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1.
Vet Res ; 53(1): 108, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517883

RESUMO

To improve understanding of the pathobiology of highly pathogenic avian influenza virus (HPAIV) infections in wild birds, pathogenicity and transmissibility of HPAIV H5N8 subtype clade 2.3.4.4b was evaluated in ~ 8-week-old herring gulls (Larus argentatus) divided into 3 groups: naïve birds (group A), birds previously exposed to low pathogenic avian influenza virus (LPAIV) H5N1 (group B) and LPAIV H13N6 (group C). The HPAIV H5N8 virus was highly virulent for naïve gulls, that showed early morbidity, high mortality, a broad spectrum of clinical signs, including violent neurological disorders, systemic distribution of the virus in organs accompanied by high level of shedding and transmission to contact birds. Pre-exposure to homologous and heterologous LPAIV subtypes conferred only partial protection: we observed increased survival rate (statistically significant only in group B), nervous signs, pantropic distribution of virus in organs, shedding (significantly reduced in gulls of group C in the early phase of disease and asymptomatic shedding in the late phase), transmission to contact gulls (more pronounced in group B) and near-complete seroconversion in survivors. Histopathological and immunohistochemical results indicate virus tropism for the neural, respiratory and myocardial tissues. In conclusion, we demonstrate that HPAIV H5N8 clade 2.3.4.4b is highly virulent and lethal for fully susceptible herring gulls and that pre-exposure to homo- and heterosubtypic LPAIV only partially modulates the disease outcome.


Assuntos
Charadriiformes , Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A Subtipo H5N8 , Vírus da Influenza A , Influenza Aviária , Animais , Virulência , Eliminação de Partículas Virais
2.
BMC Vet Res ; 15(1): 371, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655595

RESUMO

BACKGROUND: Mycoplasma bovis is a causative agent of disease in cattle causing many clinical conditions. Currently there are no commercial M. bovis vaccines in Europe and treatment is difficult with decreased antimicrobial susceptibility of M. bovis field isolates. Using an M. bovis calf infection model the effectiveness of enrofloxacin given alone; in combination with flunixin meglumine, a nonsteroidal anti-inflammatory drug; and a group with an additional treatment of pegbovigrastim, an immunostimulator, was evaluated. RESULTS: Enrofloxacin given alone stimulated a strong immune response, reduced the clinical manifestation and lung lessions of the M. bovis infection. In contrast the combination therapy appeared ineffective. CONCLUSIONS: In this experiment enrofloxacin given alone appeared to be the most effective treatment of the M. bovis affected calves, whereas co-administration with flunixin meglumine, and pegbovigrastim was not beneficial in this trial.


Assuntos
Doenças dos Bovinos/tratamento farmacológico , Infecções por Mycoplasma/veterinária , Pneumonia/veterinária , Adjuvantes Imunológicos/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Bovinos , Doenças dos Bovinos/microbiologia , Clonixina/análogos & derivados , Clonixina/uso terapêutico , Quimioterapia Combinada/veterinária , Enrofloxacina/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma bovis/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico
3.
Acta Vet Hung ; 62(1): 42-51, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23974932

RESUMO

An outbreak of fowlpox occurred in a commercial laying hen flock in one of the western provinces of Poland. Clinical signs suggested fowlpox and the diagnosis was confirmed by histopathological detection of Bollinger bodies within the epithelial cells. Detailed ultrastructural examination revealed an additional concurrent infection with chlamydia-like particles. The particles were identified by PCR as fowlpox virus and Chlamydophila psittaci. It is worth noting that both pathogens can generate morphologic forms capable of prolonged survival and inducing latent and persistent infection. We suggest a possible interaction between the two pathogens on ultrastructural level and assess the clinical consequences of the mixed infection. This study also demonstrates a potential of the transmission electron microscope (TEM) for identifying a superinfection with another pathogen (in this case C. psittaci), which may remain undetected by routine techniques.

4.
Pathogens ; 13(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38535594

RESUMO

Every year, ulcerative dermal necrosis (UDN) affects salmonids that spend most of their lives in the sea during their migration to the rivers of northern Poland to spawn. The clinical form of the disease manifests itself in ulcerative skin lesions, which lead to significant weakening of the fish and, in most cases, result in their death. This study was carried out on samples taken from sea trout in the Slupia River in northern Poland. In order to identify the pathogen, experiments on the transmission of the disease were carried out, and additional histopathological, microbiological and electron microscopic examinations were performed. As a result of these studies, it was possible to experimentally transfer the disease from sick to healthy fish. The results indicate a complex etiology of the disease (lack of a clearly defined pathogen), in which the change in the environment from salty to freshwater triggers the related changes in skin physiology, which are the main causes of increased susceptibility to the development of the disease.

5.
Acta Vet Hung ; 61(1): 51-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23439291

RESUMO

The present report describes a case of granulomatous pneumonia and hepatitis in a male crocodile monitor lizard (Varanus salvadorii). During the necropsy of the monitor lizard, multifocal to coalescing pale yellow lesions were observed in both lung lobes, as well as similar, though milder, changes in the liver, and an ulcerative lesion on the food pad of the right hindlimb. Histopathologically, the presence of multiple necrotising, chronic granulomas containing bacterial clumps were observed in the parenchyma of the lung and the liver. By microbiological examination of the pathologically altered lung tissues, Providencia rettgeri was identified. Altogether, our findings indicate that the bacterial infection resulting in extensive chronic necrotising granulomatous inflammation was the primary cause of the reptile's death. To our knowledge, this is the first report of Providencia rettgeri-associated granulomatous pneumonia and hepatitis in the monitor lizard.


Assuntos
Jacarés e Crocodilos , Providencia , Animais , DNA Bacteriano , Hepatite , Lagartos , Pneumonia
6.
J Vet Res ; 67(4): 611-618, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38130452

RESUMO

Introduction: Mast cell tumours (MCTs) arise in the dermis and subcutaneous tissues in animals and humans and are one of the most common neoplasms of the skin in dogs. Cannabinoid type 2 receptor (CB2R), cyclin-dependent kinase inhibitor (p21) and matrix metalloproteinase 1 (MMP-1) are potential targets for novel anti-tumour therapeutic strategies. This study evaluated by immunohistochemical means the reactivity of p21, MMP-1 and CB2R proteins in association with a three-tier grading system in cutaneous canine MCTs. Material and Methods: Formalin-fixed, paraffin-embedded canine MCTs were processed for histochemical analysis and immunohistochemical staining using antibodies against p21, MMP-1 and CB2R. The results were analysed statistically. Results: The strongest p21 immunolabelling was detected in grade 3 MCTs, while grade 1 tumours showed mild or no detectable p21 immunoreactivity (P-value < 0.001). Strong immunolabelling of MMP-1 was the most common in grade 1 tumours (P-value < 0.001) and CB2R was significantly less frequent in grade 3 tumours than in grade 1 (P-value < 0.001) and grade 2 (P-value < 0.001). Conclusion: High immunoreactivity of MMP-1 can be a marker of grade 1 MCTs in dogs, whereas p21 protein overexpression can be a marker of grade 3 canine MCTs. Strong CB2R immunoreactivity with simultaneous underexpression of p21 and high immunoreactivity of MMP-1 proteins may indicate that the use of cannabinoids in grade 1 MCTs in dogs is practicable.

7.
Pathogens ; 12(2)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36839489

RESUMO

In this study, we investigated the clinical response, viral shedding, transmissibility, pathologic lesions, and tropism of HPAIV Gs/Gd H5N8 subtype (clade 2.3.4.4b), following experimental infection of three groups of captive mallards (Anas platyrhynchos): (i) fully susceptible, (ii) pre-exposed to low pathogenic avian influenza virus (LPAIV) H5N1 subtype, and (iii) pre-exposed to LPAIV H3N8 subtype. Infection of naïve mallards with HPAIV H5N8 resulted in ~60% mortality, neurological signs, abundant shedding, and transmission to contact ducks, who also became sick and died. High amounts of viral RNA were found in all collected organs, with the highest RNA load recorded in the brain. The IHC examinations performed on tissues collected at 4 and 14 days post-infection (dpi) revealed tropism to nervous tissue, myocardium, respiratory epithelium, and hepatic and pancreatic cells. The mallards pre-exposed to LPAIV H5N1 and challenged with HPAIV H5N8 were asymptomatic and showed a significant reduction of viral RNA shedding, yet still sufficient to cause infection (but no disease) in the contact ducks. The AIV antigen was not detected in organs at 4 and 14 dpi, and microscopic lesions were mild and scarce. Similarly, mallards previously inoculated with LPAIV H3N8 remained healthy after challenge with HPAIV H5N8, but viral RNA was detected in large quantities in swabs and organs, particularly in the early phase of infection. However, in contrast to mallards from group I, the IHC staining yielded negative results at the selected timepoints. The virus was transmitted to contact birds, which remained symptomless but demonstrated low levels of viral RNA shedding and mild- to moderate tissue damage despite negative IHC staining. The results indicate that naïve mallards are highly susceptible to HPAIV H5N8 clade 2.3.4.4b and that homo- and heterosubtypic immunity to LPAIV can mitigate the clinical outcomes of infection.

8.
Viruses ; 14(4)2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35458465

RESUMO

Previous studies revealed that the small ruminant lentivirus (SRLV) population in Poland is highly heterogeneous. All SRLVs detected from Polish sheep and goats so far have belonged to subtypes B1, B2, A1, A5, A12, A13, A16, A17, A18, A23 and A24. However, all characterized strains originated from asymptomatic animals. This is the first study that characterizes the molecular properties of SRLVs isolated from different organs of six arthritic goats. Segments from three genomic regions (gag, LTR and env) were analyzed. In addition, we quantified the SRLV proviral load in the blood and different organs and examined its association with different degrees of histopathological lesions. All sequences obtained from the goats involved in this study were homogeneous, showing an average degree of variability of 4.8%, 3.7% and 8.8% for gag, LTR and env, respectively. Phylogenetic analysis revealed that the sequences from the analyzed goats were clustered within SRLVs group A and formed a new subtype within this group, tentatively named A27. The histopathological examination of the lung, mammary gland, synovial membranes of joints and brain of the analyzed goats revealed evidence of inflammatory processes associated with SRLV infection, which was confirmed by positive immunohistochemistry assays. No significant correlation was observed between histological features and alterations in the sequences from different tissues. No tissue-specific signature pattern was identified. It was shown that animals with a higher proviral load showed more lesion severity in various SRLV-affected tissues, indicating a positive association between these two parameters. Our results also revealed differences in the SRLV load between animals even though the sequences derived from all of the goats were closely related, suggesting that host factors may restrict and control viral replication. This study provides new information about SRLV variants isolated from arthritic goats; however, more studies, including the isolation and characterization of biological properties of these viruses, should be performed to evaluate their pathogenic potential.


Assuntos
Artrite , Doenças das Cabras , Infecções por Lentivirus , Doenças dos Ovinos , Animais , Cabras , Lentivirus/genética , Infecções por Lentivirus/veterinária , Filogenia , Polônia , Provírus/genética , Ruminantes , Ovinos
9.
J Vet Res ; 66(4): 497-510, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36846042

RESUMO

Introduction: Previous gag and env sequence studies placed Polish small ruminant lentiviruses (SRLVs) isolated from sheep and goats in subtypes B1, B2, A1, A5, A12, A13, A16-A18, A23, A24 and A27. This study extended the genetic/phylogenetic analysis of previously identified Polish SRLV strains by contributing long terminal repeat (LTR) sequences. Material and Methods: A total of 112 samples were analysed. Phylogenetic analyses were carried out on the LTR fragment using the neighbour-joining, maximum likelihood, and unweighted pair group method with arithmetic mean methods. Results: Polish caprine and ovine LTR sequences clustered within group A and grouped in at least 10 clusters (subtypes A1, A5, A12, A13, A16-A18, A23, A24 and A27). Most of the Polish strains (78%) belonged to the same subtype by the indication of the gag, env and LTR genomic regions. Discrepancies in affiliation depending on the particular sequence were observed in 24 (21%) strains, most of which came from mixed-species flocks where more than one SRLV genotype circulated. Sequences of the LTR reflected subtype-specific patterns. Several subtype-specific markers were identified, e.g. a unique substitution of T to A in the fifth position of the TATA box in A17, A27, A20 and B3. Conclusion: This study provides valuable insights into the genetic diversity of SRLV field strains in Poland, their phylogenetic relationships and their position in the recently established SRLV classification. Our results confirmed the existence of the ten subtypes listed and the readier emergence of new SRLV variants in mixed-species flocks.

10.
J Vet Res ; 66(1): 53-59, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35434415

RESUMO

Introduction: The study highlights the transboundary nature of tuberculosis (TB) in alpacas and the failure of current ante-mortem testing protocols (the tuberculin skin and Enferplex Camelid TB tests) to identify TB-free alpaca herds and individuals for export. Our research and the available literature indicate that the alpaca (Vicugna pacos) is extremely susceptible to Mycobacterium bovis infection, and that testing periodicity fails to take into account that animals do not manifest disease symptoms for a long time. The skin test failed to identify Mycobacterium bovis infection in two alpacas prior to their movement from the UK to Poland. The animals were purchased by a breeding centre in Poland, and were then shown at an international animal exhibition. The last owner of the alpacas before their deaths from TB bought the infected animals unwittingly in order to run rehabilitation activities with disabled children on his farm. Material and Methods: Thoracic lymph node, lung and liver tissue samples obtained at necropsy were examined histopathologically after Ziehl-Neelsen staining. Tissue samples were homogenised and mycobacteria present there were cultured on Stonebrink's medium during a 6-week incubation. A commercial test using polymorphism of the chromosomal direct repeat region provided species identification and additional identification was by spacer oligonucleotide typing and mycobacteria interspersed repetitive unit-variable number tandem repeat analysis with a gel electrophoresis protocol. Results: The microbiological examination confirmed multiorgan TB caused by the SB0666 spoligotype of Mycobacterium bovis. Conclusion: Due to the suboptimal performance of current diagnostic tests for TB in alpacas, there is a risk that infected animals may be moved unwittingly. A risk of TB spread associated with the international movement of alpacas is implied by this study.

11.
Pathogens ; 10(5)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926018

RESUMO

Infectious bronchitis virus (IBV) is one of the most important poultry pathogens, leading significant economic losses worldwide. IBV is characterised by highly genetic, serotype, and pathotypic variability. Despite extensive immunoprophylaxis strategies, the emergence of new genetic lineages is frequently observed in the field, causing disease control to be more complicated. In the last decade, the spread of variants assigned to the GI-23 lineage of IBV (formerly known as Var2) started from Middle-Eastern countries and reached Europe in the last few years. Recently, the introduction and fast spread of Var2-like IBVs in Poland was reported. In this study, the virulence properties and efficacy of different vaccination programmes were evaluated against infection with the IBV GI-23 strain gammaCoV/Ck/Poland/G052/2016. The pathogenicity of the Var2 isolate was conducted in one-day-old and three-week-old SPF chickens and showed that the course of the disease is age dependent. Seven vaccination programmes using Mass, 793B, QX alone or in combination, and Var2 live vaccines were tested against the GI-23 infectious bronchitis virus challenge. All groups were scored according to the ciliostasis test at 5 days post challenge. Two immunoprophylaxis strategies generated full protection against gammaCoV/Ck/Poland/G052/2016 infection-Var2 and Mass used in one-day-old chickens boosted by a combination of the QX and 793B vaccine (both with a ciliostasis score of 0 and 100% protection).

12.
Viruses ; 13(3)2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810057

RESUMO

This study aimed to indicate the influence of infection caused by genotype II African swine fever virus (ASFV)-isolate Pol18_28298_O111, currently circulating in Poland, on blood counts, biochemical parameters, as well as inflammatory and immune responses. Blood and sera collected from 21 domestic pigs infected intranasally with different doses of virulent ASFV were analysed. The infection led to variable changes in blood counts depending on the stage of the disease with a tendency towards leukopenia and thrombocytopenia. The elevated C-reactive protein (CRP) concentrations and microscopic lesions in organs confirmed the development of the inflammation process, which also resulted in an increased level of biochemical markers such as: Aspartate transaminase (AST), creatine kinase (CK), creatinine, and urea. Antibodies could be detected from 9 to 18 days post infection (dpi). Two survivors presented the highest titer of antibodies (>5 log10/mL) with a simultaneous increase in the lymphocyte T (CD3+) percentage-revealed by flow cytometry. Results confirmed a progressive inflammatory process occurring during the ASFV infection, which may lead to multiple organs failure and death of the majority of affected animals.


Assuntos
Vírus da Febre Suína Africana/patogenicidade , Febre Suína Africana , Imunidade , Proteínas Virais/metabolismo , Febre Suína Africana/epidemiologia , Febre Suína Africana/imunologia , Febre Suína Africana/virologia , Animais , Polônia/epidemiologia , Sus scrofa , Suínos , Virulência
13.
J Vet Res ; 65(4): 519-526, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35112008

RESUMO

INTRODUCTION: Apocrine sweat gland carcinomas (ASGCs) are rare malignant skin tumours in dogs and humans. The literature published so far focuses mostly on the clinico-epidemiological aspect of these tumours, but little is known about their pathogenesis. In this study we aimed to determine whether the p53 gene is involved in the carcinogenesis of the apocrine sweat gland in dogs and whether ultraviolet radiation (UV) is related to it. MATERIAL AND METHODS: Forty canine ASGCs were submitted to laser capture microdissection to isolate neoplastic cells, from which DNA was subsequently extracted. PCR amplification and sequencing of p53 exons 2-8 was then performed, followed by computer analysis of the obtained sequences. RESULTS: Sixteen mutations within the p53 gene were found in 13 tumours. The mutations involved C → T, T → C, G → A, and CC → TT transitions, C → G transversion and adenine deletion, which are gene alteration types known to be related to UV radiation in the process of skin carcinogenesis in humans. Six of the thirteen tumour cases displayed the C → T transitions in the same location in exon 4 and three of the thirteen cases displayed T → C in the same location in exon 5. CONCLUSION: The results of the present study indicate both the participation of the p53 gene and the influence of UV radiation in the formation of ASGCs in dogs.

14.
Pathogens ; 9(5)2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32456293

RESUMO

Mycoplasma bovis is known to be a cause of chronic pneumonia in cattle. To date, the disease pathomechanism has not been fully elucidated. Leukocytes play a key role in host antimicrobial defense mechanisms. Many in vitro studies of the effect of Mycoplasma bovis (M. bovis) on leukocytes have been performed, but it is difficult to apply these results to in vivo conditions. Additionally, only a few studies on a local immune response in M. bovis pneumonia have been undertaken. In this study, the experimental calf-infection model was used to determine the effect of field M. bovis strains on changes of the peripheral blood leukocyte response, including phagocytic activity and oxygen metabolism by cytometry analyses. An additional aim was to evaluate the lung local immunity of the experimentally infected calves using immunohistochemical staining. The general stimulation of phagocytic and killing activity of peripheral blood leukocytes in response to the M. bovis infection points to upregulation of cellular antimicrobial mechanisms. The local immune response in the infected lungs was characterized by the T- and B-cell stimulation, however, most seen in the increased T lymphocyte response. Post-infection, strong expression of the antigen-presenting cells and phagocytes also confirmed the activation of lung local immunity. In this study-despite the stimulation-both the peripheral and local cellular antimicrobial mechanisms seem to appear ineffective in eliminating M. bovis from the host and preventing the specific lung lesions, indicating an ability of the pathogen to avoid the host immune response in the M. bovis pneumonia.

15.
Mycotoxin Res ; 36(3): 311-318, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32372256

RESUMO

Fusarium infections have been reported in aquatic animals, but are still poorly investigated in wild salmonids. The aim of the study was to determine the impact of the fungi and their toxins on the health status of brown trout (Salmo trutta morpha trutta) migrating from the Baltic Sea to the freshwater. Individuals from the wild brown trout population exhibiting ulcerative skin lesions were collected from the Slupia River in Poland and subjected to microbiological, histopathological, and hematological examinations, as well as toxicological analysis for a presence of mycotoxins. The results of microflora isolation from the brown trout skin samples revealed the presence of conditionally pathogenic bacteria and fungi classified by molecular techniques as Fusarium spp. Toxicological analysis allowed for detection of zearalenone (ZEN) in the liver, kidney, and gastrointestinal tract of the fish. In several cases, there was α-zearalenone (α-ZEL) identified at trace levels in the liver, as well as sterigmatocystin and enniatin B at low levels in the kidney and the liver. Histopathological examination revealed the presence of fungal hyphae disrupting the epidermis and penetrating into the necrotic dermis and hypodermis. The decreased values of the blood parameters, i.e., hemoglobin concentration (HGB), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and white blood cell count (WBC), were indicative of osmoregulation failure being a consequence of the skin damage. The results of the study provide new information regarding Fusarium sp. infection in brown trout and serve as the basis for further research on the potential impact of the fungi and their mycotoxins on the Baltic salmonid population, including their role in ulcerative dermal necrosis.


Assuntos
Doenças dos Peixes/microbiologia , Fusarium/metabolismo , Micotoxinas/toxicidade , Necrose/veterinária , Dermatopatias/veterinária , Animais , Doenças dos Peixes/patologia , Fusarium/química , Micotoxinas/análise , Micotoxinas/metabolismo , Necrose/microbiologia , Necrose/patologia , Polônia , Pele/microbiologia , Dermatopatias/microbiologia , Dermatopatias/patologia , Truta/microbiologia
16.
J Vet Res ; 63(3): 311-315, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31572809

RESUMO

INTRODUCTION: Q fever (coxiellosis) is an infectious disease of animals and humans, caused by.C. burnetii and widely distributed throughout the world. It is known that people and animals acquire the disease predominantly.via inhalation of infectious aerosols. The possibility of transmission of the pathogen by the alimentary route is still a matter of debate and remains controversial. Therefore the aim of this study was to fill the gaps in knowledge of oral transmission of.C. burnetii by conducting biological tests on the guinea pig model. MATERIAL AND METHODS: Guinea pigs, divided into five groups comprising a negative control and four experimental groups, received specified concentrations of.C. burnetii per os. To determine the presence of specific antibodies, blood samples were tested using CFT. Also, internal organs collected during necropsy were screened by a real-time PCR targeting I.1111. Additionally, histopathological evaluation of the tissues was performed. RESULTS: The presence of antibodies and pathogen DNA in caecum was confirmed in one guinea pig from experimental group IV..C. burnetii was also detected in testicular tissue collected from one animal of experimental group II. CONCLUSIONS: The presence of pathogen DNA in the testicular tissue indicates that infection spreads haematogenously. In the majority of experimental animals specific antibodies and genetic material of.C. burnetii were not detected. This fact suggests that development of infection depends on many factors, such as animal immune status.

17.
Vaccine ; 37(33): 4715-4723, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-29153584

RESUMO

Rabies is invariably fatal, when post-exposure prophylaxis is administered after the onset of clinical symptoms. In many countries, rabies awareness is very low and the availability of post-exposure prophylaxis, as recommended by WHO guidelines, is very limited or non-existent, probably as a consequence of high cost. Therefore, new concepts for rabies therapy are needed. Innate immune mechanisms involving the production of pro-inflammatory cytokines and chemokines, activated after rabies infection, are thought to be involved in the neuropathogenesis of rabies. These mechanisms can contribute to a detrimental host response to the rabies virus (RABV) infection. The use of inhibitors of cytokines/chemokines are supposed to extend the survival of a sick individual. Inhibitors of TNF-α, IL-6 and MAPKs were used in RABV inoculated mice to define their influence on the survival time of rabid mice. The study demonstrated that all inhibitors extended mice survival, but at different rates. A log-rank test confirmed the statistically significant survival of mice treated with TNF-α (p = .0087) and MAPKs inhibitors (p = .0024). A delay in the time of onset of rabies was also recorded, in mice given TNF-α and MAPKs inhibitors. The highest virus load was found in the spinal cord and the lowest in the cortex, regardless of the experimental group. Significant TNF-α (p ≤ .0001) and IL-6 (p ≤ .0001) gene upregulation was observed in mice, as a consequence of RABV infection. Regarding MAPKs pathways, there was significant upregulation of the caspase 3 (p = .012, p = .0026) and Mcl-1 (p = .0348, p = .0153) genes, whereas significant downregulation of the cytochrome C (p ≤ .0001), Bcl2 (p = .0002, p = .0007) and JNK3 (p = .042) genes. Rabies pathogenesis is multifactorial, involving both virus and host influences on the course of the infection.


Assuntos
Imunidade Inata/efeitos dos fármacos , Vírus da Raiva/patogenicidade , Raiva/tratamento farmacológico , Raiva/imunologia , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Cricetinae , Modelos Animais de Doenças , Feminino , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Raiva/virologia , Vírus da Raiva/efeitos dos fármacos , Vírus da Raiva/imunologia , Sorafenibe/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo
18.
Vaccine ; 37(33): 4701-4709, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-29650384

RESUMO

Rabies is a fatal disease of all mammals causing almost 60,000 human deaths every year. To date, there is no effective treatment of clinical rabies once the symptoms appear. Here, we describe the promising effect of combination therapy composed of molecules that target replication of the rabies virus (RV) at different stages of life cycle and molecules that inhibit some pathways of the innate host immune response accompanied by a blood-brain barrier opener on the outcome of RV infection. The study reports statistically significant extension of survival of mice treated with the drug cocktail containing T-705, ribavirin, interferon α/ß, caspase-1 inhibitor, TNF-α inhibitor, MAPKs inhibitor and HRIG compared to the survival of mice in the virus control group (p = 0.0312). Furthermore, the study points to the significant impact of interferon α/ß on the survival of RV-infected mice. We have shown a significant down regulation of pro-inflammatory molecules (caspase-1 and TNF-a) in the CNS in RV-infected mice treated with a combination of drugs including interferon α/ß.


Assuntos
Antivirais/uso terapêutico , Vírus da Raiva/efeitos dos fármacos , Vírus da Raiva/patogenicidade , Amidas/uso terapêutico , Animais , Anticorpos Antivirais , Modelos Animais de Doenças , Quimioterapia Combinada/métodos , Feminino , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Pirazinas/uso terapêutico , Raiva , Ribavirina/uso terapêutico , Serpinas/uso terapêutico , Proteínas Virais/uso terapêutico , Replicação Viral/efeitos dos fármacos
19.
Postepy Hig Med Dosw (Online) ; 61: 797-804, 2007 Dec 10.
Artigo em Polonês | MEDLINE | ID: mdl-18097338

RESUMO

Lung cancer is the most frequently diagnosed of all the human neoplasms leading to death. Because twenty percent of cases are not associated with cigarette smoking, other causes and methods of early diagnosis are being sought. Bronchioloalveolar cancer, which is a subtype of the most common primary lung cancer, adenocarcinoma, is very similar to ovine pulmonary adenocarcinoma (OPA), a naturally occurring lung cancer in sheep. OPA is caused by the virus Jaagsiekte Sheep Retrovirus (JSRV), a member of the genus of beta-retroviruses. The virus induces neoplastic transformation of secretory epithelial cells of the lung, i.e. alveolar type II pneumocytes and Clara cells. JSRV's tropism for these cells is connected with viral LTR regions interacting with cellular factors that play major roles in the expression of lung-specific genes, e.g. those of surfactant proteins. Results of studies on the mechanisms of viral mutagenesis indicate a viral envelope protein (Env) as an oncogenic factor. There are two main enzymatic pathways involved in the cell transformation: PI3K-Akt and Ras-MEK-MAPK, both activated by the cytoplasmic tail of the envelope protein. Tumor development is associated with telomerase activation. Insertional mutagenesis has also been suggested because there is at least one common integration site for JSRV in OPA. Morphological and histological similarities with human bronchioloalveolar cancer and the possibility of experimental induction of the tumor in animals makes OPA a good model for the study of oncogenesis and target therapy of lung adenocarcinoma.


Assuntos
Adenocarcinoma/veterinária , Adenocarcinoma/virologia , Neoplasias Pulmonares/veterinária , Neoplasias Pulmonares/virologia , Adenomatose Pulmonar Ovina/fisiopatologia , Animais , Transformação Celular Viral , Modelos Animais de Doenças , Humanos , Retrovirus Jaagsiekte de Ovinos/patogenicidade , Adenomatose Pulmonar Ovina/virologia , Ovinos , Telomerase
20.
Vaccine ; 34(27): 3051-3058, 2016 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-27156637

RESUMO

Mycoplasma bovis is a major pathogen affecting cattle causing bronchopneumonia, mastitis, and other disorders. Only autogenous vaccines made specifically for individual farms are available in parts of Europe and the United States. A novel experimental vaccine composed of a field M. bovis isolate combined with saponin and Emulsigen(®) adjuvants was evaluated. Eighteen 3-4 week old calves were placed in three equal groups: vaccinated (Vac), positive control (PC) and negative control (NC). The Vac calves were subcutaneously injected with 8ml of the vaccine; the PC and NC calves received phosphate buffered saline (PBS). Three weeks later the Vac and PC calves were challenged with a virulent M. bovis strain, the NC group received PBS. Throughout the study clinical observations, microbiology and immunological tests were carried out. Three weeks post challenge two calves from each group were euthanased for necropsy and histopathological examination. The vaccine effectively stimulated the humoral immune response, with high titres of anti-M. bovis specific antibodies and total Ig concentration. This vaccine also intensified the IgA response. A clinically protective effect of the vaccine was demonstrated as it also reduced the gross pathological lung lesions and nasal shedding of M. bovis.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacinas Bacterianas/imunologia , Doenças dos Bovinos/prevenção & controle , Infecções por Mycoplasma/veterinária , Animais , Anticorpos Antibacterianos/sangue , Derrame de Bactérias , Bovinos , Doenças dos Bovinos/microbiologia , Feminino , Imunidade Humoral , Imunoglobulina A/sangue , Pulmão/microbiologia , Pulmão/patologia , Infecções por Mycoplasma/prevenção & controle , Mycoplasma bovis
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