Diffuse Mononuclear Cell Infiltration Research Articles

Investigation of Toxoplasma gondii and Neospora caninum in different tissues of aborted foetuses of sheep in Van Province, Türkiye: Analysis by nested PCR, histopathological and immunohistochemical methods

Toxoplasma gondii and Neospora caninum are protozoon parasites from the intracellular apicomplexan family. Toxoplasma gondii is the cause of health and economic problems in the sheep industry worldwide. Neospora caninum is usually reported in cows and leads to infections causing abortions; however, its prevalence in sheep is not clear. The present study aimed to investigate the prevalence and pathology of T. gondii and N. caninum by PCR, histopathological and immune-histochemical methods in aborted sheep foetuses collected at different sheep flocks in the Van Province, Türkiye, in 2021. Firstly, the DNA of T. gondii and N. caninum were investigated by PCR in the brain, heart, and peritoneal fluid samples from 42 sheep foetuses. Toxoplasma gondii DNA was proved in 35.7% (15/42) of foetuses whereas N. caninum DNA was not determined in any of the samples. Histopathologically, all T. gondii positive brain tissue samples showed lymphohistiocytic multifocal encephalomyelitis and additional findings included necrotizing myocarditis in the positive heart samples. Toxoplasma gondii tachyzoites were identified in the lesions (diffuse or focal mononuclear cell infiltration in the meninges, and microglia proliferation, myocarditis with oedema) by anti-T. gondii antibodies by the immunohistochemical method. Based on our results, we can conclude that T. gondii is an important agent in sheep abortions and the PCR method is a suitable method for diagnosis which can also be used in heart tissue in pathological studies.

Tubulointerstitial nephritis with IgA kappa-positive plasma cells in a patient with primary Sjögren's syndrome and monoclonal gammopathy.

This is a case report of a 69-year-old Japanese man who has been undergoing treatment for primary Sjögren's syndrome (pSS) since he was 62years. A renal biopsy, which revealed diffuse and severe mononuclear cell infiltration in the tubulointerstitium, was performed because of progressive renal dysfunction. Immunostaining demonstrated most of the infiltrating cells to be IgA, kappa, CD38, and CD138 positive. Immunofixation blood test revealed IgA kappa-type M protein; however, bone marrow abnormalities or lymph node enlargements on examination or imaging, respectively, were not observed. Tubulointerstitial nephritis caused by monotypic plasmacytic infiltration in pSS, accompanied with a monoclonal gammopathy of undetermined significance (MGUS), was diagnosed. A treatment of prednisolone 40mg/day was initiated, promptly improving the patient's serum creatinine levels from 3.0 to 1.5mg/dl. The infiltrating cells in pSS-associated tubulointerstitial nephritis are generally polytypic plasmacytes and lymphocytes, but in the present case, monotypic plasmacytes were predominant. This case is remarkable and rare and can be considered a complication of pSS or MGUS. Since it may become a new disease entity, it is important to accumulate similar cases.

ROSAI-DORFMAN'S DISEASE IN THE SUBMANDIBULAR REGION OF A PAEDIATRIC PATIENT: A CASE REPORT

Rosai-Dorfman disease is a rare histiocytic disorder of unknown etiology. This study aims to report an uncommon case of the disease in the submandibular region. A 7-year-old female patient presented with submandibular swelling of 3 months' duration. No intraoral manifestations were observed. Computed tomography scan demonstrated reabsorption of the mandibular cortical bone. An incisional biopsy was performed, and microscopic examination showed a diffuse mononuclear cell infiltration, with xanthomatous cells and emperipolesis of the lymphocytes. Immunohistochemistry was positive for LCA, CD3, CD20, VS38C, CD68, and S100 and the Ki-67 index was high, leading to the diagnosis of Rosai-Dorfman disease. Blood count evidenced anemia. Other affected sites were discarded by bone scintigraphy. Corticoid therapy with prednisone 40 mg for 6 months was prescribed. The patient was lost to follow-up. Rosai-Dorfman disease involving gnathic bones is rare and requires early diagnosis due to the possibility of spontaneous remission and conservative treatment.

Сравнительная оценка динамики патогистологической картины гнойной раны экспериментальных животных с моделью фурункула в области головы и шеи при стандартном лечении и при использовании электрорефлексотерапии

The most common neodontogenic infectious and inflammatory processes affecting the skin are furuncles in the maxillofacial area. The task of effective treatment of patients with this disease is now becoming increasingly urgent which is largely due to the deterioration of the environmental situation, changes in the nature of nutrition and chronic stress. The purpose of the study is to make a comparative assessment of the results of the standard method of postoperative treatment and complex treatment using electroacupuncture based on the dynamics of the pathohistological picture of a purulent wound in experimental animals with a model of a boil in the head and neck. Materials and methods. Experimental studies were carried out on 20 guinea pigs of the same age and body weight, on which a model of a boil in the submandibular area was created. The boil was formed within 3 days, after which all experimental animals under local infiltration anesthesia underwent primary surgical treatment of the infectious and inflammatory focus with wound drainage. Then the animals were divided into two series. Series 1 received a standard treatment package in the postoperative period (antibiotics, daily dressings with mandatory drainage changes, instillation of the wound with antiseptic solutions). For series 2 of animals, the standard treatment was combined with an electroacupuncture treatment. The material for pathohistological examination was collected in the following terms: 3, 7, 14 and 21 days after the operation. Serial sections were made according to the standard procedure. The micro-preparations were examined using a light microscope. For comparison a descriptive method was used. Results and discussion. The most significant differences were found on the 21st day of observation when diffuse mononuclear cell infiltration of all layers of the dermis was detected in most of the series 1 micro-preparations which indicated the presence of productive inflammation. During the same period of observation, all the micro-preparations of series 2 showed a multilayered flat keratinizing epithelium without violating the integrity throughout. The papillary and reticular layers of the dermis showed no signs of inflammation. The appendages of the skin were traced throughout the entire field of vision without visible pathological changes. All of the above indicated no signs of inflammation. Conclusion. The results obtained clearly indicate the positive effect of electroacupuncture on both wound cleansing and the course of the processes of reparative regeneration of the skin

Anti-ulcerogenic effect of osajin on indomethacin-induced gastric damage in rats

Ulcer is the most common undesirable result of using non-steroid anti-inflammatory drugs such as indomethacin. In the present study, osajin was experimentally used on indomethacin-induced gastric ulcer in rats. Osajin was purified from Maclura pomifera (Raf.) C. K. Schneid fruits by using the chromatographic methods. Thirty six rats were divided into six groups as follows: healthy (control), IND (indomethacin), RAN (ranitidine, 25 mg/kg), OSJ 100 (osajin, 100 mg/kg), OSJ 200 (200 mg/kg) and OSJ 400 (osajin, 400 mg/kg). Following a 24-h fasting, IND was administered to the treatment groups at a dose of 25 mg/kg. RAN and OSJ were given orally to rats following 5 min of IND administration. Then, gastric tissues were taken 6 h after the IND administration. Determination of the ulcer area, pathological evidence, and biochemical indices such as lipid peroxidation, superoxide dismutase, glutathione, and catalase were performed. IND generated diffuse ulcer areas, severe hyperaemia, oedema, necrotic epithelium, and mononuclear cell infiltration in the mucosa, and significantly increased lipid peroxidation while also decreasing the glutathione concentration, superoxide dismutase and catalase activities of the tissue. OSJ and RAN showed significant amelioration on ulcer area and biochemical indices. Therefore, OSJ may be potentially therapeutic for gastric ulcers.

1574 An Unusual Finding of Non-Hodgkin's Lymphoma in the Gastrointestinal Tract

INTRODUCTION: Primary gastrointestinal lymphomas include a small proportion of gastrointestinal cancers but rarely involve the ileocecal valve. Even though early detection and diagnosis is prudent in the care as it is associated with favorable therapeutic options, diagnosis with colonoscopy requires a high suspicion and precision. We report an unusual presentation of B-cell lymphoma at the ileocecal valve diagnosed on colonoscopy. CASE DESCRIPTION/METHODS: A 55-year-old female with no significant past medical history presented with a positive fecal occult blood test at her primary care office. Her brother was recently diagnosed with colon cancer at the age of 58. Physical examination was unremarkable and laboratory tests revealed mild iron-deficiency anemia with hemoglobin of 11 gm/dl. Colonoscopy revealed a tubular adenoma in the ascending colon. Colonoscopy is done after five years revealed a prominent ileocecal valve. Histopathological examination of the biopsy showed diffuse infiltration of mononuclear cells with large malignant cells along with pleomorphic vesicular nuclei and prominent nucleoli. A diagnosis of malignant follicular B type lymphoma was made and the patient is scheduled for treatment with an oncologist. DISCUSSION: Gastrointestinal non-Hodgkin's lymphomas are usually detected in the stomach and duodenum. As per our knowledge, this is the first case of B-cell lymphoma involving the ileocecal valve with no major derangement or deformity on the macroscopic exam. Clinicians must be wary of the clinical presentation and consider the possibility of a primary lymphoma at the ileocecal valve with minor changes in appearance, especially in patients with a family history of malignancy.

GRANULOMATOUS LYMPHOCYTIC INTERSTITIAL LUNG DISEASE: MOST COMMON NONINFECTIOUS PULMONARY COMPLICATION OF COMMON VARIABLE IMMUNODEFICIENCY

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Common Variable Immunodeficiency (CVID) is the most common primary immunodeficiency. Patients with CVID suffer from recurrent sinopulmonary infections. Granulomatous lymphocytic interstitial lung disease (GLILD) is one of the dreaded noninfectious pulmonary complication of CVID. CASE PRESENTATION: A 28-year-old female was seen in Pulmonology clinic for evaluation of an abnormal CT scan of the chest, progressively worsening chest tightness, chronic productive cough and dyspnea on exertion for last 1 year. Patient had history of CVID, Chiari I malformation, and iron deficiency anemia. She worked with construction companies to monitor archeological changes. Vitals and physical exam on presentation were normal. Initial investigations showed thrombocytopenia; Sputum gram stain, fungal and acid-fast smear and aerobic and anaerobic cultures were unremarkable. CT scan of the chest, abdomen and pelvis with contrast showed diffuse reticulonodular pulmonary infiltrates predominantly in the basal lung fields, peri bronchial thickening in the lower lobes and mildly enlarged lymphadenopathy in the axilla, retroperitoneum and mesentery, and splenomegaly (13.5 cm). Differential diagnosis at the time were sarcoidosis, GLILD, fungal/atypical infections, vasculitis and malignancy. Bronchoscopy revealed acutely inflamed mucosa throughout the tracheobronchial tree, petechiae in right lower lobe. Bronchoalveolar lavage (BAL) in right medial segment and transbronchial biopsy (TBBx) in left lower lobe showed 54% lymphocytes, but no vasculitis, fungal/bacterial/viral infection, and malignancy. Working diagnosis was narrowed down to sarcoidosis and GLILD. Video assisted thoracoscopic surgery and open lung biopsy of right middle and lower lobes revealed nodular and diffuse mononuclear cell infiltrates and scattered non-necrotizing granulomas. 2nd opinion from a tertiary care center confirmed follicular bronchiolitis with associated non-necrotizing granulomatous inflammation and foci of fibrinous organizing pneumonia consistent with GLILD seen in CVID. DISCUSSION: GLLID is the most common cause of diffuse parenchymal lung disease in patients with CVID. It occurs in 8-22% of persons with CVID. The etiology of GLILD is unknown. It presents between the ages of 20 and 50. Presence of hypersplenism and polyarthritis increases the risk of GLILD in patients with CVID. Classic histopathologic pattern of GLILD is a cellular interstitial pneumonia with a combination of granulomatous and lymphoproliferative features. Optimal treatment is unknown. Glucocorticoids, IVIGs and immunosuppressive therapies have been tried. CONCLUSIONS: In patients with CVID development of respiratory signs or symptoms should be carefully evaluated for GLILD as presence of GLILD shortens the survival by approximately 50%. Reference #1: Fernández Perez ER. 2012 November. Granulomatous Lymphocytic Interstitial Lung Disease. Immunol Allergy Clin AM. 32(2012):621-32 Reference #2: Bates CA, Ellison MC, Lynch DA, et al. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol 2004;114(2):415–21. Reference #3: Tou w CM, van de Ven AA, de Jong PA, et al. Detection of pulmonary complications in common variable immunodeficiency. Pediatric Allergy Immunol 2010;21(5):793–805. DISCLOSURES: No relevant relationships by Shujaa Faryad, source=Web Response No relevant relationships by Rajamurugan Meenakshisundaram, source=Web Response

Correlation between Different Helicobacter Morphotypes and Histological Changes in Pig Gastric Mucosa

Background: Two distinct morphologic types of bacteria which belong to the Helicobacter species, have been described in pigs: once or twice curved Helicobacter pylori-like bacteria (HLO) and the multicoiled, Gastrospirillum-like bacteria (GLO). The objective of this study was to determine the incidence of Helicobacter spp. using modified Giemsa stain and to define the relationship between presence of Helicobacter spp. and histopathological changes of gastric mucosa in pigs.Materials, Methods & Results: A total of 120 pig stomachs (60 from intensive and 60 from extensive breeding) were enrolled in this study and 240 fragments of fundic and pyloric mucosa were taken for histopathological examination. By modified Giemsa staining of gastric mucosa, Helicobacter-like organisms were confirmed in 4/60 (6.67%) of pigs in intensive and 5/60 (8.33%) of pigs in extensive breeding. The incidence of tightly spiral shaped Gastrospirillum-like organisms in pigs of intensive and extensive breeding were 5/60 (8.33%) and 9/60 (15%), respectively. The severity of gastritis was scored to the Sydney System with some modifications. There was no significant difference between HLO-positive and HLO-negative fundic mucosa in pigs of both breeding systems. In contrary, there was significant difference between HLO-positive and HLO-negative pyloric mucosa of pigs in intensive (P < 0.001) and in extensive breeding (P < 0.05). In intensive breeding, there was significant difference between GLO-positive and GLO-negative fundic mucosa (P < 0.05), while there was no significant difference between GLO-positive and GLO-negative pyloric mucosa.Discussion: The prevalence of Helicobacter spp. bacteria were in coherence with literature data. The higher prevalence of both morfological type of bacteria, were considered in pigs in extensive breeding. the hygienic conditions and managment factors in pigs farm are the possible impact for higher bacterial transmission. The association of high prevalence of H. pylori and poor hygienic condition was shown by epidemiological studies conducted on humans. In both, humans and pigs, the presence of H. pylori correlates with an inflammatory response, but there are differences in inflammatory cell population. In H. pylori infected humans, neutrophils composed the bulk of cellular infiltrate, while in pigs, the primary inflammatory cell was the lymphocyte, which is in accordance to results published by others autors. Thus it indicates that different hosts exhibit a different pathohistological response to the Helicobacter spp. infection. In human as well as in veterinary pathology, the fact of the different pathogenicity of various Helicobacter species is well known. In all HLO-positive pyloric mucosa, moderate to severe focal or diffuse infiltration of mononuclear cells and lymphoid follicles with germinal centers, were observed. A similar conclusion was drawn from results of an experimental infection study in pigs. There was signifficance between HLO-positive and HLO-negative pyloric mucosa in both, intensive and extensive breeding. In the contrast, GLO were not associated with the presence of severe gastritis, but only with mild to moderate superficial infiltration of lymphocytes and plasma cells in both, fundic and pyloric mucosa. There was no significant difference between GLO-positive and GLO-negative pyloric mucosa of pigs in both breeding systems. Despite the low gastritis score of fundic mucosa in pigs in intensive breeding, there was a significance difference between in GLO-positive and GLO-negative fundic mucosa. It is believed that the possible reason of such results is the meals with low fiber content and low particles size. These results suggest that the presence of HLO, but not of GLO is associated with the pyloric gastritis in pigs.

Induction of Tolerance to Fully Allogeneic Pulmonary Allograft by Adenosine A2A Receptor Agonist in MHC-defined CLAWN Miniature Swine

Introduction Adenosine has been found on immune cells such as neutrophils, macrophages, T-cells as well as on endothelial cells and the agonist of the adenosine A2A receptor (A2AR), one of four subtypes of the adenosine receptor family is known to potently attenuate lung ischemia-reperfusion injury (IRI). However, the long-term effects of this agonist on lung allograft survival remain unclear especially in large animals. The aim of this study is to investigate whether A2AR agonist has beneficial effects on pulmonary allograft survival using MHC-defined CLAWN miniature swine. Methods Twelve swine received fully MHC-mismatched lungs with 12 days of FK506 (35-45 ng/ml). In Group 1, six recipients received FK506 alone. In Group 2, three recipients were transplanted with lungs from brain-dead (BD) donors induced by subdural balloon inflation for 6 hours before organ procurement in order to examine whether BD affects the graft survival. In Group 3, three recipients were transplanted with lungs from BD donors treated with adenosine A2AR agonist (CGS21680: 5 μg/kg/min) starting 3 hours after BD induction. All recipients in group 3 additionally received the same dose of CGS21680 for 3 hours after reperfusion of the graft. Graft function was assessed by blood gases from the graft pulmonary vein (PV) and serial lung biopsies. The expression of mRNA of proinflammatory cytokines of the grafts (IL-1β and IL-6) were quantified by real-time RT-PCR. Results All grafts in Group 1 was rejected by day 63 with diffuse mononuclear cell infiltrates associated with intra-alveolar hemorrhage and capillary congestion. All three animals in Group 2 completely rejected the grafts by day 35, indicating rejection of grafts was accelerated by donor BD. In Group 3, CGS21680 was effective on early graft function. PO2 of graft PV in group 3 was higher than that of Group 2 (552 ± 22 vs. 414 ± 106 mmHg at 2 hour; 553 ± 19 vs. 349 ± 28 mmHg at day 2) associated with fewer inflammatory cell infiltrates both at 2-hour and day 2 biopsies. Up-regulation of proinflammatory cytokines in group 3 was markedly reduced at the time of organ procurement as well as at 2 hour and day 2 compared with Group 2. Although we lost one animal due to severe pneumonia at day 21, other two animals accepted the grafts over 150 days even after cessation of 12 days of FK506. Anti-donor T-cell responses assessed by MLR and anti-donor IgG development assessed by FACS was significantly reduced in Group3. Moreover, higher percentage of FoxP3-positive infiltrating cells were detected in Group 3, suggesting adenosine-mediated production of regulatory T cells. Conclusions Not only short-term effects, treatment of adenosine A2AR agonist with 12 days of FK506 facilitates induction of tolerance to fully allogeneic lung. This is the first evidence of successful induction of tolerance with short course of FK506 with adenosine A2AR agonist in a clinically relevant large animal model.

Role of MAdCAM-1-Expressing High Endothelial Venule-Like Vessels in Colitis Induced in Mice Lacking Sulfotransferases Catalyzing L-Selectin Ligand Biosynthesis.

Ulcerative colitis (UC) is a chronic inflammatory disease histologically characterized by diffuse mononuclear cell infiltrates in colonic mucosa. These inflammatory cells are considered to be recruited via high endothelial venule (HEV)-like vessels displaying mucosal addressin cell adhesion molecule 1 (MAdCAM-1), the ligand for α4β7 integrin, and/or peripheral lymph node addressin (PNAd), an L-selectin ligand. 6- O-sulfation of N-acetylglucosamine in the carbohydrate moiety of PNAd is catalyzed exclusively by N-acetylglucosamine-6- O-sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2. To determine the role of 6- O-sulfation of N-acetylglucosamine on HEV-like vessels in UC, we used a chronic dextran sulfate sodium-induced colitis model using mice deficient in both GlcNAc6ST-1 and GlcNAc6ST-2. We found that more inflammatory cells, with expression of tumor necrosis factor α, were infiltrated in double knockout mouse colitis compared with that in wild-type mice. Moreover, the number of MAdCAM-1-positive vessels was increased in double knockout mouse colitis, and these vessels were bound by E-selectin•IgM chimeras that bind to unsulfated sialyl Lewis X (sLeX). These findings suggest that interactions between MAdCAM-1 and α4β7 integrin and/or unsulfated sLeX and L-selectin may become a dominant mechanism for inflammatory cell recruitment in the absence of 6-sulfo sLeX and contribute to more severe colitis phenotypes seen in double knockout mice.

Dermoscopy of Cutaneous Mastocytoma.

An 8-year-old boy presented with an episodically pruritic, dome-shaped, yellowish to skin-colored papule measuring approximately 6 mm × 5 mm on the right upper chest from the past 6 months [Figure 1]. Stroking the lesion with a blunt object produced a faint perilesional erythema without whealing. The lesion was completely excised, and hematoxylin-eosin analysis revealed diffuse dermal mononuclear cell infiltrate extending into and widening the dermal papillae [Figure 2a]. The cells stained positively with toluidine blue with metachromatic intracellular granules [Figure 2b]. The clinical and histological features were consistent with solitary cutaneous mastocytoma. Dermoscopy under polarized mode revealed a central whitish structureless area with a few reddish spots surrounded by reticulate brownish pigmentary networks on a yellowish background. The periphery of the lesion was formed by a reticulate hyperpigmented rim [Figure 3].Figure 1: A 6 mm × 5 mm yellowish smooth dome shaped papule on the right upper chestFigure 2: Photomicrograph showing diffuse mononuclear cell infiltrate involving the dermis extending into and expanding the dermal papillae [a, H and E, Original magnification x40]. The cells stained positively with toluidine blue with metachromatic (pink) intracellular granules [b, Toluidine blue, Original magnification x40]Figure 3: Non-contact dermoscopy under polarized mode using DermLite™ DL3 demonstrated a central white structureless area with a few red dots surrounded by reticulate brownish pigmentary network on a yellowish background (black circles), and a marginal reticulate hyperpigmented rim (yellow arrows pointing). [Original magnification x10]Cutaneous mastocytoma usually occurs as a solitary lesion commonly involving the trunk, neck, and extremities of children. The onset is generally within the first few months of birth but late onset lesions are not infrequent. Typical lesions are yellowish-brown, smooth dome-shaped papules or nodules which may urticate on stroking (Darier's sign). Although a pathognomonic feature, the Darier's sign is seen only in half of the cases.[1] Vano-Galvan et al. delineated four predominant dermoscopic features in cutaneous lesions of mastocytosis which included light brown blot, pigment network (attributable to dermal mast cell infiltrate and basal layer hypermelanization), and yellow-orange blot (attributed to dense papillary and reticular dermal mast cell infiltrate). Among these, the yellow-orange blot was consistently associated with mastocytoma.[2] In our case, the brown reticulate network on a background of yellowish hue was seen indicative of dense dermal mast cell infiltrate with increased melanization of the overlying basal layer of the epidermis, as evident in Figure 2a. The central pale yellow to whitish structureless area is caused by the accumulation of serosanguineous fluid produced due to excoriation of the epidermis in the centre of the lesion [Figure 1] because of scratching. The linear vessels and red spots in the centre correspond to dilated vessels seen prominently due to excoriation of the epidermis. Differential diagnoses for such lesions in children include juvenile xanthogranuloma and papular or tuberous xanthomata. Juvenile xanthogranuloma is a close clinical differential diagnosis for mastocytoma. Dermoscopically as well, it exhibits yellow-orange blots, however, the color contrasts typically give a “setting sun” appearance. Additional features include fine interrupted brownish lines and peripheral vascular patterns.[3] Hence, dermoscopy is a useful investigative tool not only to support the clinical findings of cutaneous mastocytoma but also to differentiate from closer differentials such as juvenile xanthogranuloma. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

HISTOPATHOLOGICAL CHANGES IN ENDOMETRITIS OF BUFFALOES CAUSED BY BACTERIAL INFECTION

147 samples were collected from apparently healthy buffaloes and buffaloes suffering from various degrees of endometritis in dairy farms at Damieta and Dakahlia Governorates as well as from Mansoura abattoir. The isolated bacteria from healthy buffaloes were E. coli (20.5 %), S. aureus (15.4 %), K. oxytoca and S. epidermidis (10.3%), (7.7%) for each of , P. mirabilis, M. nishinomiyoensis and E. faecalis and (5.1%) for each of P. vulgaris, P. rettegri, C. freundii and P. aeruginosa. In endometritis cases, it was noticed that 30.2% of E. coli, (19.1%) S. aureus, (8.7%) S. pyogenes, (5.8) A. bovis, (5.2%) for each of K. oxytoca, E. agglomerans and K. pneumoniae, (4.6%) P. aeruginosa, (3.5%) for each of P. vulgaris and C. freundii, (2.3%) for each of P. mirabilis and Salmonellae, (1.8%) for each of Y. pseudotuberculosis and A . pyogenes and (1.2%) E. faecalis. . Histopathological study to sample collected from healthy cyclic buffaloes revealed normal endometrium. Microscopic lesions of acute endometritis revealed stromal oedema, congestion of blood vessels, mild to severe neutrophilic infiltration and mild perivascular and periglandular fibrosis. In chronic endometritis, extensive stromal fibrosis around blood vessels and gland, and diffuse mononuclear cell infiltration mostly lymphocytes and plasma cells. Sensitivity of the most prevalent isolates recovered from endometritis to 21 different types of antibiotics revealed that they were highly sensitive to enrofloxacin (96.38%), gentamicin (85.54%), chloramphenicol (83.13%), norofloxacin (80.72%) and pipracillin (78.31%), but, they were highly resistant to pencillin G (10.84%). Also, they were resistant to ampicillin (32.53%), streptomycin (36.14%), oxytetracycline (37.35%), SXT (39.7%) and lincospectinomycin (44.58 %). ,

Crystalline cast nephropathy in a patient with IgD lambda myeloma

A 72-year-old woman was admitted at our department for renal dysfunction with general fatigue and loss of appetite for 2 months. She had no remarkable past medical history except hypertension, which was treated with angiotensin-converting enzyme inhibitor and a calcium channel blocker. Physical examination was unremarkable, except for pale conjunctivae. Urinary protein to creatinine ratio was 9.5 g/gCr, revealing a large discrepancy from the result of mild proteinuria by urinary dipstick (2?; indicating 100–300 mg/L). No hematuria was found. Serum creatinine level was increased to 1.90 mg/ dL associated with anemia (hemoglobin 7.3 g/dL). Other findings were total protein 6.8 g/dL, serum albumin 4.67 g/ dL, serum IgG 516 mg/dL (normal 870–1700 mg/dL), serum IgA 17 mg/dL (normal 110–410 mg/dL), serum IgM 5 mg/ dL (normal 34–220 mg/dL), and serum IgD 306 mg/dL (normal 0–9 mg/dL). Serum and urine electrophoresis revealed a monoclonal spike and an IgD-type monoclonal k band, respectively. The free k light chain level was 3720 mg/ L; serum j/k ratio was 0.0017. On the 5th day after admission, kidney biopsy was performed (Fig. 1). On light microscopy, minor glomerular abnormalities were observed; furthermore, diffuse mononuclear cell infiltration in the interstitium and crystalline casts in the proximal tubules were observed. These crystalline casts were hematoxylin and eosin positive but periodic acid-Schiff (PAS) negative. Moreover, only k light chain staining was positive. On electron microscopy, crystalline casts were found to form gigantic plate-shaped crystalline structures. Bone marrow aspiration cytology confirmed the diagnosis of multiple myeloma. She received bortezomib–dexamethasone therapy and achieved complete remission with normal renal function for 2 years. Cast nephropathy is the most common renal complication [1]. In rare cases, the casts exclusively comprise crystals. Myeloma-free light chains (MFLCs) are usually absorbed by proximal tubular cells, leading to acute proximal tubular damage associated with needle-shaped crystals in epithelial cells. This condition is well known as acquired light chain-related Fanconi syndrome [2]. Conversely, MFLCs that are not absorbed by the proximal tubules are distributed to the distal tubules and the ascending loop of Henle, where Tamm–Horsfall protein (THP) casts are exclusively synthesized [3]. These casts usually comprise needle-shaped or rhomboid crystals. THP is one of the glycoproteins, which is invariably PAS positive. The crystalline casts that were observed in this case were PAS negative and were distributed in the proximal tubule lumen. This is understandable, considering the site of THP synthesis. Some reports described crystal formation in organs except the kidneys. In these organs, crystal formation occurred in microvasculature due to low tissue temperature and/or blood circulation stasis; however, the precise mechanism is uncertain [4]. The characteristics of this case emphasized that MFLCs may form crystals independently or at least, without THP participation. Some have reported factors that may contribute to explain MFLC precipitation for crystal formation: a large MFLC amount & Satoshi Kumakura satoshi.kuma.714@gmail.com

Patho-epidemiological study on Genotype-XIII Newcastle disease virus infection in commercial vaccinated layer farms.

Aim:The present research work was carried out to study the patho-epidemiological aspects of Genotype-XIII Newcastle disease virus (NDV) infection in commercial layer in and around Anand, Gujarat. As the outbreaks have reported in vaccinated flocks, it was felt necessary to study the disease with respect to its changing pathogenicity and relevant aspects.Materials and Methods:The study comprised of patho-epidemiology of Newcastle disease (ND) by information collected from different layer farms suffering from the disease in relation to incidence pattern and mortality, duration of mortality, susceptible age, and loss due to production performance. Clinical signs were recorded based on observations. During post-mortem, gross lesions were also recorded. For histopathological examination visceral organs according to lesions were collected in 10% formalin and processed slide stained by hematoxylin and eosin for microscopic examination. Cultivation of virus was done in embryonated specific pathogen-free (SPF) eggs of 9-11 days and isolation of virus was done for haemagglutination (HA) and haemagglutination inhibition (HI) test and to identify pathotype of virus by intracerebral pathogenicity index (ICPI) test to determine the virulence of virus. The Genotype-XIII NDV was confirmed by F gene sequence and whole genome sequence.Results:During the study mortality due to ND was recorded in 13 layer flocks in spite of routine vaccination, which usually contain Genotype-II strain of virus. The mortality was observed as high as above 50% with an average of 21.21%. The susceptible age for disease was found to be 6-14 weeks. The duration of mortality observed was 23 days. The disease resulted in a significant reduction in body weight, feed intake and drop in egg production. Majority of the outbreaks appeared during extremely hot months of April to June. Greenish diarrhoea was frequently seen in birds that survived early in infection. Mortality continued for 2-3 weeks and reduced with appearance of torticollis. Gross lesions were characterized by multifocal to diffuse hemorrhages around proventricular glands, necrotic (diphtheritic) haemorrhagic ulcers throughout the intestine, disseminated multiple foci of necrosis and pin-point hemorrhages in the spleen parenchyma. The microscopic lesions include focal to diffuse hemorrhages, diffuse infiltration of mononuclear cells, necrosis, and degeneration in visceral organs. All the 13 farm samples (n=13) resulted in death of all the embryos following incubation up to 72 h post-inoculation. All the 13 allantois fluids from field samples along with F and R2B vaccine sample were found positive for HA activity, which was further confirmed by HI using known NDV serum. The values of ICPI were 2.0 which were indicative of velogenic nature of the field NDV strain.Conclusion:The study indicated that presently available live and attenuated vaccines which include Genotype-II NDV have failed in protecting the flocks against Genotype-XIII and resulted in outbreaks with mortality above 50%. ICPI score of 2.0 confirmed that the present outbreaks were due to Genotype-XIII NDV, which is velogenic in nature.

A Case of Acute Kidney Injury in a Patient with Pulmonary Tuberculosis Receiving Ethambutol Therapy

Ethambutol is commonly used as a first-line drug for the treatment of tuberculosis. The most serious adverse effect of ethambutol therapy is optic neuropathy. However, ethambutol-induced acute kidney injury is extremely rare. We report herein a case of acute kidney injury secondary to ethambutol-associated acute interstitial nephritis. A 65-year-old man with pulmonary tuberculosis presented with a > 7-day history of nausea and vomiting. He had begun antituberculosis medications including ethambutol 3 weeks previously. His laboratory findings showed elevated blood urea nitrogen and serum creatinine levels (32.6 and 3.6 mg/dL, respectively). Examination of percutaneous renal biopsy specimens showed diffuse interstitial mononuclear cell infiltration with mild interstitial edema. The patient was treated by cessation of ethambutol and supportive care. His renal function completely recovered (creatinine, 1.1 mg/dL) and his clinical symptoms improved. (Korean J Med 2014;87:352-356)

De novo myeloid sarcoma in a 4‐month‐old infant: a case report and review of the literature

Myeloid sarcoma is a rare tumor of immature myeloid cells in an extramedullary site. Myeloid sarcoma may present in a variety of locations; skin is one of the common sites. It may precede or occur concurrently with acute myeloid leukemia, chronic myeloid leukemia, other forms of myeloproliferative disorders/myelodysplastic syndrome or de novo. We report a case of a 4-month-old female who presented with cutaneous lesions without evidence of leukemia, determined to be de novo myeloid sarcoma. She had erythematous nodules in multiple skin sites. Biopsy revealed a diffuse atypical mononuclear cell infiltrate involving the entire dermis and extending to the subcutis. The infiltrate was diffusely positive for lysozyme, CD43, CD15, CD33, CD68 and CD117 and was negative for CD3, CD20, CD34, CD56, CD79a, CD99, myeloperoxidase, desmin, chromogranin and synaptophysin, supporting a diagnosis of myeloid sarcoma. No leukemic involvement was found on evaluation of peripheral blood or bone marrow aspiration. Chromosomal abnormalities were found at chromosomes 7, 10 and 11. The skin lesions resolved following multiple chemotherapy courses, then recurred requiring additional treatment. De novo myeloid sarcoma involving skin without evidence of leukemia can occur in an infant and may present a diagnostic challenge.

Expressions of P53 and CD68 in mouse liver withSchistosoma mansoniinfection and the protective role of silymarin

Schistosomiasis is one of the major human parasitic diseases in many developing countries and is one of the causes of morbidity and mortality in the human population. The present work has been planned to study the histopathological and immunohistochemical expression of P53 and CD68 in mouse liver tissues experimentally infected with Schistosoma mansoni, in addition to the ameliorating role of silymarin. A total of 50 adult male mice were divided into 5 groups (10 animals each). Groups 1 and 2 were the control and silymarin groups, respectively, while group 3 was the infected group in which the mice were infected with S. mansoni live cercariae for 6weeks. Groups 4 and 5 were the cotreated and posttreated groups, respectively, in which mice were infected with cercariae of S. mansoni and treated with silymarin during and after Schistosoma infection, respectively. The major histopathological lesions were variable numbers of perioval granulomas, diffuse infiltration of inflammatory cells, mainly eosinophils and small mononuclear cells, and fibrosis of portal areas and interlobular septa. Treatment with silymarin led to a significant reduction in granuloma area in all treated infected mice compared with nontreated infected mice. Immunohistochemical observations of the liver tissues showed a significant increase in the apoptotic proteins P53 and CD68 after the infection with the cercariae of Schistosoma, compared with the control group. The expression of the cytoplasmic P53 and CD68 was very low in the control liver sections. A significant decrease in the expression of the cytoplasmic P53 and CD68 was observed after silymarin treatment.

Tubulointerstitial nephritis and uveitis syndrome with transient hyperthyroidism in an elderly patient

A 69-year-old Japanese woman without any specific medical or family history was admitted to our hospital for renal insufficiency with proteinuria. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 34.9 mg/dL and creatinine level was 1.78 mg/dL) and elevated urinary levels of N-acetyl-β-D-glucosaminidase (23.4 U/L) and β2-microgloblin (20200 μg/L) were observed. We performed a renal biopsy. The biopsied specimen showed severe diffuse infiltration of mononuclear cells into the interstitium, with normal glomeruli, and these findings were compatible with acute tubulointerstitial nephritis (ATIN). At that time, ATIN seemed to be idiopathic. We performed gallium scintigraphy, and the results revealed uptake by the bilateral kidneys, thyroid gland, and right parotid gland. Serum thyroid stimulating hormone (TSH) was undetectable, free triiodothyronine was normal (3.11 pg/mL), and free thyroxine was elevated to 2.4 ng/dL. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Two months later, burning pain and conjunctival congestion developed in both eyes. She had uveitis, as diagnosed by slit-lamp examination. Topical corticosteroid was used for the uveitis with success. We could not detect any cause of the uveitis, so a diagnosis of tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) with associated hyperthyroidism was made. Treatment was started with 15 mg/day of prednisolone. Now her renal function is slowly recovering. There are few reports of TINU syndrome with transient hyperthyroidism. This case suggests the possibility of thyroid dysfunction in patients with TINU syndrome. A laboratory evaluation of thyroid function should be considered in the diagnostic evaluation of TINU syndrome.

Peroxisome Proliferator-Activated Receptor (PPAR)γ Can Inhibit Chronic Renal Allograft Damage

Chronic inflammation and fibrosis are the leading causes of chronic allograft failure. The nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma is a transcription factor known to have antidiabetogenic and immune effects, and PPARgamma forms obligate heterodimers with the retinoid X receptor (RXR). We have reported that a retinoic acid (RAR)/RXR-agonist can potently influence the course of renal chronic allograft dysfunction. In this study, in a Fischer to Lewis rat renal transplantation model, administration of the PPARgamma-agonist, rosiglitazone, independent of dose (3 or 30 mg/kgBW/day), lowered serum creatinine, albuminuria, and chronic allograft damage with a chronic vascular damage score as follows: 35.0 +/- 5.8 (controls) vs. 8.1 +/- 2.4 (low dose-Rosi; P < 0.05); chronic tubulointerstitial damage score: 13.6 +/- 1.8 (controls) vs. 2.6 +/- 0.4 (low dose-Rosi; P < 0.01). The deposition of extracellular matrix proteins (collagen, fibronectin, decorin) was strikingly lower. The expression of transforming growth factor-beta1 was inhibited, whereas that of bone morphogenic protein-7 (BMP-7) was increased. Intragraft mononuclear cells and activated fibroblast numbers were reduced by 50%. In addition, the migratory and proliferative activity of these cells was significantly inhibited in vitro. PPARgamma activation diminished the number of cells expressing the proinflammatory and fibrogenic proteoglycan biglycan. In macrophages its secretion was blocked by rosiglitazone in a predominantly PPARgamma-dependent manner. The combination of PPARgamma- and RAR/RXR-agonists resulted in additive effects in the inhibition of fibrosis. In summary, PPARgamma activation was potently immunosuppressive and antifibrotic in kidney allografts, and these effects were enhanced by a RAR/RXR-agonist.

Toll‐like receptor 6 drives interleukin‐17A expression during experimental hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP) is a T-cell-driven disease that is histologically characterized by diffuse mononuclear cell infiltrates and loosely formed granulomas in the lungs. We have previously reported that interleukin-17A (IL-17A) contributes to the development of experimental HP, and that the pattern recognition receptor Toll-like receptor 6 (TLR6) might be a factor in the initiation of this response. Using a well-established murine model of Saccharopolyspora rectivirgula-induced HP, we investigated the role of TLR6 in the immunopathogenesis of this disease. In the absence of TLR6 signalling, mice that received multiple challenges with S. rectivirgula-antigen (SR-Ag) had significantly less lung inflammation compared with C57BL/6 mice (wild-type; WT) similarly challenged with SR-Ag. Flow cytometric analysis of whole lung samples from SR-Ag-challenged mice showed that TLR6(-/-) mice had a decreased CD4(+) : CD8(+) T-cell ratio compared with WT mice. Cytokine analysis at various days after the final SR-Ag challenge revealed that whole lungs from TLR6(-/-) mice contained significantly less IL-17A than lungs from WT mice with HP. The IL-17A-driving cytokines IL-21 and IL-23 were also expressed at lower levels in SR-Ag-challenged TLR6(-/-) mice, when compared with SR-Ag-challenged WT mice. Other pro-inflammatory cytokines, namely interferon-gamma and RANTES, were also found to be regulated by TLR6 signalling. Anti-TLR6 neutralizing antibody treatment of dispersed lung cells significantly impaired SR-Ag-induced IL-17A and IL-6 generation. Together, these results indicate that TLR6 plays a pivotal role in the development and severity of HP via its role in IL-17A production.