Perivascular Cuffing Research Articles

Histopathological effects of sub-chronic lamivudine-artesunate co-administration on the liver of diseased adult Wistar rats

Background:Lamivudine and artesunate are sometimes co administered in HIV-malaria co morbidity. Both drugs are used concurrently in presumptive malaria treatment and simultaneous HIV post exposure prophylaxis.Aim:The aim of this study was to investigate the effect of lamivudine-artesunate co administration on the histology of the liver of diseased adult Wistar rats.Materials and Methods:Five groups of rats of both sexes were used for the study and placed on feed and water ad libitum. Disease state consisted of immunosuppression with cyclophosphamide, and infection with Plasmodium berghei. Group 1 animals served as vehicle control, while group 2 were the diseased controls. Group 3 animals received 20 mg/kg lamivudine for three weeks, while group 4 similarly received 20 mg/kg Lamivudine but also received 10 mg/kg artesunate from day 12. Animals in group 5 received 10 mg/kg artesunate from day 12. All drugs were administered intraperitoneally. The animals were treated for twenty-one days, at the end of which they were sacrificed and their livers fixed in 10% formalin for histological studies.Result:Results from the study show the presence of regions of focal necrosis and perivascular cuffing with animals that received artesunate. Hemosiderosis was a common feature in all the parasitized groups, while fatty degeneration was observed in the group that received artesunate alone.Conclusion:Concurrent lamivudine-artesunate administration resulted in some histopathological changes in the liver. This study suggests there may be considerable histological changes with repeated occurrence of malaria and immunosuppression that may warrant intermittent lamivudine-artesunate administration, and may require evaluation as well as monitoring of liver function during such therapeutic interventions.

Voltage-Gated Potassium Channel-Complex Antibody-Associated Limbic Encephalitis

Limbic encephalitis is characterized by the subacute progression of short-term memory loss, disorientation, confusion, and agitation. Hallucinations, behavioral and personality changes, temporolimbic seizures, sleep disturbances, and dysautonomia may also occur. The pyramidal layer of the hippocampus and the amygdaloid nuclei are particularly susceptible and demonstrate neuronal loss, reactive gliosis, and perivascular lymphocytic cuffing. Magnetic resonance imaging (MRI) typically reveals increased signal in limbic structures on T2, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). Historically, limbic encephalitis has been conceptualized as a paraneoplastic process characterized by autoantibodies associated with underlying neoplasms: small cell lung, lymphoma, thymoma, testicular, breast, teratoma, prostate, rectal, retinoblastoma, oligodendroglioma, melanoma, and leiomyosarcoma. Although a definitive pathophysiologic mechanism for autoimmune limbic encephalitis remains unknown, multiple autoantibodies are implicated, including voltage-gated potassium channel complex antibodies (VGKC-complex Ab.) Idiopathic autoimmune limbic encephalitis also occurs. We present the longitudinal course of a man who developed cognitive and behavioral disturbances ultimately attributed to VGKC complex autoimmunity.

Astrocytopathy in neuromyelitis optica, multiple sclerosis and Baló's disease

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) while neuromyelitis optica (NMO) is an inflammatory disease of the CNS that selectively affects the optic nerves and spinal cord. An antibody for aquaporin-4 (AQP4), which is a water channel located in astrocyte foot process, is specifically positive for NMO and antibody and complement dependent astrocytic damage is thought to be a main cause of NMO. Baló's disease is characterized by alternating rings of demyelination and preserved myelin. We pathologically compared the astrocytic changes among autopsied cases with these CNS demyelinating diseases. NMO, MS and Baló's disease shared with reduced AQP4 immunoreactivity independent of antibodies and complements. The pathological finding was accompanied with a reduced immunoreactivity of connexin 43 and perivascular lymphocytic cuffing predominantly composed by T cells. The loss of astrocytic proteins such as AQP4 and connexin 43 preceded the loss of myelin proteins in some lesions. These features suggest astrocyte damages resulting in the loss of connexin 43 cause demyelination through the impairment of interaction between astrocytes and oligodendrocytes and the pathomechanism involves a T cell reaction.

Experimental Infection of Common Warthogs (Phacochoerus africanus) and Bushpigs (Potamochoerus larvatus) with Classical Swine Fever Virus II: A Comparative Histopathological Study

Wild African Suidae, the common warthog (Phacochoerus africanus) and bushpig (Potamochoerus larvatus), were experimentally infected with classical swine fever (CSF) virus following the diagnosis of CSF subtype 2.1 in domestic pigs in South Africa in 2005. No data regarding the susceptibility or potential lesions of these African wild suids are available. Seven subadult warthogs and six bushpigs were captured and infected intranasally with the South African isolate. Two in-contact control animals of the same species in each experiment verified intra-species transmission. Surviving animals were euthanized after 44 days. Formalin-fixed tissue samples collected from them as well as animals euthanized during the trial were evaluated for histological lesions. The warthogs, which were clinically normal throughout the study, developed histological lesions that were inconsistently present and sometimes subtle. Three individuals, including one in-contact control, developed distinct lympho-plasmacytic cuffing in their brains. Subtle lesions included scant lympho-plasmacytic infiltration of various organs, occasionally accompanied by perivascular cuffing. In contrast, the bushpigs developed overt clinical signs similar to CSF in domestic pigs. Four of six animals, including two in-contact controls, died or were euthanized during the trial. On postmortem examination, intestinal necrosis and ulceration, purulent rhinitis and pneumonia were present. Affected animals developed lymphoid necrosis and depletion whilst surviving individuals showed perivascular cuffing in multiple organs. From the present work, we conclude that these wild Suidae are susceptible to CSF virus and intra-species transmission under experimental conditions can occur.

Animal,In Vitro, andEx VivoModels of Flow-Dependent Atherosclerosis: Role of Oxidative Stress

Atherosclerosis is an inflammatory disease preferentially occurring in curved or branched arterial regions, whereas straight parts of the arteries are protected, suggesting a close relationship between flow and atherosclerosis. However, evidence directly linking disturbed flow to atherogenesis is just emerging, thanks to the recent development of suitable animal models. In this article, we review the status of various animal, in vitro, and ex vivo models that have been used to study flow-dependent vascular biology and atherosclerosis. For animal models, naturally flow-disturbed regions such as branched or curved arterial regions as well as surgically created models, including arterio-venous fistulas, vascular grafts, perivascular cuffs, and complete, incomplete, or partial ligation of arteries, are used. Although in vivo models provide the environment needed to mimic the complex pathophysiological processes, in vitro models provide simple conditions that allow the study of isolated factors. Typical in vitro models use cultured endothelial cells exposed to various flow conditions, using devices such as cone-and-plate and parallel-plate chambers. Ex vivo models using isolated vessels have been used to bridge the gap between complex in vivo models and simple in vitro systems. Here, we review these flow models in the context of the role of oxidative stress in flow-dependent inflammation, a critical proatherogenic step, and atherosclerosis.

Transmission of Ovine Herpesvirus 2 from Asymptomatic Boars to Sows

To the Editor: Malignant catarrhal fever (MCF) is an often lethal viral disease of susceptible biungulates from the Bovidae, Cervidae, and Suidae subfamilies. MCF in pigs has been associated with direct or indirect contact with sheep, which are the main reservoir of ovine herpesvirus 2 (OvHV-2) (1). A recent report detected infected but asymptomatic swine in the absence of known exposure to sheep or goats (2). Porcine MCF is difficult to diagnose because of its nonspecific clinical signs and sporadic nature; however, an outbreak involving 41 swine has been described (3). Pigs are terminal hosts and are not believed to spread the virus. Here we describe OvHV-2 DNA in the blood and semen of asymptomatic boars and from the brain of symptomatic sows and gilts with MCF that was probably transmitted by artificial insemination. The MCF cases occurred on two 3-site commercial farms with 2,700 and 1,670 sows in 2 different counties in southwestern Brazil. No MCF losses previously had been recorded in the region, and the animals had no known direct or indirect contact with sheep. The 2 farms had high biosecurity. The first case was recorded in September 2004, and the number of cases increased in July 2006. Twenty-eight sows and gilts, 20 of them pregnant and at >25 days’ gestation, died during January 2007–March 2008, when the last case was observed. Clinical features in sows and gilts were depression followed by abortion, fever (41°C), and anorexia. After the onset of clinical signs, neurologic symptoms developed such as ataxia, tremors, convulsions, and aggressive behavior. Animals that survived longer showed forelimb paralysis, stood in a dog-sit position, and gnawed with abundant salivation on pen bars. Specimens from randomly selected dead sows and gilts from the outbreaks during 2004–2008 were obtained for histopathologic examination, immunofluorescence testing for rabies virus, viral and bacterial isolation, and PCR. No bacterial or viral growth was detected, and direct immunofluorescence for rabies virus was negative. Microscopic examination showed high-grade nonpurulent meningoencephalitis characterized by lymphocytic cuffings with vasculitis in the brain hemisphere, the brainstem, the spinal cord, and, to a lesser extent, the cerebellum. Multifocal areas of edema, fibrinoid necrosis, and lymphocytic infiltration also were observed (Figure). OvHV-2 DNA was detected by using a specific PCR (4) in 5 of 7 paraffinized sections of the brainstem (5). To analyze the possible presence of other porcine lymphotropic herpesviruses in samples that reacted positively for OvHV-2, a nested PCR with degenerate primers (6,7) was applied. None of the OvHV-2–positive samples reacted positively for porcine lymphotropic herpesviruses. To confirm that the virus was a member of the MCFV group, we purified 1 amplicon and submitted it for automated sequencing. This nucleotide sequence was deposited in GenBank under accession no. {type:entrez-nucleotide,attrs:{text:HQ223415,term_id:313495121,term_text:HQ223415}}HQ223415, and it showed 99% identity with previously deposited OvHV-2 sequences. Figure Brainstem of a sow with vasculitis that was associated with ovine herpesvirus 2, showing edema, necrosis (fibrinoid necrosis), and infiltration of lymphocytes in the adventitia of the artery. Severe perivascular (Virchow-Robin space) lymphocytic cuffing ... To find possible carriers of the virus, blood samples were collected from 9 pregnant sows, 10 nonpregnant sows, and 30 breeding boars and analyzed for OvHV-2 DNA. Samples from 3 boars were positive. Nasal swabs and semen samples were collected from these infected boars to investigate the potential mode of OvHV-2 transmission, and OvHV-2 DNA was detected only in semen samples. Two of the 3 semen samples had >350 copies/2 µg of total DNA, suggesting that these animals shed virus (8,9). During this period, all infected boars remained clinically healthy. In Brazil, porcine MCF has been found primarily in pregnant sows and gilts. Our findings of OvHV-2 DNA in the semen of asymptomatic boars suggest that the OvHV-2 in the sows and gilts originated from asymptomatic boars that were responsible for maintaining the virus in the herd. Whether virus shedding in the semen was temporary or lasted for a long period is not known. Emergence of OvHV-2 in boars that had no known contact with sheep was surprising, especially given the possibility of venereal transmission through contaminated semen. The occurrence of OvHV-2 infection in other specific pathogen–free farms is unknown, and it is not possible to suggest a strategy to guarantee OvHV-2-free herds.

Ocorrência de leucoencefalomalácia (LEME) em equídeos no estado de São Paulo, Brasil: achados anatomopatológicos

O trabalho relata a ocorrência de leucoencefalomalácia em equídeos (LEME) com sintomatologia nervosa e com diagnóstico negativo para raiva, herpesvírus equino e encefalomielite equina durante o período de dois anos, no Estado de São Paulo, Brasil. Foram examinadas 67 amostras de sistema nervoso central e em 10,4% (cinco equinos, um pônei e um asinino) observaram-se lesões macroscópicas de LEME, confirmadas pela análise histopatológica. Os animais acometidos eram cinco machos e duas fêmeas, com idades que variavam de 11 meses a nove anos. Os sete casos ocorreram tanto no inverno como em outras estações do ano. As principais manifestações clínicas relatadas foram incoordenação, ataxia, paralisia dos membros posteriores, profunda depressão, levando ao óbito. Macroscopicamente, observaram-se congestão dos vasos meníngeos, áreas de malácia da substância branca, caracterizadas por coloração amarelada e/ou hemorrágica, com cavitação e amolecimento circundados por hiperemia. As lesões microscópicas observadas em todos os casos eram de necrose de liquefação da substância branca do cérebro, caracterizada por substância eosinofílica amorfa e homogênea, presença de edema axonal e perivascular, hemorragia e vacuolização do neurópilo adjacente e esferoides axonais. Em algumas áreas de malácia havia também células Gitter. Em apenas um animal observou-se manguito perivascular mononuclear. O presente trabalho confirma que o diagnóstico diferencial é importante na distinção da LEME com outras neuropatias encefálicas que acometem equídeos. A ocorrência da LEME relatada neste estudo demonstra que esta enfermidade é importante para a equideocultura do Estado de São Paulo.

Granulomatous Encephalomyelitis and Intestinal Ganglionitis in a Spectacled Amazon Parrot ( Amazona albifrons) Infected with Mycobacterium genavense

An approximately 30-year-old male spectacled Amazon parrot (Amazona albifrons) was presented with a 2-week history of ataxia, head shaking, weight loss and seizures. Gross findings on necropsy examination included atrophy of the musculature, ruffled feathers and minimal epicardial and abdominal fat. Microscopically, there were perivascular cuffs of macrophages with fewer lymphocytes in the grey and white matter of the brain and spinal cord. These lesions were accompanied by gliosis and mild vacuolation of the white matter. In the small intestine, up to 70% of the intestinal ganglia were effaced by infiltrates of macrophages and fewer lymphocytes. The intestinal lamina propria contained multiple inflammatory aggregates of a similar nature. Ziehl-Neelsen staining revealed the presence of numerous bacilli within the cytoplasm of macrophages in the central nervous system (CNS) and enteric ganglia. Amplification of the DNAJ gene confirmed a mycobacterial infection and subsequent polymerase chain reaction (PCR) using a species-specific primer confirmed the aetiology as Mycobacterium genavense. Infection of the CNS with Mycobacterium spp. is uncommon and has not been previously reported in a parrot. This case is unusual in that the organism exhibited tropism for neural tissue.

Replication and pathogenesis of the pandemic (H1N1) 2009 influenza virus in mammalian models

This study aimed to characterize the replication and pathogenic properties of a Korean pandemic (H1N1) 2009 influenza virus isolate in ferrets and mice. Ferrets infected with A/Korea/01/2009 (H1N1) virus showed mild clinical signs. The virus replicated well in lungs and slightly in brains with no replication in any other organs. Severe bronchopneumonia and thickening of alveolar walls were detected in the lungs. Viral antigens were detected in the bronchiolar epithelial cells, in peribronchial glands with severe peribronchitis and in cells present in the alveoli. A/Korea/01/2009 (H1N1) virus-infected mice showed weight loss and pathological lung lesions including perivascular cuffing, interstitial pneumonia and alveolitis. The virus replicated highly in the lungs and slightly in the nasal tissues. Viral antigens were detected in bronchiolar epithelial cells, pneumocytes and interstitial macrophages. However, seasonal H1N1 influenza virus did not replicate in the lungs of ferrets, and viral antigens were not detected. Thus, this Korean pandemic (H1N1) 2009 isolate infected the lungs of ferrets and mice successfully and caused more pathological lesions than did the seasonal influenza virus.

Chronic Morbilliviral Encephalitis in a Young Striped Dolphin from Italy

AbstractA young male striped dolphin (Stenella coeruleoalba) found stranded in November 2009 was affected by a chronic non-suppurative encephalitis, with prominent mononuclear cell perivascular cuffs, neuronal degeneration, microgliosis, neuronophagia and occasional presence of multinucleate syncytia. Immunohistochemical and biomolecular investigations for Morbillivirus were positive exclusively from the brain, but not from the cerebellum nor from any other tissue, with morbilliviral antigen being detected in neurons and astrocytes. A low neutralizing antibody titer (1:10) against Morbillivirus (CDV) was also found, with no simultaneous presence of anti-Brucella antibodies.The main reason why the present case appears to be of interest is provided by its peculiar neuro-histopathologic, immunohistochemical and biomolecular features, with Morbillivirus antigenic and genomic positivity being exclusively confined to the brain of this dolphin, which may have developed a transplacentally-acquired infection.

Pathological study on some tissues of rat experimentally infected with Toxoplasma gondii

This study was conducted to isolate Toxoplasma gondii from aborted placentae of ewes, & follow up the histopathological changes that produced in some different organs such as liver, brain & eyes of rats which inoculated experimentally by suspension of the parasite. Histopathological changes in brain represented by presence of tachyzoites & tissue cyst at 30/45 days post infection associated with encephalomeningitis-while in liver, the lesions characterized by presence of perivascular & periductular cuffing of tachyzoites associated with pyknotic nuclei of hepatocytes. Moreover, in the eye tachyzoites & tissue cyst has been seen invaded in extraocular muscles, congestion of blood vessels with lymphocytic infiltration and retinochoroiditis, also has been

Postpubertal Nonfamilial Cherubism and Teeth Transposition

Cherubism is a rare, nonneoplastic, fibro-osseous disease. It is an autosomal-dominant disorder in which the normal bone is replaced by cellular fibrous tissue and immature bone. It is genetically inherited, although many nonfamilial cases have been reported. Cherubism is a bone disease clinically characterized by bilateral, painless enlargements of the jaws. The mandible is the most severely affected craniofacial component, in which uncontrolled growth of the malady deteriorates the aesthetic balance of the face. A malocclusive and abnormal dentition, worse in the mandible, can be seen. Histopathologically, numerous randomly distributed multinucleated giant cells and vascular spaces within a fibrous connective tissue stroma with or without eosinophilic collagen perivascular cuffing were apparent. The appearance of the affected children is normal at birth. Between the ages of 2 and 7 years, swellings within the mandibular body or tuberosities of maxilla appear. This article relates to a postpubertal nonfamilial cherubism case that was noticed with multiple radiolucencies in radiographic examination and its effects on teeth.

Aquaporin-4 astrocytopathy in Baló’s disease

Baló's concentric sclerosis (BCS) is considered to be a rare variant of multiple sclerosis and characterized by alternating rings of demyelinated and preserved myelin layers. The mechanism underlying BCS remains to be elucidated. Recently, occurrence of concentric rings of Baló was described in the brainstem of a patient with neuromyelitis optica (NMO). Because selective loss of aquaporin-4 (AQP4) and vasculocentric deposition of complement and immunoglobulins are characteristic in NMO, we aimed to assess AQP4 expression in the concentric demyelinating lesions of BCS patients. We evaluated AQP4 expression relative to expression of another astrocytic marker (glial fibrillary acidic protein), the extent of demyelination, lesion staging and perivascular deposition of complement and immunoglobulin in four cases with BCS, and 30 individuals with other neurological diseases. All cases with BCS demonstrated extensive AQP4 loss in both demyelinated and myelinated layers of all actively demyelinating lesions, with perivascular lymphocytic cuffing of T cells, but no deposition of immunoglobulins or complement around vessels. These findings suggest that AQP4 loss occurs in heterogeneous demyelinating conditions, namely NMO and BCS. Furthermore, acute BCS lesions are characterized by extensive AQP4 loss without vasculocentric deposition of complement or immunoglobulin.

Sphingolipids in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the CNS. Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), are target cells in MS. Although the etiology of MS is poorly known, new insights suggest oligodendrocyte apoptosis as one of the critical events followed by glial activation and infiltration of lymphocytes and macrophages. A major breakthrough in delineation of the mechanism of cell death, perivascular cuffing, and glial activation came from elucidation of the sphingolipid signal transduction pathway. The sphingolipid signal transduction pathway induces apoptosis, differentiation, proliferation, and growth arrest depending upon cell and receptor types, and downstream targets. Sphingomyelin, a major component of myelin membrane formed by mature oligodendrocytes, is abundant in the CNS and ceramide, its primary catabolic product released by activation of either neutral or acidic sphingomyelinase, serves as a potential lipid second messenger or mediator molecule modulating diverse cellular signaling pathways. Similarly, under certain conditions, sphingosine produced from ceramide by ceramidase is phosphorylated by sphingosine kinases to sphingosine-1 phosphate, another potent second messenger molecule. Both ceramide and sphingosine-1 phosphate regulate life and death of many cell types including brain cells and participate in pathogenic processes of MS. In this review, we have made an honest attempt to compile recent findings made by others and us relating to the role of sphingolipids in the disease process of MS.

Perivascular fluid cuffs decrease lung compliance by increasing tissue resistance*

Lung inflammation causes perivascular fluid cuffs to form around extra-alveolar blood vessels; however, the physiologic consequences of such cuffs remain poorly understood. Herein, we tested the hypothesis that perivascular fluid cuffs, without concomitant alveolar edema, are sufficient to decrease lung compliance. Prospective, randomized, controlled study. Research laboratory. One hundred twenty male CD40 rats. To test this hypothesis, the plant alkaloid thapsigargin was used to activate store-operated calcium entry and increase cytosolic calcium in endothelium. Thapsigargin was infused into a central venous catheter of intact, sedated, and mechanically ventilated rats. Static and dynamic lung mechanics and hemodynamics were measured continuously. Thapsigargin produced perivascular fluid cuffs along extra-alveolar vessels but did not cause alveolar flooding or blood gas abnormalities. Lung compliance dose-dependently decreased after thapsigargin infusion, attributable to an increase in tissue resistance that was attributed to increased tissue damping and tissue elastance. Airway resistance was not changed. Neither central venous pressure nor left ventricular end diastolic pressure was altered by thapsigargin. Heart rate did not change, although thapsigargin decreased left ventricular systolic function sufficient to reduce cardiac output by 50%. Infusion of the type 4 phosphodiesterase inhibitor, rolipram, prevented thapsigargin from inducing perivascular cuffs and decreasing lung compliance. Rolipram also normalized pressure over time and corrected the deficit in cardiac output. Our findings resolve for the first time that perivascular cuff formation negatively impacts mechanical coupling between the bronchovascular bundle and the lung parenchyma, decreasing lung compliance without impacting central venous pressure.

FLT-3 expression and function on microglia in multiple sclerosis

Inflammatory cell infiltration and resident microglial activation within the central nervous system (CNS) are pathological events in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). While MS therapies target the peripheral immune system, no treatment is currently known to also modulate microglia. FMS-like tyrosine-3 (FLT-3) is expressed on hematopoietic and dendritic cells. We reported that FLT-3 inhibition ameliorates early actively induced EAE by predominantly modulating dendritic cell function as compared to microglia. We demonstrate in this report that FLT-3 is expressed in perivascular cuffs, brain parenchyma and in non-lesioned gray and white matter within MS brain but not in these regions within control brain. Furthermore, we demonstrate that FLT-3 is expressed on two populations of cells within MS brain; one which expresses the dendritic cell marker CD209, and the other which does not, suggesting that FLT-3 within MS brain is expressed on infiltrating dendritic cells and a non-dendritic cell such as microglia. Additionally, we report that FLT-3 inhibition in murine microglia blocks, in a dose-dependent manner, IFN-γ-induced expression of MHC class II and CD86, and LPS-induced secretion of IL-6. These data suggest that FLT-3 is involved in microglial cells' capacity to respond to environmental cues to function as antigen presenting cells and mediate CNS inflammation. Furthermore these data suggest that FLT-3 may be a therapeutic target on microglia to mitigate CNS inflammation.

GRANULOMATOUS MENINGOMYELOENCEPHALITIS IN A CALF CAUSED BY MYCOBACTERIUM BOVIS

ABSTRACT Bovine tuberculosis is a chronic disease caused by Mycobacterium bovis, characterized by respiratory disorders, emaciation and lymphadenomegaly. Neurological signs associated with granulomatous lesions in the central nervous system are rarely seen. In Brazil, the National Program for Control and Eradication of bovine tuberculosis has begun in 2001, and notification of the disease is compulsory. A case of tuberculous meningomyeloencephalitis is reported in a dairy calf less than one year old presenting neurological signs (irritability, aggressiveness, weakness, dizziness and recumbency) which progressed to death in three days. Brain, spinal cord, and lung tissue samples were examined histopathologically. The spinal cord showed granulomatous meningomyelitis with Langhans giant cells in the meninges and perivascular mononuclear cuffing in the white and gray matter. There were a few granulomas in the cerebral cortex with a central area of necrosis surrounded by mononuclear infiltrate. Mononuclear perivascular cuffing, satellitosis, hyperemia, and severe granulomatous meningitis with Langhans giant cells were observed in the neuropile. Samples of brain were inoculated into Petragnani and Stonebrink media. M. bovis was isolated and identified by PCR with JB21-JB22 primers. Considering the 2,888 samples of bovine CNS sent for surveillance of neurological syndrome and negative for Rabies, this was the only case of tuberculous meningomyeloencephalitis (0,035%) diagnosed from 2004 to 2008 by the Laboratory of Anatomopathology of Instituto Biológico. Although tuberculous meningomyeloencephalitis is not so frequent, it’s important to diagnose M. bovis as a causative agent of bovine neurological disorders. In accordance with Brazilian regulations, sanitary measures in the infected herd (test-and-slaughter) should be adopted.

Histopathology of Trypanosoma (Trypanozoon) evansi infection in Bandicoot rat. II. Brain and choroid plexus

Bandicoot rat, Bandicota bengalensis, received intraperitoneal inoculation of Trypanosoma (Trypanozoon) evansi flagellates and showed acute disease, leading to death during the 2nd peak of parasitaemia [14th day post infection (pi)]. Damage in brain and choroid plexus of the infected bandicoot is studied on the 5th, 8th, 12th and 14th day post inoculation. Sign of histopathological changes in the brain and choroid plexus of the bandicoot are detected after 1st peak of parasitaemia. Infiltration of lymphocyte and plasma cells, congestion, perivascular cuffing, gliosis and brain lesions are observed during 12th–14th day post intection. Multiple sclerosis, neuronophagia, focal haemorrhage, cerebral hyperplasia, oligodendrocytoma, astrocytoma and fatty degeneration of brain tissue are also found. Alteration in the ependymal cells of choroid plexus is noticed. Extensive oedema, infiltration of inflammatory cells and rupture of ventricular ependymal layer are found. Parasites are found both in the brain tissue and choroid plexus. No intracellular stage of the parasite is observed. The nature of damage in the brain tissue and choroid plexus shows similarity with the cases of African trypanosomiasis. This salivarian species cause more deleterious effect in brain much earlier in the disease course than its African relatives.

Take my breath away: Perivascular fluid cuffs impair lung mechanics*

Take my breath away: Perivascular fluid cuffs impair lung mechanics*

S1776 Chronic Lung and Liver Inflammation in a Mouse Model of Crohn's Colitis

Recent population-based studies demonstrate that in addition to the more common joint and hepatobiliary extraintestinal manifestations observed in patients with one of the inflammatory bowel diseases (IBD), pulmonary inflammation is a very common comorbidity increased in Crohn's disease. Because few studies have reported the presence of extraintestinal inflammation in mouse models of IBD, we undertook a systematic histopathological study to document the presence (or absence) of lung and liver inflammation in a mouse model of CD. Chronic colitis was induced in RAG-1-deficient (RAG-/-) mice by the adoptive transfer of naive (CD4+CD45RBhigh) T-cells (5x105 cells per mouse) obtained from the spleens of healthy donor mice. PBS-injected RAG-/mice were used as controls. Colons, lungs and liver as well as heart, kidneys, and brain were excised, fixed in formalin, embedded, sectioned and stained with H&E. Blinded histopathological analysis was performed on each organ by a pathologist not familiar with the experimental groups. We found that at 6-8 weeks post Tcell transfer, the majority of T-cell injected mice (80%) became moribund and were euthanized whereas PBS-injected animals appeared healthy throughout the entire 8week observation period. Blinded histopathological examination of the colons obtained from RAG-/mice injected with naive T-cells revealed moderate-to-severe colitis characterized by dramatic transmural T-cell and PMN infiltration, bowel wall thickening, Goblet cell dropout and epithelial cell erosions. Intracellular cytokine analysis of T-cells obtained from the colon and MLNs of colitic mice showed enhanced production of both IFNγ and IL-17. Surprisingly, we found that virtually all mice injected with naive T-cells presented with chronic bronchitis/ pulmonary inflammation. In many cases (>60%) confluent inflammation merged together between small and medium sized bronchi. Varying degrees of perivascular lymphocytic cuffing were also observed in virtually all of the mice however few PMNs were observed and vasculitis was absent. Lung parenchyma involvement was mild and patchy. In addition to gut and lung inflammation, we also observed significant hepatocellular necrosis with periportal and lobular lymphocytic inflammation. There was no evidence of bile ductal damage. No significant inflammation was observed in the heart, kidneys or brain of the colitic animals and no inflammation was observed in any organ system of the PBS controls. Taken together, these data demonstrate, for the first time, that pulmonary and liver inflammation is a occurrence in the T-cell transfer model of chronic colitis (Supported by NIH PO1 43785).