Infiltration Of Mononuclear Inflammatory Cells Research Articles

Infecção por pox vírus e Aspergillus fumigatus em Bubo virginianus (Coruja jacurutu)

Resumo: Este trabalho descreve um caso de infecção mista por pox vírus e Aspergillus fumigatus em Bubo virginianus (coruja jacurutu). A ave, um macho adulto, foi encaminhada ao Núcleo de Reabilitação da Fauna Silvestre do Instituto de Biologia da Universidade Federal de Pelotas (NURFS/CETAS/UFPEL). Apresentava bom estado corporal, estava ativa, porém com incapacidade de voo. Após três dias apresentou lesões crostosas e de aspecto verrucoso na superfície dorsal das patas. Havia, também, nódulos de mesmo aspecto na pálpebra esquerda e na cera. A ave morreu após 15 dias de sua chegada ao NURFS e foi necropsiada no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD/UFPel). Histologicamente, as lesões verrucosas caracterizavam-se por hiperplasia do epitélio e nas células das camadas basal, espinhosa, granular e córnea havia corpúsculos de inclusão intracitoplasmáticos do tipo Bollinger. Na microscopia eletrônica foram visualizadas partículas virais características de pox vírus, incluindo Bubo virginianus como um hospedeiro do vírus. Havia, ainda, infiltrado inflamatório de células mononucleares e focos de colônias bacterianas na derme. Nos pulmões havia congestão e presença de granulomas com hifas fúngicas, que pela técnica de Grocott, apresentaram ramificação dicotômica compatível com Aspergillus spp., identificado na cultura como A. fumigatus. O diagnóstico de infecção por avipoxvirus pode contribuir para estudos relacionados com a ocorrência desta doença nas populações de vida livre e como informação auxiliar para o manejo e conservação desta espécie. Sugere-se, ainda, a inclusão do uso de raios-X nos protocolos de centros de reabilitação como o diagnostico de aspergilose em aves rapinantes com bom estado corporal, porém incapazes de voar.

Assessment of pathogenicity and tissue distribution of infectious bronchitis virus strains (Italy 02 genotype) isolated from moroccan broiler chickens

BackgroundAvian infectious bronchitis (IB) is one of the most important viral diseases of poultry, affecting chickens of all ages and causing major economic losses in poultry flocks. Mass vaccination is conducted in Morocco using a vaccine against Massachusetts, which is the most dominant serotype; however no information about the pathogenesis and tissue distribution of the Moroccan Italy 02 genotype was reported.40 one-day-old specific pathogen free chickens were divided randomly into four groups. Group1, 2 and 3 were inoculated intra oculo-nasally with 103.5 EID50 of Italy02 viruses, and group 4 was kept as control. Chickens in each group were monitored for 14 days post-infection (pi).ResultsChickens in all infected groups showed severe respiratory signs, which most of them have been reproduced on 2dpi, with varying times of appearance and disappearance. The infected birds appeared lethargic, reluctant to move, with specific respiratory clinical signs and macroscopic lesions. However no nephritis lesions or mortality were recorded in all groups. The specific histological lesions finding in all infected birds, exhibited tracheal lesions with mucosal thickening, hyperplasia of the surface epithelium, mononuclear inflammatory cell infiltrate of lamina propria. Primary and secondary bronchi, epithelial hyperplasia and mononuclear inflammatory cell infiltrate of the lamina propria were also observed. Tracheal lesions developed in all infected birds, confirm the ability of the three tested strains to induce respiratory disease. The results at 14 dpi also revealed that all strains were able to induce serological response. Virus re-isolation from infected organs and amplification of the viral RNA by real-time PCR proved the presence of the virus in lung and trachea of infected chicks. Neither re-isolation nor significant viral RNA detection were detected in the kidney.ConclusionThe results demonstrated that the three strains Italy02 genotype emerging in Moroccan poultry farms have a wide distribution for respiratory system, without kidney damage and without causing mortality.

An experimental ovine Theileriosis: The effect of Theileria lestoquardi infection on cardiovascular system in sheep

The malignant ovine theileriosis is caused by Theileria lestoquardi, which is highly pathogenic in sheep. Theileriosis involves different organs in ruminants, but the effect of the disease on the cardiovascular system is unclear. To understand the pathogenesis of T. lestoquardi on the cardiovascular system, Baluchi breed sheep were infected with the mentioned parasite by releasing unfed adults of Hyalomma anatolicum anatolicum, which were infected with T. lestoquardi. The infected sheep were clinically examined on days 0, 2, 5, 7, 10, 12, 14, 17, and 21, and the blood samples were collected for biochemical parameters measurement. At termination of the experiment, the infected sheep were euthanized and pathological examinations of heart tissue were conducted. During experimental infection of sheep with T. lestoquardi, activities of cardiac troponin I (cTnI), lactate dehydrogenase, and aspartate aminotransferase, were significantly increased (P˂0.05), while a conspicuous decrease (P˂0.05) was observed in creatine phosphokinase activities. Alterations made in biochemical factors almost coincided with the presence of piroplasm in the blood and schizont in lymph nodes. Maximum and minimum of parasitemia in the sheep stood between 3.3% and 0.28%, respectively. In addition, electrocardiography revealed sinus tachycardia, sinus arrhythmia, sino-atrial block and ST-elevation, atrial premature beat, and alteration in QRS and in T waves’ amplitude. Heart histopathological examination showed hyperemia, infiltration of mononuclear inflammatory cells into interstitial tissue, endocarditis, and focal necrosis of cardiac muscle cells. In addition, in one of the sheep, definite occurrence of infarction was observed. The results indicate that T. lestoquardi infection has devastating pathological impacts on the cardiovascular system of sheep. Furthermore, measurement of the cTnI amount is a useful biochemical factor for diagnosis and for better understanding of the severity and progression of the disease and its effects on cardiac tissue.

Evaluation of autologous bone marrow-derived mesenchymal stem cells on renal regeneration after experimentally induced acute kidney injury in dogs.

To evaluate the usefulness of autologous bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for the treatment of dogs with experimentally induced acute kidney injury. 6 healthy dogs. After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), dogs immediately received saline (0.9% NaCl) solution (10 mL; n = 3) or BM-MSCs (1 × 10(6) cells/kg in 10 mL of saline solution; 3) IV. A CBC, serum biochemical analysis, and urinalysis were performed for each dog before administration of cisplatin and on days 1 through 4. Glomerular filtration rate was determined for all dogs on days -7 and 2; BM-MSC tracking by MRI was performed on BM-MSC-treated dogs on days -14 and 4. After sample collection and BM-MSC tracking on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analysis, and cytokine profiling via reverse transcriptase PCR assays. Kidney tissue from both groups had mononuclear inflammatory cell infiltration, tubular necrosis, dilated tubules, and glomerular damage. However, there was less fibrotic change and increased proliferation of renal tubular epithelial cells in the BM-MSC-treated dogs, compared with findings for the control dogs. Expressions of tumor necrosis factor-α and transforming growth factor-β were lower in the BM-MSC-treated group, compared with findings for the control group. Laboratory data revealed no improvement in the renal function in BM-MSC-treated dogs. Results of this study suggested that autologous BM-MSCs may accelerate renal regeneration after experimentally induced acute kidney injury in dogs.

Frequency of histopathological changes in Howler monkeys ( Alouatta sp.) naturally infected with yellow fever virus in Brazil.

Due to the importance that Howler monkeys have on the yellow fever (YF) epidemiological sylvatic cycle in Brazil, more accurate morphological diagnostic criteria needs to be established, especially considering the differences that may exist between the genera of Brazilian non-human primates (NHPs) involved in yellow fever virus (YFV) epizootics. Records of YF epizootics in NHPs in Brazil between 2007 and 2009 were obtained from the Brazilian Ministry of Health database to select YF positive (n=98) Howler monkeys (Alouatta sp.) for this study. The changes described in the histopathological reports were categorized by organ and their frequencies calculated. The most frequent lesions observed in the animals with YF were hepatocyte apoptosis (Councilman body formation), midzonal hepatocyte necrosis, steatosis, liver hemorrhage, inflammatory mononuclear cell infiltration of the liver, renal acute tubular necrosis and interstitial nephritis. Midzonal hepatocyte necrosis, steatosis and hemorrhage presented positive correlations with apoptosis of hepatocytes, suggesting strong YFV pathogenic effect association; they were also the main histopathological changes in the Alouatta sp. A pronounced negative correlation between apoptosis of hepatocytes and hepatic mononuclear cell infiltration pointed to significant histopathological differences between YFV infection in Howler monkeys and humans. The results warn that NHPs may exhibit different response patterns following YFV infection and require a more careful diagnosis. Presumptive diagnosis based on primate histopathological lesions may contribute to public health service control.

Immunopathological Features of Canine Myocarditis Associated with Leishmania infantum Infection.

Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection.

Can Malachite Green Concentrations Cause Hepatic Toxic Effects in Adult Albino Rats: Histological, Biochemical and Immunohistochemical

Malachite green (MG) has been widely used as the most efficacious antifungal agent in the fish farming industry. The aim of this study is to evaluate hepatotoxicity of different MG concentrations in adult albino rats. Forty five adult male albino rats were equally divided into 3 groups, each contains 15 rats. Group I (control), Group II (received daily dose of 3ug/kg b.wt of MG by oral gavage): divided into three subgroup equally according to time of taken sample and Group III (received daily gavage dose of 60ug/kg b.wt of MG by oral gavage): divided into three subgroup equally according to time of taken sample (Samples were taken 2 and 4 weeks from the start of the experiment and 2 weeks after drug stoppage (wash out). Hepatotoxicity was evaluated by biochemical, histopathological and immunohistochemical study. MG caused an increase of alanine aminotransferase, aspartate amino transferase (ALT and AST), alkaline phosphatase (ALP) levels, and decrease in total protein in animals treated with MG as compared to control. These biochemical alterations were confirmed by the presence of different histological changes as degeneration of hepatocytes with congested dilated central vein , mononuclear inflammatory cells infiltration with significant increase in caspase-3 expression with decrease in survivin expression and this changes were highly significant in rats treated with higher doses than other groups and persist even after 2 weeks from MG stoppage .We can conclude that MG and its residues in the edible tissue of fish could not be ignored due to their suspected hepatotoxicity with apoptotic changes even at lower doses. This leads us to put strict limitations on its use in the fish farming industry in Egypt.

Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration.

Experimental autoimmune encephalomyelitis (EAE) is a CD4(+)-mediated autoimmune pathology of the central nervous system (CNS) that is used as a model for the study of the human neuroinflammatory disease, multiple sclerosis. During the development of EAE, auto-reactive Th1 and Th17 CD4(+) T cells infiltrate the CNS promoting inflammatory cells recruitment, focal inflammation and tissue destruction. In this sense, statins, agents used to lower lipid levels, have recently shown to exert interesting immunomodulatory function. In fact, statins promote a bias towards a Th2 response, which ameliorates the clinical outcome of EAE. Additionally, simvastatin can inhibit Th17 differentiation. However, many other effects exerted on the immune system by statins have yet to be clarified, in particular during neuroinflammation. Thus, the aim of this study was to investigate the effects of simvastatin on the development of experimental autoimmune encephalomyelitis. Mice were immunized with MOG(35-55) and EAE severity was assessed daily and scored using a clinical scale. Cytokine secretion by mononuclear cells infiltrating the CNS was evaluated by flow cytometry. Simvastatin (5 mg/kg/day) improved clinical outcome, induced an increase in TGF-β mRNA expression and inhibited IL-6, IL-12p40, IL-12p70, RANTES and MIP-1β secretion (p < 0.05). This was accompanied by a significant decrease in CNS inflammatory mononuclear cell infiltration, with reduced frequencies of both Th1 and Th17 cells. Simvastatin inhibited the proliferation of T lymphocytes co-cultured with primary microglial cells. Simvastatin treatment promotes EAE clinical amelioration by inhibiting T cell proliferation and CNS infiltration by pathogenic Th1 and Th17 cells.

HISTOPATHOLOGICAL EFFECTS OF GLYPHOSATE HERBICIDE ON DIFFERENT ORGANS OF MALE AND FEMALE ALBINO RATS

The effect of major herbicide used worldwide glyphosate was studied on some organs of mature male and female albino rats (Rattus norvegicus). The LC50 was determined for glyphosate was 9.7% as crushed maize bait.Animals were fed on bait treated with (12 LC50) for 15 days. The organs were collected two weeks after treatment and fixed in 10% formalin saline. The results revealed that the liver of male showed necrosis of some hepatocytes with infiltration of mononuclear inflammatory cells, while the liver of females showed necrosis of some hepatocytes and dilation of blood vessels surrounded by fibrin with activation of vankopfer cells. Hemorrhage, infiltration of mononuclear inflammatory cells and necrosis of cells lining renal tubes were observed in the kidney of male, while in female ,granular degeneration changes of cells lining renal tubes with infiltration of mononuclear inflammatory cells and hyper cellularity of glomeruli with thrombosis of some blood vessels were recorded . The lung of male showed congestion of blood vessels and thickening of its wall, hyper proliferation of cells lining bronchial, infiltration of mononuclear inflammatory cell and thickening of interstitial wall, whereas hemorrhage, swelling of endothelial cells lining blood vessels, infiltration of mononuclear inflammatory cells and emphysema were observed in the lung of female.

A preliminary study on mechanisms for urinary system disorders before and after ketamine withdrawal in rats

To explore the mechanisms for urinary system disorders before and after ketamine withdrawal in rats and to evaluate the recovery degree of the urinary system damage after ketamine withdrawal. Fifteen male healthy Sprague-Dawley rats were randomly divided into 3 groups: A control group, an experimental group, and a withdrawal group. The rats in the control group were given normal saline. The rats in the experimental group were given ketamine 30 mg/(kg.day) for 30 days. The rats in the withdrawal group were treated as the experimental group except for drug withdrawal for 2 weeks. In the experimental period, we randomly selected 1 rat of kidney, ureter, and bladder from each group to perform HE staining. The bladder tissues in each group were used to detect mRNA expression by quantitative real-time polymerase chain reaction (qRT-PCR). 1) The behavior of ketamine-injected rats was obviously changed, but the weight of ketamine-induced rats was not changed. 2) As compared with the control group, the experimental and withdrawal groups showed infiltration of mononuclear inflammatory cells in the kidney tissues, the thinner epithelium of bladder and infiltration of submucosal mononuclear inflammatory cells under the optical microscope. 3) As compared with the control group, the expression of H1R mRNA was increased in the experimental group (P<0.05). As compared with the experimental group, H1R mRNA expression was significantly decreased in the withdrawal group (P<0.05). Ketamine abuse could induce behavior changes in rats. The infiltration of mononuclear inflammatory cells in kidney and bladder, the thinner bladder epithelial layer, and the increased H1R gene mRNA expression in bladder might be an important pathogenesis of KAUD. Ketamine withdrawal may effectively reverse the pathogenic process of KAUD.

Retrospective Study on the Isolation of Ornithobacterium rhinotracheale from Chickens and Turkeys in Central California: 294 cases (2000-12).

Ornithobacterium rhinotracheale is a rod-shaped, gram-negative, and mostly oxidase-positive bacterium that causes respiratory infections in chickens and turkeys worldwide and can also spread to nonrespiratory organs. The present report analyzes 294 cases in which O. rhinotracheale was isolated from turkeys or chickens in central California in the years 2000 through 2012. Two hundred sixteen cases were from turkey flocks and 78 from chicken flocks. The median age of turkey flocks was 8.7 wk; the median age of chicken flocks was 6.4 wk. From turkeys, O. rhinotracheale was more often isolated from August to January than during the rest of the year. Chickens cases were more evenly distributed throughout the year. The organs with the highest isolation rate were the infraorbital sinus and trachea, followed by lungs and air sacs. Isolation from other organs was rare. Pure cultures were obtained from relatively more turkey organs than chicken organs. The organ from which there was the highest chance to obtain a pure culture was the air sac. In 108 turkey flocks (50.0%) and 64 chicken flocks (82.1%) at least one other respiratory pathogen was detected. The most common gross lesions were increased mucus in trachea, caseous or fibrinous exudate in the air sacs, consolidated lungs indicating pneumonia, congested and edematous lungs, and a flattened trachea. For most types of lesions, the percentage of affected turkeys was higher than the percentage of affected chickens. The percentage of birds with lesions was higher if other respiratory pathogens were present. Overall, the host species (turkey or chicken) was a more important factor for the prevalence of most lesions than the detection of other respiratory pathogens. The most common histopathologic lesions in the sinus and trachea were heterophilic or mononuclear inflammatory cell infiltration. In the lungs and air sacs, the inflammation was characterized by heterophilic infiltration and/or fibrin accumulation. These results are helpful in selecting the most appropriate samples for isolation of O. rhinotracheale. In addition, they show the incidence of the bacterium in turkeys and chickens and which lesions can be expected after infection with O. rhinotracheale, and they indicate that in some cases O. rhinotracheale can be the primary, or at least the major, pathogen.

Pathological study of acute fasciolosis in goats in Karnataka

The present report pertains to the pathological investigation of anoutbreak of acute fasciolosis in goats in a private goat farm at Mysore, Karnataka. The farm comprised of 125 indigenous goats of all age groups reared under extensive system. Goats started dying without showing any clinical symptoms, except brief period of anorexia. Detailed necropsy was performed on 6 animals died over a span of 15 days. Thecarcasses were severely dehydrated, thin body condition with pallor oral and conjunctival mucosa. Post-mortem examination revealed about 500 ml of serosanguinous fluid and massive blood clots of varying sizesweighing up to of 500-600g in the abdominal cavity of few goats. The fluke migratory tracks were seen with severe haemorrhages on the liver surface. The cut surface of liver parenchyma and bile ducts showed immature liver flukes. The gall bladder was severely distended with blood, and large blood clotsin all the carcasses. The duodenal and large intestinal mucosa was moderately thickened and severely congested and clotted blood in the lumen of entire small intestine. The histological examination of liver exhibited extensive fibrosis, necrosisand haemorrhages with severe infiltration of mononuclear inflammatory cells, especially surrounding the parasites. There was mild proliferation of bile ducts around dead tissue with migratory tracts of hemosiderin. Pathological investigation confirmed the disease in goats as acute fasciolosis.

Collagenous gastritis: Review.

Collagenous gastritis is a rare disease characterized by the subepithelial deposition of collagen bands thicker than 10 μm and the infiltration of inflammatory mononuclear cells in the lamina propria. Collagenous colitis and collagenous sprue have similar histological characteristics to collagenous gastritis and are thought to be part of the same disease entity. However, while collagenous colitis has become more common in the field of gastroenterology, presenting with clinical symptoms of chronic diarrhea in older patients, collagenous gastritis is rare. Since the disease was first reported in 1989, only 60 cases have been documented in the English literature. No safe and effective treatments have been identified from randomized, controlled trials. Therefore, better understanding of the disease and the reporting of more cases will help to establish diagnostic criteria and to develop therapeutic strategies. Therefore, here we review the clinical characteristics, endoscopic and histological findings, treatment, and clinical outcomes from case reports and case series published to date, and provide a summary of the latest information on the disease. This information will contribute to improved knowledge of collagenous gastritis so physicians can recognize and correctly diagnose the disease, and will help to develop a standard therapeutic strategy for future clinical trials.

Pathological investigation of the mortality in captive Grasscutter (Thryonomys swinderianus) colonies in Accra, Ghana

Hepatorenal syndrome and clinical signs of heart failure occurred sporadically in 3-to 12-month-old Grasscutter(Thryonomys swinderianus) in captive colonies originally derived from in-bred male and female littermates. Macroscopic lesions in severely affected animals included subcutaneous edema, cervical swelling, pneumonia and hepatomegaly. 43 Grasscutters that were found dead and or were euthanatized because of dyspenia and lethargy were necropsied and representative blocks of tissues from heart, lungs, kidneys, liver and neck examined microscopically. Myocardial lesions were present in all rats and consisted of multifocalcardiac myocyte necrosis, and mononuclear inflammatory cell infiltration. 60% of the dead Grasscutters had chronic pulmonary congestion, and microscopically, livers showed chronic passive congestion. The kidneys showed tubular cell damage that appeared to be the central event in the pathogenesis of renal dysfunction and injury in Grasscutter, as evidenced by endothelial cell swelling, detachment, and accumulation of cast in the renal tubules. Swelling of the neck in these colonies of Grasscutter appeared to have resulted predominantly from unknown reasons possibly caused by stasis of venous blood secondary to right heart failure associated with a heritable cardiomyopathy.

Mitochondrial abnormalities and low grade inflammation are present in the skeletal muscle of a minority of patients with amyotrophic lateral sclerosis; an observational myopathology study.

BackgroundAmyotrophic lateral sclerosis (ALS) is a primary progressive neurodegenerative disease characterised by neuronal loss of lower motor neurons (in the spinal cord and brainstem) and/or upper motor neurons (in the motor cortex) and subsequent denervation atrophy of skeletal muscle.AimA comprehensive examination of muscle pathology from a cohort of clinically confirmed ALS patients, including an investigation of inflammation, complement activation, and deposition of abnormal proteins in order to compare them with findings from an age-matched, control group.Material and methods31 muscle biopsies from clinically confirmed ALS patients and 20 normal controls underwent a comprehensive protocol of histochemical and immunohistochemical stains, including HLA-ABC, C5b-9, p62, and TDP-43.ResultsNeurogenic changes were confirmed in 30/31 ALS cases. In one case, no neurogenic changes could be detected. Muscle fibre necrosis was seen in 5/31 cases and chronic mononuclear inflammatory cell infiltration in 5/31 (2 of them overlapped with those showing muscle necrosis). In four biopsies there was an increase in the proportion of cytochrome oxidase (COX) negative fibres (2-3%). p62 faintly stained cytoplasmic bodies in eight cases and none were immunoreactive to TDP-43.ConclusionThis large series of muscle biopsies from patients with ALS demonstrates neurogenic atrophy is a nearly uniform finding and that mild mitochondrial abnormalities and low-grade inflammation can be seen and do not rule out the diagnosis of ALS. These findings could lend support to the notion that ALS is a complex and heterogeneous disorder.

Non-clinical safety evaluation of single and repeated intramuscular administrations of MAGE-A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys.

The MAGE-A3 recombinant protein combined with AS15 immunostimulant (MAGE-A3 Cancer Immunotherapeutic) is under development by GlaxoSmithKline for the treatment of lung cancer and melanoma. We performed non-clinical safety studies evaluating potential local and systemic toxic effects induced by MAGE-A3 Cancer Immunotherapeutic in rabbits (study 1) and cynomolgus monkeys (study 2). Animals were allocated to two groups to receive a single (rabbits) or 25 repeated (every 2 weeks) injections (monkeys) of MAGE-A3 Cancer Immunotherapeutic (treatment groups) or saline (control groups). All rabbits were sacrificed 3 days post-injection and monkeys 3 days following last injection (3/5 per gender per group) or after a 3-month treatment-free period (2/5 per gender per group). Local and systemic reactions and MAGE-A3-specific immune responses (monkeys) were assessed. Macroscopic and microscopic (for rabbits, injection site only) post-mortem examinations were performed on all animals. No systemic toxicity or unscheduled mortalities were recorded. Single (rabbits) and repeated (monkeys; up to four times at the same site) injections were well tolerated. Following five to seven repeated injections, limb circumferences increased up to 26% (5 h post-injection), but returned to normal after 1-8 days. Three days after the last injection, enlargements of iliac, popliteal, axillary and inguinal lymph nodes, and increased incidence or severity of mononuclear inflammatory cell infiltrates was observed in injected muscles of treated monkeys. No treatment-related macroscopic findings were recorded after the treatment-free period. MAGE-A3-specific antibody and T-cell responses were raised in all treated monkeys, confirming test item exposure. Single or repeated intramuscular injections of MAGE-A3 Cancer Immunotherapeutic were well tolerated in rabbits and monkeys.

Characterization of vascular lesions in pigs affected by porcine circovirus type 2-systemic disease.

Vascular lesions and their association with porcine circovirus type 2 (PCV2) were evaluated in multiple organs from 10 pigs affected with PCV2-systemic disease (PCV2-SD). Animals had vascular lesions in multiple organs, consisting of lymphohistiocytic lymphangitis and/or phlebitis, mild to severe necrotizing arteritis, and thrombosis within splenic arterioles and choroid plexus capillaries. Variable amounts of PCV2 nucleic acid detected by in situ hybridization were present within endothelial cells, tunica media myocytes, and perivascular and/or intralesional inflammatory cell infiltrates. PCV2 nucleic acid was detected within endothelial cells of both lymphatic and blood vessels without lesions in the associated tissues. Necrotizing arteritis was principally present in lymph nodes and kidney and consisted of degeneration, necrosis, and pyknosis of myocytes, often with intracytoplasmic, brightly eosinophilic inclusion bodies that were strongly positive for PCV2 nucleic acid. Segmental or circumferential fibrinoid necrosis was mainly present in vessels of the lymph node, spleen, and choroid plexus and was variably associated with PCV2 nucleic acid. Severe lymphangitis associated with strong intralesional PCV2 labeling was frequently detected within the mesenteric and mediastinal lymph nodes and the lamina propria of the ileum. In most tissues, medium and large lymphatics and/or veins often had disruption of the intima and mild mononuclear inflammatory cell infiltration that was variably associated with PCV2 nucleic acid. The present study indicates that vasculitis is a frequent finding in natural cases of PCV2-SD and that PCV2 may have a direct cytopathic effect on tunica media myocytes of small- and medium-sized arteries as well as endothelium.

흰쥐의 MIA 유발 무릎 뼈관절염에 대한 840 nm LED의 효과

PURPOSE: The purpose of this study was to evaluate whether light-emitting diodes (LED) irradiation could be effective in a noninvasive, therapeutic device for the treatment of osteoarthritis(OA). METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: Vehicle control (saline); monosodium iodoacetate-injection (MIA); LED irradiation after MIA injection (MIA-LED); indomethacin-treatment after MIA injection (MIA-IMT). OA was induced by intra-articular injection of 3 mg MIA through the patellar ligament of the right knee. Vehicle control rats were injected with an equivalent volume of saline. The LED was irradiated for 15 min/day for a week after 7 days of MIA treatment. To compare with the effect of LED irradiation, the indomethacin was administrated 20 mg/kg twice a week orally after 7 days of MIA treatment. Knee joints were removed and fixed overnight in 10% neutral buffered formalin and decalcified by EDTA for 2 week before being embedded in paraffin. The assessment of OA induction were monitored by knee movement and radiographic finding. Histologic analysis were performed following staining with hematoxylin and eosin, safranin O-fast green, or toluidine blue, picrosirius red, and histologic changes were scored according to a modified Mankin system. Apoptotic cell in tissue sections was detected using TUNEL method. RESULTS: Radiographic examination could not show the differences between the MIA-treated and the MIA-LED-treated rats. In the histologic analysis, however, LED irradiation prevented cartilage damage and subchondral bone destruction, and significantly reduced mononuclear inflammatory cell infiltration and pannus formation. LED irradiation also reduced apoptosis of cartilage cells, but it prevented apoptosis of infiltrated inflammatory cells in synovium. In addition, LED irradiation showed an increase of collagen production in the meniscus. CONCLUSION: These results suggest that the 840 nm LED irradiation would be a suitable non-thermal phototherapy for the treatment of OA, as a cartilage protection and anti-inflammatory modality.

Eosinophilic granulomatosis with polyangiitis complicated by cholecystitis: a case report and review of the literature

The objectives are to report an atypical case of eosinophilic granulomatosis with polyangiitis (EGPA) associated with cholecystitis and to review the main clinical features, therapy, and prognosis of it. We present a 49-year-old male with non-classic clinical manifestations of EGPA and EGPA-related cholecystitis. EGPA was diagnosed by histology of the gallbladder after cholecystectomy. In addition, 11 cases of EGPA-associated cholecystitis have been reported and were described in details in this article. Gallbladder involvement is very uncommon in EGPA. All cases reviewed showed multiple organs involved as well as obviously elevated eosinophilic granulocyte proportion with inflammatory index, although antineutrophil cytoplasmic antibody may be negative. All patients in this cohort that showed gallbladder involvement were eventually confirmed with EGPA by histology examination after cholecystectomy. The pathological change could be infiltration of inflammatory mononuclear cells of small- and medium-sized vessels. Of the cases, 91.7% responded well to steroid and immunosuppressant therapy. Gallbladder involvement is a very rare comorbid condition in EGPA. However, it is an important symptom or secondary condition to alert physicians the diagnosis of EGPA. Moreover, timely diagnosis and correct administration in the early stage of this disease could obviously improve the prognosis.

The diagnosis and classification of giant cell arteritis

Giant-cell arteritis (GCA) involves the major branches of the aorta with predilection for the extracranial branches of the carotid artery. It occurs in individuals older than 50 years and the incidence increases with age. The signs and symptoms of giant cell arteritis can be classified into four subsets: cranial arteritis, extracranial arteritis, systemic symptoms and polymyalgia rheumatica. Patients may develop any combination of these manifestations, associated with laboratory evidence of an acute-phase reaction. The only test that confirms GCA diagnosis is a temporal artery biopsy, showing vasculitis with mononuclear cell inflammatory infiltrates, often with giant cells. Due to the focal and segmental nature of the infiltrates, areas of inflammation may be missed by the biopsy and the histological examination is normal in about 15% of the cases. Some imaging modalities may aid in the diagnosis of GCA. Among those, color duplex ultrasonography of the temporal arteries is more commonly used. There are no independent validating criteria to determine whether giant cell arteritis is present when a temporal artery biopsy is negative. The American College of Rheumatology criteria for the classification of giant cell arteritis may assist in the diagnosis. However, meeting classification criteria is not equivalent to making the diagnosis in individual patients, and the final diagnosis should be based on all clinical, laboratory, imaging and histological findings. Glucocorticoids are the treatment of choice for GCA. The initial dose is 40–60 mg/day for most uncomplicated cases. Addition of low-dose aspirin (100 mg/d) has been shown to significantly decrease the rate of vision loss and stroke during the course of the disease.