Protective and therapeutic effects of okra seed in acute nontraumatic brain injury.

AIM: The purpose of this study was to examine the protective and therapeutic effects of okra (Abelmoschus esculentus [AE]) seed extract, with its known antioxidant, immunomodulatory, and anti-inflammatory properties, in an acetaminophen (paracetamol, N-acetyl- para-aminophenol)-induced model of hepatotoxicity and subsequent acute non-traumatic brain damage. MATERIAL AND METHOD: Forty male Wistar rats were randomly divided into five equal groups, control, paracetamol (P), okra seed extract (AE), okra seed extract + paracetamol (P + AE), and okra seed extract + paracetamol + N-acetyl cysteine (NAC) (P + AE + N). AE was administered by oral gavage through a gastric tube at 600 mg/kg/day for seven days. On the eighth day of the procedure, a single 1 g/kg dose of paracetamol and 300 mg/kg NAC were injected via the intraperitoneal route 1.5 h after AE administration. Rat tissue specimens were subsequently subjected to biochemical and histopathological analyses. Levels of markers such as S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), and matrix membrane metalloproteinase-9 (MMP-9) were investigated from rat serum specimens. Malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured to determine oxidant-antioxidant status. RESULTS: S100B, NSE, MMP-9, MDA levels, and SOD enzyme activities were examined using biochemical methods. MDA levels were significantly lower in the P + AE group and MMP-9 levels in the AE, P + AE, and P + AE + N groups compared to the P group. Histopathological examination results supported the biochemical findings. CONCLUSION: Okra seed extract exhibits a protective and therapeutic effect against non-traumatic brain damage resulting from acute paracetamol intoxication. We think that this benefit of AE derives from its antioxidant property.

The prognostic importance of PD-L1, PTEN, PHH3, and KI-67 expressions in invasive breast carcinoma.

OBJECTIVE: The aim of this study was to investigate the relationship of PD-L1, PTEN, PHH3, and Ki-67 immunohistochemical stain expressions with prognostic clinicopathological parameters in breast cancer. METHODS: Lumpectomy and mastectomy materials from 85 patients operated at the Department of Pathology, Bolu Abant Izzet Baysal University, Faculty of Medicine between 2014 and 2019 were retrospectively reviewed. PD-L1, PTEN, PHH3, and Ki-67 expressions were examined. Immunohistochemical staining results were compared with clinicopathological parameters and found to be associated with prognosis. RESULTS: A statistically significant correlation was found between PD-L1 and large tumor size, high histological grade, multifocality, and lymphovascular invasion. A statistically significant correlation was found between the loss of PTEN and large tumor size and histological grade. There was a statistically significant correlation between PHH3 and advanced age, large tumor size, and high histological grade. A statistically significant correlation was found between Ki-67 and large tumor size, high histological grade, and lymphovascular invasion. CONCLUSION: PD-L1, PTEN, PHH3, and Ki-67 are regarded as potential biomarkers that can be used to predict the prognosis of breast cancer and to develop targeted therapies.

Activation of TRESK background potassium channels by cloxyquin exerts protective effects against excitotoxic-induced brain injury and neuroinflammation in neonatal rats.

We investigated effects of activation of TRESK channels by selective activator cloxyquin on excitotoxic-induced brain injury and neuroinflammation involving brain mast cells and inflammatory cytokines in neonatal rats. Three different doses of cloxyquin (0.2, 1 and 5 mg/kg) were studied in ibotenate-induced perinatal brain injury (PBI) in P5 rat-pups. Cerebral lesions and mast cells in coronal brain sections were evaluated. Concentrations of activin A, IL-1ß, IL-6 and IL-10 in brain homogenates were measured using ELISA. Cloxyquin dose-dependently exerted protective effects against excitotoxic-induced neonatal brain injury and neuroinflammation. TRESK channels may be a promising new target for the treatment of PBIs.

The prognostic importance of PD-L1, PTEN, PHH3, and KI-67 expressions in invasive breast carcinoma

SUMMARY OBJECTIVE: The aim of this study was to investigate the relationship of PD-L1, PTEN, PHH3, and Ki-67 immunohistochemical stain expressions with prognostic clinicopathological parameters in breast cancer. METHODS: Lumpectomy and mastectomy materials from 85 patients operated at the Department of Pathology, Bolu Abant Izzet Baysal University, Faculty of Medicine between 2014 and 2019 were retrospectively reviewed. PD-L1, PTEN, PHH3, and Ki-67 expressions were examined. Immunohistochemical staining results were compared with clinicopathological parameters and found to be associated with prognosis. RESULTS: A statistically significant correlation was found between PD-L1 and large tumor size, high histological grade, multifocality, and lymphovascular invasion. A statistically significant correlation was found between the loss of PTEN and large tumor size and histological grade. There was a statistically significant correlation between PHH3 and advanced age, large tumor size, and high histological grade. A statistically significant correlation was found between Ki-67 and large tumor size, high histological grade, and lymphovascular invasion. CONCLUSION: PD-L1, PTEN, PHH3, and Ki-67 are regarded as potential biomarkers that can be used to predict the prognosis of breast cancer and to develop targeted therapies.

Benign macrocystic serous cystadenoma of the pancreas.

Serous cystadenoma is a rare benign cystic lesion of pancreas. They are mostly known as benign cystic tumors of pancreas but malign transformation as serous cystadenocarcinoma is also reported. It is more commonly observed in women with the mean age of onset is 62 years. The majority of patients present nonspecific symptoms such as abdominal pain, weight loss, nausea, vomiting, fever, and melena. One-third of the patients are asymptomatic. A 60-year-old woman presents with abdominal pain and nausea for 1 month was admitted. Physical and laboratory findings were normal. Abdomen computed tomography scan confirmed a large number of millimetric cysts of 45 × 47 × 50 mm in size at the head of the pancreas. Due to patient's symptoms and mass effect, Whipple procedure was performed. In the gross examination, a nodular area of 5 × 5 × 4 cm was observed in the head of the pancreas. The microscopic examination of the material revealed cystic structures with fibrous stroma dotted with single layered cuboidal epithelium in the pancreatic tissue. The pathology report confirmed benign macrocystic serous cystadenoma. Serous cystadenomas are rare benign cystic lesions of the pancreas. Although they are benign lesions, it is crucial to differentiate them from other cystic lesions of the pancreas and malignant serous cystadenocarcinomas.

Expressions of Putative Cancer Stem Cell Markers, CD44 and CD133, are Correlated with Pathological Tumour Stage in Gastric Adenocarcinoma.

OBJECTIVE: To analyse partial and total gastrectomy specimen in items of immunohistochemical staining of the stem cell CD44 and CD133; and to determine their relationship to pathological stage, other clinicopathological prognostic parameters, and their predictive value. STUDY DESIGN: Derscriptive study. PLACE AND DURATION OF STUDY: Department of Pathology, Bolu Abant Izzet Baysal University, Medical School, Turkey, from 2013 to 2018. METHODOLOGY: Eighty-three cases, diagnosed with adenocarcinoma from stomach partial and total gastrectomy slides and blocks, were included in the study. Adenocarcinoma cases, that had received neoadjuvant treatment before gastrectomy, cases diagnosed with lymphoma and other malignancies and cases of resection performed for reasons other than tumours, were excluded. Formalin-fixed and paraffin wax-embedded gastric adenocarcinoma blocks were sliced. CD44 and CD133 were stained onto the slides in a Leica Bond Max staining device in compliance with immunohistochemical staining datasheets. Membranous staining for CD44 and cytoplasmic, membranous or luminal staining for CD133 were evaluated. Mann-Whitney U-test and Kruskal- Wallis test were used for group comparisons. For pairwise comparisons, post-hoc Dunn's tests were used. The results were assessed on the significance level of p <0.05. The analyses were performed using the Statistical Package for the Social Sciences version 22.0 for Windows (SPSS Inc., Chicago, Illinois, USA). RESULTS: Considering CD44 and CD133 expressions in terms of pathological stage, there was significantly more intense expression in the T3 and T4 cases (p=0.009, and p=0.002, respectively). CONCLUSION: Although CD44 is regarded to be associated with more prognostic parameters compared to CD133, both immunohistochemical stains were shown to be related to pathological stage. Thus, these may be guiding for determining the tumour depth. Key Words: Gastric adenocarcinoma, CD44, CD133, Stem cell marker, Prognosis.

Laryngeal Chondrosarcoma of the Thyroid Cartilage.

Laryngeal chondrosarcoma is rare and accounts for 0.2% of all larynx malignancies. Although chondrosarcoma is the most common sarcoma seen in the larynx, laryngeal involvement by cartilage tumors is rare. In this article, we aimed to present the differential diagnosis of chondrosarcoma located in the thyroid cartilage, which is a rare site, in a 75-year-old male patient. The patient underwent total laryngectomy by the otolaryngology department. The macroscopy of the laryngectomy material sent to the pathology laboratory revealed a 3x2 cm tumor with a polypoid extension to the lumen from the bottom of the right vocal cord. Although clinical and radiological findings are important in the diagnosis, the definite diagnosis is based on the pathological examination. It is especially important to differentiate the lesion from chondromas.

Expression of NGF, MCP-1, uroplakin III, and NOS in bladder urothelium after partial urethral obstruction in rats.

INTRODUCTION: Although several cytokines, chemokines, and growth factors have been suggested to play a role in the development of bladder fibrosis and functional changes, the mechanisms that are effective in the pathogenesis of partial bladder outlet obstruction (pBOO)-induced bladder fibrosis are not well understood. OBJECTIVE: We investigated the expressions of nerve growth factor (NGF), monocyte chemoattractant protein-1 (MCP-1), uroplakin III (URPIII), inducible nitric oxide synthase (iNOS), and endothelial NOS (eNOS) that may be involved in fibrosis in rats with partial urethral obstruction for 1, 2 and 3 weeks, and the changes in the associated ischemic and inflammatory processes. After 1, 2, and 3 weeks of pBOO, blood samples were collected for assessment of renal function from the rats under anesthesia. The bladders were dissected for the tissue antioxidant enzyme activities and lipid peroxidation, including malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS) and total oxidant status (TOS). The immunohistochemical studies were performed. Histopathologically, the number of urothelial layers was calculated and the thickness of the detrusor smooth muscle and lamina propria were quantitatively measured. Additionally, the edema and congestion in the submucosa were evaluated. STUDY DESIGN: Twenty-eight male Sprague-Dawley rats were used in this study. Three separate experimental groups of pBOO (1 week [n = 7], 2 weeks [n = 7], and 3 weeks [n = 7]) were created, with an additional sham-operated control group (n = 7). RESULTS: The MDA levels increased in pBOO groups. The SOD values were decreased in the pBOO group for 1 week, and higher in the 3-week pBOO group. The TAS levels were increased in the 3 week pBOO group. The TOS levels increased in the pBOO groups. The number of urothelial layers was decreased in pBOO groups. The lamina propria, the smooth muscle thickness, edema and congestion were increase in the 1 and 2 week pBOO groups. The NGF and MCP-1 expression was increased in the 1-week and 2-week pBOO groups. The expression of URPIII in the epithelium gradually increased in the pBOO groups. In the pBOO groups, iNOS expression in the epithelium cells was significantly elevated. However, the eNOS expression was also significantly increased in the 2 week pBOO group. CONCLUSION: Our study shows that overexpression of immunohistochemical parameters together with the negative effects of ischemic and inflammatory processes that subjected to pBOO for 1, 2 and 3 weeks may play a potential role in detrusor fibrosis in the rat bladders induced by pBOO. However, understanding of the immunohistochemical parameters investigated in this experimental study is limited, and further studies targeting their relationship to pBOO could help us develop new strategies.

Combination of Novel c.3484G> T/p.Glu162Ter Variant in ABCB11 and c.208G> A/p.Asp70Asn Variant in ATP8B1 Are Associated with Severe Symptoms in Progressive Family Intrahepatic Cholestasis.

Progressive family intrahepatic cholestasis (PFIC) is an autosomal recessive disease that causes chronic cholestasis. It is associated with pathogenic variants in genes that encode proteins involved in bile secretion to canaliculus from hepatocytes. In this study, we present a 16-year-old boy who presented with severe pruritus and cholestatic jaundice. All possible infectious etiologies were negative. A liver biopsy was consistent with intrahepatic cholestasis and portal fibrosis. DNA was isolated from a peripheral blood sample, and whole exome sequencing was performed. A novel c.3484G > T/p.Glu162Ter variant in the ABCB11 gene and a c.208G> A/p.Asp70Asn variant in the ATP8B1 gene were detected. Despite traditional treatment, the patient's recurrent severe symptoms did not improve. The patient was referred for a liver transplantation. This novel c.3484G > T/p.Glu162Ter variant is associated with a severe and recurrent presentation, and the two compound variants could explain the severity of PFIC.

Protective effect of pentoxifylline on oxidative renal cell injury associated with renal crystal formation in a hyperoxaluric rat model.

The aim of the study is to investigate the effects of pentoxifylline (PTX) on the renal tubular cell injury and stone formation in a hyperoxaluric rat model induced by ethylene glycol and its possible underlying mechanisms. The study was performed with 30 male Wistar rats and randomized into three groups of teen. The sham-control (group 1) received only drinking water orally. The EG/untreated (group 2) received drinking water containing 0.75% EG for 4 weeks orally. The EG/PTX treated (group 3) received drinking water containing 0.75% EG for 4 weeks orally and PTX. Urine and blood were collected to determine some parameters. The kidneys were also removed for histological examination. Serum and urinary parameters were significantly improved in the EG/PTX treated. In the EG/PTX-treated group, the MDA, TOS and MPO activity reduced and the TAS, SOD, CAT and GSH-Px activities were increased markedly compared with the group 2. In urine of the group 2 rats, a large number of CaOx crystals were displayed and most tubules that contained crystals were dilated and showed degeneration, necrosis, and desquamation of the lining epithelium. Only few CaOx crystals were r in EG/PTX-treated animal's urine. Mild tissue damage was observed in PTX-treated rats. iNOS expression was significantly elevated in the group 2. In contrast, in the EG/PTX-treated group, eNOS expression in renal tubular epithelial cells was increased. Current study indicates that PTX may partially reduce renal tubular injury resulting from hyperoxaluria-induced oxidative and nitrosative stress.

Carvacrol attenuates histopathogic and functional impairments induced by bilateral renal ischemia/reperfusion in rats.

BACKGROUND: Renal ischemia/reperfusion injury is the most common cause of acute kidney injury, which frequent occurrence in critically ill patients. OBJECTIVES: The aim of this study was to investigate the role of Carvacrol (CARV) against bilateral ischemia reperfusion (I/R) in rats. METHODS: Renal I/R injury were induced by clamping of the left and right renal arteries for 45 min followed by 24 h of reperfusion. Thirty male Sprague-Dawley rats were randomly allocated to three groups (n = 10): the sham-control group, the renal I/R-untreated (I/R-untreated) group, and the I/R-CARV-treated group. At 2 h before reperfusion, the rats in the I/R- CARV -treated group rats received an i.p. injection of 75 mg/kg CARV. Renal function and histological changes were compared and the relevant parameters of oxidative stress and inflammation were detected. RESULTS: Compared to the sham-control group, I/R led to renal dysfunction as evidenced by higher plasma urea and creatinine along with increase in oxidative stress and histological changes in renal tissues. Treatment with CARV decreased urea, creatinine, and renal MDA and MPO levels, and increased SOD, CAT, GSH activity and eNOS expression in the kidney. In the I/R-CARV-treated group, minimal hydropic changes in the tubular epithelial cells and regeneration of tubular epithelium were observed. CONCLUSION: These results suggest that CARV treatment could reduce renal injury induced by bilateral renal I/R via anti-inflammatory, antioxidant and cytoprotective effects.

Disseminated eruptive granuloma annulare induced by levetiracetam.

Granuloma annulare (GA) is a benign, granulomatous cutaneous disease without clear etiology. Disseminated and drug induced granuloma annulare is a rare presentation. We present a 47-year-old woman with diffuse circular erythematous eruptions following treatment with levetiracetam. Her clinical and histopathological findings were compatible with the diagnosis of granuloma annulare. To the best of our knowledge, there is no previous report of this skin disease as a result of levetiracetam use. We report this case to highlight this antiepileptic drug as a possible etiologic agent in disseminated granuloma annulare.