Hepatic Granulomas Research Articles

Hepatic progenitor cells promote the repair of schistosomiasis liver injury by inhibiting IL-33 secretion in mice

BackgroundHepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent or quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remains unknown.MethodsIn this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in the mice model of S. japonicum infection at different infectious stages. For validating the role of HPCs in hepatic injury, tumor necrosis factor-like-weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs in wild-type and IL-33−/− mice infected with S. japonicum.ResultsWe found that the proliferation of HPCs was accompanied by inflammatory granulomas and fibrosis formation. HPCs expansion promoted liver regeneration and inhibited inflammatory egg granulomas, as well as the deposition of fibrotic collagen. Interestingly, the expression of IL-33 was negatively associated with HPCs’ expansion. There were no obvious differences of liver injury caused by infection between wild-type and IL-33−/− mice with HPCs’ expansion. However, liver injury was more attenuated in IL-33−/− mice than wild-type mice when the proliferation of HPCs was inhibited by anti-TWEAK.ConclusionsOur data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33-dependent manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.

S2745 Chronic Lymphocytic Leukemia: An Unusual Cause of Hepatic Granulomas

Introduction: Hepatic granulomas (HG) are localized collections of inflammatory cells, found in 2 to 10% of patients who undergo liver biopsy. HG has a wide differential and, in some cases, may not lead to a definitive diagnosis. We present a rare case of chronic lymphoid leukemia (CLL) presenting as HG. Case Description/Methods: 70-year-old male with past history of CLL presented with fever, chills and night sweats for 2 weeks. Admission labs were significant for WBC count 25 and elevated LFTs with total bilirubin 3.67, Alkaline phosphatase 281, AST 41 and ALT 144. CT liver protocol showed diffuse hypodense liver lesions, classified as LIRADs 3 indeterminate lesions. MRI was contraindicated due to incompatible hardware. Infectious work up including cultures, viral and tick serologies, and acute and chronic liver serologies were negative and patient was observed off antibiotics and discharged. Subsequent liver biopsy revealed nodules of necrotizing granulomas but negative for CLL, Richter transformation, fungal or TB on special stains. Work up was expanded to rule out autoimmune causes, fungal, atypical viral, TB infections, hemochromatosis and sarcoidosis as a cause of HG, all of which resulted negative. Due to unclear diagnosis and persistent abnormal liver imaging, repeat liver biopsy was performed which revealed periportal and sinusoidal atypical lymphoid infiltrate with necrotizing granulomatous inflammation. Flow cytometry showed small CD 19+ B cells, consistent with CLL. This upstaged patient’s disease to Rai stage 2 and he was started on chemotherapy, which normalized LFTs and improved symptoms. Discussion: HG remains a diagnostic challenge for many clinicians. Common malignancies associated with hepatic granulomas are lymphoma, renal cell carcinoma and liver metastasis. CLL is not a well defined cause of hepatic granuloma. Other causes include drugs, bacterial, fungal, viral or parasitic infections, autoimmune disorders, TB and sarcoidosis. The histologic subtypes (caseating vs non caseating) may give a clue to the diagnosis. Progressive fibrosis, portal hypertension, and cirrhosis can rarely develop if not identified early. In patients with CLL, liver involvement may upstage the disease, necessitating more aggressive treatment. Assessment for associated clinical symptoms, targeted lab and radiological investigations, and characterization of the morphology and localization of granulomas will usually lead to a definitive diagnosis and appropriate treatment.

MicroRNA-21 Deficiency Promotes the Early Th1 Immune Response and Resistance toward Visceral Leishmaniasis.

MicroRNA-21 (miR-21) inhibits IL-12 expression and impairs the Th1 response necessary for control of Leishmania infection. Recent studies have shown that Leishmania infection induces miR-21 expression in dendritic cells and macrophages, and inhibition of miR-21 restores IL-12 expression. Because miR-21 is known to be expressed due to inflammatory stimuli in a wide range of hematopoietic cells, we investigated the role of miR-21 in regulating immune responses during visceral leishmaniasis (VL) caused by Leishmania donovani infection. We found that miR-21 expression was significantly elevated in dendritic cells, macrophages, inflammatory monocytes, polymorphonuclear neutrophils, and in the spleen and liver tissues after L. donovani infection, concomitant with an increased expression of disease exacerbating IL-6 and STAT3. Bone marrow dendritic cells from miR-21 knockout (miR-21KO) mice showed increased IL-12 production and decreased production of IL-10. On L. donovani infection, miR-21KO mice exhibited significantly greater numbers of IFN-γ- and TNF-α-producing CD4+ and CD8+ T cells in their organs that was associated with increased production of Th1-associated IFN-γ, TNF-α, and NO from the splenocytes. Finally, miR-21KO mice displayed significantly more developing and mature hepatic granulomas leading to reduction in organ parasitic loads compared with wild type counterparts. Similar results were noted in L. donovani-infected wild type mice after transient miR-21 depletion. These observations indicate that miR-21 plays a critical role in pathogenesis of VL by suppressing IL-12- and Th1-associated IFN-γ and also inducing disease-promoting induction of the IL-6 and STAT-3 signaling pathway. miR-21 could therefore be used as a potential target for developing host-directed treatment for VL.

The efficacy of platelet rich plasma as adjuvant therapy in the treatment of cryptosporidiosis in experimentally infected immunosuppressed rats

Background: Cryptosporidium species are zoonotic opportunistic coccidian parasites that could causedisseminated life-threatening infection in the immunocompromised host. Unfortunately, few availabledrugs effectively eradicate the infectious oocyst with limited availability in developing countries. AlthoughNitazoxanide (NTZ) is the drug of choice for the treatment of cryptosporidiosis, it has limited efficacyin malnourished and immunocompromised patients. Moreover, platelet-rich plasma (PRP) successfullyameliorated the hepatic granuloma size in patients with parasitic schistosomiasis mansoni.Objective: This study aims to test the potential therapeutic effect of PRP versus the currently used NTZ,and/or using PRP as adjuvant therapy.Material and Methods: Sixty-five immunosuppressed rats were divided into 5 groups: non-infected asnegative control (GI), infected non-treated as the positive control (GII), infected with Cryptosporidiumspp. and treated with either intraperitoneal PRP (GIII), or NTZ (GIV), or a combination of intraperitonealPRP and NTZ (GV). Parameters used for evaluation of the therapeutic efficacy included parasitologicalexamination, histopathological examination of ileocaecal and liver specimens, and quantitative analysisof reduced glutathione (GSH) and malondialdehyde (MDA) for evaluation of oxidative stress markers,glutamic-oxaloacetic transaminase (SGOT), and glutamic pyruvic transaminase (SGPT) for evaluation ofliver functions.Results: Parasitological and histopathological examinations revealed minimal improvement in GIII,marked improvement in GIV, and the best results were recorded in GV. The administration of PRP in GIIIproduced no significant changes in GSH, MDA, SGOT compared to positive control GII. Treatment withNTZ in GIV, and in addition to PRP in GV showed significant difference (P<0.05) compared to GII regardingserum results of GSH, MDA, and SGOT with the best results recorded in GV. GIV and GV showed reductionof serum levels of SGPT although there was statistically insignificant difference between the study groups.Conclusion: PRP could be used as a potential adjuvant therapy with NTZ to ameliorate the pathologic andinflammatory effects of cryptosporidiosis on the ileocaecal region. It also improves liver function in theimmunocompromised hosts.

Ataxic Gait and Back Pain in an Immunocompetent 5-Year-Old Boy

<em>Bartonella henselae</em> is a Gram-negative bacterium and the causative agent of Cat Scratch Disease (CSD). Atypical presentations of <em>B. henselae</em> that involve musculoskeletal, hepatosplenic, or neurologic systems are rare. In this case report, we describe a case of <em>B. henselae</em> osteomyelitis involving the thoracic spine at the level of T2, complicated by both hepatic and splenic granulomas in a 5-year-old generally healthy male patient. Although <em>B. henselae</em> is a rare cause of osteomyelitis, it should be considered in patients with a possible cat exposure, who present with fever, pain, and lymphadenopathy.

The Therapeutic role of Thymoquinone Bioactive Compound as Target Natural Product from Nigella sativa Loaded with Chitosan Nanoparticles on Schistosomiasis

Background: Schistosoma mansoni is a trematode helminth responsible for liver fibrosis or cirrhosis. Aim of the work: In the present work natural products Thymoquinone loaded with chitosan nanoparticle (TQ/ChNP)) (TQ/ChNP) were used to determine their therapeutic effect on S. mansoni infection. Materials and methods: A total of 40 healthy Swiss albino mice, 20-25 g in weight, procured from Theodor Bilharz Research Institute (TBRI) Imbaba, Egypt's Schistosome Biological Supply Center (SBSC). Results: The infected mice treated with TQ/ChNP showed a significant decrease in the total worm burden. Treatment with TQ/ChNP had a highly significant effect on mature worm burden, TQ/ChNP in prophylactic and therapeutic doses significantly increased the mean number of dead ova in comparison to control. TQ/ChNP had a high decrease effect on ova count in intestinal tissue and a moderate reduction on ova count in hepatic tissue. Prophylactic dose gave a high reduction effect on ova count in intestinal tissue. As regards the size of hepatic granuloma, TQ/ChNP had the highest significant reduction on mean granuloma diameter with noticeable improvement of hepatic pathology. TQ/ChNP treated group showed observable improvement of liver pathology with mild degeneration and slight-sized fibrocellular. Conclusion: Based on the outcome of this study, TQ/ChNP proved to have potential bioactivity against S. mansoni adult stages and its potentiality in improving hepatic pathology. Efficacy of TQ/ChNP to postpone progression in chronic liver diseases must be considered as preventive medicine in patients with hepatic disorders.

Calcitriol-Mediated Hypercalcemia from Hepatic Granulomatosis Following Percutaneous Cholecystostomy Tube

Granulomatous conditions can present with calcitriol-mediated hypercalcemia via increased 1-hydroxylase activity—activity that is not inhibited by calcium or calcitriol—indicating a lack of feedback inhibition. Differential diagnosis of granulomatosis is quite broad and can require extensive workup as highlighted by this case. Our patient is a 69-year-old white female admitted to the hospital with altered mental status and hypotension. Initial evaluation was concerning for infection, due to leukopenia and thrombocytopenia. CT abdomen revealed cholecystitis, percutaneous cholecystostomy tube was placed, and the patient’s mental status improved. One month after discharge, the patient presented to the hospital with a corrected calcium of 15.2 mg/dl. PTH was 22 pg/mL with normal renal function and phosphorus. The patient was treated with intravenous fluids, calcitonin, and zoledronic acid. Calcitriol was 69 pg/ml (18–75 pg/ml) and corrected calcium responded by time of discharge. During outpatient follow up, she was found to have corrected calcium 11.2 mg/dl and calcitriol 166 pg/ml with appropriately low PTH. Additional workup of apparent calcitriol-mediated hypercalcemia with whole-body CT imaging, tuberculosis screening, and flow cytometry only notable for possible right cervical lymphadenopathy on CT. Subsequent lymph node biopsy was benign. The patient completed a 30-day course of prednisone 20 mg daily followed by prednisone taper and her corrected calcium and calcitriol levels normalized. However, after discontinuation of prednisone, lab work demonstrated increase in calcium and liver enzymes. Repeat CT scan showed multiple hypoechoic areas with subsequent biopsy consistent with necrotizing hepatic granulomatosis. PAS-A, Fite, and AFB stains were negative for fungi and mycobacteria. Removal of cholecystostomy tube resulted in complete resolution of hypercalcemia and elevated calcitriol levels. Foreign body-induced granulomatosis is associated with PTH-independent hypercalcemia. Silicone has been implicated in foreign body granuloma. Hepatic granulomatosis is associated with percutaneous tube, especially with prolonged placement (approximately 11 months in this case). Removal of the foreign body is associated with improvement in hypercalcemia. Follow-up liver ultrasound demonstrated complete resolution of hepatic granulomas at three months following removal of the cholecystostomy tube.

A comparative study of the effects of chloroquine and praziquantel on splenomegaly in experimental Schistosomiasis mansoni

Background Splenomegaly is a major morbid sequela of schistosomiasis. Praziquantel (PZQ) is the only recommended schistosomicidal drug despite its erratic bioavailability and growing resistance. Moreover, neglecting early treatment of splenomegaly eventually necessitates splenectomy. With drug repurposing, the antimalarial drug chloroquine (CLQ) has gained much interest because of its anti-inflammatory effect. Additionally, CLQ inhibits hemozoin formation essential for in vivo survival of blood-feeding parasites. Aim To investigate the schistosomicidal effect of CLQ and its role in splenomegaly modification, with or without PZQ in an experimental model. Patients and methods The study was conducted on 180 mice equally divided into three groups: control; infected and early treated with CLQ, PZQ, or both drugs; and infected and late treated. In group II, each drug was given in its optimum time of action to study the effect on worm eradication/reproductivity and pathology development. In group III, repeated drug regimens were applied to study the effect on the already established splenomegaly. Mice were euthanized 7 weeks P.I. to calculate the parasitic load and 15 weeks post infection (P.I.) to assess tissue pathology by hematoxylin and eosin staining. Results Combined CLQ and PZQ administration produced a significant reduction of parasitic load compared with CLQ alone. A highly significant decrease (P&lt;0.001) in hepatic granulomas mean number and splenic index was also recorded in early combined subgroup, with improved structure. With late treatment, the combined rather than single therapy showed an overall less pathology; however, early therapy showed better outcome. Conclusions CLQ combined with PZQ has a synergistic schistosomicidal, has a valuable anti-inflammatory effect, and restrains the effect on splenomegaly, especially with early administration.

Development of dominant epitope-based vaccines encoding Gp63, Kmp-11 and Amastin against visceral leishmaniasis

The most dangerous form of leishmaniasis is Visceral leishmaniasis (VL). The elimination of VL depends not only on agent treatments but also on effective vaccines against Leishmania parasites. Epitope-based vaccines composed of alternative short antigenic epitopes have the advantages of MHC epitope easy designing, which has broad application prospects. In a previous study, we analyzed Leishmania Gp63, Kmp-11 and Amastin protein sequence in silico, and found that the amino acid fragments of Gp63 (138-360aa), Kmp-11 (1-91aa) and Amastin (1-72aa) were rich in dominant epitopes. In this study, we used the three amino acid fragments as multi-epitope vaccine candidates to construct DNA and protein vaccines. BALB/c mice were vaccinated with the DNA and protein vaccines by DNA prime-protein boost strategy and challenged with Leishmania promastigotes. To evaluate vaccine immunogenicity and immunoprotection, serum specific antibody titers and cytokines were detected using ELISA, splenic CD3+, CD4+ and CD8+ cells were analyzed by flow cytometry, livers were made into pathological sections to observe pathological changes, and splenic parasitic loads were quantified using qPCR. The results showed that the increased specific IgG titers from vaccinated mice supported the vaccine immunogenicity. The increased cytokines (IFN-γ, IL-12 and TNF-α), splenic CD3+, CD4+ and CD8+ T cells and hepatic granulomas, and the decreased splenic parasitic loads (parasite reduction rates of Gp63, Kmp-11 and Amatin groups were 89%, 86% and 79%, respectively) from immunized mice post-infection were suggested the good immunoprotection of the vaccines. Our study demonstrated that vaccines based on the dominant epitopes of Gp63, Kmp-11 and Amastin with DNA prime-protein boost vaccination strategy showed significant immune effects against Leishmania, especially the Gp63 group showed a nearly 90% parasites reduction rate. This study will provide references for visceral leishmaniasis epitope vaccine design and immune strategy selection.

Changing our view of the Schistosoma granuloma to an ecological standpoint.

Schistosomiasis, a neglected parasitic tropical disease that has plagued humans for centuries, remains a major public health burden. A primary challenge to understanding schistosomiasis is deciphering the most remarkable pathological feature of this disease, the granuloma - a highly dynamic and self-organized structure formed by both host and parasite components. Granulomas are considered a remarkable example of how parasites evolved with their hosts to establish complex and intimate associations. However, much remains unclear regarding life within the granuloma, and strategies to restrain its development are still lacking. Here we explore current information on the hepatic Schistosoma mansoni granuloma in the light of Ecology and propose that this intricate structure acts as a real ecosystem. The schistosomal granuloma is formed by cells (biotic component), protein scaffolds, fibres, and chemical compounds (abiotic components) with inputs/outputs of energy and matter, as complex as in classical ecosystems. We review the distinct cell populations ('species') within the granuloma and examine how they integrate with each other and interact with their microenvironment to form a multifaceted cell community in different space-time frames. The colonization of the hepatic tissue to form granulomas is explained from the point of view of an ecological succession whereby a community is able to modify its physical environment, creating conditions and resources for ecosystem construction. Remarkably, the granuloma represents a dynamic evolutionary system that undergoes progressive changes in the 'species' that compose its community over time. In line with ecological concepts, we examine the granuloma not only as a place where a community of cells is settled (spatial niche or habitat) but also as a site in which the functional activities of these combined populations occur in an orchestrated way in response to microenvironmental gradients such as cytokines and egg antigens. Finally, we assert how the levels of organization of cellular components in a granuloma as conventionally defined by Cell Biology can fit perfectly into a hierarchical structure of biological systems as defined by Ecology. By rethinking the granuloma as an integrating and evolving ecosystem, we draw attention to the inner workings of this structure that are central to the understanding of schistosomiasis and could guide its future treatment.

Blocking angiotensin pathway induces anti-fibrotic effects in a mouse model of schistosomiasis by decreasing egg burden and granulomatous reaction

Background: Schistosoma mansoni infection is associated with hepatic fibrosis and portal hypertension. Previous studies reported that blocking some components of rennin angiotensin system can ameliorate the liver pathology induced by S. mansoni infection. Aim: The present study investigated the potential effect of losartan, an angiotensin II receptor antagonist, and enalapril, an angiotensin-converting enzyme inhibitor, on hepatic fibrosis caused by S. mansoni in a murine model. Materials and Methods: S. mansoni-infected mice were treated at week 5 after infection with losartan, enalapril, or their combination. A group of infected mice was treated with the reference drug praziquantel (PZQ) as controls. Parasitological and histological parameters were investigated. Results: Our results showed that when compared with enalapril, treatment with losartan alone caused a considerable decrease in liver index (28.92% versus 25.09%), spleen index (47.19% versus 37.08%), worm burden (38.7% versus 24.8%), hepatic tissue egg load (62.7% versus 54%), granuloma size (40.4% versus 29.4%) and fibrosis (48.7% versus 29.4%). The combination of losartan and enalapril did not produce a more pronounced effect than those of losartan. Conclusion: Our results suggest the promising effect of enalapril and losartan in amelioration of hepatic pathology but further studies to determine their effects in combination with other antischistosomal agents such as praziquantel are recommended.

Assessment of hazards and risks associated with dietary exposure to mineral oil for the Belgian population

Recently collected dietary exposure data on mineral oil saturated (MOSH) and aromatic (MOAH) hydrocarbons were used to evaluate the risks associated with exposure to mineral oil through food for the Belgian population. For MOSH, the no observed adverse effect level (NOAEL) value of 19 mg kg−1 bw day−1 based on the hepatic inflammation-associated granulomas found in a 90-day oral study in F-344 rats was used as point of departure (PoD). Due to existing toxicological uncertainties, the margin of exposure (MOE) approach was applied. In all investigated scenarios, the MOE values were well above 100, indicating that there is no direct health concern related to MOSH exposure for the Belgian population. Nevertheless, more appropriate risk assessment approaches for MOSH based on adequate PoD are needed. For dietary exposure to MOAH, which are potentially genotoxic and carcinogenic, no MOE values could be calculated due to the lack of adequate dose-response carcinogenicity data. In two investigated worst-case scenarios, a health concern related to MOAH exposure could not be excluded, highlighting that more data are needed to perform an adequate risk assessment. The possibility to use in vitro bioassays to collect such additional toxicological information for MOAH present in food samples was also investigated.

Oral, Cloacal, and Hemipenal Actinomycosis in Captive Ball Pythons (Python regius).

Ball pythons (Python regius) are one of the most commonly kept and bred reptiles in captivity. In a large ball python breeding colony, a unique syndrome characterized by granulomatous inflammation of the cloaca and hemipenes (phalli) was observed in 140 of 481 (29.1%) breeding males, but only one of 1,446 breeding females. Lesions were absent in virgin males (n = 201) and virgin females (n = 293). On postmortem examination (n = 13, 12 males, 1 female), numerous well-defined mucosal and submucosal granulomas were present in the hemipenes (males) and cloaca (males and female). Extension into the coelomic cavity and liver was noted in a subset of these animals. An additional small subset of breeder animals (6/2027; 0.3%) presented with oral and mandibular swellings. Postmortem examination (n = 4, all female) showed oral lesions histologically indistinguishable from the cloacal/hemipenal lesions. Aerobic bacterial culture of a hepatic granuloma of one snake resulted in the isolation of filamentous, Gram-positive bacilli; amplification, and sequencing of the 16S rRNA gene and subsequent phylogenetic analysis of the isolate identified the bacterium as a novel species of Actinomyces. Screening of cloacal and oral granulomas using a specific, heminested 16S rRNA PCR assay confirmed the presence of the agent in all 17 snakes, as well as in cloacal swabs taken at the time of necropsy in 11/13 snakes. The Actinomyces sp. was also identified by PCR of cloacal swabs of unaffected snakes (n = 94) from the affected colony and two unrelated, grossly unaffected breeding colonies. In the affected colony, 65.5% of breeding animals (n = 23) but only 11.9% of virgin animals (n = 42) tested PCR positive, with breeding status being a significant predictor of bacterium presence (P < 0.00001). This study characterizes a granulomatous mucosal disease syndrome of breeding male ball pythons associated with a novel Actinomyces. In stark contrast to male snakes, the presence of the bacterium in both breeding and virgin females was very rarely associated with clinical disease. Though additional studies are necessary, these data suggest a role for the novel bacterium in the disease process, a predilection for clinical disease in male snakes, and the potential for sexual transmission of the disease.

The impact of environmental lead exposure on Whooper swan (Cygnus cygnus): Pathological and immunohistochemical studies

This study was carried out to investigate the pathology of environmental lead (Pb) poisoning in Whooper swans (Cygnus cygnus). A number of 12 out 54 swans (22.2%) randomly collected from Honshu, Japan from June 2005 to July 2007 were affected with Pb poisoning. Affected swans showed stained vent with greenish watery diarrhoea and impacted crop. The presence of Pb shots in the gizzard (50%) was confirmed by X-ray, and all cases showed a dark greenish coloured liver. Microscopically, the pathology of Pb poisoning in swans was multisystemic. The severity of the lesions was the highest in the CNS followed by the liver, kidney, spleen, lungs, gizzard, heart, bone marrow respectively and was the least in the peripheral nervous system. CNS lesions were cerebral haemorrhage, malacia, and spongiosis with astrocytic activation and increased neurofilaments accumulations. In addition, there were hepatic and renal hemosiderosis and apoptosis, hepatic granuloma, interstitial pneumonia, gizzard and myocardial necrosis and bone marrow hypoplasia. Chemical analysis of the Pb content in liver and kidneys ranged from 8.18 to 60.6 µg/g, respectively. The extent and severity of lesions varied among individuals and were mostly dose-dependent. Finally, these findings improved the diagnostic procedure of Pb poisoning in free-living Whooper swans.

Hepatic Brucelloma: An Unsual Condition

Introduction: The most common zoonosis in the world is brucellosis, which is caused by microorganisms of the genus Brucella, a gram-negative aerobic bacteria with the in vivo capability to behave like facultative intracellular parasites. Case: We present the a 49-year-old man complained of abdominal pain in the right hypochondrium associated with fever. Ultrasound, CT, and abdominal MRI scans were performed, which showed a 7-cm hypodense liver lesion in segment VII, with a 2-cm calcification (Image 1). A blood test revealed only elevated CRP levels, without leukocytosis or neutrophilia, and serology of echinococcus granules was negative. Blood cultures were also negative. The affected segment was resected. The postoperative period was satisfactory. Results: Histopathologic analysis determined the presence of a hepatic necrotizing granuloma with internal calcification. The lesion was negative for Zhiel_Neelsen, Grocott, and PAS, but compatible with bruceloma of the liver. Serological diagnosis was subsequently confirmed by means of the Bengal rose test. The patient was then treated with doxycycline with rifampicin for 6 weeks. Hepatic brucelomas appear as single lesions with a pseudotumoral appearance and typically exhibit central calcification. Serological studies are based on the detection of antibodies and are performed with Bengal rose staining. Use of the PCR technique is advisable, both in blood and in the tissue sample. Conclusion: The combination of liver surgery and antibiotic treatment for 6 to 8 weeks is ideal to guarantee complete eradication of this zoonosis, but approximately 5% to 15% of patients relapse.

Pathology of hepatic granulomas in goats

Pathology of hepatic granulomas in goats

Pathological and Immunohistochemical Examinations on Co-Infection with Coligranulomatosis and Marek's Disease in a Turkey Flock

Coligranulomatosis, which induces hepatic granulomas, and Marek's disease, one of the important neoplastic diseases in poultry, rarely causes outbreaks in turkeys. In this study, etiological diagnoses were performed in the light of post-mortem, histopathological, microbiological, and immunohistochemistry studies of turkeys that died in a commercial establishment in the region of Konya. In the post-mortem examination, many grey-white foci with a diameter of 3-10 mm, which sometimes spread from serosa to the parenchyma, were found in the liver. Mucous exudate and hyperemia were detected in all segments of the intestine. For microscopic examination, all tissues were stained with Haematoxylin-Eosin and some selected liver tissues with Periodic Acid-Schiff, Ziehl-Neelsen, and Giemsa. Typical structures of pyogranulomas with an eosinophilic necrotic core in the liver were identified. Tumor foci formed by pleomorphic histiocyte and lymphoid cells were also observed in the liver, spleen, and intestines (jejunum and cecum). In the selected liver and intestinal sections, a positive reaction was obtained in tumor cells in immunohistochemical staining with the primary antibody specific for Marek's disease virus. In addition, Escherichia coli isolation was performed microbiologically in swaps and samples taken from lesioned areas of the liver. As a result of the examinations, other etiological agents that may cause hepatic granulomas in the turkeys were excluded, and coligranulomatosis and Marek's disease were diagnosed simultaneously in this turkey flock. It was concluded that in cases in which these two diseases are observed simultaneously, the diseases might interact with each other, and casualties may increase.

EVALUATION OF THE EUCALYPTUS CAMALDULENSIS-KILLED CERCARIAE AS A CANDIDATE VACCINE FOR EXPERIMENTAL SCHISTOSOMIASIS MANSONI

Schistosomiasis is the second commonest parasitic disease worldwide. It is responsible for thousandsof deaths per year in addition to the associating serious morbidities that burden both individuals andcommunities. To date, the main preventive measure of infection is mass treatment with praziquantel. itcarries the risk of reinfection and rising resistance which makes the discovery of an effective vaccinean urgent necessity. The present study evaluated E. camaldulensis killed cercariae immunogen (KCI)as a candidate vaccine for experimental schistosomiasis mansoni and to detect the possible immunologicalmechanisms of action of this immunogen. The KCI caused a significant reduction of bothschistosomula and adult worm counts with subsequent ova count reduction. Hepatic granulomas werereduced in number or size. Also, levels of IgG, IgG1 & IgG2a as well as INF-γ & IL-10 fluctuatedlarger than in natural infection.

Anatomical MRI and [18F]FDG PET/CT imaging of Schistosoma mansoni in a NMRI mouse model

Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether discrimination of infection grade and its correlation to liver damage could be accurately performed by multimodal imaging in a mouse model of Schistosoma mansoni infection. Therefore, groups of uninfected and infected mice underwent MRI and [18F]FDG PET/CT imaging. Anatomical MRI images were used for liver volumetry and for quantification of hepatic granulomas. For PET/CT images a volume of interest based analyses were employed to calculate the [18F]FDG uptake in liver, portal vein, spleen and abdomen. Herein, we demonstrate that the combined use of [18F]FDG-PET/CT and MRI represents an appropriate diagnostic tool for Schistosoma mansoni infection, but fails to discriminate the infection grade and the linked organ damage. Only the splenic [18F]FDG uptake in the 25 cercariae group (5.68 ± 0.90%ID/cc) and 50 cercariae group (4.98 ± 1.43%ID/cc) was significantly higher compared to the control group (2.13 ± 0.69%ID/cc). Nevertheless, future multimodal imaging studies with new radiopharmaceuticals could build a highly sensitive and specific basis for the diagnosis and evaluation of organ damage of schistosomiasis.

S2643 Hepatic Sarcoidosis Manifesting With Severe Hypercalcemia in an Elderly Woman: A Rare Presentation

INTRODUCTION: Sarcoidosis is a chronic, multisystemic non-caseous granulomatous disease of unknown origin. Exclusive liver involvement without lung disease is less frequent, documented in only about 13% of patients with systemic sarcoidosis. The diagnosis of liver sarcoidosis is difficult, because symptoms or functional derangement due to involvement of the liver are uncommon in sarcoidosis. CASE DESCRIPTION/METHODS: An 83 year old woman presented with fever, chills and fatigue of 1 week duration. She further reported no alcohol or drug use, prior blood transfusions and use of herbal supplements. Her exam was unremarkable and initial laboratory data was significant for eosinophilia of 0.6 k/uL and the following liver tests: ALP 613 U/L, AST 234 U/L, ALT 224 U/L, total bilirubin 0.8 mg/dL, INR 1.0 and Gamma Glutamyl Transferase (GGT) 518 U/L. Infectious workup was negative for HBV, HCV, CMV, EBV and Quantiferon. Magnetic resonance imaging of the liver was negative for masses and biliary dilation. Chest CT was negative for pulmonary fibrosis and hilar adenopathy. Immunological workup came back negative. The patient’s ALP was of macrohepatic source and peaked to 1251 U/L over the following week, serum calcium rapidly increased to 13.6 mg/dl and Angiotensin-1 converting enzyme (ACE) was >80 U/L. At this point a liver biopsy was conducted which showed non-necrotic granulomata in a lobular and periportal distribution consistent with sarcoidosis of the liver. The patient was placed on oral prednisone after which her liver tests and severe fatigue improved rapidly. She continues to follow up outpatient and is doing well. DISCUSSION: Sarcoid hepatic granulomas are usually asymptomatic and associated with normal liver function or mild derangement. Fever, interestingly, correlates with hepatic sarcoid, like in our patient. Clinical manifestations of liver involvement are rare and may include chronic cholestasis, portal hypertension or Budd Chiari syndrome. In general, granulomas are found in 4% of all liver biopsy specimens, of these only 13.5%-22% are due to sarcoidosis. An optimal therapeutic regimen for hepatic sarcoidosis remains ill defined. In patients with symptoms or significant hepatic dysfunction, corticosteroids have been used as a first line treatment. Prednisone daily for 8-12 weeks and then gradual tapering over a period of 6-12 months is usually recommended.Figure 1.: Lobular granuloma.Figure 2.: Periportal granuloma.Figure 3.: Periportal granuloma (magnified).