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1.
Scand J Immunol ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32433774

RESUMO

Pulmonary typical carcinoid (TC) is a low-grade, rare lung cancer of neuroendocrine origin. Currently, there is very little information available about the immune cell composition in TC tumors. Here, we analyzed by flow cytometry resected tumors from four never-smoker female patients with TC. Twelve distinct immune cell types were identified in TC tumors. The most abundant immune cells were CD8+ T cells, CD4+ T cells, B cells, and macrophages, which represented 19.8%, 17.7%, 11.5%, and 11% of all tumor-infiltrating CD45+ leukocytes, respectively. Natural killer (NK) cells (8.9%) and neutrophils (3.9%) were also common. Three types of dendritic cells (DCs) were identified (plasmacytoid DCs, CD1c+ DCs, and CD141+ DCs) which together constituted 1.4% of all immune cells in TC tumors. Small populations of basophils (1.3%), mast cells (0.8%), and eosinophils (0.6%) were also present. Notably, the percentage of leukocytes (of all living cells) was much lower in TC tumors compared to high-grade non-small cell lung cancer (NSCLC) tumors, and also compared to non-cancerous lung tissue. We conclude that TC tumors are relatively non-inflammatory, although the immune landscape was found to be very complex.

2.
Neurology ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424051

RESUMO

OBJECTIVE: To delineate autoimmune disease in association with contactin-associated protein 2 (CASPR2) antibodies in childhood, we reviewed the clinical phenotype of children with CASPR2 antibodies. METHODS: Retrospective assessment of patients recruited through laboratories specialized in autoimmune CNS disease. RESULTS: Ten children with serum CASPR2 antibodies were identified (age at manifestation 18 months to 17 years). Eight children with CASPR2 antibody titers from ≥1:160 to 1:5,120 had complex autoimmune diseases with an age-dependent clinical phenotype. Two children with structural epilepsy due to CNS malformations harbored nonspecific low-titer CASPR2 antibodies (serum titers 1:80). The clinical symptoms of the 8 children with high-titer CASPR2 antibodies were general weakness (8/8), sleep dysregulation (8/8), dysautonomia (8/8) encephalopathy (7/8), neuropathic pain (7/8), neuromyotonia (3/8), and flaccid paresis (3/8). Adolescents (3/8) showed pain, neuromyotonia, and encephalopathy, whereas younger children (5/8) displayed severe hypertension, encephalopathy, and hormonal dysfunction mimicking a systemic disease. No tumors were identified. Motor symptoms remitted with immunotherapy. Mild behavioral changes persisted in 1 child, and autism spectrum disorder was diagnosed during follow-up in a young boy. CONCLUSION: High-titer CASPR2 antibodies are associated with Morvan syndrome in children as young as 2 years. However, CASPR2 autoimmunity mimics systemic disease and hypertensive encephalopathy in children younger than 7 years. The outcome following immunotherapy was mostly favorable; long-term behavioral impairment may occur in younger children.

3.
J Vet Intern Med ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32379386

RESUMO

BACKGROUND: Diagnosis of pancreatic diseases in dogs is still challenging because of variable clinical signs, which do not always correspond with clinical pathology and histopathological findings. OBJECTIVES: To characterize inflammatory and neoplastic pancreatic diseases of dogs and to correlate these findings with clinical findings and canine pancreatic lipase immunoreactivity (cPLI) results. ANIMALS: Tissue specimens and corresponding blood samples from 72 dogs submitted for routine diagnostic testing. METHODS: Four groups were defined histologically: (1) normal pancreas (n = 40), (2) mild pancreatitis (n = 8), (3) moderate or severe pancreatitis (acute, n = 11; chronic, n = 1), and (4) pancreatic neoplasms (n = 12). An in-house cPLI ELISA (<180 µg/L, normal; >310 µg/L, pancreatitis) was performed. RESULTS: In dogs with normal pancreas, 92.5% of serum cPLI results were within the reference range and significantly lower than in dogs with mild acute pancreatitis, moderate or severe acute pancreatitis and pancreatic tumors. In dogs with moderate or severe acute pancreatitis, cPLI sensitivity was 90.9% (95% confidence interval [CI], 58.7%-99.8%). Most dogs (9/12) with pancreatic tumors (group 4) had additional pancreatic inflammation and cPLI results were increased in 10 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: High cPLI indicates serious acute pancreatitis but underlying pancreatic neoplasms should also be taken into consideration. This study confirms the relevance of histopathology in the diagnostic evaluation of pancreatic diseases.

4.
Artigo em Alemão | MEDLINE | ID: mdl-32325523

RESUMO

OBJECTIVE: Bacterial skin infections are common in reptiles. Although many such infections are influenced by multifactorial problems, specific treatment of bacterial infections is an important consideration. The objective of this study was to evaluate the range of aerobic bacteria in skin lesions of reptiles and to determine their antimicrobial susceptibility. MATERIAL AND METHODS: Swabs of skin lesions from 219 reptiles were cultured for aerobic bacteria between January 2017 and June 2018. Isolates were identified based on growth on selective agar plates, biochemical parameters, as well as MALDI-TOF MS. Antibiotic susceptibility testing was carried out using the microdilution method. RESULTS: A total of 306 isolates were identified, mostly gram-negative, including Pseudomonas spp. (n = 48), Citrobacter spp. (n = 31, only in chelonians), aerobic spore-forming bacteria (n = 30), Aeromonas spp. (n = 20), Acinetobacter spp. (n = 20), Proteus spp. (n = 15), Staphylococcus spp. (n = 15), Klebsiella spp. (n = 13), Enterococcus spp. (n = 13), Morganella spp. (n = 11) as well as 78 other gram-negative and 12 other gram-positive bacteria. Colonization with 2 (n = 80) or more (n = 16) bacterial isolates was seen in 96 animals. Antibiotic susceptibility testing was carried out with 208 of the 306 isolated bacteria. Many isolates were sensitive (minimal inhibitory concentration [MIC] in µg/ml ≤ breakpoint) to enro- (E) and marbofloxacin (M): 86.4 % MIC ≤ 0.5 (E) and 95.5 % MIC ≤ 1 (M) for Pseudomonas spp., 86.4 % MIC ≤ 0.5 (E) and 90.9 % MIC ≤ 1 (M) for Citrobacter spp., 75.0 % MIC ≤ 0.5 (E) and 100 % MIC ≤ 1 (M) for Aeromonas spp. Trimethoprim/sulfamethoxazol proved to be effective against most of the Citrobacter spp. (90.9 % MIC ≤ 2/38) and Aeromonas spp. (75.0 % MIC ≤ 2/38). Amikacin was effective against nearly all Pseudomonas spp. (97.7 % MIC ≤ 16), Citrobacter spp. (95.5 % MIC ≤ 16) and Aeromonas spp. (93.8 % MIC ≤ 16). CONCLUSION AND CLINICAL RELEVANCE: The majority of isolates were gram-negative; the clinical relevance of individual isolates must, however, be evaluated on a case by case basis. Many of the isolated bacteria were sensitive to fluoroquinolones as well as aminoglycosides. Susceptibility testing is recommended since use of these antibiotics should be limited and for every tested group of antibiotics resistant isolates were found.

5.
J Pharm Biomed Anal ; 179: 113010, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31816469

RESUMO

Measurement of Tumour Necrosis Factor alpha (TNF-α) in peripheral blood is a useful tool to assess inflammatory responses in a large range of diseases. One of the major challenges for cytokine analysis is the availability of a proper analytical tool with high specificity, accuracy, linearity, precision, stability, and analytical sensitivity. Although available immunoassays are usually robust and reproducible, it is also true that they are not interchangeable. Two ELISA, four flow cytometric bead array (CBA) and four Luminex immunoassays were compared. Correlation between different techniques was almost absent, while some immunoassays based on the same technique showed significant correlation. Among the ten different assays evaluated, just few of them complied with the pre-established acceptance validation criteria. Interestingly, sera and plasma collected from the same healthy donor had significant different reference values. Samples stability was maintained in serum up to one week at four degrees, while plasma was stable only when it was frozen. Since several anti-inflammatory treatments are based on biologics targeting TNF-α (anti-TNF-α antibodies), potential interference with the immunoassays was tested and resulted relevant. This study shows that although each immunoassay presents benefits and drawbacks, just few assays are suitable for the measurement of TNF-α in clinical laboratories, demonstrating that, so far, the measurement of TNF-α in human blood is still not yet harmonised. In addition, we found that false negative results caused by anti-TNF-α treatments should be carefully considered for results interpretation.

6.
Urology ; 137: 84-90, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31877313

RESUMO

OBJECTIVE: To investigate the influence of CYP2D6 polymorphisms on outcomes and health-related quality of life of patients with retroperitoneal fibrosis (RPF) receiving tamoxifen (TMX). TMX is an effective alternative to corticosteroids for patients with RPF. Conversion of TMX to more potent endoxifen is dependent on enzyme activity of CYP2D6. MATERIALS AND METHODS: CYP2D6 genotyping and phenotype prediction of all patients treated with TMX between 02/2007 and 01/2018 was assessed using multiplex polymerase chain reaction (PCR). Groups were classified by phenotype: extensive (EM) vs poor and intermediate (PM + IM) vs ultrarapid metabolizer (UM). Retrospective evaluation of outcome (including magnetic resonance imaging and positron emission tomography-computed tomography) and health-related quality of life using the SF-36 was performed. RESULTS: A total of 63/194 patients received TMX, 40/63 with complete follow-up were sequenced: Twenty-nine patients with EM phenotype, 8 PM + IM and 3 UM. The median therapy duration was 364.5 days with a mean follow-up of 62.9 months. Seven therapy terminations occurred due to lack of response (17.5%), including all UM patients (P <.001). Magnetic resonance imagings showed a regression of fibrosis for EM and PM + IM in 69% and 62.5% of cases and a progression for UM in 100% (P = .004). In positron emission tomography-computed tomography, glucose utilization of RPF decreased significantly for EM and PM + IM. The physical sum-score of SF-36 improved for EM and PM + IM and decreased for UM (P <.05). The removal of DJ-stents was successful for EM, PM + IM, and UM in 48.3%, 75%, and 0% of cases (P = .0581). CONCLUSION: Contrary to expectations, UM showed the lowest success rate, which concludes that genotyping of RPF-patients may be useful in the sense of a tailored-therapy.


Assuntos
Citocromo P-450 CYP2D6/genética , Qualidade de Vida , Fibrose Retroperitoneal , Tamoxifeno , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos/métodos , Polimorfismo de Nucleotídeo Único , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Fibrose Retroperitoneal/diagnóstico por imagem , Fibrose Retroperitoneal/tratamento farmacológico , Fibrose Retroperitoneal/genética , Fibrose Retroperitoneal/psicologia , Espaço Retroperitoneal/diagnóstico por imagem , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Resultado do Tratamento
7.
Cytokine ; 125: 154794, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31400641

RESUMO

Early diagnosis and treatment of acute cellular rejection (ACR) may improve long-term outcome for lung transplant recipients (LTRs). Cytokines have become valuable diagnostic tools in many medical fields. The role of bronchoalveolar lavage (BAL) cytokines is of unknown value to diagnose ACR and distinguish rejection from infection. We hypothesized that distinct cytokine patterns obtained by surveillance bronchoscopies during the first year after transplantation are associated with ACR and microbiologic findings. We retrospectively analyzed data from 319 patients undergoing lung transplantation at University Hospital Zurich from 1998 to 2016. We compared levels of IL-6, IL-8, IFN-γ and TNF-α in 747 BAL samples with transbronchial biopsies (TBB) and microbiologic results from surveillance bronchoscopies. We aimed to define reference values that would allow distinction between four specific groups "ACR", "infection", "combined ACR and infection" and "no pathologic process". No definitive pattern was identified. Given the overlap between groups, these four cytokines are not suitable diagnostic markers for ACR or infection after lung transplantation.

8.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-31814091

RESUMO

In feline practice, blood groups were considered unimportant until the 1980s. Since then much has been learned. The most important blood group system in cats is the AB (renamed here as ABC) blood group system consisting of blood types A, B and AB (better referred to as C). Type B cats have strong anti-A alloantibodies potentially leading to incompatibility reactions during A-B mismatched transfusions or neonatal isoerythrolysis (NI) in type A and C (AB) kittens born to type B queens. Acute hemolytic transfusion reactions as well as NI have been clinically well documented in cats. Immunological and genetic tests have been established and blood typing and crossmatching test kits have become commercially available. This review updates the current knowledge of these blood types, their genetics, associated incompatibility reactions, and different diagnostic tools for avoiding such reactions in clinical practice.

9.
Anim Reprod Sci ; 211: 106202, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31785623

RESUMO

Warmblood fragile foal syndrome (WFFS) is a monogenetic defect with autosomal recessive inheritance. The WFFS homozygosity is non-compatible with extra-uterine life. Although as many as 15% of Warmblood horses are WFFS carriers, there has been little veterinary focus on this condition. The aim of this study was to determine outcomes and symptoms of clinical signs and pathological abnormalities during pregnancies when there were WFFS homozygous foetuses. Diagnostic material of 15 abortion or stillbirth cases with suspected diagnosis of WFFS was available for this study. Additionally, there were examinations in 37 cases where there were no indications of WFFS when submitted for routine diagnostic procedures. Foals in all cases were genotyped and external morphological defects were recorded. Amongst the 15 cases in which WFSS was suspected, there were 14 homozygous foetuses with the WFFS allele (WFFS/WFFS). Three heterozygous WFFS foetuses (N/WFFS) were detected in the cases submitted for routine diagnostic procedures. Of the 14 WFFS homozygous foetuses, 11 of mares had a gestation length of at least 320 days. Nine foals were born alive but died within a short time. Skin defects were obvious in 12 WFFS homozygous foals, and there was abnormal flexibility in the digital joints, flexed forelegs and incomplete closure of the abdominal wall in five, four, and one of the foals, respectively. In conclusion, the predominant manifestation of WFFS are death during the latter stages of gestation or live births with foals being non-viable. Losses in Warmblood horse breeding caused by WFFS are greater than previously assumed.

10.
PLoS One ; 14(12): e0226336, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31841533

RESUMO

INTRODUCTION: In southern European countries, multicentric lymphoma and leishmaniosis are the main differential diagnoses in dogs presented with generalized lymphadenomegaly. The cytological examination is in some cases inconclusive and polymerase chain reaction (PCR) for antigen receptor rearrangement (PARR) has become a common method to confirm or rule out a lymphoproliferative neoplasia. According to the literature, leishmaniosis may lead to clonal arrangements and therefore to a false diagnosis of lymphoma, but this assumption is made from a single leishmania infected dog. Therefore, the objective of this study was to prospectively evaluate results from PARR in dogs with lymphadenomegaly due to clinical leishmaniosis at the moment of diagnosis. MATERIALS AND METHODS: 31 dogs with a diagnosis of leishmaniosis based on the LeishVet guidelines were included in the study. Samples from enlarged lymph nodes were taken for cytological examination, clonality testing and Leishmania infantum PCR. RESULTS: All 31 dogs had medium to high positive antibody titers against Leishmania spp. and 30/31 had a positive Leishmania PCR from the lymph node. A polyclonal arrangement for B cells (immunoglobulin heavy chain gene) and T cells (T-cell receptor gamma chain gene) antigen receptors was found in 28/31 dogs. Two out of 31 dogs showed a monoclonal arrangement for Ig with high (1:2) and low (1:7) polyclonal background respectively; and one of the 31 dogs showed a monoclonal arrangement for T cell receptor with low (1:3) polyclonal background. CONCLUSION: Infections with Leishmania infantum resulted in clonal rearrangement, and therefore in a possible false diagnosis of lymphoma, in 3 out of 31 dogs (9.7%). Although, PARR is a useful method to differentiate lymphoma from reactive lymphoid hyperplasia in dogs with leishmaniosis, mono-/biclonal results should be interpreted carefully, especially in the presence of any degree of polyclonal background, and together with other clinicopathological findings.


Assuntos
Evolução Clonal , Doenças do Cão/imunologia , Leishmania infantum/imunologia , Leishmaniose Visceral/diagnóstico , Linfonodos/metabolismo , Linfadenopatia/diagnóstico , Animais , Evolução Clonal/genética , Evolução Clonal/imunologia , Diagnóstico Diferencial , Doenças do Cão/diagnóstico , Doenças do Cão/genética , Doenças do Cão/patologia , Cães , Feminino , Rearranjo Gênico do Linfócito B , Rearranjo Gênico do Linfócito T , Testes Genéticos/métodos , Testes Genéticos/veterinária , Leishmania infantum/genética , Leishmaniose Visceral/genética , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/patologia , Linfonodos/imunologia , Linfadenopatia/genética , Linfadenopatia/imunologia , Linfadenopatia/parasitologia , Linfoma/diagnóstico , Linfoma/genética , Linfoma/veterinária , Masculino , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Estudos Prospectivos , Esplenomegalia/diagnóstico , Esplenomegalia/veterinária
11.
Complement Med Res ; : 1-12, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775141

RESUMO

BACKGROUND: The yeast Malassezia pachydermatis is a commensal but also the most isolated pathogenic yeast in canine otitis externa. Essential oils (EOs) exhibit antimicrobial activity and thus could be an alternative for treatment of otitis. OBJECTIVE: The aim of this study was to analyse the in vitro efficacy of EOs against M. pachydermatis isolates from canine ears. MATERIALS AND METHODS: Twenty-two EOs were tested for their in vitro activity against 15 M. pachydermatis isolates by agar disc diffusion. In addition, diluted EOs were tested and volatile antifungal activity was analysed by vapour assay. RESULTS: Most EOs showed in vitro efficacy against M. pachydermatis. A different susceptibility pattern of tested isolates was found. Overall, the most potential EO was lemon grass. Also, cinnamon leaf, clove, manuka, Indian melissa, oregano, palmarosa, and winter savory oil exhibited a strong antifungal activity. Volatile activity was proven by the inhibiting effect in vapour assay. CONCLUSION: EOs show in vitro activity against M. pachydermatis. This study gives scientific background for the use of EOs in veterinary medicine. Diverse susceptibility patterns of different M. pachydermatis strains emphasise the helpfulness of an aromatogram as one lead for the best choice of an EO for therapy.

12.
BMC Vet Res ; 15(1): 281, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387580

RESUMO

BACKGROUND: Ferlaviruses are important pathogens in snakes often associated with respiratory and neurological disease. The detection of ferlaviral RNA by PCR is considered to be the most reliable method for the diagnosis of infection. The PCRs that have been used most commonly for this purpose have not been properly assessed to determine their sensitivity, specificity and ability to detect the known genetic diversity of this group of viruses. The aim of this study was to compare three published PCR protocols so that a single method could be recommended to laboratories that perform this testing. RESULTS: Comparisons were carried out using cell culture isolates and tissues from snakes infected with specific virus genotypes. A single round PCR targeting a short segment of the viral polymerase (L) gene provided the highest sensitivity and specificity, and detected isolated ferlaviruses from all four described genogroups, as well as from tissues of infected snakes. CONCLUSION: A broadly-reactive PCR for the detection of all known ferlaviruses was found to provide a good combination of detection limit, specificity and speed. Based on these criteria, this method is recommended for the diagnosis of ferlavirus infections.


Assuntos
Paramyxoviridae/genética , Reação em Cadeia da Polimerase/veterinária , Animais , Células Cultivadas , Genótipo , Limite de Detecção , Paramyxoviridae/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Serpentes/virologia
13.
Acta Crystallogr D Struct Biol ; 75(Pt 5): 458-466, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31063148

RESUMO

3D electron diffraction has reached a stage where the structures of chemical compounds can be solved productively. Instrumentation is lagging behind this development, and to date dedicated electron diffractometers for data collection based on the rotation method do not exist. Current studies use transmission electron microscopes as a workaround. These are optimized for imaging, which is not optimal for diffraction studies. The beam intensity is very high, it is difficult to create parallel beam illumination and the detectors used for imaging are of only limited use for diffraction studies. In this work, the combination of an EIGER hybrid pixel detector with a transmission electron microscope to construct a productive electron diffractometer is described. The construction not only refers to the combination of hardware but also to the calibration of the system, so that it provides rapid access to the experimental parameters that are necessary for processing diffraction data. Until fully integrated electron diffractometers become available, this describes a setup for productive and efficient operation in chemical crystallography.


Assuntos
Elétrons , Proteínas/química , Cristalografia por Raios X , Desenho de Equipamento , Humanos
14.
Vet Microbiol ; 233: 196-203, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31053353

RESUMO

In recent years an increasing number of methicillin-resistant S. pseudintermedius (MRSP) has been observed in both, healthy and clinically infected dogs. The aim of the study was the characterisation of MRSP isolates from clinical routine diagnostics of a German laboratory in order to assess the abundancy of resistance genes and SCCmec elements. 97 isolates from 96 dogs were analysed using microarrays detecting resistance genes and SCCmec-associated markers. All isolates harboured mecA and blaZ. Other abundant resistance markers (in >80% of isolates) included aacA-aphD, aphA3 and sat as well as erm(B). Tetracycline resistance genes (tet(K), tet(M)) and cat also were common (in >20%). The vast majority (n = 59) of isolates carried SCCmec III elements. SCCmec IV and V elements were identified in 21 and 15 isolates, respectively. Irregular or pseudo-SCCmec elements were found in 2 isolates. The high degree of uniformity of hybridisation patterns of tested strains suggest that the majority of MRSP infections was caused by one single strain and comparison to previously published reports and sequences suggest that this was the ST71-SCCmec III strain that also predominates elsewhere in Western Europe.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Variação Genética , Resistência a Meticilina/genética , Infecções Estafilocócicas/veterinária , Staphylococcus/classificação , Animais , Técnicas de Tipagem Bacteriana , Doenças do Cão/microbiologia , Cães , Meticilina/farmacologia , Análise em Microsséries , Tipagem de Sequências Multilocus , Infecções Estafilocócicas/microbiologia , Staphylococcus/efeitos dos fármacos
15.
Parasit Vectors ; 12(1): 30, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635034

RESUMO

BACKGROUND: Canine vector-borne infections have gained importance in Germany due to growing tourist traffic and an increased import of dogs from abroad. Endemic regions for pathogens such as Leishmania infantum, Hepatozoon canis, Ehrlichia canis, Anaplasma platys and Dirofilaria spp. are the Mediterranean area and southeastern Europe. Babesia species and Anaplasma phagocytophilum are present all over Europe. The objective of this retrospective study was to evaluate the prevalence of vector-borne infections in dogs imported from defined endemic countries in the Mediterranean area and southeastern Europe. METHODS: Medical records and laboratory test results of 345 dogs that were imported to Germany from 17 endemic countries and that were presented to the Small Animal Clinic at Freie Universität Berlin between 2007 and 2015 were retrospectively reviewed. A total of 1368 test results from external laboratories were descriptively analysed including 576 and 792 test results of direct and indirect detection methods, respectively. RESULTS: Overall, 35% (122/345 dogs) were positive for at least one pathogen. Concurrent infections with two to four pathogens were detected in 8% of the dogs (27/345). The positive results were: L. infantum 21% (66/314 dogs; methods: PCR 20/79, IFAT or ELISA 63/308 dogs), E. canis 16% (45/278 dogs; methods: PCR 8/68, IFAT 43/257 dogs), H. canis 11% (3/28 dogs; method: PCR), Babesia spp. 10% (25/251 dogs; methods: Babesia spp. PCR 3/98, B. canis/vogeli IFAT or ELISA 22/214 and B. gibsoni IFAT 0/13 dogs), Dirofilaria spp. 7% (13/178 dogs; methods: D. immitis Ag-ELISA 8/156, Knott's test 7/95, microfilariae PCR 5/23 dogs) and A. platys 5% (1/21 dogs; method: PCR). None of 8 tested dogs were positive in a combined Babesia spp./Hepatozoon spp. PCR test. CONCLUSIONS: Dogs, which are imported from countries which are endemic for vector-borne infections should be thoroughly tested using direct and indirect detection methods. Potential owners of imported dogs should be informed about the diseases, risks and incubation periods.


Assuntos
Doenças do Cão/transmissão , Doenças Parasitárias em Animais/transmissão , Animais , Doenças do Cão/epidemiologia , Cães , Europa (Continente)/epidemiologia , Feminino , Masculino , Doenças Parasitárias em Animais/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Viagem
16.
Vet Ophthalmol ; 22(3): 328-336, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30095211

RESUMO

OBJECTIVES: To describe the bacterial and fungal microbiota of the conjunctiva and factors influencing these microbiota of healthy cats. To evaluate the antimicrobial resistance profile and discuss the use of appropriate antimicrobial drugs. ANIMALS STUDIED: One hundred and twenty healthy cats PROCEDURES: Conjunctival samples with dry or premoistened swabs were obtained from both eyes and cultured for aerobic and anaerobic bacteria and fungi. In vitro bacterial, susceptibility testing was performed. The effects of age, sex, breed, season, living environment, and sample collection technique on the frequency and composition of microbial isolation were evaluated. RESULTS: In 49 of 120 cats (40.8%) and 73 of 240 swabs (30.4%), microorganisms were isolated. Of the isolates, 71% (61/86) were Gram-positive bacteria, 26% (22/86) were Gram-negative bacteria, and 3% (3/86) were fungi. Staphylococcus felis (17/86; 19.8%) was the most commonly isolated species. Moraxella osloensis (5/86; 5.8%) was the most frequent Gram-negative species. The season had a statistically significant influence (P = 0.04) on the frequency of isolation. The use of premoistened swabs increased the rate of Gram-positive bacterial detection significantly (P = 0.03). The in vitro susceptibility testing showed high efficacy of chloramphenicol, gentamicin, pradofloxacin, and enrofloxacin. CONCLUSIONS: The isolated microbiota aligns with previous studies performed in other countries, although the microbiota of cats in the present study showed wider bacterial diversity, and more Gram-negative species were isolated. Swab sampling should be performed with premoistened swabs. The topical antimicrobials gentamicin and chloramphenicol are suitable therapeutics for first-line treatment.


Assuntos
Antibacterianos/farmacologia , Gatos/microbiologia , Túnica Conjuntiva/microbiologia , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Animais , Antibacterianos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/veterinária , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/veterinária , Feminino , Fungos/isolamento & purificação , Alemanha , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Masculino , Testes de Sensibilidade Microbiana/veterinária , Linhagem , Valores de Referência , Estações do Ano
17.
Scand J Immunol ; 89(3): e12741, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30549299

RESUMO

Novel therapies to treat patients with solid cancers that have developed resistance to chemotherapy represent unmet needs of considerable dimensions. In the present review, we will address the attempts to develop chimeric antigen receptor (CAR) targeted immunotherapy against osteosarcoma (OS). This aggressive cancer displays its peak incidence in children and young adults. The main cause of patient death is lung metastases with a 5-year survival as low as 5%-10% in the primary metastatic setting and 30% in the relapse situation, respectively. Effective adjuvant combination chemotherapy introduced more than 40 years ago improved the survival rates from below 20% to around 60% in patients; however, since then, no major breakthroughs have been made. The use of immune checkpoint inhibitors has been disappointing in OS, while other types of immunotherapies such as CAR T cells remain largely unexplored. Indeed, for CAR T-cell therapy to be efficacious, two main criteria need to be fulfilled: (a) CAR T cells should target an epitope selectively expressed on the cell surface of OS in order to prevent toxicities in normal tissues and (b) the target should also be widely expressed on OS metastases. These challenges have already been undertaken in OS and illustrate the difficulties in developing tomorrow's CAR-T treatment in a solid tumour. We will discuss the experiences with CAR-T therapy development and efficacy to combat the clinical challenges in OS.


Assuntos
Neoplasias Ósseas/terapia , Imunoterapia Adotiva/métodos , Osteossarcoma/terapia , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/mortalidade , Fibroblastos Associados a Câncer/fisiologia , Gangliosídeos/antagonistas & inibidores , Gelatinases/fisiologia , Humanos , Proteínas de Membrana/fisiologia , Osteossarcoma/imunologia , Osteossarcoma/mortalidade , Receptor ErbB-2/análise , Receptor IGF Tipo 1/fisiologia , Receptores de Interleucina-11/antagonistas & inibidores , Serina Endopeptidases/fisiologia , Microambiente Tumoral
18.
Zoonoses Public Health ; 66(1): 117-124, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30460763

RESUMO

Giardia duodenalis is a relevant gastrointestinal protozoan pathogen of humans and animals. This species complex consists of eight genetically different assemblages. Assemblages A and B are pathogenic to humans and pets, thus confer zoonotic potential. The risk of zoonotic transmission has been controversially discussed. The aim of this monocentric cross-sectional pilot study was to investigate G. duodenalis assemblages in humans and pets living in common households in Berlin/Brandenburg (Germany). Samples from dogs, cats and humans sharing the same households were screened for Giardia infection by antigen-detecting assays. All human samples were additionally analysed by a Giardia-specific qPCR. Cyst quantification and sequences of different gene loci (triosephosphate isomerase (tpi), glutamate dehydrogenase (gdh), ß-giardin (bg) and for dogs SSUrDNA) were analysed. A total of 38 households (31 households with dogs and seven with cats) with 69 human individuals participated in the study. Initial antigen-detecting assays revealed Giardia-positive results for 13 (39%) canine, one (14%) feline and one human sample. Reanalysis of the human samples by qPCR revealed two more positive specimens (4%). Two of these three samples were identified as assemblage B at all tested loci. Success rate of assemblage typing for pet samples was generally low and comprised mainly the SSUrDNA locus only. Overall, six of 13 Giardia-positive canine samples were typable (2× A, 1× co-infection: A and B, 1× C; 2× D). One pair of samples (dog and human) from the same household had a similar but not identical assemblage B sequence at tpi locus. Assemblage A was also detected in the dog specimen, which hampered sequence analysis. In conclusion, although exhibiting limitations due to the sample size, our study highlights the need for better and standardized typing tools to distinguish G. duodenalis strains with higher resolution in order to perform proper case-control studies for a realistic estimation of zoonotic risk.


Assuntos
Giardia lamblia/isolamento & purificação , Giardíase/veterinária , Animais de Estimação , Animais , Doenças do Gato/epidemiologia , Doenças do Gato/parasitologia , Gatos , Estudos Transversais , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Alemanha/epidemiologia , Giardia lamblia/genética , Giardíase/epidemiologia , Giardíase/parasitologia , Humanos , Propriedade , Projetos Piloto , Zoonoses
19.
Front Immunol ; 9: 2520, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30450098

RESUMO

Triggering or enhancing antitumor activity of tumor-associated macrophages is an attractive strategy for cancer treatment. We have previously shown that the cytokine interferon-γ (IFN-γ), a type II IFN, could synergize with toll-like receptor (TLR) agonists for induction of antitumor M1 macrophages. However, the toxicity of IFN-γ limits its clinical use. Here, we investigated whether the less toxic type I IFNs, IFN-α, and IFN-ß, could potentially replace IFN-γ for induction of antitumor M1 macrophages. We measured in vitro the ability of type I and II IFNs to synergize with TLR agonists for transcription of inducible nitric oxide synthase (iNOS) mRNA and secretion of nitric oxide (NO) by mouse bone marrow-derived macrophages (BMDMs). An in vitro growth inhibition assay was used to measure both cytotoxic and cytostatic activity of activated macrophages against Lewis lung carcinoma (LLC) cancer cells. We found that both type I and II IFNs could synergize with TLR agonists in inducing macrophage-mediated inhibition of cancer cell growth, which was dependent on NO. The ability of high dose lipopolysaccharide (LPS) to induce tumoricidal activity in macrophages in the absence of IFN-γ was shown to depend on induction of autocrine type I IFNs. Antitumor M1 macrophages could also be generated in the absence of IFN-γ by a combination of two TLR ligands when using the TLR3 agonist poly(I:C) which induces autocrine type I IFNs. Finally, we show that encapsulation of poly(I:C) into nanoparticles improved its potency to induce M1 macrophages up to 100-fold. This study reveals the potential of type I IFNs for activation of antitumor macrophages and indicates new avenues for cancer immunotherapy based on type I IFN signaling, including combination of TLR agonists.


Assuntos
Interferon Tipo I/metabolismo , Interferon gama/metabolismo , Ativação de Macrófagos/fisiologia , Macrófagos/metabolismo , Receptores Toll-Like/metabolismo , Animais , Carcinoma Pulmonar de Lewis/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Poli I-C/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
20.
Angew Chem Int Ed Engl ; 57(50): 16313-16317, 2018 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-30325568

RESUMO

Chemists of all fields currently publish about 50 000 crystal structures per year, the vast majority of which are X-ray structures. We determined two molecular structures by employing electron rather than X-ray diffraction. For this purpose, an EIGER hybrid pixel detector was fitted to a transmission electron microscope, yielding an electron diffractometer. The structure of a new methylene blue derivative was determined at 0.9 Šresolution from a crystal smaller than 1×2 µm2 . Several thousand active pharmaceutical ingredients (APIs) are only available as submicrocrystalline powders. To illustrate the potential of electron crystallography for the pharmaceutical industry, we also determined the structure of an API from its pill. We demonstrate that electron crystallography complements X-ray crystallography and is the technique of choice for all unsolved cases in which submicrometer-sized crystals were the limiting factor.

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