Future strategies to improve short- and long-term outcomes of renal transplantation in dogs / Estratégias futuras para melhorar os resultados de transplante renal em cães a curto e longo prazo

ABSTRACT: Transplants for cats with naturally occurring renal disease have been introduced into clinical practice, but canine renal transplantation represents a greater challenge because of the lack of a balanced immunosuppressive protocol, difficulty in selecting compatible canine kidney donors, and absence of transplantation monitoring protocols. This and other important factors will be discussed in this review to help improve short- and long-term outcomes for renal transplantation in dogs.

RESUMO: O transplante renal em gatos com doença renal naturalmente adquirida está cada vez mais sendo introduzido na prática clínica. O transplante renal em cães, por sua vez, representa um desafio maior devido a falta da definição de um protocolo imunossupressor equilibrado, dificuldade na seleção de doadores compatíveis e ausência de protocolos de monitoramento de transplantes. Esses e outros fatores serão abordados nesta revisão afim de melhorar os resultados, tanto a curto quanto a longo prazo do transplante renal em cães.

DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection.

Several arenaviruses cause hemorrhagic fever (HF) diseases that are associated with high morbidity and mortality in humans. Accordingly, HF arenaviruses have been listed as top-priority emerging diseases for which countermeasures are urgently needed. Because arenavirus nucleoprotein (NP) plays critical roles in both virus multiplication and immune-evasion, we used an unbiased proteomic approach to identify NP-interacting proteins in human cells. DDX3, a DEAD-box ATP-dependent-RNA-helicase, interacted with NP in both NP-transfected and virus-infected cells. Importantly, DDX3 deficiency compromised the propagation of both Old and New World arenaviruses, including the HF arenaviruses Lassa and Junin viruses. The DDX3 role in promoting arenavirus multiplication associated with both a previously un-recognized DDX3 inhibitory role in type I interferon production in arenavirus infected cells and a positive DDX3 effect on arenavirus RNA synthesis that was dependent on its ATPase and Helicase activities. Our results uncover novel mechanisms used by arenaviruses to exploit the host machinery and subvert immunity, singling out DDX3 as a potential host target for developing new therapies against highly pathogenic arenaviruses.

Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM.

Recent advances in glycobiology have revealed the essential role of lectins in deciphering the glycocodes at the cell surface to generate important biological signaling responses. ArtinM, a d-mannose-binding lectin isolated from the seeds of jackfruit (Artocarpus heterophyllus), is composed of 16 kDa subunits that are associated to form a homotetramer. Native ArtinM (n-ArtinM) exerts immunomodulatory and regenerative effects, but the potential pharmaceutical applicability of the lectin is highly limited by the fact that its production is expensive, laborious, and impossible to be scaled up. This led us to characterize a recombinant form of the lectin obtained by expression in Saccharomyces cerevisiae (y-ArtinM). In the present study, we demonstrated that y-ArtinM is similar to n-ArtinM in subunit arrangement, oligomerization and carbohydrate binding specificity. We showed that y-ArtinM can exert n-ArtinM biological activities such as erythrocyte agglutination, stimulation of neutrophil migration and degranulation, mast cell degranulation, and induction of interleukin-12 and interleukin-10 production by macrophages. In summary, the expression of ArtinM in yeast resulted in successful production of an active, recombinant form of ArtinM that is potentially useful for pharmaceutical application.

Evidence for Conformational Mechanism on the Binding of TgMIC4 with ß-Galactose-Containing Carbohydrate Ligand.

A deeper understanding of the role of sialic/desialylated groups during TgMIC4-glycoproteins interactions has importance to better clarify the odd process of host cell invasion by members of the apicomplexan phylum. Within this context, we evaluated the interaction established by recombinant TgMIC4 (the whole molecule) with sialylated (bovine fetuin) and desialylated (asialofetuin) glycoproteins by using functionalized quartz crystal microbalance with dissipation monitoring (QCM-D). A suitable receptive surface containing recombinant TgMIC4 for monitoring ß-galactose-containing carbohydrate ligand (limit of quantification ∼ 40 µM) was designed and used as biomolecular recognition platform to study the binding and conformational mechanisms of TgMIC4 during the interaction with glycoprotein containing (fetuin), or not, terminal sialic group (asialofetuin). It was inferred that the binding/interaction monitoring depends on the presence/absence of sialic groups in target protein and is possible to be differentiated through a slower binding kinetic step using QCM-D approach (which we are inferring to be thus associated with ß-galactose ligand). This slower binding/interaction step is likely supposed (from mechanical energetic analysis obtained in QCM-D measurements) to be involved with Toxoplasma gondii (the causative agent of toxoplasmosis) parasitic invasion accompanied by ligand (galactose) induced binding conformational change (i.e., cell internalization process can be additionally dependent on structural conformational changes, controlled by the absence of sialic groups and to the specific binding with galactose), in addition to TgMIC4-glycoprotein solely recognition binding process.

Recognition of TLR2 N-glycans: critical role in ArtinM immunomodulatory activity.

TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL)-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties.

Analysis of spermiogenesis like a tool in the study of the triatomines of the Brasiliensis subcomplex.

The specific identification and systematic of triatomines have been based fundamentally on morphological observations. These organisms are classified into complexes and specific subcomplexes, principally for morphological parameters and geographical disposition. The use of cytogenetic analyzes has been represented as a tool in systematic and taxonomy of triatomines. Thus, the present work, through the analysis of spermiogenesis, aims to characterize this stage of spermatogenesis in triatomines little studied, and especially to compare it among the species Triatoma lenti and T. sherlocki, to assist in the diagnosis of differentiation of these insects. The presence of the heteropyknotic corpuscle is shown as a diagnostic tool to differentiate T. sherlocki and T. lenti, since it is absent in T. lenti. The analysis of the spermiogenesis in T. sherlocki also allowed us to address morphological differences between elongating cells, which were relatively smaller and more filamentous when compared to T lenti. Furthermore, the flagellum was observed in all stages of cell differentiation and elongation. This structure, which helps in the locomotion of the sperm, is hardly observed in cytogenetic analysis, especially throughout spermiogenesis. Thus, although other comparative approaches should be taken, this paper allowed emphasizing the analysis of spermiogenesis as an important cytotaxonomic tool that assists in the differentiation of morphologically related species, such as T. lenti and T. sherlocki.

Embolização intra-arterial pré-operatória de tumor do corpo carotídeo / Preoperative intraarterial embolization of carotid body tumor

Os autores relatam um caso de tumor de corpo carotídeo (paraganglioma) em um paciente de 74 anos de idade, submetido a embolização intra-arterial com micropartículas esféricas, de polivinil acetato, com casca de polivinil álcool (PVAc + PVA), previamente à ressecção do tumor. O estudo angiográfico demonstrou massa altamente vascularizada na bifurcação carotídea esquerda, sendo a embolização pré-operatória utilizada no intuito de diminuir a vascularização e reduzir a perda sangüínea, aumentando a segurança do tratamento cirúrgico. O estudo histopatológico confirmou a presença de trombose e isquemia tecidual.

The authors report a case of carotid body tumor (paraganglioma) in a 74-year-old male patient, submitted to intraarterial embolization with spherical core/shield polyvinyl acetate and polyvinyl alcohol (PVAc + PVA) microparticles prior to surgical excision. Angiography has demonstrated a highly vascularized mass in the left carotid bifurcation, and preoperative embolization was used in order to decrease vascularity, reduce blood loss and improve safety of surgical treatment. Microscopic study confirmed presence of thrombosis and tissue ischemia.

Estenose arterial nos transplantes renais / Arterial stenosis after renal transplantation

OBJETIVO: Relacionar a influência dos dois tipos de anastomoses arteriais empregadas (término-terminal e término-lateral), da idade do receptor, do rim de doador vivo ou cadáver e do uso de remendo aórtico ("patch") quanto à presença ou não de estenose da artéria renal e, avaliar o tratamento destas estenoses. MÉTODO: Estudo retrospectivo de 278 pacientes submetidos a transplante renal no Hospital Universitário Clementino Fraga Filho (HUCFF), de maio de 1989 a maio de 2001. RESULTADOS: Não se mostrou relação entre as variáveis estudadas com a presença ou não de estenose da artéria renal. A estenose da artéria renal foi detectada em oito casos, que foram tratados, com sucesso, mediante angioplastia transluminal percutânea (ATP), com implante primário de "stent" (n = 7) ou sem implante de "stent" (n = 1). CONCLUSÕES: As variáveis estudadas não influenciaram no aparecimento da estenose da artéria renal e o tratamento endovascular foi efetivo na correção destas lesões estenóticas.

Correção de aneurisma de aorta abdominal em paciente com dois rins pélvicos / Abdominal aortic aneurysm repair in patient with two pelvic kidneys

Abdominal aortic aneurysm reconstruction is usually performed in vascular surgical practice. However, the repair of an abdominal aortic aneurysm associated with a pelvic kidney is rare. Our goal is to present a case report of an abdominal aortic aneurysm associated with two congenital pelvic kidneys wich was treated successfully by aneurysmectomy and inclusion of an aortoaortic graft.

Pseudoaneurismas como manifestaçäo da Doença de Behçet / False aneurysm at manifestation of Belçet's disease

Os autores relatam um caso de doença de Behçet, evoluindo com pseudoaneurismas das artérias femoral superficial direita, femoral comum direita e subclávia direita, relatando o tratamento cirúrgico e discutindo a evoluçäo.