RESUMEN
BACKGROUND: Radiosynoviorthesis (RSO) is a nuclear medical local treatment modality for inflammatory joint diseases. It is indicated in patients with rheumatoid arthritis (RA) in joints with persistent synovitis despite adequate pharmacotherapy. Arthritis of the elbow joint occurs in up to 2/3 of patients with RA. Intra-articular radiotherapy using the beta emitter [186Re] rhenium sulfide leads to sclerosis of the inflamed synovial membrane with subsequent pain alleviation. The clinical efficacy in cubital arthritis, however, has so far only been described in small monocentric studies. OBJECTIVE: The degree of pain alleviation by RSO was analyzed in patients with rheumatoid cubital arthritis, treated in several nuclear medical practices specialized in RSO. MATERIAL AND METHODS: The subjective pain intensity before and after RSO was documented in a total of 107 patients with rheumatic cubital arthritis using a 10-step numeric rating scale (NRS). A difference of ≥â¯-2 is rated as a significant improvement. Follow-up examinations were done after a mean interval of 14 months after RSO (at least 3 months, maximum 50 months). RESULTS: The mean NRS value was 7.3⯱ 2.1 before RSO and 2.8⯱ 2.2 after RSO. A significant pain alleviation was seen in 78.5% of all patients treated. The subgroup analysis also showed a significant improvement in the pain symptoms in all groups depending on the time interval between the RSO and the control examination. A significant pain progression was not observed. The degree of pain relief was independent of the time of follow-up. CONCLUSION: Using RSO for local treatment of rheumatoid cubital arthritis leads to a significant and long-lasting pain relief in more than ¾ of the treated patients.
Asunto(s)
Artritis Reumatoide , Enfermedades del Colágeno , Articulación del Codo , Enfermedades Reumáticas , Sinovitis , Humanos , Radioisótopos/efectos adversos , Codo , Sinovitis/diagnóstico , Sinovitis/radioterapia , Enfermedades Reumáticas/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/radioterapia , Enfermedades del Colágeno/tratamiento farmacológico , Resultado del Tratamiento , Dolor/diagnóstico , Dolor/etiología , Dolor/radioterapiaRESUMEN
Radiosynoviorthesis (RSO) is a decades known, effective intra-articular nuclear medicine local therapy, with few rare side-effects, in which inflamed synovial membrane is treated by means of colloidal beta-emitters. There are major variations worldwide in terms of acceptance, frequency of use and approved indications for this procedure. Thus, reliable figures that reflect reality are only available for a few countries. A Europe-wide survey revealed that RSO is carried out most frequently in Germany, where RSO is the most common nuclear medicine therapy with about 70,000 joints treated per year. The main indications include synovitis due to rheumatoid arthritis, hemophilia and pigmented villonodular synovitis (PVNS), and depending on national approvals, osteoarthritis. Despite the many indications, there are very few published scientific studies and therefore, RSO evidence is lacking. Reliable data on the clinical usage of RSO and demographics of RSO specialists are only available in Germany, thus we discuss the future challenges of RSO mainly from a German perspective. In the German healthcare system, RSO is performed primarily on an outpatient basis and plays only a minor role in the university setting. The necessary expertise for RSO is therefore lacking, for the most part, at university training centers. Currently, nearly more than three quarters of the German RSO experts are over fifty years old, illustrating a shortage of young talent. In the future, RSO providers from the non-university or private sector will have to cooperate with universities through networks and will have to intensify their cooperation with referring physicians, such as rheumatologist and orthopedic surgeons, and patients in order to maintain a timely and beneficial exchange of information. In networks of RSO experts, the participants must jointly develop and establish training concepts and facilities for future talents, elaborate on guidelines, if clinically useful expand the range of indications, initiate studies to generate further evidence and finally make the procedure more public. In addition, it is worthwhile to apply this process beyond human medicine to other fields, such as medical physics and veterinary medicine. If these points are implemented, the future of RSO will be bright, if it fails, it looks bleak.
Asunto(s)
Artritis Reumatoide , Medicina Nuclear , Sinovitis , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , CintigrafíaRESUMEN
Although equine herpesvirus myeloencephalopathy (EHM) is a relatively uncommon manifestation of equine herpesvirus-1 (EHV-1) infection, it can cause devastating losses during outbreaks. Antemortem diagnosis of EHM relies mainly on the molecular detection of EHV-1 in nasal secretions and blood. Management of horses affected by EHM is aimed at supportive nursing and nutritional care, at reducing central nervous system inflammation and preventing thromboembolic sequelae. Horses exhibiting sudden and severe neurologic signs consistent with a diagnosis of EHM pose a definite risk to the surrounding horse population. Consequently, early intervention to prevent the spread of infection is required.
Asunto(s)
Infecciones por Herpesviridae , Herpesvirus Équido 1 , Enfermedades de los Caballos , Animales , Brotes de Enfermedades/veterinaria , Infecciones por Herpesviridae/veterinaria , Enfermedades de los Caballos/prevención & control , CaballosRESUMEN
AIM: As a follow-up to the international survey conducted by the International Atomic Energy Agency (IAEA) in April 2020, this survey aims to provide a situational snapshot of the COVID-19 impact on nuclear medicine services worldwide, 1 year later. The survey was designed to determine the impact of the pandemic at two specific time points: June and October 2020, and compare them to the previously collected data. MATERIALS AND METHODS: A web-based questionnaire, in the same format as the April 2020 survey was disseminated to nuclear medicine facilities worldwide. Survey data was collected using a secure software platform hosted by the IAEA; it was made available for 6 weeks, from November 23 to December 31, 2020. RESULTS: From 505 replies received from 96 countries, data was extracted from 355 questionnaires (of which 338 were fully completed). The responses came from centres across varying regions of the world and with heterogeneous income distributions. Regional differences and challenges across the world were identified and analysed. Globally, the volume of nuclear medicine procedures decreased by 73.3% in June 2020 and 56.9% in October 2020. Among the nuclear medicine procedures, oncological PET studies showed less of a decline in utilization compared to conventional nuclear medicine, particularly nuclear cardiology. The negative impact was also significantly less pronounced in high-income countries. A trend towards a gradual return to the pre-COVID-19 situation of the supply chains of radioisotopes, generators, and other essential materials was evident. CONCLUSION: The year 2020 has a significant decrease in nuclear medicine diagnostic and therapeutic procedures as a result of the pandemic-related challenges. In June, the global decline recorded in the survey was greater than in October when the situation began to show improvement. However, the total number of procedures remained below those recorded in April 2020 and fell to less than half of the volumes normally carried out pre-pandemic.
Asunto(s)
COVID-19 , Medicina Nuclear , Estudios de Seguimiento , Humanos , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Cigarette smoking is a leading cause of preventable mortality worldwide. Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with sequence variants in nicotine acetylcholine receptor genes and at other loci. To search for additional loci, we conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers (28,677 Europeans/European Americans and 9925 African Americans) across 15 studies. In this largest-ever GWAS meta-analysis for nicotine dependence and the largest-ever cross-ancestry GWAS meta-analysis for any smoking phenotype, we reconfirmed the well-known CHRNA5-CHRNA3-CHRNB4 genes and further yielded a novel association in the DNA methyltransferase gene DNMT3B. The intronic DNMT3B rs910083-C allele (frequency=44-77%) was associated with increased risk of nicotine dependence at P=3.7 × 10-8 (odds ratio (OR)=1.06 and 95% confidence interval (CI)=1.04-1.07 for severe vs mild dependence). The association was independently confirmed in the UK Biobank (N=48,931) using heavy vs never smoking as a proxy phenotype (P=3.6 × 10-4, OR=1.05, and 95% CI=1.02-1.08). Rs910083-C is also associated with increased risk of squamous cell lung carcinoma in the International Lung Cancer Consortium (N=60,586, meta-analysis P=0.0095, OR=1.05, and 95% CI=1.01-1.09). Moreover, rs910083-C was implicated as a cis-methylation quantitative trait locus (QTL) variant associated with higher DNMT3B methylation in fetal brain (N=166, P=2.3 × 10-26) and a cis-expression QTL variant associated with higher DNMT3B expression in adult cerebellum from the Genotype-Tissue Expression project (N=103, P=3.0 × 10-6) and the independent Brain eQTL Almanac (N=134, P=0.028). This novel DNMT3B cis-acting QTL variant highlights the importance of genetically influenced regulation in brain on the risks of nicotine dependence, heavy smoking and consequent lung cancer.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasas/genética , Tabaquismo/genética , Adulto , Negro o Afroamericano/genética , Anciano , Alelos , Población Negra/genética , ADN (Citosina-5-)-Metiltransferasas/fisiología , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Sitios de Carácter Cuantitativo/genética , Fumar/genética , Población Blanca/genética , ADN Metiltransferasa 3BRESUMEN
Over the past ten years, scientific and technological advances have established biocatalysis as a practical and environmentally friendly alternative to traditional metallo- and organocatalysis in chemical synthesis, both in the laboratory and on an industrial scale. Key advances in DNA sequencing and gene synthesis are at the base of tremendous progress in tailoring biocatalysts by protein engineering and design, and the ability to reorganize enzymes into new biosynthetic pathways. To highlight these achievements, here we discuss applications of protein-engineered biocatalysts ranging from commodity chemicals to advanced pharmaceutical intermediates that use enzyme catalysis as a key step.
Asunto(s)
Biocatálisis , Enzimas/genética , Enzimas/metabolismo , Ingeniería de Proteínas , Biotecnología/métodos , Biotecnología/tendencias , Biología Computacional/métodos , Biología Computacional/tendencias , Evolución Molecular Dirigida , Tecnología Química Verde , Ingeniería de Proteínas/métodos , Ingeniería de Proteínas/tendenciasRESUMEN
Despite the importance of neurological disorders associated with herpesviruses, the mechanism by which these viruses influence the central nervous system (CNS) has not been definitively established. Owing to the limitations of studying neuropathogenicity of human herpesviruses in their natural host, many aspects of their pathogenicity and immune response are studied in animal models. Here, we present an important model system that enables studying neuropathogenicity of herpesviruses in the natural host. Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus that causes a devastating neurological disease (EHV-1 myeloencephalopathy; EHM) in horses. Like other alphaherpesviruses, our understanding of virus neuropathogenicity in the natural host beyond the essential role of viraemia is limited. In particular, information on the role of different viral proteins for virus transfer to the spinal cord endothelium in vivo is lacking. In this study, the contribution of two viral proteins, DNA polymerase (ORF30) and glycoprotein D (gD), to the pathogenicity of EHM was addressed. Furthermore, different cellular immune markers, including alpha-interferon (IFN-α), gamma-interferon (IFN-γ), interleukin-10 (IL-10) and interleukin-1 beta (IL-1ß), were identified to play a role during the course of the disease.
Asunto(s)
Biomarcadores/análisis , Encefalitis Viral/patología , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/virología , Herpesvirus Équido 1/patogenicidad , Interacciones Huésped-Patógeno , Proteínas Virales/metabolismo , Animales , Femenino , Infecciones por Herpesviridae/patología , Caballos , Masculino , Modelos Animales , Factores de Virulencia/metabolismoRESUMEN
Human γδ T cells are innate-like T cells which are able to kill a broad range of tumour cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumour cell killing. The two immunoligands, designated MICA:7D8 and ULBP2:7D8, respectively, enhanced cytotoxicity of ex vivo-expanded γδ T cells against CD20-positive lymphoma cells. Both Vδ1 and Vδ2 γδ T cells were triggered by MICA:7D8 or ULBP2:7D8. Killing of CD20-negative tumour cells was not induced by the immunoligands, indicating their antigen specificity. MICA:7D8 and ULBP2:7D8 acted in a dose-dependent manner and induced cytotoxicity at nanomolar concentrations. Importantly, chronic lymphocytic leukaemia (CLL) cells isolated from patients were sensitized by the two immunoligands for γδ T cell cytotoxicity. In a combination approach, the immunoligands were combined with bromohydrin pyrophosphate (BrHPP), an agonist for Vδ2 γδ T cells, which further enhanced the efficacy in target cell killing. Thus, employing tumour-directed recombinant immunoligands which engage NKG2D may represent an attractive strategy to enhance antitumour cytotoxicity of γδ T cells.
Asunto(s)
Antígenos CD20/metabolismo , Citotoxicidad Inmunológica , Inmunoterapia/métodos , Linfoma/terapia , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Anticuerpos de Cadena Única/uso terapéutico , Linfocitos T/fisiología , Antígenos CD20/inmunología , Difosfatos/uso terapéutico , Quimioterapia Combinada , Proteínas Ligadas a GPI/genética , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Inmunización , Péptidos y Proteínas de Señalización Intercelular/genética , Linfoma/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Anticuerpos de Cadena Única/genética , Células Tumorales CultivadasRESUMEN
In the folate cycle MTHFD1, encoded by MTHFD1, is a trifunctional enzyme containing 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase activity. To date, only one patient with MTHFD1 deficiency, presenting with hyperhomocysteinemia, megaloblastic anaemia, hemolytic uremic syndrome (HUS) and severe combined immunodeficiency, has been identified (Watkins et al J Med Genet 48:590-2, 2011). We now describe four additional patients from two different families. The second patient presented with hyperhomocysteinemia, megaloblastic anaemia, HUS, microangiopathy and retinopathy; all except the retinopathy resolved after treatment with hydroxocobalamin, betaine and folinic acid. The third patient developed megaloblastic anaemia, infection, autoimmune disease and moderate liver fibrosis but not hyperhomocysteinemia, and was successfully treated with a regime that included and was eventually reduced to folic acid. The other two, elder siblings of the third patient, died at 9 weeks of age with megaloblastic anaemia, infection and severe acidosis and had MTFHD1 deficiency diagnosed retrospectively. We identified a missense mutation (c.806C > T, p.Thr296Ile) and a splice site mutation (c.1674G > A) leading to exon skipping in the second patient, while the other three harboured a missense mutation (c.146C > T, p.Ser49Phe) and a premature stop mutation (c.673G > T, p.Glu225*), all of which were novel. Patient fibroblast studies revealed severely reduced methionine formation from [(14)C]-formate, which did not increase in cobalamin supplemented culture medium but was responsive to folic and folinic acid. These additional cases increase the clinical spectrum of this intriguing defect, provide in vitro evidence of disturbed methionine synthesis and substantiate the effectiveness of folic or folinic acid treatment.
Asunto(s)
Ácido Fólico/uso terapéutico , Leucovorina/uso terapéutico , Metilenotetrahidrofolato Deshidrogenasa (NADP)/deficiencia , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , Anemia Megaloblástica/tratamiento farmacológico , Anemia Megaloblástica/genética , Anemia Megaloblástica/patología , Células Cultivadas , Resultado Fatal , Femenino , Deficiencia de Ácido Fólico/tratamiento farmacológico , Deficiencia de Ácido Fólico/genética , Deficiencia de Ácido Fólico/patología , Humanos , Hiperhomocisteinemia/tratamiento farmacológico , Hiperhomocisteinemia/genética , Hiperhomocisteinemia/patología , Lactante , Recién Nacido , Masculino , Antígenos de Histocompatibilidad Menor , Inmunodeficiencia Combinada Grave/tratamiento farmacológico , Inmunodeficiencia Combinada Grave/genética , Inmunodeficiencia Combinada Grave/patología , Adulto JovenRESUMEN
Recent studies suggest that the signal molecules cAMP and cGMP have antifibrotic effects by negatively regulating pathways associated with fibroblast to myofibroblast (MyoCF) conversion. The phosphodiesterase 2 (PDE2) has the unique property to be stimulated by cGMP, which leads to a remarkable increase in cAMP hydrolysis and thus mediates a negative cross-talk between both pathways. PDE2 has been recently investigated in cardiomyocytes; here we specifically addressed its role in fibroblast conversion and cardiac fibrosis. PDE2 is abundantly expressed in both neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes. The overexpression of PDE2 in CFs strongly reduced basal and isoprenaline-induced cAMP synthesis, and this decrease was sufficient to induce MyoCF conversion even in the absence of exogenous profibrotic stimuli. Functional stress-strain experiments with fibroblast-derived engineered connective tissue (ECT) demonstrated higher stiffness in ECTs overexpressing PDE2. In regard to cGMP, neither basal nor atrial natriuretic peptide-induced cGMP levels were affected by PDE2, whereas the response to nitric oxide donor sodium nitroprusside was slightly but significantly reduced. Interestingly, despite persistently depressed cAMP levels, both cGMP-elevating stimuli were able to completely prevent the PDE2-induced MyoCF phenotype, arguing for a double-tracked mechanism. In conclusion, PDE2 accelerates CF to MyoCF conversion, which leads to greater stiffness in ECTs. Atrial natriuretic peptide- and sodium nitroprusside-mediated cGMP synthesis completely reverses PDE2-induced fibroblast conversion. Thus PDE2 may augment cardiac remodeling, but this effect can also be overcome by enhanced cGMP. The redundant role of cAMP and cGMP as antifibrotic meditators may be viewed as a protective mechanism in heart failure.
Asunto(s)
AMP Cíclico/metabolismo , GMP Cíclico/fisiología , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 2/fisiología , Miocardio/citología , Miofibroblastos/fisiología , Transducción de Señal/fisiología , Animales , Animales Recién Nacidos , Factor Natriurético Atrial/farmacología , Células Cultivadas , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 2/genética , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Fibroblastos/fisiología , Expresión Génica , Hidrólisis , Miocitos Cardíacos/enzimología , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Ratas , Receptores Adrenérgicos beta/fisiologíaRESUMEN
Compound-specific stable isotope analysis (CSIA) serves as a tool for source apportionment (SA) and for the quantification of the extent of degradation (QED) of organic pollutants. However, simultaneous occurrence of mixing of sources and degradation is generally believed to hamper both SA and QED. On the basis of the linear stable isotope mixing model and the Rayleigh equation, we developed the stable isotope sources and sinks model, which allows for simultaneous SA and QED of a pollutant that is emitted by two sources and degrades via one transformation process. It was shown that the model necessitates at least dual-element CSIA for unequivocal SA in the presence of degradation-induced isotope fractionation, as illustrated for perchlorate in groundwater. The model also enables QED, provided degradation follows instantaneous mixing of two sources. If mixing occurs after two sources have degraded separately, the model can still provide a conservative estimate of the overall extent of degradation. The model can be extended to a larger number of sources and sinks as outlined. It may aid in forensics and natural attenuation assessment of soil, groundwater, surface water, or atmospheric pollution.
Asunto(s)
Monitoreo del Ambiente/métodos , Contaminantes Ambientales/química , Isótopos/química , Contaminantes Ambientales/análisis , Isótopos/análisis , Modelos TeóricosRESUMEN
Compound-specific stable isotope analysis (CSIA) has proven a useful tool for the quantification of the extent of degradation (QED), and for source identification and source apportionment (SA) in contaminated environmental systems. However, the simultaneous occurrence of degradation processes and mixing of emission sources complicates the use of CSIA in combined SA and QED. In a companion study, we developed a mathematical model that allows for combined SA and QED of organic pollutants (and inorganic compounds such as nitrate) in a scenario of two emission sources and degradation via one reaction pathway. This work presents a validation of the model against virtual data from a two-dimensional reactive transport model. The model calculations for SA and QED were in good agreement with the simulation results, which suggests the correctness of the model assumptions. However, the application of the model to field data of benzene contamination was challenged by large uncertainties in CSIA data and the unknown interplay between competing degradation pathways. Nonetheless, the use of the model allowed for the identification of a prevailing contribution of one emission source and revealed a low overall extent of degradation at the field site. This indicates that the model can, for example, facilitate the characterization of air pollution or aquifer contamination with organic pollutants.
Asunto(s)
Monitoreo del Ambiente/métodos , Contaminantes Ambientales/química , Modelos Químicos , Isótopos de Carbono/análisis , Isótopos de Carbono/química , Contaminantes Ambientales/análisis , Hidrógeno/química , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Contagious equine metritis (CEM) is caused by Taylorella equigenitalis. It is a venereal disease that is detected in some breeds more than others and can cause temporary infertility with substantial costs for regular testing, sanitation and retesting. There was a perceived increase in T. equigenitalis-positive cases in Icelandic intact males where natural cover is common. OBJECTIVES: We aimed to investigate the prevalence of T. equigenitalis in Icelandic intact males and compare to draught horse and Haflinger intact males. We hypothesised that prevalence of T. equigenitalis is higher in Icelandic compared with draught and Haflinger intact males. STUDY DESIGN: Cross sectional. METHODS: Swabs from 76 Icelandic, 35 Haflinger, and 51 draught horse intact males were collected on 38 different farms and analysed by qPCR. Animals were further stratified into active breeding and non-breeding animals and age groups (1.5-7.0 and 8.0-26.0 years). Fisher's exact tests and mixed effect logistic regression with 'farm' as random effect were used to estimate differences in odds for T. equigenitalis-positive test results. RESULTS: The overall prevalence of T. equigenitalis in included intact males was 16.7% (27/162). The odds for T. equigenitalis-positive intact males were significantly higher in Icelandic compared with draught and Haflinger intact males (Odds ratio [OR] = 6.42, 95% confidence interval (CI) = 1.43-28.8, p = 0.02). Odds for T. equigenitalis-positive intact males were significantly lower in active breeding compared with non-breeding animals (OR = 0.09, 95% CI = 0.01-0.54, p = 0.009). Age had no significant influence on test results. MAIN LIMITATIONS: Convenience sampling with regional restrictions to Southern Germany and Austria, small sample size. CONCLUSIONS: Significantly higher odds for T. equigenitalis-positive intact males were found within Icelandic over draught and Haflinger and within non-breeding animals compared with active breeding animals. Findings suggest that non-breeding animals could be a reservoir for T. equigenitalis. Testing for CEM should therefore be routinely performed in Icelandic horses prior to breeding and investigations into epidemiology and reservoirs on affected farms should be initiated.
RESUMEN
BACKGROUND: Equid alphaherpesvirus 1 (EHV-1) is a highly contagious respiratory tract pathogen of horses, and infection may be followed by myeloencephalopathy or abortion. Surveillance and early detection have focused on PCR assays using less tolerated nasal swabs. Here, we assess non-invasive non-contact sampling techniques as surveillance tools in naturally equid gammaherpesvirus 2-shedding horses as surrogates for EHV-1. METHODS: Horses were individually housed for 10 h periods on 2 consecutive days. Sampling included nasal swabs, nostril wipes, environmental swabs, droplet-catching devices, and air sampling. The latter was completed via two strategies: a combined air sample collected while going from horse to horse and a collective air sample collected at a stationary central point for 6 h. Samples were screened through quantitative PCR and digital PCR. RESULTS: Nine horses on day 1 and 11 horses on day 2 were positive for EHV-1; overall, 90.9% of the nostril wipes, 81.8% of the environmental surfaces, and 90.9% of the droplet-catching devices were found to be positive. Quantitative analysis showed that the mean DNA copies detection per cm2 of nostril wipe sampled concentration (4.3 × 105 per day) was significantly (p < 0.05) comparable to that of nasal swabs (3.6 × 105 per day) followed by environmental swabs (4.3 × 105 per day) and droplet catchers (3.5 × 103 per day), respectively. Overall, 100% of the air samples collected were positive on both qPCR and dPCR. In individual air samples, a mean concentration of 1.0 × 104 copies of DNA were detected in per m3 air sampled per day, while in the collective air samples, the mean concentration was 1.1 × 103. CONCLUSIONS: Environmental samples look promising in replacing direct contact sampling. Environmental and air sampling could become efficient surveillance tools at equestrian events; however, it needs threshold calculations for minimum detection levels.
Asunto(s)
Infecciones por Herpesviridae , Herpesvirus Équido 1 , Enfermedades de los Caballos , Animales , Caballos/virología , Enfermedades de los Caballos/virología , Enfermedades de los Caballos/diagnóstico , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/diagnóstico , Herpesvirus Équido 1/aislamiento & purificación , Herpesvirus Équido 1/genética , Manejo de Especímenes/métodos , Femenino , Esparcimiento de VirusRESUMEN
Equine herpesvirus-1 (EHV-1) is a highly prevalent and frequently pathogenic infection of equids. The most serious clinical consequences of infection are abortion and equine herpesvirus myeloencephalopathy (EHM). The previous consensus statement was published in 2009 and considered pathogenesis, strain variation, epidemiology, diagnostic testing, vaccination, outbreak prevention and control, and treatment. A recent survey of American College of Veterinary Internal Medicine large animal diplomates identified the need for a revision to this original consensus statement. This updated consensus statement is underpinned by 4 systematic reviews that addressed key questions concerning vaccination, pharmaceutical treatment, pathogenesis, and diagnostic testing. Evidence for successful vaccination against, or effective treatment of EHV-1 infection was limited, and improvements in experimental design and reporting of results are needed in future studies of this important disease. This consensus statement also updates the topics considered previously in 2009.
Asunto(s)
Infecciones por Herpesviridae , Herpesvirus Équido 1 , Enfermedades de los Caballos , Animales , Caballos , Enfermedades de los Caballos/virología , Enfermedades de los Caballos/prevención & control , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/virología , Embarazo , FemeninoRESUMEN
Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating manifestations of equine herpesvirus type 1 (EHV-1) infection but our understanding of its pathogenesis remains rudimentary, partly because of a lack of adequate experimental models. EHV-1 infection of the ocular vasculature may offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and to determine the frequency of ocular EHV-1, our goal was to study: (1) Dissemination of virus following acute infection, (2) Development and frequency of ocular lesions following infection, and (3) Utility of a GFP-expressing virus for localization of the virus in vivo. Viral antigen could be detected following acute infection in ocular tissues and the central nervous system (experiment 1). Furthermore, EHV-1 infection resulted in multifocal choroidal lesions in 90% (experiment 2) and 50% (experiment 3) of experimentally infected horses, however ocular lesions did not appear in vivo until between 3 weeks and 3 months post-infection. Taken together, the timing of the appearance of lesions and their ophthalmoscopic features suggest that their pathogenesis may involve ischemic injury to the chorioretina following viremic delivery of virus to the eye, mirroring the vascular events that result in EHM. In summary, we show that the frequency of ocular EHV-1 is 50-90% following experimental infection making this model attractive for testing future vaccines or therapeutics in an immunologically relevant age group.
Asunto(s)
Coriorretinitis/veterinaria , Encefalomielitis/veterinaria , Angiografía con Fluoresceína/métodos , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1/aislamiento & purificación , Animales , Coriorretinitis/epidemiología , Coriorretinitis/patología , Coriorretinitis/virología , Encefalomielitis/epidemiología , Encefalomielitis/patología , Encefalomielitis/virología , Angiografía con Fluoresceína/veterinaria , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/patología , Infecciones por Herpesviridae/virología , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/virología , Caballos , Pruebas de Neutralización/veterinaria , Nariz/virología , Distribución Aleatoria , Viremia/veterinaria , Viremia/virología , Esparcimiento de VirusRESUMEN
Biocatalysis harnesses enzymes to make valuable products. This green technology is used in countless applications from bench scale to industrial production and allows practitioners to access complex organic molecules, often with fewer synthetic steps and reduced waste. The last decade has seen an explosion in the development of experimental and computational tools to tailor enzymatic properties, equipping enzyme engineers with the ability to create biocatalysts that perform reactions not present in nature. By using (chemo)-enzymatic synthesis routes or orchestrating intricate enzyme cascades, scientists can synthesize elaborate targets ranging from DNA and complex pharmaceuticals to starch made in vitro from CO2-derived methanol. In addition, new chemistries have emerged through the combination of biocatalysis with transition metal catalysis, photocatalysis, and electrocatalysis. This review highlights recent key developments, identifies current limitations, and provides a future prospect for this rapidly developing technology.
Asunto(s)
Biocatálisis , Enzimas , Ingeniería de Proteínas , Enzimas/química , Enzimas/genética , Metanol , Tecnología , Especificidad por SustratoRESUMEN
BACKGROUND: Equine herpes virus type 1 (EHV-1) infection in horses is associated with respiratory and neurologic disease, abortion, and neonatal death. HYPOTHESIS: Vaccines decrease the occurrence of clinical disease in EHV-1-infected horses. METHODS: A systematic review was performed searching multiple databases to identify relevant studies. Selection criteria were original peer-reviewed research reports that investigated the in vivo use of vaccines for the prevention of disease caused by EHV-1 in domesticated horses. Main outcomes of interest included pyrexia, abortion, neurologic disease, viremia, and nasal shedding. We evaluated risk of bias, conducted exploratory meta-analyses of incidence data for the main outcomes, and performed a GRADE evaluation of the quality of evidence for each vaccine subtype. RESULTS: A total of 1018 unique studies were identified, of which 35 met the inclusion criteria. Experimental studies accounted for 31/35 studies, with the remainder being observational studies. Eight vaccine subclasses were identified including commercial (modified-live, inactivated, mixed) and experimental (modified-live, inactivated, deletion mutant, DNA, recombinant). Risk of bias was generally moderate, often because of underreporting of research methods, and sample sizes were small leading to imprecision in the estimate of the effect size. Several studies reported either no benefit or minimal vaccine efficacy for the primary outcomes of interest. Meta-analyses revealed significant heterogeneity was present, and our confidence in the quality of evidence for most outcomes was low to moderate. CONCLUSIONS AND CLINICAL IMPORTANCE: Our review indicates that commercial and experimental vaccines minimally reduce the incidence of clinical disease associated with EHV-1 infection.
RESUMEN
Glutamic acid decarboxylase (GAD) converts glutamic acid into the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Increased serum GAD (auto) antibody concentrations were found in a mare with increased postural musculature tone resulting in stiffness and recumbence. The mare was treated with dexamethasone which resulted in resolution of clinical signs and decreased GAD antibody concentrations.
Asunto(s)
Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Glutamato Descarboxilasa/metabolismo , Enfermedades de los Caballos/diagnóstico , Síndrome de la Persona Rígida/veterinaria , Ácido gamma-Aminobutírico/metabolismo , Animales , Autoanticuerpos/inmunología , Electromiografía/veterinaria , Femenino , Glutamato Descarboxilasa/inmunología , Ácido Glutámico/metabolismo , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/inmunología , Caballos , Síndrome de la Persona Rígida/diagnóstico , Síndrome de la Persona Rígida/tratamiento farmacológico , Síndrome de la Persona Rígida/inmunología , Transmisión Sináptica , Resultado del Tratamiento , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
Medical records of 261 cats presenting with gastrointestinal disease that had a serum cobalamin concentration measured were reviewed. In addition, a reference range for cobalamin (305 - 1.967ng/L) was established using 22 healthy adult cats with undetectable levels of urinary methylmalonic acid. A total of 108 of 261 cats (41.4 %) had hypocobalaminemia; 69 cats (26.4 %) had cobalamin concentrations below the detection limit of the assay (< 150ng/L, group A) and 39 (15 %) had concentrations between 150 - 304ng/L (group B). The remaining 153 (58.6 %) cats had normal cobalamin concentrations (group C). Diarrhea was the most common clinical sign in hypocobalaminemic cats and vomiting or anorexia was the most common sign in normocobalaminemic cats. Only cats with both, vomiting and diarrhea were more likely to have hypocobalaminemia than cats with other clinical signs (odds ratio, 2.879; 95 % CI, 1.313 - 6.310). Serum cobalamin concentration was negatively correlated with age of the patient and positively correlated with body condition score. Cats of group A had a significantly higher neutrophil count (p = 0.0009) and higher MCV (p = 0.0064) and significantly lower hematocrit (p = 0.0018) and albumin concentration (p = 0.0037) than cats in other groups. There was no difference between cats of groups B and C with respect to complete blood cell counts and metabolic profiles. Among the diagnoses made in 125 cats (A 69.6 %, B 59 %, C 35.3 %), lymphoma and inflammatory enteropathy were most common. Lymphoma was diagnosed in 31.2 % (A 53.8 %, B 15.4 %, C 30.8 %) and inflammatory enteropathy in 22.4 % (A 35.7 %, B 7.1 %, C 57.2 %) of cats. Hypocobalaminemia is a frequent problem in cats with gastrointestinal disease. Presenting clinical signs as well as laboratory results may already indicate its probability and severity. However, only values below the detection limit of the assay seem to affect routine bloodwork results. Cobalamin should be routinely measured in feline gastrointestinal disease, as its serum concentration may influence the choice of further diagnostics.