The effect of Vortioxetine on the NLRP3 pathway and microglial activity in the prefrontal cortex in an experimental model of depression.

BACKGROUND: Increasing evidence suggests that early life stress (ELS) and neuroinflammation are associated with the pathophysiology of depression. The purpose of this study was to determine the effects of Vortioxetine (VOR), a novel antidepressant, on ELS-induced behavioral changes and neuroinflammation. METHOD: Wistar Albino 4-week-old male rats were divided into four groups: control; chronic unpredictable stress (CUMS), VOR, CUMS + VOR. Neurobehavioral assessment was performed on the first, 21st, and 42nd days. RT-PCR was used to detect the expression of P2X7, NLRP3, IL1ß, IL18 in the prefrontal cortex. To assess the microglial activities of the prefrontal cortex, immunohistochemically stained CD68, and leukocyte common antigen (LCA) preparations were scanned with Manual WSI software, Basler camera, and scored. RESULT AND DISCUSSION: Exposure to CUMS was associated with depression and anxiety-like behaviors, and administration of VOR led to improvement in these behaviors. NLRP3, IL-1ß, and IL-18 were shown to be upregulated in the prefrontal cortex of CUMS rats, while their high expression was inhibited by VOR treatment. CD68 and LCA expressions were significantly higher in the CUMS group compared to the other groups. CONCLUSION: According to these results, it may be considered that NLRP3 inflammasome-associated neuroinflammatory response and microglial activation may play a role in the etiopathogenesis of ELS.

The beneficial effects of vortioxetine on BDNF, CREB, S100B, ß amyloid, and glutamate NR2b receptors in chronic unpredictable mild stress model of depression.

BACKGROUND: Depression, one of the most significant mental disorders, is still poorly understood in terms of its pathogenetic mechanisms despite its well-recognized association with stress. OBJECTIVES: The current study's goal was to ascertain how the novel antidepressant drug vortioxetine (VOR) affected the BDNF (brain-derived neurotrophic factor), S100, amyloid ß (Aß), CREB (cAMP response element-binding protein), and NR2B, as well as its impact on depression-like behaviors, and tissue damage in an experimental rodent model of depression caused by chronic unpredictable stress. METHODS: We employed twenty-eight Wistar albino male rats, and we randomly divided them into four groups, each consisting of 7 rats: control, CUMS (chronic unpredictable mild stress), CUMS+vortioxetine (CUMS+VOR), and CUMS+fluoxetine (CUMS+FLU). Sucrose preference and forced swimming tests (SPT and FST, respectively), PCR, ELISA, and histopathological and immunohistochemical evaluation were made on brains. RESULTS: The behaviors of reduced immobility in the FST and increased sucrose preference were observed in the CUMS group and they improved in the groups treated with VOR and FLU. Compared with the control group, the group exposed to CUMS showed increased Aß and decreased BDNF, CREB, and S-100 expressions, as well as neuronal degeneration (p<0.001). VOR and FLU treatment ameliorate the findings. CONCLUSIONS: This study demonstrated significant ameliorative effects of VOR in an experimental model of chronic unpredictable depression to reduce brain tissue damage and depression-like behaviors in rats. Effects of CUMS on the brain and possible effects of VOR.

The expression of stanniocalcin-1, estrogen receptor and progesterone receptor in endometrioid endometrial cancer.

Objective: To evaluate the expression of stanniocalcin-1 (STC-1) and to investigate the correlation of STC-1 with expression of estrogen receptor (ER), progesterone receptor (PR) and clinical parameters, histopathological findings and prognostic factors in endometrioid endometrial cancer (EEC). Materials and Methods: In this retrospective study, STC-1 (cytoplasmic), ER (nuclear), and PR (nuclear) stainings were applied to tissue microarray sections of 89 EEC, 27 endometrial intraepithelial neoplasia (EIN), and 21 normal endometrium (NE). Prognostic factors such as age, tumor size, depth of myometrial invasion, lymphovascular invasion, perineural invasion, and lymph node metastasis were compared with the expression of these markers. Results: ER showed significantly higher positivity in grade 1 EEC. PR expression was also higher in grade 1 EEC, but these findings were not statistically significant. Strong expression of STC-1 was observed in EIN and EECs compared with NE. STC-1 showed low staining in the NE, and high staining was also noted in the EIN foci adjacent to the NE. STC-1 expression was positively correlated with grade 1 EECs. Conclusion: STC-1 expression was positively correlated with low histologic grade in EECs. STC-1 can be used for distinguishing low-grade endometrioid tumors and high -grade endometrioid tumors in curretage specimens. Since STC-1 is related to well differentiated tumors, it can also be regarded as a good prognostic factor in EECs.

Frozen Section Evaluation for Surgical Margins in Laryngeal Squamous Cell Carcinoma: Is it a Reliable Method for Partial and Total Laryngectomies?

BACKGROUND: In this study, we aimed to compare the accuracy of frozen section evaluation in partial and total laryngectomies performed to treat laryngeal squamous cell carcinoma . METHODS: A retrospective study was conducted to evaluate the efficacy and accuracy of frozen section analysis for laryngeal squamous cell carcinoma of 65 patients, operated at a tertiary hospital. Two groups were recruited according to the surgical procedure. RESULTS: The sensitivity and specificity of frozen section diagnosis in laryngeal cancer were 20% and 99.73%, respectively. For partial laryngectomy, the sensitivity was 16.66% and specificity was 100%. For total laryngectomy, sensitivity was 22.2% and specificity 99.13%. Discordances between the initial frozen section diagnosis and the subsequent permanent section diagnosis were found in 13 (3.35%) pairs (3.37% partial laryngectomy and 3.33% total laryngectomy). CONCLUSION: Our study shows that the surgical method applied has no effect on discordances. However, sampling errors are likely to be more common in partial laryngectomy procedures. It should be kept in mind that the sensitivity of frozen section evaluation is low.

Evaluation of histopathological results of minor salivary gland biopsies in patients with the diagnosis of Sjögren's syndrome.

Objectives: This study aims to evaluate which of the histomorphological criteria defined in labial salivary gland biopsy are more valuable in diagnosing Sjögren's syndrome (SS) and to examine its correlation with clinical and laboratory findings. Patients and methods: Between January 2005 and January 2019, a total of 927 patients (104 males, 823 females; mean age: 51 years; range, 19 to 85 years) who underwent minor salivary gland biopsies with the suspicion of SS were retrospectively analyzed. The American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2016 classification criteria were used for the classification of SS. We evaluated salivary gland biopsies histomorphologically for the presence and number of lymphocytic focus, as well as chronicity findings (acinar atrophy, ductal dilatation, fibrosis), the presence of lymphocytic infiltration, distribution, localization, ectopic germinal center, and mast cell count. The presence of accompanying diseases, clinical and laboratory findings including age, sex, the presence of dry eye and mouth, and autoantibodies for discriminating SS were noted. Histomorphologically, salivary gland biopsy which fulfilled the adequacy criteria for glandular tissue were compared with the other criteria used to diagnose SS. Results: Strong chronicity and diffuse lymphocytic infiltration were significantly higher in the SS group compared to the non-SS group (p<0.001). Lymphocytic focus score >1 was significantly higher in the SS group compared to the non-SS group (p<0.001). Strong chronicity, acinar atrophy, andductal dilatation were significantly higher in the SS group compared to the non-SS group (p<0.001). Conclusion: More than one lymphocytic focus is the most valuable finding in diagnosing SS. However, it should be kept in mind that, in cases of SS, ductal dilatation, acinar atrophy, and chronicity may be present without lymphocytic infiltration.

Expression of prostate-specific membrane antigen in the neovasculature of primary tumors and lymph node metastasis of laryngeal squamous cell carcinomas.

BACKGROUND: Prostate-specific membrane antigen (PSMA) expression is encountered in tumor-associated neovascularization. METHODS: PSMA-antibody was applied to the paraffin blocks of 51 patients who were diagnosed with squamous cell carcinoma of the larynx and underwent laryngectomy and one who underwent lymph node dissection. The percentage of vascular expression in tumoral and extratumoral stroma and lymph nodes and intensity score in tumoral epithelium were evaluated and divided into groups according to the level of PSMA expression. Final PSMA expression was determined by multiplying intensity and percentage scores. RESULTS: The mean age was 61±10 years. Patients with perineural invasion, cartilage invasion, and local invasion exhibited higher PSMA expression scores. Age, tumor differentiation, tumor diameter, perineural invasion, tumor localization, capsular invasion, depth of invasion, surgical margin status, local invasion, nodal metastasis, TNM classification, and stage were similar in high and low PSMA expression groups. There was no PSMA expression in extratumoral vascular stroma. Significantly higher PSMA expression was observed in the vascular endothelium of metastatic lymph nodes compared with reactive lymph nodes. Patients with advanced-stage disease exhibited higher PSMA vascular expression scores compared to those with earlier stages (p<.001). PSMA expression was not correlated with overall survival, disease-specific survival, or disease-free survival (p>.05). CONCLUSIONS: Our study suggests that higher PSMA expression is associated with cartilage invasion, local invasion, and advanced-stage of disease. PSMA expression can be utilized for detection of lymph node metastasis and has some predictive role in cases of neck metastasis.

Maternal prenatal stress and depression-like behavior associated with hippocampal and cortical neuroinflammation in the offspring: An experimental study.

Prenatal stress can negatively impact neonatal health, growth, and bonding with the mother. However, molecular basis of these modifications is not completely understood. The aim of this experimental study was to test the hypothesis that intrauterine stress exposure may contribute to subsequent depression-like comorbidities associated with neuroinflammation. Wistar Albino nulliparous female rats were divided into two groups (each, n = 6): controls and pregnancy stress (Days 1 through 21). Two live rat pups (one female and one male) from each term delivery were randomly selected, and depression-like behavior tests were performed on Postpartum Days 30-34, followed by euthanasia on Day 35. NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) pathway gene expressions in the hippocampus and immunohistochemical caspase 3 (cas-3), mammalian target of rapamycin (mTOR), and transient receptor potential melastatin (TRPM) staining in the temporal and prefrontal cortices were evaluated. Compared with controls, exposure to prenatal stress was associated with increased depression and anxiety-like behavior, hippocampal NLRP3 inflammasome activation (p = 0.022 and p = 0.035 for female and male pups, respectively), neuronal degeneration and increased cas-3, mTOR, and TRPM immunostaining in the prefrontal and temporal cortices of both female and male offspring (p < 0.05 for all comparisons except p < 0.01 for cas-3 in the male cortex and female temporal cortex). Exposure to antenatal stress can lead to depression-like behavior in the infant, mainly driven by hippocampal NLRP3 inflammasome activation, cortical neuroinflammation, and neurodegeneration. Future perspectives include NLRP3-targeted therapies with anti-inflammatory and anti-apoptotic effects against adverse prenatal effects of maternal stress.

Cartilaginous choristomas in tonsillectomy specimen: A prospective analysis.

OBJECTIVE: Cartilaginous Choristomas (CC) are rare benign lesion in the head and neck. In our study, we aimed to share the findings we have observed in CC cases in tonsillectomy specimens in daily practice. MATERIALS AND METHODS: This is a prospective analysis done at Department of Pathology, Süleyman Demirel University Faculty of Medicine between 2002 and 2018. All of the tonsillectomy materials fixed in 10% formaldehyde were followed up by sampling one side of the cross-sections if no macroscopically specific pathology was observed routinely. All the specimens were processed and embedded in paraffin. The paraffin sections are stained with hematoxylin and eosin and examined under microscope. RESULTS: Tonsils of 141 patients among 2355 tonsillectomy patients had CC in their specimens. A total of 155 (3.68%) CC were detected because they were seen in bilaterally in 14 patients. More than one CC was observed in 20 patients. Two of the CC was observed calcification and one have ossification. No salivary gland was observed adjecent to the choristomas in 29 patients. Significant fibrosis was more frequent in patients 15 years of age and older. CONCLUSION: The presence of hyaline cartilage in the tonsil is hamartomatous development. The CC observed in the tonsil is non fibrotic and not related to age. They can be unilateral, multifocal or bilateral in tonsil. None of the cases we have seen with the CC found a primary malignancy associated with tonsillitis. The incidence of ectopic cartilage in tonsillectomy specimen is %5.99.

The Effect of Adenomyosis in Myometrial Invasion and Overall Survival in Endometrial Cancer.

AIM: The aim of this study was to evaluate whether adenomyosis had an effect on myometrial tumor invasion, stage of the disease, and survival in endometrial cancer. METHODS: Endometrial cancer patients encountered between 2007 and 2016 were identified from pathology records. Patients who underwent suboptimal surgical or medical treatment or with insufficient clinical or surgical data were excluded. Patients diagnosed as having concurrent adenomyosis constituted the study group. Control group patients were randomly selected in a paired design according to the tumor grades in the study group, and for each tumor grade, 4 times as many as patients were included. Tumor stage, histologic type and grade, myometrial invasion, lymphovascular space invasion, presence and location of the adenomyosis in myometrial wall, distance from endometrial line, tumor in adenomyosis, adjuvant treatment, and relapse were primary outcomes.Age, body mass index, medical comorbidities, and type of operation were also recorded. Univariate and multivariate Cox proportional hazards regression models were performed for overall survival. RESULTS: Of those 1242 endometrial cancer patients, 80 with concurrent adenomyosis were identified and compared with 320 patients without adenomyosis following a paired selection based on tumor grade. Higher rates of myometrial invasion, lymphovascular space invasion, tumor diameter, and adjuvant treatments were found in the nonadenomyosis group compared with adenomyosis group (P ≤ 0.001). In patients with adenomyosis, rates of early-stage disease and overall survival were significantly higher compared with the control group (P = 0.001 and 0.01, respectively). CONCLUSIONS: Our results showed that adenomyosis is significantly associated with lower stage in endometrial cancer that may suggest a possible limiting effect on endometrial cancer spread. In addition, despite similar rates in disease-free survival and endometrial cancer-related death, overall survival rate was significantly higher in the presence of adenomyosis and might be considered as a good prognostic factor for endometrial cancer.

Effects of Remote Ischemic Conditioning Methods on Ischemia-Reperfusion Injury in Muscle Flaps: An Experimental Study in Rats.

BACKGROUND: The aim of this study was to investigate the effects of remote ischemic conditioning on ischemia-reperfusion injury in rat muscle flaps histopathologically and biochemically. METHODS: Thirty albino rats were divided into 5 groups. No procedure was performed in the rats in group 1, and only blood samples were taken. A gracilis muscle flap was elevated in all the other groups. Microclamps were applied to the vascular pedicle for 4 hours in order to achieve tissue ischemia. In group 2, no additional procedure was performed. In groups 3, 4, and 5, the right hind limb was used and 3 cycles of ischemia-reperfusion for 5 minutes each (total, 30 minutes) was applied with a latex tourniquet (remote ischemic conditioning). In group 3, this procedure was performed before flap elevation (remote ischemic preconditoning). In group 4, the procedure was performed 4 hours after flap ischemia (remote ischemic postconditioning). In group 5, the procedure was performed after the flap was elevated, during the muscle flap ischemia episode (remote ischemic perconditioning). RESULTS: The histopathological damage score in all remote conditioning ischemia groups was lower than in the ischemic-reperfusion group. The lowest histopathological damage score was observed in group 5 (remote ischemic perconditioning). CONCLUSIONS: The nitric oxide levels were higher in the blood samples obtained from the remote ischemic perconditioning group. This study showed the effectiveness of remote ischemic conditioning procedures and compared their usefulness for preventing ischemia-reperfusion injury in muscle flaps.

Imp3 expression in benign and malignant thyroid tumors and hyperplastic nodules.

BACKGROUND: IMP3, a member of insulin-like growth factor II m RNA binding protein family, seems to be promising in the diagnosis of carcinomas of many organs as well as malignant melanomas and some sarcomas. It is postulated that it might be a marker of malignancy. The results of the few prior studies indicate that IMP3 has the potential to be useful in distinguishing benign and malignant tumors of thyroid. AIMS: We aimed to evaluate the immunohistochemical expression of IMP3 in non-neoplastic nodules and benign and malignant tumors of the thyroid. STUDY DESIGN: Diagnostic accuracy study. METHODS: Overall, 92 thyroid lesions, including 22 nodular hyperplasia (NH), 14 follicular adenoma (FA), 9 follicular carcinoma (FC), 37 papillary carcinoma (PC) (15 follicular variant), 3 well differentiated carcinoma-not otherwise specified (WDC-NOS), 4 poorly differentiated carcinoma (PDC) and anaplastic carcinoma (AC) were included. Immunohistochemically, cytoplasmic expression of IMP3 was evaluated in terms of extent and intensity of the staining semi-quantitatively and an immunohistochemical score (IHS) was obtained for each case. A score higher than 2 was considered positive staining. RESULTS: In contrast with previous studies, we observed positive staining in benign lesions, especially in benign tumors. For identifying malignant tumors, the sensitivity of IMP3 was 82.1%, specificity was 33.3%, positive predictive value (PPV) was 65.7% and negative predictive value (NPV) was 54.5%. In distinguishing neoplastic and hyperplastic lesions, the sensitivity was 50%, specificity was 15.7%, PPV was 15.7% and NPV was 50%. The IMP3 expression was similar for FA and well differentiated carcinomas (p=0.434), but there was a significant difference between hyperplastic nodules and FA (p=0.011). CONCLUSION: Our data suggest that IMP3 is effective in discriminating hyperplastic and neoplastic lesions but not useful in differentiating benign tumors from malignant tumors.