Granulomatous meningoencephalitis and blindness associated with Mycobacterium tuberculosis complex infection in a senile female chimpanzee (Pan troglodytes).

A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.

PARASITOLOGIC AND PATHOLOGIC STUDY OF FREE-RANGING SOUTH AMERICAN RATTLESNAKES (CROTALUS DURISSUS TERRIFICUS) IN BRAZIL.

This study assesses parasitism and pathologic manifestations in free-ranging Crotalus durissus terrificus. A total of 96 rattlesnakes from the State of Minas Gerais (southeast Brazil) were necropsied between September 2019 and February 2020. Granulomatous gastritis affected 48% (46 of 96) of the snakes evaluated, which were associated with the ascaridid nematodes Ophidascaris sp. and Hexametra sp. Other nematodes found included Kalicephalus costatus costatus and Kalicephalus inermis inermis (Diaphanocephalidae; 7%, 7 of 96) in the intestines, Serpentirhabdias sp. (Rhabdiasidae; 18%, 17 of 96) in the lungs, and Hastospiculum sp. (Diplotriaenidae; 2%, 2 of 96) encapsulated in the serosa of the mesentery. Larval cestodes, probably spargana of Spirometra sp. (Diphyllobothriidae; 2%, 2 of 96), were found in the skeletal muscle and unidentified acanthocephalan cystacanths (Oligacanthorhynchidae; 5%, 5 of 96) in the subcutis and coelomic cavity. The pentastome Porocephalus crotali (Porocephalidae; 2%, 2 of 96) was also found in the lungs. Microscopically, intestinal disease was caused by Sarcocystis sp. (7%, 7 of 96), Cryptosporidium sp. (1%, 1 of 96), and Entamoeba sp. (1%, 1 of 96) and fungi (7%, 7 of 96). In addition, hemoparasites such as Hepatozoon spp. (23%, 22 of 96) and Trypanosoma sp. (1%, 1 of 96) were observed in blood smears. This study expands the knowledge of diseases, parasites, and other infectious agents affecting free-ranging C. durissus terrificus in Brazil.

A RETROSPECTIVE STUDY OF HEPATIC HEMOSIDEROSIS AND IRON STORAGE DISEASE IN SEVERAL CAPTIVE AND FREE-RANGING AVIAN SPECIES.

Some wild species of mammals and birds are prone to excessive iron accumulation, especially when maintained in human care. Hemosiderosis is the process of intracellular accumulation of iron without evidence of toxicity, whereas hemochromatosis is characterized by severe iron accumulation with accompanying organ damage. Iron storage disease (ISD) occurs when organ damage is severe and causing clinical signs. This retrospective study investigated the occurrence of hemosiderosis and ISD across a variety of avian taxa, including captive and free-ranging birds. Archived paraffin-embedded hepatic samples from 103 birds from Belo Horizonte Zoo that died naturally in the period of 2008 to 2018 were re-evaluated with histologic and morphometric techniques, focusing on the identification and scoring of iron deposits in hepatocytes and the quantification of total affected hepatic area. The birds represented 13 orders, 22 families, and 52 genera, and 66 (64.0%) had some degree of iron accumulation in their liver. Importantly, no statistical difference was observed in the occurrence of iron accumulation between families, orders, or origin (free-ranging or captive). Direct and positive correlation was observed between the total area affected by the iron deposits and the histologic score. In this study, there were two cases with severe iron accumulation and clinical signs compatible with ISD: a barefaced curassow (Crax fasciolata) and a channel-billed toucan (Ramphastos vitellinus). This study indicates that iron accumulation may occur in a wide range of avian species, with frequencies and intensities that are similar between free-ranging birds and those in human care. It describes for the first time the occurrence of ISD in a Galliform species.

Natural cururu toad (Rhinella sp.) poisoning in a free-ranging lesser grison (Galictis cuja): Outcomes in a new susceptible predator with a novel peptide description.

Cururu toad (Rhinella marina group) is widely distributed in Brazil. Lesser grison (Galitic cuja) is a South American mustelid. This is the first report of natural poisoning in a free-ranging lesser grison by Rhinella toad parotoid gland secretion (PGS). Five minutes after biting a toad, the lesser grison developed convulsion, dying within 1.5 h. Mass spectrometry analysis of a milky-whitish secretion found in the lesser grison oral cavity allowed identification of a bufotoxin and a new bufonid peptide.

Histopathologic and immunophenotypic profile of a spontaneous mammary carcinoma in a male Humboldt's white-fronted capuchin (Cebus albifrons).

A 20-year-old male captive Humboldt's white-fronted capuchin (Cebus albifrons) that died accidentally had a small non-ulcerative mammary nodule diagnosed as a mammary carcinoma. Immunohistochemistry demonstrated that neoplastic cells were positive for pan-cytokeratin and cytokeratin-7. Approximately 20% of neoplastic cells were positive for Ki-67. Neoplastic cells expressed estrogen and progesterone receptors.

Production of IL-1ß, IL-6 and CXCL8 by endometrium of crossbred heifers stimulated with various pathogen-associated molecular patterns.

Uterine bacterial infections are common during the post-partum period of dairy herds and, apparently, incidences in crossbred cattle are less than in Holsteins. The aims of this study were (I) to evaluate production of interleukin 1-ß (IL-1ß), interleukin-6 (IL-6) and chemokine CXCL8 using endometrial explants from Bos indicus crossbred heifers at diestrous, stimulated by various pathogen-associated molecular patterns (PAMP), and (II) assess production of these cytokines by lipopolysaccharide-stimulated endometrial explants from heifers when samples were collected at different stages of estrous cycle. In the first experiment, endometrial explants from heifers at diestrous were stimulated by ten-fold serial dilutions of lipopolysaccharide (LPS), triacylated lipopeptide (PAM3) or peptidoglycan (PGN). In the second experiment, endometrial explants collected at different stages of the estrous cycle were treated with LPS. Concentrations of IL-1ß, IL-6 and CXCL8 were quantified in supernatant. There was a marked (P < 0.05) production of IL-1ß, IL-6, and CXCL8 in response to LPS treatment. There was also production of IL-1ß (P < 0.05) in response to PGN treatment. Explant samples collected at different stages of the estrous cycle responded to LPS treatment with production of IL-1ß and IL-6, but with no differences (P > 0.05) between stages of estrous cycle. In conclusion, endometrial samples of crossbred Zebu-based heifers collected during diestrous produced IL-1ß, IL-6 and CXCL8 in response to LPS and IL-1ß in response to PGN. The cytokine production in response to LPS, however, was not affected by the stage of the estrous cycle in Bos indicus crossbred heifers.

Necrotizing placentitis in a cow caused by Bacillus cereus / Placentite necrotizante em uma vaca por Bacillus cereus

ABSTRACT: This report described a case of necrotizing placentitis caused by Bacillus cereus in a cow associated with abortion and maternal lethality. The etiological diagnosis of placentitis by B. cereus was based on histopathology of placenta, cytology and bacterial isolation from intrauterine aminiotic fluid in retained placenta and further characterization of the pathogen by the MALDI-TOF. Although, B. cereus abortions are sporadic, the bacterium has the ability to release necrotizing toxins that can lead to placentitis, fetal death and abortion.

RESUMO: Este relato descreve a placentite necrotizante causada por Bacillus cereus em uma vaca associada a aborto e mortalidade materna. O diagnóstico etiológico de placentite por B. cereus foi baseado na histopatologia da placenta, citologia e isolamento bacteriano partir do líquido aminiótico em placenta retida e identificação do patógeno pela técnica de MALDI-TOF. Embora abortos por B. cereus sejam esporádicos, a bactéria tem a capacidade de liberar toxinas necrotizantes que podem levar a placentite e aborto.

N-acetylcysteine reduces amphotericin B deoxycholate nephrotoxicity and improves the outcome of murine cryptococcosis.

Cryptococcosis is a life-threatening fungal infection, and its current treatment is toxic and subject to resistance. Drug repurposing represents an interesting approach to find drugs to reduce the toxicity of antifungals. In this study, we evaluated the combination of N-acetylcysteine (NAC) with amphotericin B (AMB) for the treatment of cryptococcosis. We examined the effects of NAC on fungal morphophysiology and on the macrophage fungicidal activity 3 and 24 hours post inoculation. The therapeutic effects of NAC combination with AMB were investigated in a murine model with daily treatments regimens. NAC alone reduced the oxidative burst generated by AMB in yeast cells, but did not inhibit fungal growth. The combination NAC + AMB decreased capsule size, zeta potential, superoxide dismutase activity and lipid peroxidation. In macrophage assays, NAC + AMB did not influence the phagocytosis, but induced fungal killing with different levels of oxidative bursts when compared to AMB alone: there was an increased reactive oxygen species (ROS) after 3 hours and reduced levels after 24 hours. By contrast, ROS remained elevated when AMB was tested alone, demonstrating that NAC reduced AMB oxidative effects without influencing its antifungal activity. Uninfected mice treated with NAC + AMB had lower concentrations of serum creatinine and glutamate-pyruvate transaminase in comparison to AMB. The combination of NAC + AMB was far better than AMB alone in increasing survival and reducing morbidity in murine-induced cryptococcosis, leading to reduced fungal burden in lungs and brain and also lower concentrations of pro-inflammatory cytokines in the lungs. In conclusion, NAC + AMB may represent an alternative adjuvant for the treatment of cryptococcosis.

Tissue distribution and cell tropism of Brucella canis in naturally infected canine foetuses and neonates.

Brucella canis infection is an underdiagnosed zoonotic disease. Knowledge about perinatal brucellosis in dogs is extremely limited, although foetuses and neonates are under risk of infection due to vertical transmission. In this study, immunohistochemistry was used to determine tissue distribution and cell tropism of B. canis in canine foetuses and neonates. Diagnosis of B. canis in tissues of naturally infected pups was based on PCR and sequencing of amplicons, bacterial isolation, and immunohistochemistry, whose specificity was confirmed by laser capture microdissection. PCR positivity among 200 puppies was 21%, and nine isolates of B. canis were obtained. Tissues from 13 PCR-positive puppies (4 stillborn and 9 neonates) presented widespread immunolabeling. Stomach, intestines, kidney, nervous system, and umbilicus were positive in all animals tested. Other frequently infected organs included the liver (92%), lungs (85%), lymph nodes (69%), and spleen (62%). Immunolabeled coccobacilli occurred mostly in macrophages, but they were also observed in erythrocytes, epithelial cells of gastrointestinal mucosa, renal tubules, epidermis, adipocytes, choroid plexus, ependyma, neuroblasts, blood vessels endothelium, muscle cells, and in the intestinal lumen. These results largely expand our knowledge about perinatal brucellosis in the dog, clearly demonstrating a pantropic distribution of B. canis in naturally infected foetuses and neonates.

Hepatocellular carcinoma in two captive golden-headed lion tamarins (Leontopithecus chrysomelas).

Two cases of hepatocellular carcinoma (HCC) in 2 female captive golden-headed lion tamarins (Leontopithecus chrysomelas) are described. HCC was diagnosed in both, with pulmonary metastasis in one of them. Neoplastic cells were positive for hepatocyte-specific antigen (HSA) by immunohistochemistry, confirming the diagnosis.

Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection.

Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+ T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries.

Intracellular survival of Clostridium chauvoei in bovine macrophages.

Clostridium chauvoei is the etiological agent of blackleg, a severe disease of domestic ruminants, causing myonecrosis and serious toxemia with high mortality. Despite the known importance of this agent, studies evaluating its pathogenesis of blackleg are scarce, and many are based on an unproven hypothesis that states that macrophages are responsible for carrying C. chauvoei spores from the intestines to muscles in the early stages of blackleg. Therefore, the present study aimed to investigate the survival of C. chauvoei vegetative cells or spores after phagocytosis by a murine macrophage cell line (RAW 264.7) and bovine monocyte-derived macrophages and to profile inflammatory and anti-inflammatory cytokine transcripts of bovine macrophages infected with C. chauvoei vegetative cells or spores. Both vegetative cells and spores of C. chauvoei remain viable after internalization by murine and bovine macrophages. Bovine macrophages infected with vegetative cells showed a pro-inflammatory profile, while those infected with spores displayed an anti-inflammatory profile. Together, these results corroborate the classical hypothesis that macrophages may play a role in the early pathogenesis of blackleg. Moreover, this is the first study to evaluate the infection kinetics and cytokine profile of bovine monocyte-derived macrophages infected with a Clostridium species.

Alterações anatomopatológicas em rete ovarii de fêmeas bovinas mestiças / Anatomopathological changes in rete ovarii of mestizo cattle

O objetivo do presente estudo foi identificar e caracterizar as principais alterações patológicas em rete ovarii, observadas em rebanho bovino mestiço. Foram coletadas amostras de 467 pares de ovários de fêmeas bovinas (gestantes e não gestantes), com idades variáveis, provenientes de dois frigoríficos da região metropolitana de Belo Horizonte, Minas Gerais, Brasil, no período de setembro a dezembro de 2012, para avaliação anatomopatológica. Das amostras coletadas, observou-se a rete ovarii em ambos os lados de 417/467 animais (89,3%). Na análise macroscópica, verificou-se a presença de cistos foliculares (5,03%), cistos de corpo lúteo (0,72%) e secreções purulentas (0,48%) de coloração amarela intensa e consistência viscosa, indicativo de processo inflamatório supurativo. No exame microscópico, observaram-se em 23/417 amostras (5,51%), um processo hiperplásico adenomatoso de rete ovarii, com espessamento da camada epitelial, modificação do padrão de epitélio variando de cúbico a colunar, com duas ou três camadas de células, sendo em alguns momentos ciliadas e com dilatação tubular. Destas amostras, verificou-se associação de lesão hiperplásica com infiltrado inflamatório predominantemente linfomacrofágico em 15/23 amostras (65,22%). Ainda em relação às amostras confirmadas para hiperplasia, observou-se reação proliferativa estromal com característica fibroplástica em 21/23 amostras (91,30%). Conclui-se que em fêmeas bovinas mestiças a frequência de alterações encontradas em rete ovarii é baixa ou rara e o conhecimento desta lesão pode auxiliar no manejo reprodutivo desta espécie animal, a fim de diagnosticar possíveis alterações patológicas que podem promover subfertilidade e até infertilidade do rebanho bovino, que resultam em significativas perdas econômicas.

The aim of this study was to identify and characterize the main pathological changes in rete ovarii observed in cattle herd mestizo. Samples were collected from 467 pairs of ovaries of cows (pregnant and non-pregnant), with varying ages, from two refrigerators in the metropolitan region of Belo Horizonte, Minas Gerais, Brazil, in the period from September to December 2012 for anatomopathological evaluation. From samples collected, the rete ovarii was observed on both sides of 417/467 animals (89.3%). In macroscopic analysis, the presence of follicular cysts (5.03%), corpus luteum cyst (0.72%) and purulent discharge (0.48%) with yellow color and viscous consistency indicating a suppurative inflammatory process. At microscopic analysis, were observed in 23/417 samples (5.51%), a hyperplastic adenomatous rete ovarii process, and thickening of the epithelial cell layer, with two or three cell layers of cuboidal to columnar cells, and some cilia and tubular dilatation. From these samples, there was association between hyperplastic lesions with predominantly a lymphomacrofagic inflammatory cell infiltrate in 15/23 samples (65.22%). Also in relation to the samples confirmed for hyperplasia, there was proliferating fibroblasts in 21/23 samples (91.30%). It is concluded that in mestizo cattle the frequency of alterations found in rete ovarii is low or rarity, and the knowledge of this lesion may assist in the reproductive management of this animals species, in order to diagnose possible pathological alterations that can promote subfertility and even infertility of the herd that results in significant economic losses

SYSTEMIC HISTIOCYTIC SARCOMA IN A COMMON HIPPOPOTAMUS (HIPPOPOTAMUS AMPHIBIUS).

A 37-yr-old captive common hippopotamus (Hippopotamus amphibius) developed lethargy and decline in mobility that progressed to death, despite supportive therapy. Histopathologic examination revealed severe, diffuse, intravascular and interstitial infiltration of neoplastic histiocytes in the spleen, liver, lymph nodes, lungs, large intestine, kidneys, and thyroid gland. Neoplastic cells were pleomorphic with marked anisocytosis and anisokaryosis, scattered multinucleated giant cells, numerous bizarre mitotic figures, and marked erythrophagocytosis. Immunohistochemistry demonstrated that neoplastic cells were positive for ionized calcium-binding adapter molecule 1 (a histiocytic marker) and negative for CD3 (a T-cell marker) and myeloperoxidase, confirming the diagnosis of systemic histiocytic sarcoma.

The absence of microbiota delays the inflammatory response to Cryptococcus gattii.

The inflammatory response plays a crucial role in infectious diseases, and the intestinal microbiota is linked to maturation of the immune system. However, the association between microbiota and the response against fungal infections has not been elucidated. Our aim was to evaluate the influence of microbiota on Cryptococcus gattii infection. Germ-free (GF), conventional (CV), conventionalized (CVN-mice that received feces from conventional animals), and LPS-stimulated mice were infected with C. gattii. GF mice were more susceptible to infection, showing lower survival, higher fungal burden in the lungs and brain, increased behavioral changes, reduced levels of IFN-γ, IL-1ß and IL-17, and lower NFκBp65 phosphorylation compared to CV mice. Low expression of inflammatory cytokines was associated with smaller yeast cells and polysaccharide capsules (the main virulence factor of C. gattii) in the lungs, and less tissue damage. Furthermore, macrophages from GF mice showed reduced ability to engulf, produce ROS, and kill C. gattii. Restoration of microbiota (CVN mice) or LPS administration made GF mice more responsive to infection, which was associated with increased survival and higher levels of inflammatory mediators. This study is the first to demonstrate the influence of microbiota in the host response against C. gattii.

Systemic infection by Spencermartinsiella sp. in a Nile crocodile (Crocodylus niloticus) / Infecção sistêmica por Spencermartinsiella sp. em um crocodilo do Nilo (Crocodylus niloticus)

A male adult crocodile (Crocodylus niloticus) was diagnosed with systemic yeast infection. Histologically, there were extensive areas of necrosis in the lung, which were associated with a diffuse severe lympho-plasmo-histiocytic inflammatory infiltrate, with numerous multinucleated giant cells, and myriads of intralesional pseudo-hyphae and yeast like organisms within distended foveolae. Necrotic foci were also observed in the mucosa of the digestive tract, trachea, tunica intima of arteries, liver, and heart, with a marked inflammatory lympho-histiocytic infiltrate, with large numbers of epithelioid macrophages and giant cells, and intralesional and intravascular pseudo-hyphae and yeast-like organisms. Oval yeast structures with 4 to 6 µm in diameter and 5 to 8 µm thick paralleled-wall pseudo-hyphae were observed in PAS or GMS stained sections. PCR with DNA template extracted from paraffin embedded tissues amplified the D1/D2 domains of the large subunit rRNA gene, which was sequenced and found to be identical to sequences of a new species, isolated from rotting wood in Brazil, of the genus Spencermartinsiella, which its closest relative is Spencermartinsiella cellulosicola.(AU)

Um crocodilo macho adulto (Crocodylus niloticus) foi diagnosticado com infecção fúngica sustêmica. Histologicamente, havia extensas áreas de necrose no pulmão, que estavam associadas com infiltrado inflamatório linfo-plasmo-histiocitário, com numerosas células gigantes multinucleadas e miríade de pseudo-hifas e organismos leveduriformes intralesionais, dentro de favéolas distendidas. Focos necróticos também foram observados na mucosa do trato digestório, traquéia, túnica íntima de artérias, fígado e coração, com acentuado infiltrado inflamatório linfo-histiocitário, com grande número de macrófagos epitelioides e células gigantes e hifas e organismos leveduriformes intralesionais e intravasculares. Cortes corados por PAS e GMS evidenciaram estruturas leveduriformes ovais com 4 a 6 µm de diâmetro e pseudo-hifas de paredes espessas e paralelas com 5 a 8 µm. PCR realizado com DNA extraído de material parafinizado amplificou os domínios D1/D2 da subunidade maior do gene rRNA, cuja sequencia foi idêntica a sequências de uma nova espécie, isolada no Brasil de madeira em decomposição, do gênero Spencermartinsiella, cuja espécie mais próxima é Spencermartinsiella cellulosicola.(AU)

Heteroresistance to Itraconazole Alters the Morphology and Increases the Virulence of Cryptococcus gattii.

Cryptococcus gattii is the main etiological agent of cryptococcosis in immunocompetent individuals. The triazole drug itraconazole is one of the antifungals used to treat patients with cryptococcosis. Heteroresistance is an adaptive mechanism to counteract the stress of increasing drug concentrations, and it can enhance the ability of a microorganism to survive under antifungal pressure. In this study, we evaluated the ability of 11 C. gattii strains to develop itraconazole heteroresistance. Heteroresistant clones were analyzed for drug susceptibility, alterations in cell diameter, capsule properties, and virulence in a murine model. Heteroresistance to itraconazole was intrinsic in all of the strains analyzed, reduced both the capsule size and the cell diameter, induced molecular heterogeneity at the chromosomal level, changed the negatively charged cells, reduced ergosterol content, and improved the antioxidant system. A positive correlation between surface/volume ratio of original cells and the level of heteroresistance to itraconazole (LHI) was observed in addition to a negative correlation between capsule size of heteroresistant clones and LHI. Moreover, heteroresistance to itraconazole increased the engulfment of C. gattii by macrophages and augmented fungal proliferation inside these cells, which probably accounted for the reduced survival of the mice infected with the heteroresistant clones and the higher fungal burden in lungs and brain. Our results indicate that heteroresistance to itraconazole is intrinsic and increases the virulence of C. gattii. This phenomenon may represent an additional mechanism that contributes to relapses of cryptococcosis in patients during itraconazole therapy.

Transcription of innate immunity genes and cytokine secretion by canine macrophages resistant or susceptible to intracellular survival of Leishmania infantum.

In this study we assessed the basal transcription of genes associated with innate immunity (i.e. Nramp1, NOD1, NOD2, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, and TLR9) in canine monocyte-derived macrophages from Leishmania-free dogs. Additionally, secretion of cytokines (IL-10, IL-12, TNF-α and IFN-γ) and nitric oxide in culture supernatants of macrophages with higher or lower resistance to intracellular survival of Leishmania infantum was also measured. Constitutive transcription of TLR9 and NOD2 were negligible; NOD1, TLR1, and TLR7 had low levels of transcription, whereas Nramp1 and TLR2, 3, 4, 5, and 6 had higher levels of constitutive transcription in canine monocyte-derived macrophages. There were no significant differences in transcription between macrophages with higher or lower resistance to intracellular survival of L. infantum. Secretion of TNF-α was higher in more resistant macrophages (designated as resistant) at 24h after infection when compared to less resistant macrophages (designated as susceptible), as well as the secretion of IFN-γ at 72 h post infection. Secretion of IL-10 was lower in resistant macrophages at 24h after infection. No detectable production of nitric oxide was observed. Interestingly, there was a negative correlation between NOD2 transcript levels and intracellular survival of L. infantum in resistant macrophages. This study demonstrated that decreased intracellular survival of L. infantum in canine macrophages was associated with increased production of TNF-α and IFN-γ and decreased production of IL-10; and that constitutive transcription of Nramp1, TLR and NLR does not interfere in intracellular survival of L. infantum.

Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis.

Cryptococcus gattii is an emergent human pathogen. Fluconazole is commonly used for treatment of cryptococcosis, but the emergence of less susceptible strains to this azole is a global problem and also the data regarding fluconazole-resistant cryptococcosis are scarce. We evaluate the influence of fluconazole on murine cryptococcosis and whether this azole alters the polysaccharide (PS) from cryptococcal cells. L27/01 strain of C. gattii was cultivated in high fluconazole concentrations and developed decreased drug susceptibility. This phenotype was named L27/01F, that was less virulent than L27/01 in mice. The physical, structural and electrophoretic properties of the PS capsule of L27/01F were altered by fluconazole. L27/01F presented lower antiphagocytic properties and reduced survival inside macrophages. The L27/01F did not affect the central nervous system, while the effect in brain caused by L27/01 strain began after only 12 hours. Mice infected with L27/01F presented lower production of the pro-inflammatory cytokines, with increased cellular recruitment in the lungs and severe pulmonary disease. The behavioral alterations were affected by L27/01, but no effects were detected after infection with L27/01F. Our results suggest that stress to fluconazole alters the capsule of C. gattii and influences the clinical manifestations of cryptococcosis.

Squamous metaplasia of the rete ovarii in a Zebu cow.

BACKGROUND: Stratified keratinizing squamous epithelium in the ovary has been associated with the diagnosis of ovarian teratoma in cows. Recently, the diagnosis of "epidermoid cyst" has been proposed. A case of squamous metaplasia of the rete ovarii in a Zebu cow is described in this report. CASE PRESENTATION: A crossbreed Zebu cow had both ovaries enlarged with multiple cysts. Most cysts were lined by well differentiated keratinizing stratified squamous epithelium and filled with keratinized lamellar material. Some cysts were lined by an epithelial layer that ranged from single cuboidal, double cuboidal epithelium, stratified non keratinized epithelium, and areas of keratinizing stratified squamous epithelium. Single or double layered cuboidal epithelia of the cysts expressed low molecular weight cytokeratin 7, whose expression was absent in the keratinizing stratified squamous epithelia of same cysts. Conversely, high molecular weight cytokeratins 1, 5, 10, and 14 were strongly expressed by the keratinizing stratified epithelium. CONCLUSION: Squamous metaplasia of the rete ovarii was diagnosed. Squamous metaplasia of the rete ovarii, may account for some of the previously described squamous lesions in the ovary, which may have been misinterpreted as teratoma or epidermoid cysts.