RESUMEN
At "Instituto de Alergias y Autoinmunidad Dr. Maximiliano Ruiz Castañeda, A.C." in Mexico City, a non-traditional health care center focused on the treatment of autoimmune and allergic diseases using personalized medicine, an alternative treatment referred to as an "immune-modulator" has been developed. In this study, we will refer to this treatment substance as the "immune-modulator." In brief, a urine sample is collected from the patient and processed to obtain the peptide fraction, which is conditioned and then administered sublingually to the patient. Sample processing involves multiple steps aimed at the removal of toxic compounds and enrichment for cytokines, growth factors, and other immune peptides that may contribute to the function of the immune-modulator. This treatment has been administered for many years, and patients testify that it is useful and reliable. Despite the benefits of this treatment, the molecular mechanisms underlying its effects have not been thoroughly investigated. Therefore, this study aims to identify immunoregulatory peptides, such as cytokines and growth factors, in the immune-modulator. Urine and immune-modulator concentrations of cytokines and growth factors were assessed using a Luminex assay. Twenty-one cytokines and growth factors were identified in immune-modulator samples. MCP-1 was identified in 100% of the samples; MIP-1ß, IL-8, RANTES, INF-γ, and IP-10 were identified in approximately 65-70% of samples; IL5, IL-1B, and IL-17 in 50-60%; eotaxin, VEGF, IL-6, and FGF in about 40%; MIP-1α, IL-9, GM-CSF, G-CSF, IL-12, and IL-15 in about 20-30%; and IL-13 and PDGF-bb were identified in <6% of samples. Additionally, patients exhibited significant changes in IL-1ß, IFN-γ, and MCP-1 concentrations after treatment with the immune-modulator, whereas healthy individuals showed no significant change in response to the treatment. The immune-modulator is an alternative treatment based on the administration of cytokines and growth factors obtained from the urine of patients. In this study, its composition was characterized. The isolated products could be responsible for the effects of the immune-modulator. Further trials are required to evaluate the effective delivery of these molecules by the administration route described.
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Enfermedades Autoinmunes/orina , Citocinas/orina , Hipersensibilidad/orina , Adulto , Anciano , Enfermedades Autoinmunes/terapia , Enfermedad Crónica , Femenino , Humanos , Hipersensibilidad/terapia , Masculino , Persona de Mediana EdadRESUMEN
Piaractus orinoquensis, a new species of serrasalmid fish, is described from the Orinoco River basin. The new species differs from congeners by having a slenderer body, relatively smaller head and snout, more compressed mid-body, fewer scales above and below the lateral line and diagnostic molecular characters in the coI mitochondrial gene region. We also provide a re-description of Piaractus brachypomus, restricting its geographic distribution to the Amazon River basin. Both species are economically important in their respective basins and need to be independently managed as distinct species.
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Characiformes/clasificación , ADN Mitocondrial/química , Complejo IV de Transporte de Electrones/genética , Aletas de Animales/anatomía & histología , Escamas de Animales/anatomía & histología , Animales , Brasil , Characiformes/anatomía & histología , Characiformes/genética , Colombia , Explotaciones Pesqueras/organización & administración , Sistema de la Línea Lateral/anatomía & histología , Funciones de Verosimilitud , Maxilar/anatomía & histología , Mitocondrias/genética , Filogenia , Pigmentación , Distribución de Poisson , Ríos , Alineación de Secuencia , Programas Informáticos , Columna Vertebral/anatomía & histología , Terminología como AsuntoRESUMEN
AIMS: The present study analyses molecular characteristics of the locus coeruleus (LC) and projections to the amygdala and hippocampus at asymptomatic early and middle Braak stages of neurofibrillary tangle (NFT) pathology. METHODS: Immunohistochemistry, whole-transcriptome arrays and RT-qPCR in LC and western blotting in hippocampus and amygdala in a cohort of asymptomatic individuals at stages I-IV of NFT pathology were used. RESULTS: NFTs in the LC increased in parallel with colocalized expression of tau kinases, increased neuroketal adducts and decreased superoxide dismutase 1 in neurons with hyperphosphorylated tau and decreased voltage-dependent anion channel in neurons containing truncated tau were found. These were accompanied by increased microglia and AIF1, CD68, PTGS2, IL1ß, IL6 and TNF-α gene expression. Whole-transcriptome arrays revealed upregulation of genes coding for proteins associated with heat shock protein binding and genes associated with ATP metabolism and downregulation of genes coding for DNA-binding proteins and members of the small nucleolar RNAs family, at stage IV when compared with stage I. Tyrosine hydroxylase (TH) immunoreactivity was preserved in neurons of the LC, but decreased TH and increased α2A adrenergic receptor protein levels were found in the hippocampus and the amygdala. CONCLUSIONS: Complex alteration of several metabolic pathways occurs in the LC accompanying NFT formation at early and middle asymptomatic stages of NFT pathology. Dopaminergic/noradrenergic denervation and increased expression of α2A adrenergic receptor in the hippocampus and amygdala occur at first stage of NFT pathology, suggesting compensatory activation in the face of decreased adrenergic input occurring before clinical evidence of cognitive impairment and depression.
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Locus Coeruleus/metabolismo , Locus Coeruleus/patología , Ovillos Neurofibrilares/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Viral haemorrhagic septicaemia virus (VHSV) genotype IVb has been responsible for large-scale fish mortality events in the Great Lakes of North America. Anticipating the areas of potential VHSV occurrence is key to designing epidemiological surveillance and disease prevention strategies in the Great Lakes basin. We explored the environmental features that could shape the distribution of VHSV, based on remote sensing and climate data via ecological niche modelling. Variables included temperature measured during the day and night, precipitation, vegetation, bathymetry, solar radiation and topographic wetness. VHSV occurrences were obtained from available reports of virus confirmation in laboratory facilities. We fit a Maxent model using VHSV-IVb reports and environmental variables under different parameterizations to identify the best model to determine potential VHSV occurrence based on environmental suitability. VHSV reports were generated from both passive and active surveillance. VHSV occurrences were most abundant near shore sites. We were, however, able to capture the environmental signature of VHSV based on the environmental variables employed in our model, allowing us to identify patterns of VHSV potential occurrence. Our findings suggest that VHSV is not at an ecological equilibrium and more areas could be affected, including areas not in close geographic proximity to past VHSV reports.
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Ecosistema , Novirhabdovirus/fisiología , Animales , Great Lakes Region/epidemiología , Septicemia Hemorrágica Viral/epidemiología , Septicemia Hemorrágica Viral/virología , Modelos Biológicos , Ontario/epidemiologíaRESUMEN
In Chile, while dog rabies has decreased markedly over the last 30 years, bat rabies is still reported frequently. In order to shed new light on the spatiotemporal trends of these reports, we analysed active and passive data from years 1985 and 2012, which included 61 076 samples from 289 counties of Chile. We found that from 1994 to 2012, more than 15 000 bat samples were submitted for diagnostics through passive surveillance, 9·5% of which tested positive for rabies. By contrast, the prevalence of infection was only ~0·4% among the nearly 12 000 bat samples submitted through active surveillance. We found that the prevalence of dog rabies dropped steadily over the same period, with just a single confirmed case since 1998. None of the 928 samples from wild animals, other than bats, were positive for rabies. Although there has been only one confirmed case of human rabies in Chile since 1985, and a single confirmed case in a dog since 1998, bats remain a reservoir for rabies viruses. While active surveillance indicates that rabies prevalence is low in bat colonies, the high proportion of positive bats submitted through passive surveillance is a concern. To prevent human rabies, local public health agencies should increase research on the basic ecology of bats and the role of stray dogs and cats as potential rabies amplifiers.
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Quirópteros , Virus de la Rabia/aislamiento & purificación , Rabia/epidemiología , Animales , Chile/epidemiología , Prevalencia , Salud Pública/tendencias , Rabia/prevención & control , Rabia/transmisión , Rabia/virología , Virus de la Rabia/clasificación , Estaciones del Año , Especificidad de la Especie , Factores de TiempoRESUMEN
OBJECTIVES: To determine the frequency of clinically significant chromosomal abnormalities identified by chromosomal microarray in pregnancy losses at any gestational age and to compare microarray performance with that of traditional cytogenetic analysis when testing pregnancy losses. METHODS: Among 535 fetal demise specimens of any gestational age, clinical microarray-based comparative genomic hybridization (aCGH) was performed successfully on 515, and a subset of 107 specimens underwent additional single nucleotide polymorphism (SNP) analysis. RESULTS: Overall, clinically significant abnormalities were identified in 12.8% (64/499) of specimens referred with normal or unknown karyotypes. Detection rates were significantly higher with earlier gestational age. In the subset with normal karyotype, clinically significant abnormalities were identified in 6.9% (20/288). This detection rate did not vary significantly with gestational age, suggesting that, unlike aneuploidy, the contribution of submicroscopic chromosomal abnormalities to fetal demise does not vary with gestational age. In the 107 specimens that underwent aCGH and SNP analysis, seven cases (6.5%) had abnormalities of potential clinical significance detected by the SNP component, including female triploidy. aCGH failed to yield fetal results in 8.3%, which is an improvement over traditional cytogenetic analysis of fetal demise specimens. CONCLUSIONS: Both the provision of results in cases in which karyotype fails and the detection of abnormalities in the presence of a normal karyotype demonstrate the increased diagnostic utility of microarray in pregnancy loss. Thus, chromosomal microarray testing is a preferable, robust method of analyzing cases of pregnancy loss to better delineate possible genetic etiologies, regardless of gestational age.
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Aborto Espontáneo/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Mortinato/genética , Aneuploidia , Aberraciones Cromosómicas , Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/genética , Hibridación Genómica Comparativa/métodos , Análisis Citogenético/métodos , Femenino , Feto , Humanos , Cariotipificación/métodos , Masculino , Polimorfismo de Nucleótido Simple , Embarazo , Diagnóstico Prenatal/métodos , TriploidíaRESUMEN
BACKGROUND: Brucellosis is a disease of worldwide public health and economic importance. Successful control is based on knowledge of epidemiology and strains present in an area. In developing countries, most investigations are based on serological assays. This study aimed at investigating a dairy herd experiencing abortions in order to establish within-herd seroprevalence to Brucella spp., identify, characterize Brucella strains by Multiple Loci Variable Number of Tandem Repeats Analysis (MLVA-VNTR) and investigate possible spillover to other species. RESULTS: The within-herd seroprevalence in cattle (n = 200) was 48 % (95 % CI 41-55), using an indirect ELISA, while the Rose Bengal Test (RBT) yielded lower prevalence (21.5 %; 95 % CI 16-27). Two sheep (n = 35) and one goat (n = 50) were seropositive using ELISA while none of the dogs (n = 6) was positive with the RBT. Three Brucella were isolated from an aborted fetus and associated membranes. Real time PCR (IS711), Bruce-ladder and classical biotyping classified the isolates as B. abortus biovar 3. MLVA-VNTR revealed two different but closely related genotypes. The isolates showed unique profiles, providing the first genotypic data from Tanzania. These genotypes were not related to B. abortus biovar 3 reference strain Tulya originally isolated from a human patient in Uganda in 1958, unlike the genotypes isolated and characterized recently in Kenya. High within-herd prevalence, isolation of the pathogen and abortion confirm that B. abortus is circulating in this herd with cattle as reservoir hosts. A low seroprevalence in sheep and goats suggests a spillover of B. abortus from cattle to small ruminants in the herd. CONCLUSIONS: This is the first isolation and characterization of B. abortus biovar 3 from a dairy cow with abortion in Tanzania. The origin of the Tanzanian genotypes remain elusive, although they seem to be related to genotypes found in Europe, Turkey and China but not related to B. abortus biovar 3 reference strain or genotypes from Kenya. Importantly, replacement heifers are commonly sourced from large farms like this to smallholder farmers, which poses risk of spread of bacteria to other herds. B. abortus is a significant zoonotic risk and animal health problem in this production system, therefore further studies on humans is recommended.
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Brucella abortus/genética , Brucelosis Bovina/microbiología , Animales , Brucella abortus/clasificación , Brucella abortus/aislamiento & purificación , Brucelosis Bovina/epidemiología , Bovinos , Genotipo , Estudios Seroepidemiológicos , Tanzanía/epidemiologíaRESUMEN
In the past, the use of animals for transport and traction has been of economic importance all over the world, and this is still the case in certain areas of the world today, especially in rural and peri-urban areas of developing and transition countries. In Chile, for example, thousands of families rely on draught animal power as a fundamental source of income. This provides an opportunity to generate scientific information to increase understanding of the relationship between human well-being and that of domestic animals. Minimising the risks associated with poor draught animal welfare should be beneficial for this relationship. Given the important role of working equids as a source of wealth, in Chile and similar countries, different strategies have been implemented to address the health and welfare of these animals. For these strategies to be successful it is essential to establish appropriate government policies as well as to consider the cultural, political and geographical situation of the regions in which these equids work.
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Crianza de Animales Domésticos/métodos , Bienestar del Animal/normas , Caballos , Crianza de Animales Domésticos/economía , Bienestar del Animal/economía , Animales , Chile , PobrezaRESUMEN
Cerebral palsy (CP) affects body posture and movement coordination and is the most common cause of severe disability in the pediatric population. The diagnosis of CP is not a description of a person's functioning or interaction with their environment. Therefore, the diagnosis should be complemented with a description of functioning, using tools based on the biopsychosocial model proposed by the World Health Organization's International Classification of Functioning, Disability and Health (ICF). This report describes the preliminary data from a multicenter study conducted in Argentina with the aim of standardizing the description of the profiles of functioning of children and adolescents with CP. These data showed that the participants had some skills in sleep functions, mental functions of language, seeing functions, and in some environmental factors. They showed significant difficulties in categories such as maintaining body position, walking, and toileting.
La parálisis cerebral (PC) afecta la postura y la coordinación del movimiento, y es la causa más común de discapacidad grave en la población pediátrica. El diagnóstico de PC no describe el funcionamiento ni la interacción de la persona con el contexto en el cual se desarrolla. Por lo tanto, el diagnóstico se debe complementar con una descripción del funcionamiento, utilizando herramientas basadas en el modelo biopsicosocial de la Clasificación del Funcionamiento (CIF) de la Organización Mundial de la Salud (OMS). En esta comunicación, describimos los datos preliminares de un estudio multicéntrico en Argentina destinado a estandarizar la descripción del perfil de funcionamiento en niños y adolescentes con PC. Estos datos mostraron que los participantes tienen algunas habilidades en las funciones del sueño, las funciones mentales del lenguaje y las visuales, así como en algunas relacionadas con el contexto. Presentan dificultades importantes en categorías tales como mantener la posición del cuerpo, el andar y la higiene.
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Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new clinical practice guide is presented, addressing the most relevant management and intervention aspects based on the recent literature. A group of 24 intensivists from 9 countries of the Pan-American and Iberian Federation of Societies of Critical Medicine and Intensive Therapy met to develop the guidelines. Assessment of evidence quality and recommendations was made according to the Grading of Recommendations Assessment, Development and Evaluation Working Group. A systematic search of the literature was carried out using MEDLINE, Cochrane Library databases such as the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects, the National Health Service Economic Evaluation Database and the database of Latin American and Caribbean Literature in Health Sciences (LILACS). A total of 438 references were selected. After consensus, 47 strong recommendations with high and moderate quality evidence, 14 conditional recommendations with moderate quality evidence, and 65 conditional recommendations with low quality evidence were established. Finally, the importance of initial and multimodal pain management was underscored. Emphasis was placed on decreasing sedation levels and the use of deep sedation only in specific cases. The evidence and recommendations for the use of drugs such as dexmedetomidine, remifentanil, ketamine and others were incremented.
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Analgesia/métodos , Anestesia/métodos , Enfermedad Crítica/terapia , Delirio/terapia , Analgesia/normas , Anestesia/normas , Benzodiazepinas/administración & dosificación , Sedación Consciente/métodos , Sedación Consciente/normas , Cuidados Críticos/métodos , Cuidados Críticos/normas , Medicina Basada en la Evidencia/normas , Humanos , Hipnóticos y Sedantes/administración & dosificación , Unidades de Cuidados Intensivos , Midazolam/administración & dosificación , Manejo del Dolor/normasRESUMEN
We describe the synthesis of a tetrapyridinium phenyl extended calix[4]pyrrole that is soluble in neutral water solution at mM concentrations. We show that, in pure water, the synthesized calix[4]pyrrole receptor selectively binds the cis-(E) conformers of secondary N-phenyl-amides and tertiary N-methyl-N-phenyl-formamide with binding affinities larger than 103 M-1. The conformational selectivity is remarkable owing to the energetic preference of amides to adopt the trans-(Z) conformation in solution. In this respect, we used two binding models for the mathematical analyses of the titration data and calculated apparent and intrinsic binding constants. The combined action of hydrogen bonding and the hydrophobic effect that operates in the binding of the amides in water is responsible for the large affinities displayed by the receptor.
RESUMEN
Alginate encapsulation is one of the most widely used techniques for introducing cell-based therapeutics into the body. Numerous encapsulation methodologies exist, utilizing a variety of alginates, purification technologies, and unique polycationic membrane components. The stability of a conventional alginate formulation encapsulated using a commercially available technique and apparatus has been characterized extensively. The current study employs an encapsulation protocol and ultra-pure alginate pioneered at the University of Perugia. The enhanced microcapsules were produced, characterized, and implanted into the brain, peritoneal cavity, and subcutaneous space of Long-Evans rats. After 14, 28, 60, 90, 120, and 180 or 215 days, capsules were explanted and the surface was analyzed using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Image analysis was carried out to measure changes in diameter and wall thickness. FTIR peak analysis and surface morphology from SEM indicated that the enhanced encapsulation technique and formulation produced a stable biocapsule capable of survival in all sites, including the harsh peritoneal environment, for at least 215 days. Preimplant analysis showed a marked increase in the structural integrity of the enhanced formulation with improved elasticity and burst strength compared with the baseline formulation, which remained stable for less than 60 days. The enhanced microcapsule composition showed advantages in physical strength and longevity, indicating that small changes in encapsulation methodologies and materials selection can dramatically impact the stability and longevity of alginate microcapsules and their contents.
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Alginatos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/metabolismo , Cápsulas/síntesis química , Cápsulas/metabolismo , Ensayo de Materiales/métodos , Péptidos/química , Alginatos/metabolismo , Animales , Materiales Biocompatibles/química , Cápsulas/química , Cromatografía en Gel , Ácido Glucurónico/química , Ácido Glucurónico/metabolismo , Ácidos Hexurónicos/química , Ácidos Hexurónicos/metabolismo , Luz , Masculino , Péptidos/metabolismo , Peritoneo/ultraestructura , Prótesis e Implantes , Ratas , Ratas Long-Evans , Dispersión de Radiación , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Chromosomal abnormalities are implicated in a substantial number of human developmental syndromes, but for many such disorders little is known about the causative genes. The recently described 1q41q42 microdeletion syndrome is characterized by characteristic dysmorphic features, intellectual disability and brain morphological abnormalities, but the precise genetic basis for these abnormalities remains unknown. Here, our detailed analysis of the genetic abnormalities of 1q41q42 microdeletion cases identified TP53BP2, which encodes apoptosis-stimulating protein of p53 2 (ASPP2), as a candidate gene for brain abnormalities. Consistent with this, Trp53bp2-deficient mice show dilation of lateral ventricles resembling the phenotype of 1q41q42 microdeletion patients. Trp53bp2 deficiency causes 100% neonatal lethality in the C57BL/6 background associated with a high incidence of neural tube defects and a range of developmental abnormalities such as congenital heart defects, coloboma, microphthalmia, urogenital and craniofacial abnormalities. Interestingly, abnormalities show a high degree of overlap with 1q41q42 microdeletion-associated abnormalities. These findings identify TP53BP2 as a strong candidate causative gene for central nervous system (CNS) defects in 1q41q42 microdeletion syndrome, and open new avenues for investigation of the mechanisms underlying CNS abnormalities.
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Proteínas Reguladoras de la Apoptosis/deficiencia , Deleción Cromosómica , Proteínas Supresoras de Tumor/deficiencia , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Encéfalo/anomalías , Encéfalo/patología , Embrión de Mamíferos/anomalías , Embrión de Mamíferos/patología , Femenino , Eliminación de Gen , Ventrículos Cardíacos/anomalías , Ventrículos Cardíacos/patología , Imagen por Resonancia Magnética , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Defectos del Tubo Neural/patología , Fenotipo , Síndrome , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Xenopus laevis oocytes codify a G-protein-activated inward rectifier potassium channel (GIRK5 or Kir3.5). Coinjection of other GIRKs, the muscarinic m2 receptor, or Gbetagamma protein cRNAs is required to observe functional GIRKx-GIRK5 heteromultimers in oocytes. Studies with GIRK2 isoforms have shown that the size of the amino or carboxyl terminus plays a crucial role on giving functional K(+) channels. In this work we studied the properties of a GIRK5 with 25 amino acids deleted toward its amino-terminal domain. Injection of GIRK5-Delta25 cRNA alone displayed large basal and transient inward rectifying currents in oocytes. The instantaneous currents reached a stationary level after a long duration voltage pulse (10 s). For this relaxation, fast (tau(1)) and slow (tau(2)) time constants were estimated at different voltages. Recovery from inactivation followed a monoexponential function (tau=0.95+/-0.07 s). By contrast with other inward rectifier channels, blockade of GIRK5-Delta25 by extracellular Ba(2+) was voltage-independent (K(d)=102+/-2 microM), suggesting the presence of a Ba(2+) site at the external channel vestibule. To confirm this hypothesis, the Ba(2+) sensitivity of two charged mutants GIRK5-Delta25(N129E) and GIRK5-Delta25(K157E) at each of the external loops was determined. GIRK5-Delta25(N129E) and GIRK5-Delta25(K157E) showed a 100-fold and 2-fold higher affinity to Ba(2+), respectively, supporting the existence of this Ba(2+) binding site.
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Oocitos/metabolismo , Canales de Potasio de Rectificación Interna , Canales de Potasio/metabolismo , Animales , Bario/química , Bario/metabolismo , Compuestos de Bario/farmacología , Sitios de Unión , Cationes Bivalentes , Cloruros/farmacología , Electrofisiología , Canales de Potasio Rectificados Internamente Asociados a la Proteína G , Mutación , Bloqueadores de los Canales de Potasio , Canales de Potasio/genética , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes/metabolismo , Electricidad Estática , Transfección , Xenopus laevisRESUMEN
Neonatal porcine islets within alginate microcapsules transplanted intraperitoneally (IP) or within semi-permeable macrocapsules (TheraCyte) and transplanted subcutaneously (SC) survive and reverse diabetes for up to 16 weeks in diabetic autoimmune nonobese diabetic (NOD) mice. The islets in microcapsules transplanted IP into nondiabetic cynomolgus monkeys survived for 8 weeks. Similar results were shown with islets transplanted in TheraCytes. Neither species showed adverse effects or evidence of infection with porcine endogenous retroviruses or other endemic pig viruses. Proof of principle is illustrated for successful xenotransplantation in humans.
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Cápsulas , Trasplante de Islotes Pancreáticos/fisiología , Trasplante Heterólogo/fisiología , Animales , Diabetes Mellitus Tipo 1/cirugía , Trasplante de Islotes Pancreáticos/métodos , Trasplante de Islotes Pancreáticos/patología , Macaca fascicularis , Ratones , Ratones Endogámicos NOD , Porcinos , Trasplante Heterólogo/patologíaRESUMEN
The testis has been shown to be a privileged site for transplantation of allogenic islets in rodents, and the testicular cell aggregates are thought to confer this immunologic privilege. Recently, a group in Mexico reported transplantation of cocultured neonatal porcine islets and Sertoli cells resulting in insulin independence in nonimmunosuppressed type 1 diabetes patients. We have transplanted similar islets alone (naked islets) or cocultured islets with Sertoli cells (islet/Sertoli cells) into an omental site and other locations of nonimmunosuppressed, streptozotocin-induced diabetic male Sprague Dawley (SD) rats. Histologic examination showed viable neonatal porcine islets survived in xenografted rodents for at least 2 days, and some glucagon and inhibin stained cells appear to have survived for 4 days posttransplantation. However, histological examination did not demonstrate any difference in xenograft survival in the islets/Sertoli cells mixture compared to naked islets when transplanted into these nonimmunosuppressed diabetic rats.
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Diabetes Mellitus Experimental/cirugía , Trasplante de Islotes Pancreáticos/patología , Células de Sertoli/trasplante , Trasplante Heterólogo/patología , Animales , Animales Recién Nacidos , Células Cultivadas , Técnicas de Cocultivo , Glucagón/metabolismo , Inmunohistoquímica , Inhibinas/metabolismo , Islotes Pancreáticos , Masculino , Ratas , Células de Sertoli/citología , Porcinos , Factores de TiempoRESUMEN
BACKGROUND: A nonhuman primate model of diabetes is valuable for assessing porcine pancreatic islet transplants that might have clinical benefits in humans. METHODS: Neonatal porcine islets, microencapsulated in alginate-polyornithine-alginate, were injected intraperitoneally (10,000 IEQs/kg islets) into eight adult male cynomolgus monkeys rendered diabetic with streptozotocin. Eight diabetic controls were given an equivalent dose of empty placebo capsules. All subjects received a repeat transplant 3 months after the first. RESULTS: The transplant was well tolerated and no adverse or hypoglycemic events occurred. There were two deaths from nontransplant treatment or diabetic complications unrelated to the transplants. After transplantation, the average insulin dose was reduced in the islet-treated group and increased in the control group. At 12 weeks after the first transplant there was a mean 36% (95% CI: 6% to 65%, P = .02) drop in daily insulin dose compared with the control group. After 24 weeks the difference increased to a mean of 43% (95% CI: 12% to 75%, P = .01) without significant differences in blood glucose values between the two groups. Individual responses after islet transplant varied and one monkey was weaned off insulin by 36 weeks. At terminal autopsy, organs appeared normal and there was no visible peritoneal reaction. No animal had polymerase chain reaction (PCR)-amplified signals of porcine endogenous retrovirus or exogenous virus infections in blood or tissues. CONCLUSION: Repeated intraperitoneal transplantation of microencapsulated neonatal porcine islets is a safe procedure in diabetic primates. It was shown to result in a significant reduction in insulin dose requirement in the majority of animals studied, whereas insulin requirement increased in controls.
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Alginatos , Diabetes Mellitus Experimental/cirugía , Trasplante de Islotes Pancreáticos/métodos , Trasplante Heterólogo/métodos , Animales , Animales Recién Nacidos , Glucemia/metabolismo , Cápsulas , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Modelos Animales de Enfermedad , Ácido Glucurónico , Ácidos Hexurónicos , Insulina/uso terapéutico , Macaca fascicularis , Masculino , PorcinosRESUMEN
Rabies is a viral infectious disease that affects all mammals, including humans. Factors associated with the incidence of rabies include the presence and density of susceptible hosts and potential reservoirs. Currently, Chile is declared free of canine-related rabies, but there is an overpopulation of dogs within the country and an emergence of rabies in bats. Our objectives are to determine potential areas for bat-borne rabies spillover into dog populations expressed as a risk map, and to explore some key features of dog ownership, abundance, and management in Chile. For the risk map, our variables included a dog density surface (dog/km(2)) and a distribution model of bat-borne rabies presence. From literature review, we obtained dog data from 112 municipalities, which represent 33% of the total municipalities (339). At country level, based on previous studies the median human per dog ratio was 4.8, with 64% of houses containing at least one dog, and a median of 0.9 dog per house. We estimate a national median of 5.3 dog/km(2), and a median of 3680 dogs by municipality, from which we estimate a total population of 3.5×10(6) owned dogs. The antirabies vaccination presented a median of 21% of dogs by municipality, and 29% are unrestricted to some degree. Human per dog ratio have a significant (but weak) negative association with human density. Unrestricted dogs have a negative association with human density and income, and a positive association with the number of dogs per house. Considering dog density by municipality, and areas of potential bat-borne rabies occurrence, we found that 163 (â¼48%) of Chilean municipalities are at risk of rabies spillover from bats to dogs. Risk areas are concentrated in urban settlements, including Santiago, Chile's capital. To validate the risk map, we included cases of rabies in dogs from the last 27 years; all fell within high-risk areas of our map, confirming the assertive risk prediction. Our results suggest that the use of dog population parameters may be informative to determine risk areas for bat-rabies spillover events. In addition, we confirm that dog abundance is a neglected and emerging public health concern in Chile, particularly within urban areas, which deserves prompt intervention.
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Quirópteros/virología , Enfermedades de los Perros/transmisión , Rabia/transmisión , Animales , Censos , Chile , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/prevención & control , Perros , Mapas como Asunto , Propiedad , Rabia/epidemiología , Rabia/prevención & control , Vacunas Antirrábicas/uso terapéutico , Análisis de Regresión , Medición de RiesgoRESUMEN
Inflammatory bowel Disease (IBD) is a group of chronic inflammatory diseases that can be associated with different autoimmune diseases, including autoimmune hepatitis (AIH). Some specific and differential characteristics in children with IBD associated to AIH have been described. Our aim is to describe the clinical pattern of this association observed in our patients, confirming its differential characteristics as compared to classical IBD in children.