African swine fever virus evasion of host defences.

African swine fever virus causes a haemorrhagic fever in domestic pigs and wild boar. The continuing spread in Africa, Europe and Asia threatens the global pig industry. The lack of a vaccine limits disease control. To underpin rational strategies for vaccine development improved knowledge is needed of how the virus interacts with and modulates the host's responses to infection. The virus long double-stranded DNA genome codes for more than 160 proteins of which many are non-essential for replication in cells but can have important roles in evading the host's defences. Here we review knowledge of the pathways targeted by ASFV and the mechanisms by which these are inhibited. The impact of deleting single or multiple ASFV genes on virus replication in cells and infection in pigs is summarised providing information on strategies for rational development of modified live vaccines.

Cytokine expression in response to root repair agents.

AIM: To evaluate the expression of TNF-α, IL-6, IFN-γ, TGF-ß, IL-4, IL-10, RANKL, RANK and OPG on mouse calvarial bone treated with MTA, Geristore® and Emdogain® . METHODOLOGY: Bone wounds were made on the heads of C57BL/6 mice, breaking the periosteum and the cortical surface of the calvaria. Each repair agent was inserted into sectioned Eppendorf microtubes and placed on the bone wound, and soft tissues were sutured. At 14 and 21 days, animals were sacrificed and the treated region was dissected. The calvaria bone was removed, and RNA was extracted. mRNA expression of the aforementioned cytokines was assessed using real-time PCR. Data were analysed by nonparametric methods, including the Mann-Whitney and Kruskal-Wallis tests (P < 0.05). RESULTS: Following treatment with Emdogain® and MTA, mRNA expression of RANKL, RANK and OPG increased significantly (P < 0.05) between days 14 to 21. Geristore® did not alter the basal expression of these mediators during the same period of evaluation. Whilst treatment with Emdogain® did cause a significant increase in TNF-α mRNA expression between days 14 and 21 (P < 0.05), treatment with MTA did not alter the basal expression of this cytokine at either experimental time point. However, TNF-α mRNA expression was down-regulated significantly at day 21 (P < 0.05) when Geristore® was applied. A significant increase in the mRNA expression of IL-6, TGF-ß, IL-10, IL-4 and IFN-γ was observed with Emdogain® and MTA treatment between days 14 to 21, whereas Geristore® reduced significantly the expression of IL-6, TGF-ß and IL-4 (P < 0.05). CONCLUSION: The clinical indication of these repair agents depends on the root resorption diagnosis. Whilst MTA and Emdogain® induce a pro- and anti-inflammatory response early and late, respectively, Geristore® was not associated with an inflammatory reaction when compared with both repair agents.

African swine fever: A re-emerging viral disease threatening the global pig industry.

African swine fever (ASF) recently has spread beyond sub-Saharan Africa to the Trans-Caucasus region, parts of the Russian Federation and Eastern Europe. In this new epidemiological scenario, the disease has similarities, but also important differences, compared to the situation in Africa, including the substantial involvement of wild boar. A better understanding of this new situation will enable better control and prevent further spread of disease. In this article, these different scenarios are compared, and recent information on the pathogenesis of ASF virus strains, the immune response to infection and prospects for developing vaccines is presented. Knowledge gaps and the prospects for future control are discussed.

Survival of African Swine Fever Virus in Excretions from Pigs Experimentally Infected with the Georgia 2007/1 Isolate.

African swine fever virus (ASFV) causes a lethal haemorrhagic disease of swine which can be transmitted through direct contact with infected animals and their excretions or indirect contact with contaminated fomites. The shedding of ASFV by infected pigs and the stability of ASFV in the environment will determine the extent of environmental contamination. The recent outbreaks of ASF in Europe make it essential to develop disease transmission models in order to design effective control strategies to prevent further spread of ASF. In this study, we assessed the shedding and stability of ASFV in faeces, urine and oral fluid from pigs infected with the Georgia 2007/1 ASFV isolate. The half-life of infectious ASFV in faeces was found to range from 0.65 days when stored at 4°C to 0.29 days when stored at 37°C, while in urine it was found to range from 2.19 days (4°C) to 0.41 days (37°C). Based on these half-lives and the estimated dose required for infection, faeces and urine would be estimated to remain infectious for 8.48 and 15.33 days at 4°C and 3.71 and 2.88 days at 37°C, respectively. The half-life of ASFV DNA was 8 to 9 days in faeces and 2 to 3 days in oral fluid at all temperatures. In urine, the half-life of ASFV DNA was found to be 32.54 days at 4°C decreasing to 19.48 days at 37°C. These results indicate that ASFV in excretions may be an important route of ASFV transmission.

Resistência a antimicrobianos dependente do sistema de efluxo multidrogas em Escherichia coli isoladas de leite mastítico / Antimicrobial resistance dependent on multidrugs efflux in Escherichia coli isolated from the mastitic milk

Identificaram-se e caracterizaram-se a resistência e a multirresistência aos principais antimicrobianos usados no tratamento de mastite bovina causada por Escherichia coli. A concentração inibitória mínima (MIC) e o sistema de efluxo foram detectados pelas curvas de crescimento, com base na densidade óptica, em diferentes concentrações da droga e na presença e na ausência do desacoplador da força próton-motora (PMF). E. coli 1 foi resistente à neomicina e à gentamicina; E. coli 3 e 4, à tetraciclina e à estreptomicina; e E. coli 2 e 6 à gentamicina. E. coli 5 apresentou modelo de sensibilidade. Observou-se que MICs de todos os antimicrobianos dos multirresistentes (E. coli 1, 3 e 4) diminuíram na presença do desacoplador, o que sugere sistema de efluxo multidrogas. Após cura, apenas E. coli 1 apresentou modelo de sensibilidade, porém não houve alterações das MICs, antes e após adição do desacoplador. Os resultados indicam possível presença de mecanismo de resistência dependente da PMF codificado, ou parte dele, em plasmídeo.

Resistance and multiresistance to main antimicrobials used for treating bovine mastitis caused by Escherichia coli were identified and characterized. The minimal inhibitory concentration (MIC) and efflux systems were detected by the use of growth curves based on optical density at different drug concentrations and both presence and absence of uncoupler of the proton-motive force (PMF). E. coli 1 was resistant to neomycin and gentamycin, E. coli 3 and 4 were resistant to tetracycline and streptomycin, whereas E. coli 2 and 6 were resistant to gentamycin. E. coli 5 showed sensibility model. MICs of all antimicrobials of the multiresistant samples (E. coli 1, 3, and 4) were decreased in presence of the uncoupler, therefore suggesting the presence of the multidrug efflux system. After healing, only E. coli 1 showed sensibility model, however no alteration occurred in MIC(s) before and after adding the uncoupler. Those data inform the possible presence of a PMF dependent resistance mechanism that is totally or partly codified in plasmid.

Expression, cellular localization and antibody responses of the African swine fever virus genes B602L and K205R.

Previously, we identified serological immunodeterminants of African swine fever virus (ASFV), including pK205R and pB602L, without homologues in the database. pK205R is expressed as a 33-kD protein from 4 h post-infection onward, initially diffusely distributed throughout cells, and subsequently in viral factories. pK205R was not found in purified virus. Both pK205R and pB602L are recognised by hyperimmune antisera from domestic pigs and bushpigs at late time points after infection, suggesting they may be useful diagnostically to distinguish animals persistently infected with virus.

Immunohistochemical study of the expression of E-cadherin in canine mammary tumours.

To investigate the possible role of E-cadherin in canine mammary tumours 20 benign and 40 malignant tumours were evaluated by immunohistochemistry in formalin-fixed paraffin wax-embedded samples. In all the benign tumours, E-cadherin was strongly expressed at the intercellular borders of epithelial cells, but it was less strongly expressed in 17 (43 per cent) of the malignant tumours. Furthermore, poorly differentiated carcinomas were less immunoreactive for E-cadherin than moderately and well differentiated carcinomas.

[Pharmaceutical care in primary health care: the experience of 3 Brazilian States]. / Assistência farmacêutica na atenção básica de saúde: a experiência de três estados brasileiros.

In the context of recent changes in the Brazilian drug supply system at the national level, mainly the deactivation of CEME (a government agency under the Ministry of Health that dealt with drug supply policy) and the increasing decentralization of activities under the Unified National Health System (SUS), three Brazilian States - Paraná, São Paulo, and Minas Gerais - have established programs for the distribution of essential drugs for primary health care. A nationwide program for the procurement and supply of 32 drugs for primary health care (the so-called "Basic Pharmacy Program") is currently being implemented by the Ministry of Health, to be decentralized subsequently. This article discusses the establishment of State-level drug policies for primary health care through the analysis of the three pioneering programs encompassing drug selection, procurement, storage, distribution, and use.

Studies on antiplatelet agents from natural safrole. II. Synthesis and pharmacological properties of novel functionalized oxime O-benzylether derivatives.

In an ongoing research program aiming at the synthesis and pharmacological evaluation of new possible prototype candidates exploring the molecular hybridation and bioisosterism principles for molecular designing, we describe in this paper the design and synthesis of a series of new functionalized oxime O-benzylethers (4a-b) and (14a-b) as antiplatelet agents based on the inhibition of arachidonic acid (AA) cascade enzymes. For the synthesis of these new bioactive derivatives we used safrole (5), a Brazilian abundant natural product, as starting material. The platelet anti-aggregating evaluation of these oxime O-benzylether compounds (4a-b) and (14a-b) in model induced by ADP, collagen and AA, has permitted to evidence an antithrombotic profile to these new derivatives, being the most active the derivative methyl [[3,4-methylenedioxyphenyl]methylene]amino]oxy]-4-methylenephenylacet ic acid (14a).

[Psychosurgery in behavior disorders]. / Psicocirurgia nos distúrbios do comportamento.

The results obtained in a casuistic of 170 patients with mental diseases and behavior disturbances treated by neurosurgical procedures are reported. The authors call attention to the advantages of the atraumatic stereotaxic psychosurgery over the major surgical procedures on the frontal lobes for the treatment of psychoses and intractable psychoneurosis.