A Partially Protective Vaccine for Fasciola hepatica Induced Degeneration of Adult Flukes Associated to a Severe Granulomatous Reaction in Sheep

Fasciolosis is an important economic disease of livestock. There is a global interest in the development of protective vaccines since current anthelmintic therapy is no longer sustainable. A better knowledge of the host-parasite interaction is needed for the design of effective vaccines. The present study evaluates the microscopical hepatic lesions in sheep immunized with a partially protective vaccine (VAC1), a non-protective vaccine (VAC2), and an infected control group (IC). The nature of granulomatous inflammation associated with degeneration of adult flukes found in the VAC1 group was characterized by immunohistochemistry. Hepatic lesions (fibrous perihepatitis, chronic tracts, bile duct hyperplasia, infiltration of eosinophils and lymphocytes and plasma cells) were significantly less severe in the VAC1 group than in the IC group. Dead adult flukes within bile ducts were observed only in the VAC1 group and were surrounded by a severe granulomatous inflammation composed by macrophages and multinucleate giant cells with a high expression of lysozyme, CD163 and S100 markers, and a low expression of CD68. Numerous CD3+ T lymphocytes and scarce infiltrate of FoxP3+ Treg and CD208+ dendritic cells were present. This is the first report describing degenerated flukes associated to a severe granulomatous inflammation in bile ducts in a F. hepatica vaccine trial.

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Efficacy of a multivalent vaccine against Fasciola hepatica infection in sheep

Veterinary Research ◽

10.1186/s13567-021-00895-0 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Rafael Zafra ◽

Leandro Buffoni ◽

Raúl Pérez-Caballero ◽

Verónica Molina-Hernández ◽

María T. Ruiz-Campillo ◽

...

Keyword(s):

Fasciola Hepatica ◽

Control Group ◽

Serological Study ◽

Infected Control ◽

Vaccination Trial ◽

Faecal Egg Count ◽

Infected Control Group ◽

Group 2 ◽

Hepatic Lesions ◽

Group 1

AbstractIn this work we report the protection found in a vaccination trial performed in sheep with two different vaccines composed each one by a cocktail of antigens (rCL1, rPrx, rHDM and rLAP) formulated in two different adjuvants (Montanide ISA 61 VG (G1) and Alhydrogel®(G2)). The parameters of protection tested were fluke burden, faecal egg count and evaluation of hepatic lesions. In vaccinated group 1 we found a significant decrease in fluke burden in comparison to both unimmunised and infected control group (37.2%; p = 0.002) and to vaccinated group 2 (Alhydrogel®) (27.08%; p = 0.016). The lower fluke burden found in G1 was accompanied by a decrease in egg output of 28.71% in comparison with the infected control group. Additionally, gross hepatic lesions found in vaccine 1 group showed a significant decrease (p = 0.03) in comparison with unimmunised-infected group. The serological study showed the highest level for both IgG1 and IgG2 in animals from group 1. All these data support the hypothesis of protection found in vaccine 1 group.

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Hepatic Lesions in Rabbits Infected with Encephalitozoon cuniculi Administered per Rectum

Veterinary Pathology ◽

10.1177/030098589202900608 ◽

1992 ◽

Vol 29 (6) ◽

pp. 536-540 ◽

Cited By ~ 23

Author(s):

I. C. Fuentealba ◽

N. T. Mahoney ◽

J. A. Shadduck ◽

J. Harvill ◽

V. Wicher ◽

...

Keyword(s):

New York ◽

Plasma Cells ◽

Inflammatory Cells ◽

Giant Cells ◽

Encephalitozoon Cuniculi ◽

Acquired Immunodeficiency ◽

Portal Veins ◽

Hepatic Lesions ◽

Hepatic Portal ◽

Immunodeficiency Syndrome

Microsporidia have been recognized recently as opportunistic pathogens in acquired immunodeficiency syndrome patients. In an attempt to develop an animal model of enteric microsporidiosis, adult (5 to 6 months old) male Flemish Giant rabbits from a closed New York colony were administered 5 × 103, 5 × 105, and 5 × 107 Encephalitozoon cuniculi per rectum. Rabbits given 5 × 105 and 5 × 107 E. cuniculi had moderate granulomatous periportal infiltrates, characterized by the presence of numerous macrophages, epithelioid cells, and a few multinucleated giant cells, lymphocytes, and plasma cells. Inflammatory cells also were seen infiltrating the tunica adventitia and tunica media of hepatic portal veins and branches of the hepatic artery. This study demonstrates that administration of E. cuniculi per rectum to rabbits results in infection that is characterized by high frequency and severity of hepatic lesions.

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Microscopic analisys of porous microgranular bovine anorganic bone implanted in rat subcutaneous tissue

Journal of Applied Oral Science ◽

10.1590/s1678-77572005000400013 ◽

2005 ◽

Vol 13 (4) ◽

pp. 382-386 ◽

Cited By ~ 10

Author(s):

Willian Fernando Zambuzzi ◽

Rodrigo Cardoso de Oliveira ◽

Danilo Alanis ◽

Renato Menezes ◽

Ariadne Letra ◽

...

Keyword(s):

Connective Tissue ◽

Plasma Cells ◽

Subcutaneous Tissue ◽

Repair Process ◽

Giant Cells ◽

Tissue Response ◽

Control Group ◽

Microscopy Analysis ◽

Light Microscopy Analysis ◽

Severe Adverse Reactions

The tissue response to porous bovine anorganic bone implanted in rat connective tissue was evaluated by subjective light microscopy analysis. Forty rats were divided into two groups: control (empty collagen capsules) and test (collagen capsule filled with 0.1g biomaterial) and killed 10, 20, 30 and 60 days after implantation. At 10 days, intense chronic inflammatory infiltrate consisting mainly of macrophages and inflammatory multinucleated giant cells (IMGC) was observed. Neutrophils, plasma cells and lymphocytes were present in discrete amounts and slowly disappeared along the repair process. Porosity of the material was filled by reaction connective tissue exhibiting IMGC. The fibrosis was more intense after 60 days and clearly higher than the control group. Thus, the material did not cause any severe adverse reactions and did not stimulate the immune system. Based on the results it could be concluded that deproteinized bovine cancelous bone was well tolerated by rat connective tissue.

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A 62-Year-Old African American Woman With Stable Lymphadenopathy Over 5 Years

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz121.014 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S110-S110

Author(s):

Hanadi El Achi ◽

William Glass ◽

Miriam Velazquez ◽

Zhihong Hu

Keyword(s):

African American ◽

Plasma Cells ◽

African American Woman ◽

American Woman ◽

Granulomatous Inflammation ◽

Chronic Fatigue ◽

Giant Cells ◽

Castleman Disease ◽

African American Female ◽

Mantle Zone

Abstract The patient is a 62-year-old African American female with medical history of Plummer Vinson syndrome and CT scan in 2014 showing lymphadenopathy of the porta hepatis. Needle core biopsy of enlarged lymph nodes revealed sheets of polytypic plasma cells with no aberrant B or T cells or granulomas or hyaline-like depositions identified. The findings were suspicious for unicentric Castleman disease. In 2019, the patient presented with chronic fatigue without other systemic symptoms. Contrast CT revealed persistent retroperitoneal lymphadenopathy and calcified granulomas in the liver, spleen, and lung. Excision of portal and celiac nodes showed preserved nodal architecture with mild mantle zone expansion and marked hyaline-like deposition in the follicles. Sheets of mature plasma cells and focally increased vasculatures were seen in the interfollicular areas. Focally frequent nonnecrotizing granulomas were noted. Occasional giant cells and rare asteroid bodies were identified in the granulomas. Immunohistochemistry stain workup revealed normal distribution of the B and T lymphocytes. CD138 stain highlighted marked increased plasma cells and HHV8 was negative. Immunofluorescence microscopy for kappa and lambda did not show monoclonality; IgA was positive in <10% of plasma cells; special stain for Congo red and serum amyloid associated protein (SSA) IHC stain were strongly positive in the follicles. The overall findings are consistent with reactive lymphadenopathy with interfollicular polytypic plasmacytosis, noncaseating granuloma formation, and reactive amyloidosis. The features of mantle zone hyperplasia and polytypic plasmacytosis are suggestive of HHV8-negative/idiopathic unicentric Castleman disease. This case possibly represents an example of concurrent amyloidosis, sarcoidosis, and idiopathic unicentric Castleman disease. Given that SSA was recently reported to have a pathogenic role in granulomatous inflammation of sarcoidosis through sustained inflammatory reaction, the possibility of increased SSA triggering sarcoidoisis in this patient can be considered. However, the exact pathogenesis of these concurrent findings needs further investigation and clarification.

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Equine Granulomatous Enteritis

Veterinary Pathology ◽

10.1177/030098587401100608 ◽

1974 ◽

Vol 11 (6) ◽

pp. 535-547 ◽

Cited By ~ 40

Author(s):

R. E. Cimprich

Keyword(s):

Weight Loss ◽

Mycobacterium Tuberculosis ◽

Plasma Cells ◽

Granulomatous Inflammation ◽

Giant Cells ◽

Gut Content ◽

Epithelioid Cells ◽

History Of ◽

Microscopic Change ◽

Granulomatous Enteritis

The gross abnormalities in the intestines of 10 horses with a history of chronic weight loss varied greatly. The principal microscopic change was granulomatous inflammation characterized by lymphocytes, plasma cells, macrophages, epithelioid cells and giant cells. Mycobacterium tuberculosis, avian type, was isolated from the gut content of one horse, but no cause was found in the others. Horses previously reported to have tuberculosis had lesions similar to those described here. These lesions are also similar to those in Crohn's disease of man.

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Infection in a female Komodo dragon (Varanus komodoensis) caused by Mycobacterium intracellulare: a case report

Veterinární Medicína ◽

10.17221/5857-vetmed ◽

2012 ◽

Vol 57 (No. 3) ◽

pp. 163-168 ◽

Cited By ~ 2

Author(s):

M. Skoric ◽

V. Mrlik ◽

J. Svobodova ◽

V. Beran ◽

M. Slany ◽

...

Keyword(s):

Environmental Samples ◽

Plasma Cells ◽

Histopathological Examination ◽

Granulomatous Inflammation ◽

Giant Cells ◽

Tissue Samples ◽

The Czech Republic ◽

Mycobacterium Intracellulare ◽

Granulomatous Pneumonia ◽

Variable Layer

In early 2002, a bean-like whitish nodule 2 × 1 × 1 cm in size was diagnosed on the tongue of a female Komodo dragon (Varanus komodoensis) kept in a zoological garden in the Czech Republic. The nodule was removed at surgery and histopathological examination revealed a specific granulomatous inflammation. The granuloma contained a necrotic mass surrounded by a variable layer of palisading epithelioid macrophages and multinucleated giant cells with a variable admixture of lymphocytes and plasma cells. Signs of mineralisation within the granuloma were not observed. Using Ziehl-Neelsen (ZN) staining the presence of acid-fast rods (AFR) was determined and the presence of mycobacteria was confirmed by PCR. Four years later, this female died after multiple injuries caused by a male during mating. Necropsy and histopathological examinations revealed granulomatous pneumonia and myocarditis with ZN-positive AFR within granulomas. Mycobacteria were cultured from 13 of 19 tissue samples: Mycobacterium intracellulare was confirmed by sequencing of isolates from multiple affected organs including the respiratory tract, tail muscle, inguinal lymph nodes and blood; Mycobacterium sp. were also isolated from the tongue. In addition, mycobacteria were detected in 15 (46.9%) of 32 environmental samples examined in both years. M. intracellulare was detected in water sediment from the female’s terrarium in 2002, and in faeces and peat from the terrarium and in water sediment from the male terrarium in 2006. Except for M. intracellulare (n = 4), M. smegmatis (n = 1), M. a. hominissuis (n = 3), M. fortuitum (n = 2), M. interjectum (n = 1), M. peregrinum/alvei/septicum (n = 1) and Mycobacterium sp. (n = 2) were also isolated from different environmental samples.    

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Avian tuberculosis in a captured Ruppell's griffon vulture (Gyps ruppellii): a case report

Veterinární Medicína ◽

10.17221/2929-vetmed ◽

2010 ◽

Vol 55 (No. 7) ◽

pp. 348-352 ◽

Cited By ~ 2

Author(s):

M. Skoric ◽

P. Fictum ◽

L. Frgelecova ◽

P. Kriz ◽

I. Slana ◽

...

Keyword(s):

Plasma Cells ◽

Granulomatous Inflammation ◽

Giant Cells ◽

Body Cavity ◽

The Body ◽

Multinucleated Giant Cells ◽

Quantitative Real Time Pcr ◽

Griffon Vulture ◽

Avium Infection ◽

Variable Layer

Avian tuberculosis was diagnosed in a captured female Ruppell's griffon vulture (Gyps ruppellii) with granulomatous splenitis and hepatitis. At necropsy, whitish to yellow nodules of various sizes were found in the spleen and liver, and fibrinous coelomitis was present in the body cavity. Histopathologically, the granulomas appeared to be typical of avian tuberculosis. In some granulomas, necrotic centres surrounded by a variable layer of palisading epithelioid macrophages and multinucleated giant cells with variable admixture of lymphocytes and plasma cells were present. Signs of mineralization in granulomas were not observed. Using Ziehl-Neelsen staining the presence of acid-fast bacilli was demonstrated in organs affected by granulomatous inflammation. A diagnosis of Mycobacterium avium subsp. avium infection was confirmed by culture and quantitative Real-Time PCR examination for the presence of specific insertion sequences for avian tuberculosis (IS901 and IS1245) in the liver and spleen.  

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The histopathology of Fasciola hepatica infections in sheep

Parasitology ◽

10.1017/s0031182000073480 ◽

1968 ◽

Vol 58 (1) ◽

pp. 129-135 ◽

Cited By ~ 29

Author(s):

C. Dow ◽

J. G. Ross ◽

J. R. Todd

Keyword(s):

Growth Rate ◽

Hepatic Fibrosis ◽

Bile Ducts ◽

Fasciola Hepatica ◽

Liver Parenchyma ◽

Giant Cells ◽

Hepatic Cell ◽

Cell Regeneration ◽

Experimental Infections ◽

Two Phases

Experimental infections of lambs with Fasciola hepatica are described. The growth rate of the parasite, time of entry to the bile ducts, and time of patency are recorded and a preferential migration of the parasite in the liver parenchyma noted. The gross and histological lesions produced in the liver from 1 to 40 weeks after infection are described and compared with previous observations in cattle.The parenchymal migration of the parasite is shown to consist of two phases, a free migrating phase up to the 6th week, and a localized phase after the 6th week prior to entry into the bile ducts. Hepatic cell regeneration is observed and hepatic fibrosis is minimal. The localized phase of migration is associated with a unique peripheral palisade of giant cells in the fluke tracts and with the formation of pseudofollicular aggregation of lymphocytes. The presence of flukes in the bile ducts produces fibrosis of the duct walls. The walls, however, remain pliable and expanded to accommodate the parasites and calcification was never observed.

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Superficial Granulomatous Pyoderma Gangrenosum Involving the Face: A Case Series of Five Patients and a Review of the Literature

Journal of Cutaneous Medicine and Surgery ◽

10.1177/1203475420988864 ◽

2021 ◽

pp. 120347542098886

Author(s):

Eran Shavit ◽

Michael Cecchini ◽

James J. Limacher ◽

Scott Walsh ◽

Ashely Wentworth ◽

...

Keyword(s):

Pyoderma Gangrenosum ◽

Plasma Cells ◽

Relevant Literature ◽

Case Series ◽

Granulomatous Inflammation ◽

Final Diagnosis ◽

Giant Cells ◽

Neutrophilic Dermatosis ◽

The Face ◽

Inflammatory Infiltrates

Background Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful and ulcerating lesions on the skin. It rarely involves the face and is often difficult to diagnose. There are few cases reported in the literature of PG involving the face. Aim To share our experience with 5 patients in whom the final diagnosis was PG involving the face, and to review the literature. Methods We report a series of 5 patients with a final diagnosis of PG involving the face and reviewed relevant literature. We searched through PubMed and EMBASE using keywords such as “face” and “pyoderma gangrenosum,” “blastomycosis-like pyoderma gangrenosum, vegetative pyoderma gangrenosum and granulomatous pyoderma gangrenosum.” Results We report 5 patients (4 females) with pyoderma gangrenosum involving the face. All 5 had a final diagnosis of superficial granulomatous PG. All cases presented with nonhealing facial ulcer most commonly on cheeks and a common histopathology of mixed inflammatory infiltrates, multinucleated giant cells, and plasma cells with some granulomatous inflammation. Conclusions PG can involve the face, and all 5 of our patients had the superficial granulomatous as the most common form.

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Ruxolitinib Regulates the Autophagy Machinery in Multiple Myeloma Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200218105159 ◽

2020 ◽

Vol 20 (18) ◽

pp. 2316-2323 ◽

Cited By ~ 3

Author(s):

Alican Kusoglu ◽

Bakiye G. Bagca ◽

Neslihan P.O. Ay ◽

Guray Saydam ◽

Cigir B. Avci

Keyword(s):

Multiple Myeloma ◽

Cell Line ◽

B Lymphocyte ◽

Plasma Cells ◽

Annexin V ◽

Myeloma Cell ◽

Control Group ◽

Multiple Myeloma Cell ◽

Ic50 Values ◽

Stat Pathway

Background: Ruxolitinib is a selective JAK1/2 inhibitor approved by the FDA for myelofibrosis in 2014 and nowadays, comprehensive investigations on the potential of the agent as a targeted therapy for haematological malignancies are on the rise. In multiple myeloma which is a cancer of plasma cells, the Interleukin- 6/JAK/STAT pathway is emerging as a therapeutic target since the overactivation of the pathway is associated with poor prognosis. Objective: In this study, our purpose was to discover the potential anticancer effects of ruxolitinib in ARH-77 multiple myeloma cell line compared to NCI-BL 2171 human healthy B lymphocyte cell line. Methods: Cytotoxic effects of ruxolitinib in ARH-77 and NCI-BL 2171 cells were determined via WST-1 assay. The autophagy mechanism induced by ruxolitinib measured by detecting autophagosome formation was investigated. Apoptotic effects of ruxolitinib were analyzed with Annexin V-FITC Detection Kit and flow cytometry. We performed RT-qPCR to demonstrate the expression changes of the genes in the IL-6/JAK/STAT pathway in ARH-77 and NCI-BL 2171 cells treated with ruxolitinib. Results: We identified the IC50 values of ruxolitinib for ARH-77 and NCI-BL 2171 as 20.03 and 33.9μM at the 72nd hour, respectively. We showed that ruxolitinib induced autophagosome accumulation by 3.45 and 1.70 folds in ARH-77 and NCI-BL 2171 cells compared to the control group, respectively. Treatment with ruxolitinib decreased the expressions of IL-6, IL-18, JAK2, TYK2, and AKT genes, which play significant roles in MM pathogenesis. Conclusion: All in all, ruxolitinib is a promising agent for the regulation of the IL-6/JAK/STAT pathway and interferes with the autophagy mechanism in MM.

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