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Background: Inborn errors of immunity have been implicated in causing immune dysregulation, including allergic diseases. STAT6 is a key regulator of allergic responses. Objectives: This study sought to characterize a novel gain-of-function STAT6 mutation identified in a child with severe allergic manifestations. Methods: Whole-exome and targeted gene sequencing, lymphocyte characterization, and molecular and functional analyses of mutated STAT6 were performed. Results: This study reports a child with a missense mutation in the DNA binding domain of STAT6 (c.1114G>A, p.E372K) who presented with severe atopic dermatitis, eosinophilia, and elevated IgE. Naive lymphocytes from the affected patient displayed increased TH2- and suppressed TH1- and TH17-cell responses. The mutation augmented both basal and cytokine-induced STAT6 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reversed STAT6 hyperresponsiveness to IL-4, normalized TH1 and TH17 cells, suppressed the eosinophilia, and improved the patient\"s atopic dermatitis. Conclusions: This study identified a novel inborn error of immunity due to a STAT6 gain-of-function mutation that gave rise to severe allergic dysregulation. Janus kinase inhibitor therapy could represent an effective targeted treatment for this disorder.

Introduction: Salivary gland malignancies account for 2 to 4% of head and neck cancers. Fine needle aspiration cytology (FNAC) is used in preoperative diagnosis of salivary gland lesions. Although FNAC is a highly reliable technique for preoperative diagnosis, there were no consensus on salivary gland cytopathology reporting. Recently, an international group has recommended a classification system for salivary gland FNAC reporting titled “Milan System for Reporting Salivary Gland Cytopathology” (MSRSGC). In this study, we aimed to evaluate the usability of the Milan System, its ability to determine the risk of malignancy for each category, with comparisons of inital cytologic and final histopathological diagnosis. Materials and Methods: We performed a retrospective analysis of salivary gland lesion FNAC in our department from 2013 to 2019. A total of 578 FNACs were performed in 514 patients. Of these, 85 cases had surgical follow-up (parotid gland, n = 73, submandibular gland, n = 12). The cytological samples were categorized according to the MSRSGC into six categories by two pathologists. The risk of malignancy (ROM) and diagnostic accuracy values were calculated for each diagnostic categories. Results: A total of 85 aspirates of the patients with follow-up, the MSRSGC diagnostic categories were as follows: non-diagnostic in 7 aspirates (8.2%), non-neoplastic in 3 (3.5%), atypia of undetermined significance (AUS) in 9 (10.5%), benign neoplasm in 43 (50.5%), salivary gland neoplasm of undetermined malignant potential in 7 (8.2%), suspicious for malignancy in 10 (11.7%), and malignant in 6 (7%). The ROM for each category was 28, 5%, 0%, 33%, 0%, 28.5%, 90%, and 100%, respectively. Conclusion: FNAC plays a critical role in the evaluation of patients with salivary gland lesions. The MSRSGC helps in the standardization of the process of diagnosis and clinical management of salivary gland lesions, especially of AUS and SUMP categories that are indeterminate categories in nature.

Aim: To report an ocular juvenile xanthogranuloma (JXG) case presented with buphthalmos, corneal cloudiness, and normal intraocular pressure (IOP) in the neonatal period and treated with Ahmed glaucoma valve (AGV) implantation. Background: JXG is a rare disorder predominantly seen in infants, but the neonatal presentation is extraordinary. Although spontaneous hyphema is a common presenting sign in JXG, buphthalmos and corneal opacity in the neonatal period were reported only in one case, which had high IOP values at presentation. Case presentation: Sixteen-day-old male patient presented with buphthalmos, diffuse corneal clouding, and 11 mm Hg of IOP value in the right eye. IOP increased to 28 mm Hg three weeks later, and spontaneous hyphema developed, which did not respond to antiglaucomatous medications and topical corticosteroids. AGV was implanted, and the IOP decreased to 13 mm Hg postoperatively. In the follow-ups, numerous firm yellowish nodules were noticed on the patient’s skin during the examination under general anesthesia. Histopathological examination of the skin nodules was compatible with the diagnosis of JXG. Lens subluxation and phacodonesis were developed during the follow-up and were managed with pars plana lensectomy. After a silent period of 3 months, epithelial ingrowth was determined around the side port entrance. Unfortunately, the ingrowth did not respond to cryotherapy and resulted in phthisis bulbi. Pathological evaluation of the enucleated phthisic eye revealed posterior segment involvement. Conclusion: Ocular JXG can be present with buphthalmos, corneal opacity, and normal IOP values without any skin lesions in the neonatal period. Neonatal presentation of JXG may be associated with limited medical therapy response and aggressive disease course. Clinical significance: This case report introduces the second ocular JXG case, which presented with buphthalmos and corneal cloudiness, and the third pathologically proven posterior segment involvement of JXG in the literature.

NF-κB essential modulator (NEMO, IKK-γ) deficiency is a rare combined immunodeficiency caused by mutations in the IKBKG gene. Conventionally, patients are afflicted with life threatening recurrent microbial infections. Paradoxically, the spectrum of clinical manifestations includes severe inflammatory disorders. The mechanisms leading to autoinflammation in NEMO deficiency are currently unknown. Herein, we sought to investigate the underlying mechanisms of clinical autoinflammatory manifestations in a 12-years old male NEMO deficiency (EDA-ID, OMIM #300,291) patient by comparing the immune profile of the patient before and after hematopoietic stem cell transplantation (HSCT). Response to NF-kB activators were measured by cytokine ELISA. Neutrophil and low-density granulocyte (LDG) populations were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) transcriptome before and after HSCT and transcriptome of sorted normal-density neutrophils and LDGs were determined using the NanoString nCounter gene expression panels. ISG15 expression and protein ISGylation was based on Immunoblotting. Consistent with the immune deficiency, PBMCs of the patient were unresponsive to toll-like and T cell receptor-activators. Paradoxically, LDGs comprised 35% of patient PBMCs and elevated expression of genes such as MMP9, LTF, and LCN2 in the granulocytic lineage, high levels of IP-10 in the patient’s plasma, spontaneous ISG15 expression and protein ISGylation indicative of a spontaneous type I interferon (IFN) signature were observed, all of which normalized after HSCT. Collectively, our results suggest that type I IFN signature observed in the patient, dysregulated LDGs and spontaneously activated neutrophils, potentially contribute to tissue damage in NEMO deficiency. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Objective: Trichoblastomas are rare benign tumors of the skin appendages with epithelial and mesenchymal components that exhibit differentiation to the follicular germinative epithelium and particularly to the follicular stroma of the skin. Our aim was to contribute to already limited literature data in order to gain more insights into the treatment and follow-up of patients with this condition. Methods and Materials: A total of 9 patients with trichoblastoma and 1 patient with malignant trichoblastoma were surgically treated between 2016 and 2020 at the Department of Plastic, Reconstructive and Aesthetic Surgery, School of Medicine, Marmara University. Results: Of the 10 patients with trichoblastoma, 5 were female and 5 were male, with a median age of 49 years. The smallest and largest lesion lenghts were 0.4 and 2 cm, respectively. Seven lesions had developed in the head and neck region, while 2 were in the trunk. One of our cases was a 45-year old female patient with a malignant trichoblastoma presented with a lesion in the right side of the lower lip. Conclusion: Trichoblastomas are rare tumors that affect both sexes equally and are seen most commonly in the head and neck region. Recurrence rates were found to be low when they were treated with negative surgical margins.

Introduction Gelsolin protein has important cellular functions, including cell motility and apoptosis. Altered gelsolin expression has been reported in several types of neoplasms, but clinicopathological features of gelsolin are currently unclear in patients with laryngeal squamous cell carcinoma. Objectives Our aim is to investigate the clinicopathological significance of gelsolin as a prognostic biomarker for laryngeal squamous cell carcinoma. Methods Tissue specimens from 168 patients with laryngeal squamous cell carcinoma were immunohistochemically assessed for the Gelsolin expression. Prognostic significance of Gelsolin and its interaction with clinical parameters was analysed. Results Gelsolin expression was confirmed in 70.2% of cases. Gelsolin expression is significantly associated with tumor stage, tumor grade, and locoregional recurrence. Kaplan–Meier survival curves revealed that Gelsolin expression inversely correlated with both disease-specific and overall survival. Conclusion This research is the first to demonstrate that Gelsolin expression is associated with a poor prognosis in laryngeal squamous cell carcinoma. Gelsolin is a novel promising biomarker and attractive target for the treatment of laryngeal squamous cell carcinoma.

Adenoid cystic carcinoma is a malignant tumor usually localized in the salivary glands. It can also develop in serous glands such as the breast, main bronchi, uterine cervix, Bartholin's gland of the vulva, prostate gland, and external auditory canal. It is more common in the white race. Most of the primary cutaneous adenoid cystic carcinoma cases occur on the scalp. Despite the high rate of metastasis, long-term survival can be observed because the progression of the disease is slow. Distant organ metastases such as lungs, bone, liver and brain have also been reported in the literature at 40%. Its treatment is wide excision of the lesion and demonstration of tumor negative margin in pathological sampling. In this case report, we wanted to present surgical and oncological treatment to a 65-year-old female patient with lung metastasis diagnosed with adenoid cystic carcinoma on the scalp.

Background Mesenchymal stem cells may be used for the treatment of sepsis. Dental follicle stem cells (DFSCs) are easily accessible but have not been studied in vivo or in clinical trials in sepsis models. Aim of the study We aim to elucidate DFSC effects on host immunological functions in a rat cecal ligation and perforation (CLP) sepsis model. Methods Adult male rats were categorized into group 1 (sham procedure SP), group 2 (SP + 1 × 106 DFSCs administered 0 h after SP), group 3 (CLP + saline), group 4 (CLP + 1 × 106 DFSCs administered 0 h after CLP), and group 5 (CLP + 1 × 106 DFSCs administered 4 h after CLP). Green fluorescent protein–labeled cells were used for imaging. Histopathological examination of ileal tissues was performed. Results A significant increase in the percentage of CD4+/CD25+/Foxp3+ Treg cells in groups 4 and 5 occurred compared with that in group 3. No significant changes in CD3+/CD4+ helper T-cells and CD3+/CD8+ cytotoxic T-cells were observed. Treatment with DFSCs at 4 h significantly decreased the level of TNF-α compared with that in group 3. No significant changes in IL-10 levels and lymphocyte proliferation suppression were observed. During histopathological examination, no high scoring (Chiu scores: 3 or 4) rats were observed in the curative treatment group (group 5). Conclusions Treatment with DFSC after 4 h of sepsis induction downregulates tissue inflammatory responses by decreasing TNF-α levels and increasing Treg cell ratio. This also has a protective effect on intestinal tissues during sepsis.

BACKGROUND Free jejunal flaps are among the most commonly used flaps for esophageal reconstruction. However, ischemia-reperfusion injury caused by warm ischemia seen during transfer limits their use. Iloprost, a prostacyclin analogue, has been shown to reduce ischemia-reperfusion injury in various organs. The authors investigated tissue damage in jejunal flaps with iloprost and ischemic preconditioning and compared the effectiveness of these two modalities. METHODS Thirty-four Sprague-Dawley rats were randomized into five groups: sham, ischemia-reperfusion (control), ischemic preconditioning, iloprost, and ischemic preconditioning plus iloprost. All flaps, except those in the sham group, underwent ischemia for 60 minutes and reperfusion for 2 hours. Flap perfusion was assessed by laser Doppler perfusion monitoring. Histologic sections were scored using the Chiu scoring system. Superoxide dismutase and myeloperoxidase levels were measured spectrophotometrically. RESULTS Animals that were administered iloprost and/or underwent ischemic preconditioning had better postischemic recovery of mesenteric perfusion (ischemic preconditioning, 78 percent; iloprost, 83 percent; ischemic preconditioning plus iloprost, 90 percent; versus ischemia-reperfusion, 50 percent; p < 0.05). All intervention groups showed improved histology of jejunal flaps following ischemia-reperfusion injury (ischemic preconditioning, 3; iloprost, 2.3; ischemic preconditioning plus iloprost, 3.2; versus ischemia-reperfusion, 4.7; p < 0.01, p < 0.001, and p < 0.05, respectively). Superoxide dismutase levels were higher in ischemic preconditioning, iloprost plus ischemic preconditioning, and iloprost groups (ischemic preconditioning, 2.7 ± 0.2; ischemic preconditioning plus iloprost, 2.5 ± 0.3; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.01; iloprost, 2.4 ± 1.1; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.05). Myeloperoxidase, a marker for neutrophil infiltration, was lower in the iloprost group (iloprost, 222 ± 5; versus ischemia-reperfusion, 291 ± 25; p < 0.05). CONCLUSIONS This study showed that both iloprost and ischemic preconditioning reduced reperfusion injury in jejunal flaps. Based on histologic results, iloprost may be a novel treatment alternative to ischemic preconditioning.

Merkel cell carcinoma (MCC) is an uncommon primary neuroendocrine carcinoma of the skin. Nowadays, pathologists are required to perform immunohistochemistry to demonstrate neuroendocrine and epithelial differentiation for diagnosis of MCC. Insulinoma-associated protein 1 (INSM1) is a zinc-finger transcription factor expressed in tissues undergoing terminal neuroendocrine differentiation, and INSM1 immunohistochemistry is a well-validated nuclear marker of neuroendocrine differentiation. We evaluated 24 cases of MCC for the expression of INSM1 and compared it with frequently used neuroendocrine markers, Chromogranin A, Synaptophysin, and CD56. INSM1 was positive in all cases, and its expression was stronger, more extensive, clean and homogeneous compared to other markers. As a consequence, INSM1 can be used to serve as a solitary marker for neuroendocrine differentiation due to high sensitivity and specificity in MCC cases.

Reninoma, jukstaglomerüler hücrelerden köken alan nadir bir tümördür. Bu çalışmamızda sekonder hipertansiyon ve yan ağrısı ile üroloji polikliniğine başvuran 17 yaşında bir erkek hastayı ve ardından literatürde reninoma ile ilgili bilgileri sunmayı amaçladık. Hastanın yapılan değerlendirmesinde hipokalemik olduğu görüldü ve çekilen batın manyetik rezonans (MR) görüntülemesinde sağ böbrekte 4.8x4.8 cm’lik kontrast tutan ekzofitik lezyon saptandı. Hastaya açık nefron koruyucu cerrahi operasyon uygulandı ve patolojik inceleme ile eksize edilen lezyonun jukstaglomerüler hücreli tümör (reninoma) olduğu saptandı. Operasyondan kısa bir süre sonra hastanın hipertansiyon tedavisi amacıyla aldığı tüm ilaçlar kesildi ve kan basıncının normal seyrettiği ve hipokaleminin ortadan kalktığı görüldü. Bu vaka, sekonder hipertansiyonun sebeplerinden biri olan reninoma tedavisinin önemini ve tanısal yaklaşımın tedavinin temeli olduğunu gösteren, klinisyenlere yön verebilecek önemli bir vakadır., Reninomas are rare tumors derived from juxtaglomerular cells. Here, we report a case of a 17-year-old male patient who presented to our outpatient clinic with secondary hypertension and flank pain. Initial work-up revealed hypokalemia, and magnetic resonance imaging (MRI) revealed a solid lesion as a 4.8×4.8-cm contrast-enhanced exophytic mass. He underwent open nephron-sparing surgery, and the lesion was excised. The pathological study revealed a juxtaglomerular cell tumor (reninoma). Shortly after the surgery, all medications were withdrawn, and his blood pressure and hypokalemia normalized. This case can lead physicians to better understand the importance of the management of reninomas as a curable cause of secondary hypertension and also points out the importance of diagnostic care.

Memenin noduler musinozu (NM), genellikle meme basi ve areolar bolgeyi etkileyen, nadir gorulen bir hastaliktir. Siklikla kadinlarda, yavas buyume seyri gosteren, asemptomatik, deri alti kitleler halinde ortaya cikar. Burada, sol meme basinda deri alti kitle ile basvuran 43 yasinda bir erkek hasta sunulmaktadir. Histopatolojik degerlendirme sonucunda memenin NM tanisi dogrulanmistir. Bu olgu, bu nadir hastaliga dikkat cekmek ve klinisyenler ve patologlar acisindan onemli bu durum hakkinda farkindaligin arttirilmasi amaciyla sunulmustur.

Clinical and experimental studies have shown that the laparoscopic procedure provides a typical model of ischemia-reperfusion injury in the organs by oxygen-derived free radicals. A pneumoperitoneum produces ischemia during insufflation and reperfusion during desufflation. The aim of this study was to assess the causative role of free radical-mediated reactions in tissue damage under different intra-abdominal insufflation pressures.Thirty five mature New Zealand white rabbits were assigned to three groups of 10 animals. In groups 1, 2, and 3, the designated pressures of 10, 15, and 20 mm Hg, respectively. The remaining 5 animals underwent laparotomy, using a 10-cm midline incision taken as group 4 (control). Blood samples were collected before (0 minutes) and at the end of the procedure (60 minutes). After the collection of the last blood samples, all animals were sacrificed and the samples from the liver, kidney, and gut were obtained for histologic evaluation and also measurements of tissue malondialdehyde (MDA) levels.The nitric oxide levels were not changed in groups 1 and 2, but increased significantly in group 3. Tissue MDA levels were significantly higher in groups 1 and 2 than groups 3 and 4. Histopathologic examination of the kidney revealed some findings of reversible hypoxic cell injury, including acute cellular swelling, vascular congestion, and some early findings of irreversible injury, such as lysis of the cytoplasmic membrane in all groups and focal parancymal bleeding area in only group 3 as a consequence of increased pressure. Liver histology revealed cellular swelling and karyorhexis in hepatocytes in group 1, whereas only congestion and sinusoidal dilatation was observed in groups 2 and 3.Our experimental study showed that abdominal insufflation causes ischemia and free radical production, which seems responsible for the cell damage that occured during laparoscopic surgery.

It is known that cancer is not a single transformational event. It is rather a multistage process involving complex interactions with the surrounding cellular microenvironment. Mast cells accumulate at sites of tumor growth in response to numerous chemoattractants. Our aim was to investigate the relationship between mast cell density (MCD) and myometrial invasion in endometrial carcinomas. Immunohistochemistry was performed on 35 unselected consecutive hysterectomy specimens from patients with endometrial adenocarcinoma. C-kit-positive mast cell assessment was performed in the myometrium adjacent to tumor tissue. A mean number of ?15 mast cells per high power field (HPF) were regarded as low mast cell density (L-MCD), and a count of ?16 mast cells was regarded as high mast cell density (H-MCD). A significant correlation (p=0.018, Pearson Chi-Square test) between H-MCD and the presence of myometrial invasion was demonstrated in endometrial carcinomas. H-MCD was found in 54% of all cases, and 94% of H-MCD cases had myometrial invasion, suggesting a role of mast cells or an interaction with tumor. Therapeutic modalities orientated to these cells or their microenvironment as a new target for adjuvant treatment might determine the prognosis in endometrial carcinomas. © 2008 Elsevier GmbH. All rights reserved.

Purpose Pterygium is a proliferative, inflammatory, and invasive ocular surface disease associated with excessive ultraviolet radiation exposure and has several tumor-like characteristics. Cyclooxygenase-2 (COX-2) is an inducible enzyme and recently increased expression of the enzyme was found in many cancers and premalign lesions. This study was conducted to identify the COX-2 expression in pterygium tissues. Methods Immunohistochemical staining using a primary antibody for COX-2 was performed on 30 specimens with primary pterygium (20 pterygium without recurrence and 10 pterygium which recurred during a 12-month follow-up), 11 specimens with recurrent pterygium, and 8 specimens of conjunctival tumor. As a control we used 10 specimens of normal conjunctiva. Extent and intensity of cytoplasmic and membranous staining in epithelial cells were evaluated. Results Higher expression of COX-2 was detected in conjunctival tumor (87.5%) specimens and recurrent pterygium specimens (72.7%) compared to the both normal conjunctiva (30%) and primary pterygium without recurrence (30%). COX-2 expression in primary pterygium tissues with recurrence (60%) was not different from primary pterygium without recurrence (p=0.114) and recurrent pterygium (p=0.537). However, recurrent pterygium tissues were found to express higher COX-2 than primary pterygium without recurrence (p=0.022). Conclusions COX-2 expression is increased in recurrent pterygium tissues and COX-2 expression may be a marker for the prediction of recurrence.

The objective of this study was to investigate the effects of 3-aminobenzamide (3-AB) on tissue damage in lung after hind limb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Thirty-five adult Wistar rats were divided into five groups. After application of anaesthesia both hind limbs were occluded with tourniquets. Following ischemia period for 60 min, the tourniquets were removed allowing reperfusion for 120 min. The IR group received 0.5 ml of saline while the IR+AB group received 3-AB (10 mgkg(-1) intraperitoneally). The IR+DMSO group was given 0.5 ml 10% DMSO 30 min before the removal of the tourniquets. The control group received 0.5 ml saline and the AB group received 0.5 ml 3-AB (10 mgkg(-1)) intraperitoneally. At the end of the reperfusion period, mid-line sternotomy was performed. Blood samples were taken with cardiac puncture. Bronchoalveolar lavage (BAL) of the left lung was performed with saline. Right lung was preserved for histopathological evaluation and biochemical examination. Lung tissue malondialdehyde (MDA) and 3-nitrotyrosine levels, myeloperoxidase and Na+/K+ ATP-ase activities, wet to dry weight ratios, and plasma and BAL fluid MDA levels were determined. Histopathological evaluation was performed, too. Hind limb IR caused significant increase in the lung tissue 3-NT to total tyrosine ratio (p = 0.014), wet to dry weight ratio (p = 0.000), MPO activity (p = 0.000), and MDA levels (p = 0.000). The animals treated with 3-AB showed a statistically significant decrease in these values (p < 0.05). Na+/K+ ATP-ase activity which was found to be decreased significantly with IR, returned to near normal levels with 3-AB treatment. Additionally, lung tissue injury in IR group characterized with moderate interstitial congestion and neutrophil infiltration, showed remarkable amelioration following 3-AB treatment. Our results strongly support the view that poly(ADP-ribose) polymerase (PARP) plays an important role in the inflammatory process in hind limb I/R-induced lung injury and as a PARP inhibitor, 3-AB seems to have a potential to treat this inflammatory injury.

The possible contribution of Rho/Rho-kinase signalling in oleic acid (100 mg kg −1 , i.v., for 4 h)-induced lung injury was investigated in rats. Furthermore, the possible protective effect of the administration of a Rho-kinase inhibitor, (+)-( R )- trans -4-(1-aminoethyl)- N -(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 0.5–5 mg kg −1 , i.v., 15 min before the administration of oleic acid), was also examined. Western blot analysis as well as histopathological examination revealed that Rho-kinase (ROCK-1 and ROCK-2) was upregulated in lungs obtained from oleic acid-administrated rats. In addition, the markers of oxidative and nitrosative stress, i.e., malondialdehyde, myeloperoxidase, 3-nitro- l -tyrosine and nitrite/nitrate, in serum and lung tissue were also increased in the injury group. Treatment of rats with 5 mg kg −1 Y-27632 reversed the oleic acid-induced lung damage, which was demonstrated by histopathological assessment and confirmed in Western blot experiments: ROCK-blots were more intense in the oleic acid group than in control and Y-27632 treatment reversed ROCK upregulation. In addition, malondialdehyde, myeloperoxidase, 3-nitro- l -tyrosine and nitrite/nitrate were also normalized after the administration of Y-27632 (0.5 mg kg −1 and 5 mg kg −1 ). These findings suggest that ROCK-1 and ROCK-2 are involved in oleic acid-induced lung damage in rats, and that inhibition of this enzyme by Y-27632 may have a protective effect against such damage. Consequently, Rho kinase inhibitors may be potential therapeutic agents in the treatment of acute respiratory distress syndrome (ARDS).

Purpose To investigate retinal cell apoptosis in an experimental transient, short duration ocular ischemia model. Methods An experimental ischemia model, which simulates creating temporary high intraocular pressure to control intraocular bleeding during pars plana vitrectomy, was set up. Rabbits were randomly divided into three groups. Group 1 was the control group. In Group 2, intraocular pressure was increased to 97 mmHg for 5 minutes. In Group 3, intraocular pressure was increased to 97 mmHg for 10 minutes. After 24 hours, terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling assay was used to detect retinal apoptosis in rabbit eyes. Only nuclear staining in retinal cells was counted. Results Groups with 5 minutes and 10 minutes of ischemia showed significantly higher amount of ganglion cell layer apoptosis when compared with the control group (pConclusions Apoptotic cell death in the retinal cell layers occurs in temporary ischemia-reperfusion as early as 5 and 10 minutes duration.

Background: Low muscle glutamine levels during sepsis are associated with reduced protein synthesis and elevated protein breakdown, in particular myofibrillar protein breakdown. Thus, in a cecal ligation and puncture (CLP)-induced sepsis model in the rat, we hypothesized that glutamine pretreatment would protect the diaphragm muscle function. Methods: Eighty-four male Wistar rats weighing between 180 g and 200 g received standard amino acid solution 1.2 g kg -1 per day intraperitoneally (IP) or standard amino acid solution 1.2 g kg -1 per day plus alanyl-glutamine (GLN) 0.25 g kg -1 per day (IP) during the first 6 days of the experiment. On the seventh day, CLP or sham procedures were applied. The sham and CLP groups were equally divided into 3 subgroups according to the termination of the experiment, which took place at either the 24 th hour, 48 th hour, or 72 nd hour. After the compound muscle action potentials (CMAP) were recorded from the diaphragms of the rats at these selected times, they were decapitated under ketamine/xylazine anesthesia, and diaphragms were harvested for biochemical and histopathological examination. Results: The mean area and amplitude of CMAP were significantly larger in sham+GLN groups when compared with CLP and CLP+GLN groups at all times (p

We experienced a very rare case of thyroidal Aspergillus in a 65-year-old man who came to our hospital complaining of fever and persistent pain in the articulations. The patient had a history of chronic renal failure. After physical examination and imaging tests, fine-needle biopsy of the thyroid showed fungus hyphae angling at a45-degree compatibility with Aspergillus and thyrocites, with Hurthle cell differentiation. We performed left thyroidectomy without any complications. Because most of thyroidal Aspergillus diagnoses are made after autopsy and insufficient data about its management, we present, to the best of our knowledge, the first case of thyroidal Aspergillus in the literature that was treated by left thyroidectomy successfully.

Oxidative and nitrosative stressor agents can trigger DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation of the enzyme depletes the intracellular concentration of energetic substrates such as nicotinamide adenine dinucleotide (NAD). This process can result in cell dysfunction and cell death. PARS inhibitors have been successfully used in ischemia-reperfusion injury, inflammation and sepsis in several experimental models. In our experimental study, we investigated the role of 3-aminobeanzamide (3-AB), a non-specific PARS inhibitor, on the intestinal mucosal barrier after burn injury. Twenty-four Wistar rats were randomly divided into three groups. The sham group (n = 8) was exposed to 21 degrees C water while the burn group (n = 8) and the burn + 3-AB group (n = 9) were exposed to boiling water for 12s to produce a full thickness burn in 35-40% of total body surface area. In the burn + 3-AB group, 10mg/kg of 3-AB was given intraperitoneally 10min before thermal injury. Twenty-four hours later, tissue samples from mesenteric lymph nodes (MLN), spleen and liver were obtained under sterile conditions for microbiological analysis and ileum samples were obtained for biochemical and histopathological analysis. In burn group, the incidence of bacteria isolated from MLN and spleen was significantly higher than other groups (P < 0.05). 3-AB pre-treatment prevented burn induced bacterial translocation and it significantly reduced burn induced intestinal injury. Tissue malondialdehyde and 3-nitrotyrozine levels were found significantly lower than that of the burn group. These data suggest that the relationship between PARS pathway and lipid peroxidation in intestinal tissue and PARS has a role in intestinal injury caused by thermal injury.

The antioxidant and anti-inflammatory properties of N-acetylcysteine has been documented in many experimental lung injury models. Because intravenous injection of oleic acid induces histopathologic changes similar to those seen in human acute lung injury or acute respiratory distress syndrome, the authors evaluated the effects of N-acetylcysteine (NAC) on oxidative stress and lung damage in an oleic acid (OA)-induced lung injury model. Thirty-five rats were divided into 5 groups as sham, NAC, OA, pre-OA-NAC, and post-OA-NAC. Lung damage was induced by intravenous administration of oleic acid. Pre-OA-NACgroup received intravenous (IV) N-acetylcysteine 15 minutes before oleic acid infusion and post-OA-NAC group received IV N-acetylcysteine 2 hours after oleic acid infusion. In both of the N-acetylcysteine treatment groups, blood and tissue samples were collected 4 hours after oleic acid infusion, independent from the time of N-acetylcysteine infusion. In other groups, blood and tissue samples were collected 4 hours after ethanol, NAC, or OA infusions. Serum myeloperoxidase activity, total antioxidant capacity, malondialdehyde levels, and lung tissue Na+ - K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The administration of N-acetylcysteine significantly restored Na+ - K+ ATPase activity and total antioxidant capacity levels and ameliorated lung architecture. N-acetylcysteine has been shown to have some attenuating effects in experimental animal studies. However, further investigations are necessary to suggest N-acetylcysteine as a treatment agent in critically ill patients with lung injury.

Preeclampsia affects 7-10% of all pregnancies, and is a major cause of maternal and fetal morbidity and mortality. Although enhanced apoptosis is well known in placentas with preeclampsia, the role of transcription factor nuclear factor-kappa B (NF-kappa B) in the process is still being debated. In this work, we investigate the relationship between NF-kappa B expression and trophoblastic cell apoptosis in pregnancies complicated with preeclampsia or intrauterine growth restriction (IUGR) by immunohistochemical analysis of NF-kappa B and three apoptosis related markers: bcl-2, caspase-3, and M30 CytoDeath antibody that identifies early apoptotic changes in the cytoskeleton related to action of caspase. The study was conducted on placental samples from 19 preeclamptic, 5 IUGR-complicated and 10 normal pregnant women. The three conclusions from the statistical analysis of the data are obtained; (i) Significantly higher expression of NF-kappa B in IUGR-complicated (p = 0.003) and preeclamptic placentas (p = 0.004) than the control placentas, (ii) significantly higher M30 index and caspase 3 expression in IUGR and preeclampsia placentas (p = 0.003), and (iii) decreased expression of bcl-2 in IUGR and preeclampsia placentas (p = 0.001). Based on these observations, we suggest that increased trophoblastic apoptosis is at least partially induced by NF-kappa B and reduced bcl-2 expression.

Jejunum is one of the most frequently used free flaps in esophagus reconstruction. However, the sensitivity of intestinal tissue to ischemia decreases the margin of safety of this donor site while increasing the risk of postoperative complications such as fistula formation and stenosis. Ischemic preconditioning can increase the tolerance of jejunal tissue to ischemia. In this study, the authors investigated the effects of chemical preconditioning with adenosine infusion on ischemia reperfusion injury in the rat jejunum, and evaluated the presence of any additive effects of adenosine administration when used together with ischemic preconditioning. Forty Sprague-Dawley rats weighting 200 to 250 mg were used in the study. Rats were randomly divided into five groups. In group I (sham-operated controls), only laparotomy was performed. In group II (ischemia-reperfusion injury), the superior mesenteric artery was clamped for 40 minutes to induce ischemia in the small bowel, followed by 60 minutes of reperfusion. In group III (ischemic preconditioning), two cycles of 5-minute ischemia and 5-minute reperfusion were performed before implementation of the ischemia-reperfusion protocol used in group II. In group IV (chemical preconditioning), adenosine (1000 microg/kg) was infused into the internal jugular vein before the group II ischemia-reperfusion schedule was implemented. In group V (adenosine-enhanced ischemic preconditioning), adenosine (1000 microg/kg) was infused into the internal jugular vein before ischemic preconditioning, followed by 40 minutes of ischemia and 60 minutes of reperfusion. At the end of the reperfusion period, samples from the jejunum were harvested and myeloperoxidase activity was determined as a measure of leukocyte accumulation. Malondialdehyde levels were measured to assess lipid peroxidation. Histopathologic sections stained with hematoxylin-eosin were evaluated for the presence of mucosal damage according to the Chiu scoring method. Immunohistochemical staining by M30 monoclonal antibodies was performed to quantify the number of ischemia-induced apoptotic cells in the intestinal mucosa. The myeloperoxidase and malondialdehyde levels were significantly lower in groups I, III, IV, and V when compared with group II. Although there were no significant differences among myeloperoxidase and malondialdehyde levels in groups III, IV, and V, group I had significantly lower levels of activity compared with the other three groups. Histological scoring reflected significantly less damage in groups I, III, IV, and V compared with group II. Similarly, the number of apoptotic cells was significantly lower in groups I, III, IV, and V when compared with group II. However, no difference was detected among these four groups with regard to either histopathological scoring or apoptosis numbers. This is the first study showing that adenosine administration is as effective as ischemic preconditioning in inducing ischemic tolerance in the rat jejunum. However, there was no enhancement of ischemic preconditioning with prior adenosine infusion.

Ischemic preconditioning (IPC) was first demonstrated in the heart, but this protective effect has been also recently described in the intestine. The aim of this study was to determine the effects of intestinal ischemic preconditioning on the morphology of intestine and bacterial translocation. Twenty-four male Wistar rats weighting 250 to 300 g were randomized into three groups. A control group of rats (n = 8) were subjected laparotomy. In an ischemic group (n = 8), laparotomy was performed and the superior mesenteric artery was occluded by an atraumatic clamp for 30 min. In the preconditioned group (n = 8), before the ischemia-reperfusion (I/R) period (as in ischemic group), rats were subjected to an initial 10 min of intestinal ischemia and 10 min of reperfusion. Twenty-four hours later, to evaluate whether the I/R induced intestinal injury and bacterial translocation (BT), tissue and blood samples were collected, and liver, spleen, and mesenteric lymph node specimens were obtained under sterile conditions for microbiological analysis. Samples of ileum were removed for both biochemical and histopathological evaluation. In the I/R group, the incidence of bacteria-isolated mesenteric lymph nodes, spleen, liver, and blood was significantly higher than other groups (P < 0.05). IPC prevented I/R-induced BT and it significantly reduced the I/R-induced intestinal injury (P < 0.05). Increased inducible nitric oxide (NO) synthase (iNOS) expression observed on the ileal specimens of the I/R group was found to be prevented by IPC. Our data suggest IPC as a key factor that reduces BT and iNOS activation in intestinal I/R. This is the first study showing that intestinal IPC blocks the cascade of events that causes BT and intestinal injury that may lead to sepsis.

The absence of bile in the gastrointestinal tract stimulates bacterial overgrowth and bacterial translocation. In the response to endotoxin and LPS-induced endotoxemia which may be prevented by antithrombin-III (AT-III); endothelial cells; and various cells release cytokines, nitric oxide (NO) and other mediators. The purpose of this study was to examine blood NO levels and renal inducible NO synthase (iNOS) expression and determine whether AT-III has an inhibiting effect on renal injury and iNOS expression in obstructive jaundice (OJ). Forty rats were randomized into four groups: group A (Sham), group B (Sham+AT-III, 250 IU kg −1 ), group C (OJ), group D (OJ+AT-III, 250 IU kg −1 ). All animals were sacrificed on the 10th day and blood samples were taken for bilirubin and NO level determination. In addition, iNOS expression of the renal tissues was evaluated immunohistochemically. Blood NO levels were found to be 32.99 μ mol l −1 in group A, 32.26 μ mol l −1 in group B, 46.33 μ mol l −1 in group C, and 34.71 μ mol l −1 in group D. The intensity of iNOS staining in the OJ+AT-III group was less than the intensity of iNOS staining in the OJ group in the renal tissue. This study shows that OJ causes increased production of NO in blood and increased iNOS expression in the kidney. AT-III inhibits iNOS expression and reduces the level of blood NO. Thus, our findings indicate that under conditions of OJ, AT-III limits renal cellular injury by inhibiting LPS-induced iNOS expression.

In this lipopolysaccharide (LPS)-induced endotoxemia model, the effects of 3-aminobenzamide (3-AB), a poly(ADP-ribose) synthetase (PARS) inhibitor, on ileal apoptosis were evaluated by light microscopy and M30 cell death staining. Moreover, the relationship between Bcl-2, iNOS expression, and serum nitrate (NO(3)(-)) levels were investigated. Thirty-two male Wistar rats, weighing 180-220g were randomly divided into four groups. The group I (control; n=8) received saline and group II (sepsis; n=8) received 10 mg kg(-1) LPS intraperitoneally. 3-AB was given to the group IV (S+3-AB; n=8) 20 min before giving LPS and to the group III (C+3-AB; n=8) 20 min before giving saline. Six hours later, blood and ileum samples were taken. Endotoxemic group exhibited significant apoptosis in intestinal epithelial cells and the immunohistochemical examination with M30 was demonstrated that the 3-AB reduced the LPS-induced intestinal apoptosis. Serum NO(3)(-) level was increased in endotoxemic group, whereas the elevation of NO(3)(-) level was prevented in LPS+3-AB group (P0.05). The increased iNOS expression observed in the LPS group was also prevented by 3-AB. Compared with the endotoxemic group, ileal epithelial columnar cells from LPS+3-AB group had a dense Bcl-2 staining which was almost identical with control. In conclusion, 3-AB decreases LPS-induced apoptosis in ileum by preventing LPS-induced depletion of Bcl-2 and blocking iNOS gene. Modification of Bcl-2 expression by PARS inhibitors should further be investigated as a new therapeutic alternatives in septic states.

Although the precise mechanism by which sepsis causes impairment of respiratory muscle contractility has not been fully elucidated, oxygen-derived free radicals are thought to play an important role. In our experimental study, the effects of poly(ADP-ribose) synthetase (PARS) inhibition on the diaphragmatic Ca(2+)-ATPase, malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) levels and additionally histopathology of the diaphragm in lipopolysaccharide (LPS)-induced endotoxemia are investigated.Thirty-two male Wistar rats, weighing between 180-200 g were randomly divided into four groups. The first group (control; n=8) received saline solution and the second (LPS group; n=8) 10 mgkg(-1) LPS i.p. 3-Aminobenzamide (3-AB) as a PARS inhibitor; was given to the third group (C+3-AB, n=8) 20 min before administration of saline solution while the fourth group (LPS+3-AB, n=8) received 3-AB 20 min before LPS injection. Six hours later, under ketamin/xylasine anesthesia diapraghmatic specimens were obtained and the rats were decapitated. Diaphragmatic specimens were divided into four parts, three for biochemical analyses and one for histopathologic assessment. In the LPS group, tissue Ca(2+)-ATPase levels were found to be decreased and tissue MDA and 3-NT levels were found to be increased (P0.05). In the LPS+3-AB group, 3-AB pretreatment inhibited the increase in MDA and 3-NT levels and Ca(2+)-ATPase activity remained similar to those in the control group (P0.05). Histopathologic examination of diaphragm showed edema between muscle fibers only in LPS group. PARS inhibition with 3-AB prevented not only lipid peroxidation but also the decrease of Ca(2+)-ATPase activity in endotoxemia. These results highlights the importance of nitric oxide (NO)-peroxynitrite (ONOO(-))-PARS pathway in preventing free radical mediated injury. PARS inhibitors should further be investigated as a new thearapetic alternative in sepsis treatment.

Objective: Myringosclerosis often occurs in patients in whom ventilation tube insertion and tympanoplasty procedures are performed. Recent studies have revealed a relationship between the development of myringosclerosis and oxygen-derived free radicals, and some investigations have demonstrated that free radical scavengers prevent the development of myringosclerosis. N-acetylcysteine is a well-known anti-oxidant and anti-inflammatory agent. In this study, we aimed to investigate the preventive effect of N-acetylcysteine on myringosclerosis in myringotomized rat tympanic membranes. Methods: Twenty Sprague–Dawley rats were bilaterally myringotomized and divided into four groups. Group 1 received no treatment, group 2 was treated with topical saline solution in Spongostan, group 3 received topical 0.6 mg N-acetylcysteine in Spongostan and group 4 received 1.2 mg N-acetylcysteine in Spongostan daily for 12 days. Tympanic membranes were examined by otomicroscopy on day 12. Then, the membranes were harvested and evaluated histologically by light microscopy. Results: The tympanic membranes of groups 1 and 2 (saline and non-treated) showed extensive occurrence of myringosclerosis, whereas groups 3 and 4 (treated with N-acetylcysteine) showed lesser occurrence of myringosclerosis in otomicroscopic evaluation (P

This study was designed to investigate the efficacy of intravitreal levofloxacin, and intravitreal levofloxacin and dexamethasone combined in Staphylococcus epidermidis endophthalmitis. Albino rabbits (n = 25), infected with an intravitreal inoculum of S. epidermidis (1.0 × 105 colony forming units/0.1 ml), were divided into five groups (n = 5). Groups 1 and 2 received treatment 24 h after the inoculation, and groups 3 and 4 48 h after the inoculation. No treatment was given to the control group. Treatment efficacy was assessed by vitreous culture, clinical examination and histopathology. Five days after treatment, groups 1 and 2 had significantly lower clinical scores than the control group (p = 0.004, p = 0.007). The culture results of the treatment groups were sterile. The histopathological scores of the treatment groups were lower than the control group (p = 0.007). Studies on retinal toxicity and dose-response relation are needed to prove the efficacy of levofloxacin in S. epidermidis endophthalmitis.

Sir,A wide variety of unusual mesenchymal lesions may arise in the lower female genital tract. Among these are aggressive angiomyxoma, angiomyofibroblastoma, cellular angiofibroma and fibroepitheli...

A 37-year-old male case was admitted with goiter. Ultrasonography of thyroid showed a 5 cm cystic nodule in the left lobe with a 1.5 cm solid component. Fine needle aspiration biopsy revealed atypia of undetermined significance or follicular lesion. The patient was operated on. The pathological diagnosis was reported as papillary thyroid carcinoma. The immunohistochemical examination showed multiple foci of Langerhans cell histiocytosis involving both lobes. The patient died due to cardiac arrest with respiratory causes in the early postoperative period. Langerhans cell histiocytosis is a rare primary condition which involves abnormal clonal proliferation of Langerhans cells in various tissues and organs. Thyroid involvement is infrequently seen. Although the etiology is unknown, genetic components may be linked to the disease. It is also associated with a family history of thyroid disease. Papillary thyroid carcinoma is the most common malignant epithelial tumor of the thyroid gland. Langerhans cell histiocytosis presenting with papillary thyroid carcinoma is rare. The privilege of our case is langerhans cell histiocytosis of the thyroid with multiple cervical lymph node involvement accompanying cervical lymph node metastatic thyroid papillary carcinoma.