Mild Hyperplasia Research Articles

The p64 Flow Diverter-Mid-term and Long-term Results from aSingle Center.

The p64 is aflow modulation device designed to be used in endovascular treatment of intracranial aneurysms. There is limited data on the long-term effectiveness of the device. This study sought to determine the safety and long-term efficacy of this device. Aretrospective review of aprospectively maintained database was performed to identify all patients treated with ap64 between March 2015 and November 2018 at University Hospital St.Ivan Rilski. Anatomical features, intraprocedural complications, clinical, and angiographic outcomes were also taken into account and reviewed. A total of 72patients with 72aneurysms who met the inclusion criteria were identified. Device placement was successful in all patients. Follow-up angiographic imaging at 6months showed complete occlusion (O'Kelly-Marotta scale [OKM]D) in 55 (76.3%) patients, subtotal aneurysmal filling (OKMB) in 10 (13.8%) patients, and neck remnant (OKMC) in 7 (9.7%) patients. Catheter angiography at 12months was available for 70patients (97.2%) and of these patients 91.4% of the aneurysms were completely occluded (OKMD) (64/72). Delayed angiography at 24months was available for 68patients (94.4%) and of these 98.5% (67/68) had completely occluded aneurysms. A36-month angiography was available for 61patients (84.4%) by which point all aneurysms had been completely occluded (100%). Permanent morbidity due to delayed aneurysmal rupture occurred in one patient (1.38%). The mortality rate was 0%. Self-limiting mild intimal hyperplasia was seen in 2patients (2.72%). Treatment of intracranial aneurysms with ap64 flow modulation device is safe and effective with ahigh success rate and only infrequent complications.

POEMS Syndrome: Bone Marrow, Laboratory, and Clinical Findings in 24 Korean Patients.

POEMS syndrome is a rare paraneoplastic syndrome, which includes polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes due to plasma cell (PC) neoplasm. Diagnosis of this disease is challenging because of its rarity and complex clinical manifestations. We attempted to identify the key clinical features and characteristic bone marrow (BM) findings of POEMS syndrome, by reviewing the medical records and BM analyses of 24 Korean patients. Frequent clinical manifestations included polyneuropathy (100%), monoclonal gammopathy (100%), organomegaly (92%), extravascular volume overload (79%), and endocrinopathy (63%). The BM analyses revealed mild PC hyperplasia (median PCs: 5.5%) and frequent megakaryocytic hyperplasia (88%), megakaryocyte clusters (88%), and hyperlobation (100%). Flow cytometry of BM aspirates using CD138/CD38/CD45/CD19/CD56 showed normal (67%, 4/6) or neoplastic PC immunophenotypes (33%, 2/6). A diagnosis of POEMS syndrome must be considered when a patient suspected of having PC dyscrasia shows the above clinical presentation and BM findings.

Histological Study of Molar Pregnancy by using some of the Special Stains

Background: Molar pregnancy (hydatidiform mole HM) is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus and will fail to come to term. A molar pregnancy is a gestational trophoblastic disease which grows into a mass in the uterus that has swollen chorionic villi. These villi grow in clusters that resemble grapes. A molar pregnancy can develop when a fertilized egg does not contain an original maternal nucleus. The diagnosis of HM is based on its morphology. In classic cases, the abnormally large villi have a vesicular or a grape like appearance. Histologically, HM presents variable degrees of circumferential trophoblastic hyperplasia and epithelial atypia. Distinguish between complete mole (CM) and partial mole (PM) is difficult especially with early diagnosis and evacuation of molar pregnancies, however, the criteria are subjective and show considerable inter-observer variability. Unfortunately in our country the histological diagnosis is depend only on routine stain (H&E) which is not giving a clear results in some cases because of that, the study design to find the similarities and differences between the two types of molar pregnancy by using some of special stains which surely distinguish between complete and partial moles samples using immunohistochemical marker P57KIP2. Objective: To detecting if the special stain can be helpful to distinguish between the two types of molar pregnancy also to find the accuracy of the routine diagnosis of hydatidiform mole comparing with P57 immunohistochemistry stain. Patients and Methods: The study conducted at the maternal teaching hospital in Erbil city. Thirty cases of Molar Pregnancy diagnosed, 15 of them were complete and the others were partial mole. All the samples studied histologically using H&E and some of special stains including: PAS stain, Congo red, and Trichrom, to describe the morphological differences between the two types of mole. Also immunohistological P57 stain was used in this study to confirm the type of mole. Results: The study result shows the morphological variation between complete and partial hydatidiform through using the routine H&E stain and special stains. The complete hydatidiform mole sections showed vesicular swelling of chorionic villi and circumferential trophoblastic hyperplasia, the trophoblastic proliferation grade varying in complete samples, most samples showed grade II (46.6%) of trophoblastic proliferation, while few of samples showed grade III (13.3%). The cases of partial hydatidiform mole showed scattered hydropic villi with irregular scalloped villous outlines and mild trophoblastic hyperplasia, trophoblastic distribution elucidate that the majority (60%) of samples show zonal distribution and high percentage (73.3%) of focal trophoblastic proliferation. The vessels in the villous stroma of most of partial molar samples (80%) was obviously seen also the cistern appear clearly in 73.33% of the samples and all partial molar pregnancy samples showed presence of fetal part in contrast to complete mole. The PAS stain show no different between the two types of molar pregnancy samples while the Congo red stained the partial molar samples intensely comparing with complete samples opposite to the trichrome stain which showed highly color intensity in complete than in partial samples. In this study the most important noticed results was high percentage (26.66) of positive result of P57 in complete diagnosed sample by routine way. Conclusion: The special stains can be helpful in diagnosis of hydatidiform mole and The study of p57 immunohistochemistry stain indicate present of misread in routine diagnoses of complete hydatidiform due to mimic morphological characters.

Assessment of a Vacuum-Based Intra-Colonic Diverting Device: A Preclinical Study.

Purpose. Anastomotic leak is the main complication after low colorectal anastomosis. Defunctioning ileostomy is therefore recommended, which carries its own morbidity. The aim of this study was to assess the technical feasibility, safety, and preliminary efficacy of a vacuum-based intra-colonic diverting device (Colovac) to reduce the impact of anastomotic leak. Methods. This prospective preclinical study was conducted on living swine. The device was surgically inserted transanally, proximal to a colorectal anastomosis, and removed endoscopically at day 14. Then, open surgery was performed to look for deep sepsis and/or anastomotic leak, and the remaining colorectal anastomosis was resected for histopathological analysis. The endpoints were successful insertion and delivery of the device, postoperative morbidity, successful maintaining of the device, and absence of feces spillage and/or abscess in the abdominal cavity. Results. The Colovac was inserted in 22 swine. Stent migration occurred in 7 of the first 8 specimens, leading to natural expulsion of the device. After diet adaptation, a subsequent group of 14 swine was undertaken, of which 13 did not show any sign of migration post-implantation. Disconnection of the suction drain occurred in 1 case, leading to device expulsion on day 10. Colovac retrieval was achieved successfully in 13 cases. The endoscopic assessment of the anchorage site showed limited mucosal injury, whereas histopathological findings revealed mild hyperplasia. One swine died prematurely of postoperative colonic ischemia. Conclusion. This new device appears to be safe in the swine model and may prevent peritonitis or abscess due to colorectal anastomotic leak.

Acute changes in morphology and renal vascular relaxation function after renal denervation using temperature-controlled radiofrequency catheter

BackgroundResistant hypertension and renal sympathetic hyperactivity are closely linked, and catheter-based renal denervation (RDN) is regarded as a new treatment strategy. However, the acute changes in vascular morphology and relaxation function have yet to be evaluated, and these may be important for the efficacy and safety of the procedure. In this study, we explored these questions by conventional temperature-controlled cardiac radiofrequency catheter-based RDN in a pig model.MethodsSix mini-pigs were randomly divided into the renal denervation (RDN) group (n = 3) and the Sham-RDN group (n = 3). Animals in the RDN group underwent unilateral radiofrequency ablation, and those in the Sham-RDN group underwent the same procedure except for the ablation. The pigs were examined by angiography pre- and post-RDN and were euthanized immediately thereafter. Renal arteries were processed for histological and molecular biology analyses as well as for in vitro vascular tension testing.ResultsCompared with the Sham-RDN group, the RDN caused vascular intima and media injury, renal nerve vacuolization, mild collagen fiber hyperplasia and elastic fiber cleavage (all p < 0.05). The RDN group also significantly exhibited nitric oxide synthase pathway inhibition and decreased endothelium-independent vascular relaxation function Compared to the Sham-RDN group (all p < 0.05).ConclusionsIn this porcine model, renal artery denervation led to vascular wall injury and endothelial dysfunction in the acute phase, which negatively affected vascular relaxation function. Thus, this process may be detrimental to the prognosis and progress of hypertension patients.

194. DISTRIBUTION OF MACROPHAGE SUBSETS IN TEMPORAL ARTERY BIOPSIES OF PATIENTS WITH GIANT CELL ARTERITIS

Background: Giant cell arteritis (GCA) is a granulomatous vasculitis characterized by recruitment of T-cells and monocytes to the vessel wall. Upon recruitment, monocytes are activated and differentiate into macrophages. These lesional macrophages take on different phenotypes depending on cues from the microenvironment. These macrophages are known to produce pro-inflammatory cytokines, chemokines, matrix-metalloproteinases (MMPs), and growth factors contributing to amplification of the inflammatory response, vessel wall injury and remodeling. However, current knowledge regarding macrophage subsets in GCA lesions is limited. Objectives: To examine the distribution of macrophage subsets in GCA lesions. Methods: Immunohistochemistry was performed on consecutive sections of paraffin-embedded temporal arteries of biopsy-confirmed GCA patients (n = 11) with antibodies to selected markers of inflammation and tissue remodeling (Table 1). Positive cells were scored in three layers of the vessel wall (adventitia, media-intima, inner-intima) using a semi-quantitative scoring system. Expression by macrophages was confirmed by double staining with the macrophage transcription factor PU.1. Results: The pro-inflammatory marker CD64 and pro-inflammatory cytokines (IL-12, IL-23 and IL-1β) were strongly expressed by macrophages throughout the vessel wall, most prominently in the adventitia. However, subsets of these CD64+ macrophages also showed concomitant expression of the tissue remodelling markers CD206 and FR-β in specific compartments of the lesions. More specifically, CD206+ macrophages were mainly found along the media borders which co-localized with positive MMP-9 staining. Interestingly, FR-β positivity was also found in the inner-intima of TABs with a high degree of intimal hyperplasia. FR-β expression was significantly higher in the inner-intima region in TABs with massive intimal hyperplasia compared to TABs with mild intimal hyperplasia (p = 0.01). Conclusion: Based on the expression of markers of inflammation and tissue remodeling, different subsets of infiltrating macrophages can be distinguished. Macrophages in vascular lesions of GCA patients display a distinct spatial distribution pattern within the inflamed vessel wall (Figure 1). Adventitial macrophages express highest level of pro-inflammatory cytokines indicating pro-inflammatory functions of these macrophages. Co-localization of CD206 and MMP-9 along media borders indicates a role for CD206+ macrophages in collagen digestion and angiogenesis. Additionally, the association of increased numbers of FR-β+ macrophages with extensive intimal hyperplasia suggests that FR-β+ macrophages promote myofibroblast proliferation. Reference [1] Watanabe R, Maeda T, Zhang H, Berry GJ, Zeisbrich M, Brockett R, Greenstein AE, Tian L, Goronzy JJ, Weyand CM. MMP (Matrix Metalloprotease)-9-Producing Monocytes Enable T Cells to Invade the Vessel Wall and Cause Vasculitis. Circ Res. 2018 Aug 31;123(6):700-715. Disclosure of Interests: William Febry Jiemy: None declared, Yannick van Sleen: None declared, Annemieke Boots Grant/research support from: grant from MSD in 2010-2015, Consultant for: I was a consultant for Grunenthal Germany 2016-2017, Employee of: I was an employee of Organon, Shering-Plough and MSD from 1991-2011, Riemer Slart: None declared, Peter Heeringa: None declared, Elisabeth Brouwer Speakers bureau: Dr. Brouwer as an employee of the UMCG received speaker fees and consulting fees from Roche which were paid to the UMCG

Effects of Spondias mombin and Aspilia africana Aqueous Extracts on Rats with Monosodium Glutamate-Induced Leiomyoma

Uterine leiomyoma is commonly known as fibroid. Increased use of chemicals is believed to enhance its prevalence and monosodium glutamate is implicated. Fibroid is prevalent among black women with no known drug for its treatment. It is therefore necessary to determine a safer method for fibroid treatment. This work investigated effects of different aqueous extracts of Spondias mombin (hog plum) and Aspilia africana (wild sunflower) leaves on uterus and kidney cells of rats with monosodium glutamate (MSG)-induced fibroid. Twenty-eight rats used in this study were divided into four groups of seven rats each and acclimatized. Fibroid was induced on the Positive control, Groups III and IV, after daily ingestion of 750mg/kg body weight of MSG for 28 days. Negative control had no fibroid but the Positive control remained untreated. Groups III and IV were continuously ingested with same dose of MSG for the next 28 days with daily oral treatment using 250mg/kg body weight aqueous extracts of hog plum and wild sunflower, respectively. Histological examinations were performed on the 2nd and 4th weeks, respectively, on two rats from each group for the next 28 days. Results showed degenerated endometrial cells and preserved nephritic tissues after treatment with aqueous extracts of S. mombin leaves. There was mild hyperplasia of endometrial cells after treatment with extract of A. africana in the 2nd week which differed from the 4th week. MSG has nephrotoxic properties and aqueous extract of S. mombin alleviated MSG oxidative powers on rats’ endometrial cells. With continuous ingestion, A. africana aqueous extract better preserved rat’s endometrium from oxidizing action of MSG. These extracts could be used as safer chemotherapy in fibroid management.

Malignant basomelanocytic tumour: a case report

To our knowledge there are about 40 reported cases of combined melanoma and basal cell carcinoma (BCC), known as basomelanocytic tumours. We report a case of malignant basomelanocytic tumour in the lower canthus of an 84-year-old gentleman who went under an excisional biopsy with suspected BCC. Histopathological examination of the skin revealed an invasive nodular mass with solid and infiltrating basaloid cells, reminiscent of BCC. In addition, this lesion had a focal mild lentiginous hyperplasia adjacent to the main lesion with scattered melanin pigments. These findings led to apply an immunohistochemistry panel including BerEp4, P40, Melan-A and HMB45. The basaloid cells were highlighted by BerEp4 and P40 while the melanocytic cells were highlighted by Melan-A and HMB45, which confirmed the malignant basomelanocytic tumour diagnosis. As these lesions are rare, the treatment of choice is not established yet and each case is evaluated considering patient comorbidities and anatomical site of the lesion. It is outlined in the literature that in cases in which melanomas are confined to the boundary of BCC, no recurrence is diagnosed after follow up and their melanoma component behaves like a melanoma in situ.1,2 However, further investigation is needed to establish the true nature of these lesions.

Schamberg's disease; a forgotten dermatoses: A case report with review

Schamberg's Disease (SD) also known as progressive pigmented purpuric dermatitis is the most common PPD (Pigmented Purpuric Dermatitis). PPD includes a spectrum of vascular diseases with an incidence of 0.18% of all skin and VD lesions. SD has Idiopathic aetiology, affects all races and ages (with mean age of 34 years). Males are affected more, especially the legs showing reddish brown purpuric patch/macules which has a chronic slow progression to other body parts. Long standing medications are thought to be one of the precipitating factor. Extravasation of RBCs from the superficial venous plexus of skin is thought to be the cause of skin discoloration. Histopapathology (HP) of the skin lesion show mild epithelial hyperplasia, occasional foci of spongiosis and lymphohistiocytic infiltrate with extravasation of RBCs. The disease has a cosmetic problem. No malignant transformation has been documented yet and to date there is no effective treatment. It is usually diagnosed by Clinical suspicion followed by HP confirmation.

Multistep carcinogenesis of 7,12-Dimethylbenz(a)anthracene (DMBA)-induced skin tumours in rats: An immunohistochemical study

The present study was aimed to induce skin tumours in rats by chemical carcinogen 7,12-dimethybenz(a)anthracene (DMBA), to ascertain the different stages of tumorigenesis with molecular markers and application of these markers in diagnosis of neoplasms. DMBA solution (5 pmol in 0.25 ml acetone per dose) was applied fortnightly on the skin of 35 rats in one group (Group A) for a maximum of 20 doses. In another group of 35 rats (Group B), DMBA was applied initially for three consecutive weeks as initiator followed by weekly croton oil (1% w/v in acetone) applications as promoter for 60 weeks. Control groups (10 rats each) were also taken for both the treatment groups. Skin tumours were induced in only DMBA treated rats after latent period of 22 weeks, comprising of papillomas (47%), squamous cell carcinomas (43%) and fibrosarcomas (13%). Adnexal tumours consisted only two cases, one each of sebaceous basal cell carcinoma and sweat gland adenocarcinoma. Tumours arose as soft sessile/pedunculated, multicentric growths which became large cauliflower like and multiple confluencing lesions to become bigger masses. Histopatho- logically, sequential alterations seen were epidermal hyperplasia, severe epidermal hyperplasia, papilloma, papillary carcinoma, squamous cell carcinoma and its metastasis in lungs. The indices for proliferation markers (mitoses, AgNORs and PCNA) were significantly higher for squamous cell carcinoma (9.14, 15.44 and 181.63) and papillary carcinoma (3.09, 6.40 and 79.13) compared to mild epidermal hyperplasia (1.03, 4.17 and 0.53). Immunohistochemically, epidermal cells revealed p53, c-Myc and PCNA positive nuclear labelling for initiation and proliferation; strongly positive labelling for pre-malignant lesions, and strong p53, c-Myc, PCNA and hTERT labelling for malignant transformation, and additional abnormal cadherin and fibronectin for invasion and metastasis. c-Myc oncoprotein was demonstrated in nucleus and cytoplasm of cancer cells by immuno-electron microscopy. In conclusion, different stages of tumour development and progression was ascertained by using molecular markers: early detection of p53 and c-Myc for cell initiation and transformation; PCNA for cell proliferative activity; p53, c-Myc and PCNA overexpression in many cells for pre-malignant lesions; excessively increased p53, c-Myc and PCNA with additional expression of hTERT and abnormal cadherin and fibronectin for invasiveness, and additional loss of cadherin and fibronectin for metastasis. Mitotic index, AgNOR counts and PCNA index were independent cell proliferation markers, each being equally capable of ranking neoplastic lesions as benign and/or malignant tumours. Overall, PCNA index had high sensitivity and reliability for differentiating borderline tumours (papillary carcinomas) from benign (papilloma). Further studies are needed to elucidate the functional differences of excessively expressed, stabilized normal p53 protein and/or mutant p53 protein vis-a-vis their ultimate impact in the oncogenesis. Role of cytoplasmic accumulation of c-Myc in malignant tumours, particularly in malignant differentiated cells with the possibility of exploitation of this property of c-Myc oncoprotein for diagnosis of cancers needs further investigation.

Can You See the Carcinoid Tumor? A Case of Autoimmune Metaplastic Atrophic Gastritis (AMAG) and Carcinoid Tumor

Atrophic gastritis is a known risk factor for the development of carcinoid tumor and gastric adenocarcinoma. In AMAG, there is destruction of parietal cells which leads to G-cell hyperplasia and elevated gastrin levels resulting in the proliferation of enterochrommaffin-like cells. These cells serve as precursors to carcinoid tumors, thus can be neoplastic in nature. A majority of carcinoid tumors appear on upper endoscopy (EGD) as polypoid lesions in the gastric body or fundus. We would like to present a unique case of carcinoid tumor in the context of AMAG, with grossly normal EGD. Our patient is a 25 year old female without significant past medical history with sole complaint of chronic dyspepsia and upper abdominal pain. She presented to clinic for a second opinion after a recent diagnosis of a neuroendocrine malignancy on EGD one month prior. The patient underwent repeat EGD with biopsies taken from the antrum, body, and fundus. An area of hypopigmented mucosa was identified in the antrum, prompting biopsies. The remainder of the stomach, duodenum, and esophagus were grossly normal. Pathology from the antrum and fundus all revealed chronic gastritis with mild enterochromaffin-like cell hyperplasia and severe reactive changes. The fundic biopsy showed chronic atrophic gastritis with antralized mucosa, suggestive of AMAG. The biopsies from the body of the stomach demonstrated well-differentiated neuroendocrine tumor (NET) grade 1, arising in the background of chronic atrophic gastritis. KI67 demonstrates proliferation index less than 2%. No lymphovascular invasion was seen. Her prior EGD showed well differentiated NET on antral biopsy. Patient underwent EGD/EUS with biopsies at a tertiary center, which was unremarkable, and biopsy showed atrophic gastritis. She was advised to repeat EGD every 6-12 months. This case raises concern for therapy modalities as minimal literature exists in regards to treatment of NET in the setting of AMAG with normal EGD. Given the lack of gross focality to the carcinoid lesion, does one resect or surveil? Although gastric carcinoid in the setting of atrophic gastritis is rarely malignant, one must ponder the malignancy potential given that we were unable to pinpoint the lesion despite multiple EGD's. Further cases must be studied to adequately manage such patients and better understand disease progression.3087_A Figure 1. EGD with normal appearing mucosa3087_B Figure 2. EGD with normal appearing mucosa and narrow band imaging

Correlation of T Cell Immunoglobulin and ITIM Domain (TIGIT) and Programmed Death 1 (PD-1) with Clinicopathological Characteristics of Renal Cell Carcinoma May Indicate Potential Targets for Treatment.

BackgroundThis study investigated the correlation of programmed death 1 (PD-1) and T cell immunoglobulin and ITIM domain (TIGIT) with clinicopathological characteristics of renal cell carcinoma (RCC) and explored the biological roles of both proteins in the development, metastasis, and invasion of RCC.Material/MethodsThe expressions of PD-1 and TIGIT were detected in the RCC and adjacent normal tissues, and their correlation with the clinicopathological characteristics of RCC, relationship between PD-1 and TIGIT in RCC, and the correlation of PD-1 and TIGIT expression with distance of adjacent normal tissues to RCC were further evaluated.ResultsTIGIT and PD-1 expression was detectable in the immune cells of peripheral blood mononuclear cells and lymphoid tumor infiltrating lymphocytes, and TIGIT expression was significantly higher than PD-1 expression in the same sample. Cells with transparent cytoplasm were diffuse, and several cells showed dark nuclear staining with mild atypia; the interstitium was rich in blood vessels and had mild fibrous hyperplasia, and immunofluorescence staining showed cells were positive for TIGIT. The expression of PD-1 and TIGIT was significantly different between RCC and adjacent normal tissues (P<0.05). Positive PD-1 expression was closely related to tumor size and Fuhrman grade (P<0.05). The expression of TIGIT and PD-1 was related to the distance of adjacent normal tissues to RCC (P<0.05).ConclusionsThe activation of PD-1 and TIGIT may exert negative regulatory effects and inhibit the immune response to cancer cells, resulting in immune escape of cancer cells. Both PD-1 and TIGIT may serve as potential targets for the treatment of RCC.

Non-classical 11\u03b2-hydroxylase deficiency caused by compound heterozygous mutations: a case study and literature review

Background11β-hydroxylase deficiency (11OHD) is extremely rare, and reports of non-classical 11OHD are even rarer. Non-classical 11OHD usually presents as premature adrenarche, hyperandrogenism, menstrual disorders, and hypertension. Because the symptoms of non-classical 11OHD are mild, delayed diagnosis or misdiagnosis as polycystic ovary syndrome or primary hypertension is common.Case presentationThis paper introduces a case of a young female patient presenting hypertension and menstrual disorders. Laboratory examination revealed increased androgen levels, mild adrenal hyperplasia, mild left ventricular hypertrophy, and mild sclerosis of the lower limb arteries. 11OHD was confirmed by genetic testing, and the patient was found to carry compound heterozygous mutations in CYP11B1 (c.583 T > C and c.1358G > A). The mutation Y195H is located in exon 3 and has not been reported previously. In silico studies indicated that this mutation may cause reduced enzymatic activity. After treatment with hydrocortisone and spironolactone, blood pressure was brought under good control, and menstruation returned to normal. We also conducted a retrospective review of previously reported cases in the literature (over 170 cases since 1991).ConclusionsEarly diagnosis of non-classical 11OHD is difficult because its symptoms are mild. The possibility of this disease should be considered in patients with early-onset hypertension, menstrual disorders, and hyperandrogenism to provide early treatment and prevent organ damage due to hypertension and hyperandrogenism. CYP11B1 mutations are known to be race-specific and are concentrated in exons 3 and 8, of which mutations in the former are mostly associated with non-classical 11OHD, whereas mutations in the latter are mostly found in classical 11OHD, characterized by severe loss of enzymatic activity.

Keratinocyte Expression of A20/TNFAIP3 Controls Skin Inflammation Associated with Atopic Dermatitis and Psoriasis

Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of proinflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of microdissected epidermis showed that A20 is down-regulated in involved epidermis, but not in dermis, of psoriasis and atopic dermatitis patients, suggesting that loss of A20 expression in keratinocytes increases the vulnerability for psoriasis/atopic dermatitis induction. We have previously shown that epidermis-specific A20 knockout mice (A20EKO) develop mild epidermal hyperplasia but no macroscopic skin inflammation. We now show that various cytokines and chemokines are up-regulated in A20EKO mouse skin. A20EKO mice also display systemic proinflammatory changes, even in the absence of skin immune cell infiltration, and an exacerbated disease severity upon induction of experimental psoriasis, atopic dermatitis, or skin barrier disruption. Keratinocytes showed increased proinflammatory gene expression in the absence of A20 in unstimulated and IL-17A-stimulated conditions, in part resulting from uncontrolled MyD88-dependent signaling. Our findings indicate that absence of A20 in keratinocytes leads to systemic inflammation at homeostatic conditions and is sufficient to exacerbate inflammatory skin disorders associated with different immune profiles by increasing cytokine and chemokine expression.

Flow diverter for endovascular treatment of intracranial mirror segment internal carotid artery aneurysms.

To evaluate the feasibility and efficacy of the pipeline embolization device in the treatment of unruptured intracranial mirror segment aneurysms. Out of a total of 338 subjects, 14 were identified harboring a total of 32 internal carotid artery mirror segment aneurysms that were treated with the pipeline embolization device and were consecutively enrolled into our study. We collected data on patient demographics, modified Rankin scale (mRS) at admission, aneurysm characteristics, clinical outcome at discharge, 3-9 and at 12-18 months as well as angiography results at follow-up. Patients' mean age was 52.9 years; baseline mRS was 0 in all subjects. Pipeline embolization device placement was successful in all cases. Post-treatment mRS remained 0 in 13/14 patients. One patient experienced a small intraparenchymal hemorrhage and subarachnoid hemorrhage, associated with a frontoparietal infarction resulting in right upper extremity weakness and aphasia (post-treatment mRS 3). His mRS evaluation remained stable at the 3-9-month follow-up. Three to 9-month follow-up angiography (13/14 subjects) showed complete aneurysm occlusion in 24/30 aneurysms (80%), near complete and partial occlusion in three of 30 (10%) aneurysms each. At the 9-month follow-up, one patient experienced a complete occlusion of the anterior temporal artery branch but did not present with any clinical deficits. No mRS changes were encountered over a median 6-month follow-up period. Mid-term follow-up angiography (12-18 months) available in eight of 14 subjects showed complete aneurysm occlusion in all patients. Mild intimal hyperplasia was observed in one patient. Flow diversion technology can be used for the treatment of unruptured mirror segment aneurysms in selected patients.

A CASE REPORT OF PRIMARY MUCOSA ASSOCIATED LYMPHOID TISSUE LYMPHOMA OF THE PROSTATE

The patient was a 53-year-old man who was referred to the department of urology of our hospital after screening results indicated elevated prostate-specific antigen (PSA) levels. The PSA level was 5.33 ng/ml, and rectal examination revealed that the prostate was elastic and hard with mild prostatic hyperplasia. Because magnetic resonance imaging revealed abnormal signals in the prostatic transition area, prostate cancer was suspected and the patient underwent transrectal prostate needle biopsy. The pathological diagnosis was adenocarcinoma (Gleason score 5+5 = 10). After using thoracic, abdominal, and pelvic computed tomography (CT) and bone scintigraphy to confirm that metastasis had not occurred, robot-assisted radical prostatectomy (RARP) was performed. Prostate cancer was not detected during pathologic diagnosis of the surgical specimen, and on the basis of the results of re-examination with immunostaining, a diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma was made. In addition, an upper and lower endoscopy examination, positron emission tomography (PET) -CT, and bone marrow biopsy confirmed that generalized tumor lesions and lymph node swelling were not present, and the patient was diagnosed with primary MALT lymphoma of the prostate. Currently, 12 months since surgery, the patient continues to undergo follow-up as an outpatient and no recurrence has been observed. There have been only a few reports of primary MALT lymphoma of the prostate, in English or Japanese, and herein, we present our experience with a patient for whom a definitive diagnosis was difficult, along with a review of the literature.

Desmoplastic trichoepithelioma complicated by sebaceous hyperplasia: a case report

A 67-year-old male patient presented with a plaque on the top of the head for more than 1 year. Physical examination showed an annular pale red plaque sized about 1.5 cm × 1 cm on the top of the head. It had a depressed center and papule-like elevated faint yellow boundaries, and there was no hair on the surface of the lesion. Histopathologic examination revealed milder epidermal hyperplasia, a small area of epidermal depression, confluence and hyperplasia of multiple sebaceous glands in the dermis, many keratinous cysts and funicular basophilic epithelial cells surrounded by hyperplastic collagen fibers in the superficial dermis. Immunohistochemical study showed positive staining for CD34 (hair mesenchymal cells) , epithelial membrane antigen (EMA) , cytokeratin 20 (CK20) , but negative staining for bcl-2, P53, CD56 and collagen Ⅳ, with the proliferation index Ki-67 of 2% - 5%. Based on the pathological results, the patient was diagnosed with desmoplastic trichoepithelioma complicated by sebaceous hyperplasia. Key words: Sebaceous gland diseases; Desmoplastic trichoepithelioma

SEASONAL VARIATION OF GILL, SKIN, MUSCLE, LIVER AND KIDNEY PATHOLOGY OF MRIGAL (Cirrhinus cirrhosus) IN CULTURAL POND FISHERIES, MYMENSINGH, BANGLADESH

An investigation on the seasonal variation of gill, skin muscle, liver and kidney pathology of Mrigal (Cirrhinus cirrhosus) was carried out from four Government (Govt.) and four Private (Pvt.) fish farms, Mymensingh, Bangladesh during June, 2010 to May, 2012. Fish sampling and water quality parameters were monitored monthly basis. For histopathological studies skin, muscle, gill, liver and kidney were collected, processed and stained in Haematoxylin and Eosin. Histologically, Mrigal of different fish farms were more affected in colder months. All the investigated organs of Mrigal were exhibited few abnormalities during summer, however, mild hyperplasia, haemorrhage, partial loss of secondary gill lamellae, marked and hypertrophy was observed during the rainy season. Several pathological changes like necrosis, fungal granuloma, protozoan and monogenean cyst, vacuolation, melanomacrophase, haemorrhage, hypertrophy, hyperplasia and clubbing were recorded in all the investigated organs. Among them fish gills and skin were more affected followed by liver and kidney. In some cases, large bacterial colony and protozoan cyst were observed in the secondary gill lamellae of Mrigal. The ectoparasites were very common in gills and skin of all fishes. Water quality parameters were taken and management practices were investigated fortnightly interval in different farms. These were almost similar for all experimental ponds. The risk of being infestation by parasites of carp significantly (p&lt;0.001) increased when the water quality parameters such as temperature, dissolved oxygen, pH, ammonia, hardness, alkalinity, transparency and depth of water etc. were not maintained the optimum level.

Histomorphological Effects of Nicotine on Selected Parts of the Brain of Adult Wistar Rats

Nicotine has been defined as a potent parasympathomimetic alkaloid that accumulates in the roots and leaves of Nightshade family of plants Aim: This study was aimed at evaluating the effects of orally ingested nicotine in the histology of hippocampus, substantia nigra and cerebellum.Materials and Methods: Twenty four adult male Wistar rats (100g – 200g) were randomly divided into 4 groups (group 1 – group 4). Group 1 served as the control group, while groups 2 - 4 were the treated groups. Nicotine was diluted in water and 1ml of the different dosage (2mg/kg/day, 4mg/kg/day and 6mg/kg/day) were administered to the treated groups respectively with the aid of orogastric cannula for 42 days. Animals were euthanized by cervical dislocation at the end of 7, 21 and 42 days so as to demonstrate the dose and time dependant effect of this agent. Brain tissues were harvested, processed and stained using Haematoxylin and eosin according to standard histological techniques. Stained tissue images were captured using digital micrometer eyepiece and cell count was determined using stereological technique.Statistical analysis: Data obtained were subjected to statistical analysis with the use of statistical package for social sciences (SPSS version 20). Significant differences were obtained using One Way Analysis of Variance with a probability of 0.05 (95% confidence limit) and Tukeys post hoc test was further used to determine the mean significant differences between specific groups.Results: Histological findings showed mild, moderate and severe hyperplasia in a dose and time dependant manner. However, observations from quantitative analysisalso revealed a dose and time dependant significant increase in neuronal cell count and cell diameter of the hippocampus, Substantia nigra and cerebellum.Conclusion: This study has demonstrated that oral exposure of Nicotine in rats display proliferative adaptive changes on the hippocampus, substantia nigra and cerebellum in a dose/time dependent manner.

Effect of chronic heat stress on some physiological and immunological parameters in different breed of broilers.

ABSTRACTThe differences in physiological and immunological parameters and pathological damage to organ tissues exposed to chronic heat stress provide the basis for evaluating heat resistance of different chicken breeds (white recessive rock [WRR] and The Lingshan [LS]). Ninety broilers of each breed were divided equally into a chronic heat stress group and a no heat stress group. The effects of chronic heat stress on the physiological and immunological parameters of broilers were analyzed using flow cytometry, ELISA, RT-qPCR, etc. Under heat stress conditions: (1) H and H/L values were significantly increased (P < 0.01) in the 2 breeds, and were higher in the WRR broilers than in the LS broilers at a late stage (P < 0.05). Although the corticosterone levels were also significantly increased (P < 0.01) in both breeds, they were lower in the 49 d WRR broilers than in the LS broilers (P < 0.01). The number of leukocytes were significantly increased in the 49 d WRR broilers (P < 0.01), whereas the number of CD3+, CD8+ cells, and erythrocytes were significantly reduced (P < 0.05). A significantly (P < 0.01) lower number of CD3+, CD4+ T-lymphocytes, and CD4+/CD8+ were present in WRR compared to that in the LS broilers. (2) The HSP70 transcript was significantly increased in the WRR broilers (P < 0.01), and was higher than the level in the LS broilers. The expression level of HSP70 protein was significantly (P < 0.05) increased in WRR broilers. (3) The WRR broilers developed cardiac and leg muscle inflammatory cellular hyperplasia and local inflammatory lesions, as well as cerebral meningitis and inflammatory hyperplasia of the brain tissue. The LS broilers developed mild cerebral inflammatory hyperplasia and mild inflammatory cellular proliferation in the leg muscle. In conclusion, under heat stress conditions, the relative physiological and immunological parameters were worse in the WRR broilers than in the LS broilers. The WRR broilers showed poor heat tolerance as evidenced from the expression of HSP70 and the extent of histopathological damages.