (11-12) were significantly lower (p < 0.01), the levels of GSH (11-12) and the activities of CAT (23-24) were significantly higher (p < 0.01) in linalool groups (100 and 200 mg/kg) compared to the CCl4 (18-5-10 respectively) group. These results were also supported by histopathological findings and indicate that Cs and Ln shows hepatoprotective activity against liver damage. In this regard, evaluation of activities of major components are needed to compare to medicinal plants in experimental diseases models.

Nobiletin attenuates acetaminophen-induced hepatorenal toxicity in rats.

The study aimed to examine the effects of nobiletin on the toxicity model induced with acetaminophen (APAP). For this purpose, 24 adult male rats were equally divided into four groups. The groups were the control group (group 1); dimethyl sulfoxide only, the APAP group (group 2) received a single dose of APAP 1000 mg/kg on the 10th day of experiment; the Nobiletin group (group 3), nobiletin (10 mg/kg) for 10 days; and the APAP + Nobiletin group (group 4), nobiletin (10 mg/kg) for 10 days with a single dose of APAP (1000 mg/kg) administered on the 10th day and the experiment ended after 48 hours. At the end of the study, a significant increase in malondialdehyde, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels and a significant decrease in glutathione levels, glutathione peroxidase activities and nuclear factor erythroid-derived 2-like 2 (Nrf-2) and heme oxygenase-1 (HO-1) expressions were observed with APAP application in liver and kidney tissues. Serum aspartate transaminase (AST), alanine transaminase (ALT), urea, and creatinine levels were also significantly increased in the APAP group. However, nobiletin treatment in group 4 reversed oxidative stress and inflammatory and histopathological signs caused by APAP. It is concluded that nobiletin may be a beneficial substance that confers hepatorenal protection to APAP-induced toxicity via antioxidant and anti-inflammatory mechanisms.

Primary triple head and neck tumors: Laryngeal squamous cell carcinomas, Kaposi's sarcoma, and non-Hodgkin's lymphoma.

Simultaneously triple head and neck malignancies are extremely rare. We report a case who had epithelial and mesenchymal malignant tumor with lymphoid malignancy in head and neck area. A patient who is 74 year old male patient presented to the otorhinolaryngology department with severe breathing difficulty due to laryngeal mass. The result of laryngeal biopsy was invasive SCCs, so patient underwent total larygectomy and bilateral level 2,3,4 neck disection operation. Primary 3 different type head and neck tumors were observed with histopathological examination. These were orderly invasive SCCs in larynx, B-cell Non-Hodgkin's lymphoma in tongue root and one lymph node of left neck dissection material, Kaposi's sarcoma in one lymph node of right neck dissection material. Although synchronous head and neck tumors occurs very rare with laryngeal carcinoma, the neck dissection materials should be researched for synchronous tumors.

Effects of thymol and carvacrol on sperm quality and oxidant/antioxidant balance in rats.

In this study, we have investigated the effects of different doses of thymol (T) and carvacrol (C) on sperm quality oxidative stress and antioxidant system. For this purpose, 49 rats were divided into seven groups (7 rats in each group): 1st Group (control); 2nd Group T-10 (thymol 10 mg/kg), 3rd Group T-20 (thymol 20 mg/kg), 4th Group C-10 (carvacrol 10 mg/kg), 5th Group C-20 (carvacrol 20 mg/kg), 6th Group T + C-10 (thymol 10 mg/kg + carvacrol 10 mg/kg) and 7th Group T + C-20 (thymol 20 mg/kg + carvacrol 20 mg/kg). The duration of the experiment was 10 weeks for all animals. During the study, sperm quality parameters (motility, concentration, abnormal spermatozoa and live-dead sperm ratio), biochemical parameters [malondialdehyde (MDA), reduced glutathione(GSH), glutathione peroxidase (GSH-Px), catalase (CAT), AST, ALT, GGT, urea and creatinine] were analysed, and histopathological examination was performed. The study results showed that monotherapies of thymol and carvacrol significantly decreased MDA levels in testicles, liver and kidney tissues compared to the control group (p < .001). GSH levels increased only with the thymol administration and GSH-Px and catalase activity increased only with the carvacrol administration compared to the control group (p < .05). The combined administration of these two agents did not cause any significant change in any parameter. Regarding the sperm quality parameters, only the spermatozoa concentration and motility increased significantly in the thymol and carvacrol groups compared to the control group (p < .01). However, these parameters decreased in the 7th Group (T + C-20) compared to the control group (p < .001). Considering the dead sperm ratio decreased significantly in the 2nd (T-10), 3rd (T-20), 4th (C-10), 5th (C-20) and 6th Group (T + C-10) compared to the control group (p < .001). In respect of spermatozoon anomaly, there was a significant decrease in thymol and carvacrol monotherapy groups. The histopathological analysis of the testicle, liver and kidney tissues of the animals showed no difference between the groups. In conclusion, we have determined that thymol and carvacrol administration decreased the oxidative damage and increased the antioxidant levels and improved the sperm quality parameters. However, the combined use of these two active ingredients had a limited therapeutic effect on the mentioned parameters.

Significant Neutrophilic Emperipolesis in Squamous Cell Carcinoma.

A 53-year-old man was admitted for tooth mobility. A mass was identified at the tooth base by CT. Histopathology of the excisional biopsy revealed a moderately differentiated squamous cell carcinoma. Many intact neutrophils were observed within the malignant cell cytoplasm. The patient underwent partial maxillectomy and bilateral neck dissection. Significant neutrophilic emperipolesis was detected in the resected material. Four tumor recurrences developed in the head and neck region during follow-up. Surgery and chemoradiotherapy was performed. The latest tumor recurrence occurred in the peripharyngeal and the posterior parotideal region. The patient was started on pembrolizumab therapy and nearly complete treatment response occurred. Pembrolizumab was discontinued due to the adrenal insufficiency and pulmonary tuberculosis that developed as a treatment side effect. Pembrolizumab was commenced again when tumor recurrence occurred. The patient is currently alive with ongoing pembrolizumab and antituberculous treatment. We present this case to remark the presence of a significant neutrophilic emperipolesis in the squamous cell carcinoma of the hard palate and maxilla which is rarely encountered. Emperipolesis may predict tumor behavior and the consequences of immune-modulating treatment response in squamous cell carcinomas of the head and neck in regard to the findings of our case.