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1.
Cryo Letters ; 45(2): 134-138, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38557992

RESUMEN

BACKGROUND: Examining semen cryopreservation in Calomys laucha offers valuable insights for reproductive research and species conservation. OBJECTIVE: To determine the most effective sugar for the cryopreservation of C. laucha semen. MATERIALS AND METHODS: Using 36 epididymides from C. laucha, semen samples were diluted in a 3% skimmed milk medium supplemented with one of four sugars (glucose, fructose, lactose, or sucrose) at a concentration of 0.3 M. These mixtures underwent a conditioning phase at 37 degree C for 10 min, cooled to -80 degree C for another 10 min, and were subsequently stored in liquid nitrogen. RESULTS: Upon thawing, samples treated with lactose and glucose solutions show superior sperm motility, achieving 8.2% and 10.0% respectively, in contrast to the fructose (2.0%) and sucrose (4.1%) mixtures. Furthermore, samples preserved in glucose registered the highest sperm penetration rates, reaching 44.9%. CONCLUSION: Our findings suggest that a cryopreservation medium containing 0.3 M glucose can contribute to the safeguarding C. laucha rodent semen. https://doi.org/10.54680/fr24210110612.


Asunto(s)
Preservación de Semen , Semen , Animales , Masculino , Criopreservación , Lactosa , Roedores , Motilidad Espermática , Glucosa/farmacología , Fructosa , Sacarosa/farmacología , Espermatozoides , Crioprotectores
2.
Biol Sex Differ ; 15(1): 13, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297404

RESUMEN

BACKGROUND: The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment. METHODS: A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms. RESULTS: Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process. CONCLUSIONS: Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.


Alzheimer's disease (AD)­a neurodegenerative disease mainly affecting older patients­is characterized by cognitive deterioration, memory loss, and progressive incapacitation in daily activities. While AD affects almost twice as many females as males, and cognitive deterioration and brain atrophy develop more rapidly in females, the biological causes of these differences remain poorly understood. MicroRNAs (miRNAs) regulate gene expression and impact a wide variety of biological processes; therefore, studying the differential expression of miRNAs in female and male AD patients could contribute to a better understanding of the disease. We reviewed studies of miRNA expression in female and male AD patients and integrated results using a meta-analysis methodology and then identified those genes regulated by the altered miRNAs to establish an association with biological processes. We found 16 (females) and 22 (males) miRNAs altered in the blood of AD patients. Functional enrichment revealed sex-based differences in the affected altered biological processes­protein modification and degradation and cell death in male AD patients and RNA processing in female AD patients. A similar analysis in the brains of AD patients revealed six (females) and four (males) miRNAs with altered expression; however, our analysis failed to highlight any specifically altered biological processes. Overall, we highlight the sex-based differential expression of miRNAs (and biological processes affected) in the blood and brain of AD patients.


Asunto(s)
Enfermedad de Alzheimer , MicroARNs , Humanos , Masculino , Femenino , Enfermedad de Alzheimer/genética , MicroARNs/metabolismo , Encéfalo/metabolismo
3.
Oper Dent ; 48(6): 689-699, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37881035

RESUMEN

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of glazing, two zirconia, and two lithium disilicate polishing systems on surface roughness of a CAD/CAM lithium disilicate and virgilite ceramic with atomic force microscopy (AFM) and visual assessment performed by dental students and faculty. METHODS AND MATERIALS: Sixty maxillary right central incisor crowns made of a novel chairside CAD/CAM lithium disilicate and virgilite (CEREC Tessera) were milled for glazing and polishing. The crowns were divided into six groups: no polishing/glazing provided (NoP/G); glazed (GZ); glazed and polished with Brasseler Dialite LD Lithium Disilicate (DiLD); glazed and polished with Meisinger Luster Lithium Disilicate (LuLD); glazed and polished with Brasseler Dialite ZR Zirconia (DiZR); and glazed and polished with Meisinger Luster Zirconia (LuZR). Surfaces were scanned with AFM to measure roughness (Ra) and root mean square roughness (Rq) and generate micrographs. Crowns were visually assessed by 10 dental students and 10 dental school faculty members to determine clinical acceptableness. RESULTS: Glazing and all polishing kits significantly reduced Ra and Rq compared to no polishing/glazing. No significant Ra differences were found between glazing and all polishing kits (p>0.05). DiZR significantly reduced Rq compared to other groups (p<0.05). Visual assessment showed that GZ, LuLD, and DiZR were the most clinically acceptable crowns. CONCLUSION: Polishing and glazing considerably improve the surface smoothness of maxillary central incisor crowns fabricated out of a chairside CAD/CAM lithium disilicate and virgilite ceramic. Altogether, zirconia polishing systems provided smoother and more clinically acceptable surfaces than the lithium disilicate kits.


Asunto(s)
Pulido Dental , Porcelana Dental , Humanos , Ensayo de Materiales , Pulido Dental/métodos , Propiedades de Superficie , Cerámica , Coronas , Diseño Asistido por Computadora , Microscopía Electrónica de Rastreo
4.
Minerva Pediatr (Torino) ; 75(4): 460-467, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-29968451

RESUMEN

BACKGROUND: Many studies have already shown that individuals suffering from autism spectrum disorders (ASD) present low levels of empathy: in fact, reduced emotional reciprocity is considered a clinically significant indicator of autistic functioning. We decided to investigate the role of empathy in determining pathological behaviors in children affected by ASD considering parents' point of view; and to evaluate the presence of differences between mothers and fathers' perception of their child's empathy and behaviors. METHODS: We compared empathy levels in a sample of 58 patients with ASD as reported by a parent-filled questionnaire with the results of a global evaluation conducted by means of play observations, clinician-rated scales, a semistructured interview with both caregivers and parent-filled questionnaires. RESULTS: The majority of ASD patients have low levels of empathy according to both parents' points of view; noteworthy, mothers and fathers are highly concordant in this respect. Children's levels of empathy negatively correlate with many behavioral problems, both internalizing and externalizing. Furthermore, we found that mothers tend to perceive more internalizing problems, while fathers are more willing to notice externalizing ones. CONCLUSIONS: Involving both caregivers in children's diagnostic assessment could deepen patient's evaluation and finally the therapeutic results. Mothers and fathers seem to be highly consistent in describing the psychological characteristics of their child, but not in respect to symptoms.


Asunto(s)
Trastorno del Espectro Autista , Masculino , Femenino , Humanos , Niño , Trastorno del Espectro Autista/diagnóstico , Padre/psicología , Empatía , Madres/psicología , Padres
5.
Minerva Pediatr (Torino) ; 75(5): 719-726, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32274908

RESUMEN

BACKGROUND: Literature states that parents of individuals affected by autism spectrum disorder (ASD) can present social and cognitive deficits, restricted behavior patterns and psychiatric difficulties, without meeting standard diagnostic criteria for ASD ("broader autism phenotype"). We explored the relationship between parenting of children affected by ASD and levels of empathy and lack of emotion understanding (alexithymia). METHODS: We enlisted 58 families in which a child was affected by ASD. Parents' empathy and alexithymia were respectively assessed by means of Empathy Quotient (EQ) and Toronto Alexithymia Scale (TAS-20). Additionally, we included the assessment of the perception of children's behavior through the Child Behavior Checklist (CBCL). RESULTS: Our findings suggest that most parents have normal empathy and do not show significant alexithymia. We found lower EQ and higher TAS-20 scores being more frequent in fathers. Moreover, each parent's empathy degree negatively relates to his/her alexithymia and vice versa, showing that these two features are inversely correlated. Our study unveiled a strong correlation between maternal empathy and alexithymia and child's externalizing problems, as reported by mothers. CONCLUSIONS: Our data reveal differences in mothers and fathers' empathy and alexithymia profiles and confirm the importance of considering both parents' points of view either in the diagnostic and the therapeutic interventions. Parental empathy and alexithymia levels not only play a fundamental role in the evaluation of child's difficulties but can also influence the development of a good relationship with the child for what concerns affective resonance.

7.
Arq. bras. med. vet. zootec. (Online) ; 73(6): 1431-1435, Nov.-Dec. 2021. tab, ilus
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1355672

RESUMEN

A radiologia é uma importante ferramenta complementar para o diagnóstico de diversas afecções em diferentes espécies. O uso de exames complementares na medicina de animais silvestres, em especial o exame de imagem, traz inúmeras informações acerca do paciente. Este trabalho apresenta os dados obtidos por meio de um levantamento dos exames radiográficos realizados em animais silvestres entre os anos de 2017 e 2020, no Laboratório de Diagnóstico de Imagem e Cardiologia (LADIC), do Hospital de Clínicas Veterinárias da Universidade Federal de Pelotas (HCV/UFPel). Ao todo, foram avaliados 464 prontuários, sendo 293 (63,1%) de aves, 135 (29,1%) de mamíferos e 36 (7,8%) de répteis. As alterações mais encontradas nos exames radiológicos foram fratura de membros torácicos para as duas primeiras classes, e pneumonia para a última.(AU)


Asunto(s)
Animales , Neumonía/diagnóstico por imagen , Traumatismos Torácicos/diagnóstico por imagen , Animales Salvajes/lesiones , Brasil , Radiografía/veterinaria , Radiografía/estadística & datos numéricos
8.
Expert Opin Drug Metab Toxicol ; 17(10): 1187-1198, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34452592

RESUMEN

INTRODUCTION: Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurines (mercaptopurine (MP) and tioguanine (TG)), chemotherapeutic agents used in the treatment of acute lymphoblastic leukemia (ALL). Polymorphisms in TPMT gene encode diminished activity enzyme, enhancing accumulation of active metabolites, and partially explaining the inter-individual differences in patients' clinical response. AREAS COVERED: This review gives an overview on TPMT gene and function, and discusses the pharmacogenomic implications of TPMT variants in the prevention of severe thiopurine-induced hematological toxicities and the less known implication on TG-induced sinusoidal obstruction syndrome. Additional genetic and non-genetic factors impairing TPMT activity are considered. Literature search was done in PubMed for English articles published since1990, and on PharmGKB. EXPERT OPINION: To titrate thiopurines safely and effectively, achieve the right degree of lymphotoxic effect and avoid excessive myelosuppression, the optimal management will combine a preemptive TPMT genotyping to establish a safe initial dose with a close phenotypic monitoring of TPMT activity and/or of active metabolites during long-term treatment. Compared to current ALL protocols, replacement of TG by MP during reinduction phase in TPMT heterozygotes and novel individualized TG regimens in maintenance for TPMT wild-type subjects could be investigated to improve outcomes while avoiding risk of severe hepatotoxicity.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Metiltransferasas/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Animales , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/farmacocinética , Genotipo , Humanos , Mercaptopurina/administración & dosificación , Mercaptopurina/efectos adversos , Mercaptopurina/farmacocinética , Metiltransferasas/metabolismo , Terapia Molecular Dirigida , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimología , Tioguanina/administración & dosificación , Tioguanina/efectos adversos , Tioguanina/farmacocinética
9.
Vaccines (Basel) ; 9(7)2021 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-34206597

RESUMEN

The etiology of Parkinson's disease (PD), a progressive nervous system disorder that affects movement, is still unknown; both genetic and environmental factor are believed to be involved in onset of the disease and its development. Herpes simplex virus type 1 (HSV-1), in particular, is suspected to have a role in PD. Paired Immunoglobulin-like type 2 receptor alpha (PILRA) is an inhibitory receptor that down-regulates inflammation and is expressed on innate immune cells. The PILRA rs1859788 polymorphism is protective against Alzheimer's disease, even in relation with HSV-1 antibody titers, but no data are available in PD. We analyzed HSV-1 antibody titers and PILRA rs1859788 in PD (n = 51) and age-and sex-matched healthy controls (HC; n = 73). Results showed that HSV-1, but not cytomegalovirus (CMV) or human herpes virus type 6 (HHV-6) antibody titers were significantly higher in PD compared to HC (p = 0.045). The rs1859788 polymorphism was not differentially distributed between PD and HC, but the minor allele A was more frequently carried by PD (68%) compared to HC (50%) (p = 0.06). Notably, the rs1859788 minor allele A was statically more frequent in male PD (65%) compared to male HC (37%) (p = 0.036). Finally, no relation was found between HSV-1 antibody titers and PILRA genotype. Results herein suggest an involvement of HSV-1 in PD and indicate a possible interaction between PILRA gene polymorphisms and this neuropathology.

10.
Mult Scler J Exp Transl Clin ; 7(2): 20552173211017301, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34104473

RESUMEN

BACKGROUND: Childhood neurodevelopmental disorders (NDDs), including specific learning disorders (SLD), attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are pathogenically linked to familial autoimmunity and maternal immune-mediated diseases during pregnancy. OBJECTIVE: We studied maternal MS as a potential risk factor for NDDs occurrence in offspring. METHODS: MS and control mothers were subjected to questionnaires to ascertain NDD diagnosis in their progeny and the occurrence of both autoimmune and neurodevelopment disorders in their families. Suspected NDD cases were evaluated to confirm or rule out the diagnosis. RESULTS: Of the 322 MS women, 206 (64%) have 361 children; of these, 27 (7.5%) were diagnosed with NDD (11% ADHD; 22% ASD; 67% SLD). NDD-risk in offspring was associated to family history of autoimmunity and to NDDs both in MS and non-MS mother families (r = 0.75; p = 0.005) whereas it was not associated to maternal MS. CONCLUSIONS: For the first time, we demonstrate that maternal MS does not predispose children to higher risk for NDD. On a mechanistic view, we suggest that the intrinsic organ-specific nature of MS does not impair the mother-child cross-talk in decidua nor does it influence fetal neurodevelopment.

11.
Br J Haematol ; 193(6): 1228-1237, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34046885

RESUMEN

Sickle cell disease (SCD) is a widespread genetic disease associated with severe disability and multi-organ damage, resulting in a reduced life expectancy. None of the existing clinical treatments provide a solution for all patients. Gene therapy and fetal haemoglobin (HbF) reactivation through genetic approaches have obtained promising, but early, results in patients. Furthermore, the search for active molecules to increase HbF is still ongoing. The delta-globin gene produces the delta-globin of haemoglobin A2 (HbA2). Although expressed at a low level, HbA2 is fully functional and could be a valid anti-sickling agent in SCD. To evaluate the therapeutic potential of a strategy aimed to over-express the delta-globin gene in vivo, we crossed transgenic mice carrying a single copy of the delta-globin gene, genetically modified to be expressed at a higher level (activated), with a humanised mouse model of SCD. The activated delta-globin gene gives rise to a consistent production of HbA2, effectively improving the SCD phenotype. For the first time in vivo, these results demonstrate the therapeutic potential of delta-globin, which could lead to novel approaches to the cure of SCD.


Asunto(s)
Anemia de Células Falciformes/metabolismo , Regulación de la Expresión Génica , Globinas delta/biosíntesis , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/terapia , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Transgénicos , Globinas delta/genética
12.
Medicine (Baltimore) ; 98(24): e15846, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31192914

RESUMEN

Ischemic heart disease (IHD) has a genetic predisposition and a number of cardiovascular risk factors are known to be affected by genetic factors. Development of metabolic syndrome and insulin resistance, strongly influenced by lifestyle and environmental factors, frequently occur in subjects with a genetic susceptibility. The definition of genetic factors influencing disease susceptibility would allow to identify individuals at higher risk and thus needing to be closely monitored.To this end, we focused on a complex of soluble-N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), playing an important role in metabolic syndrome and insulin resistance, involved in endothelial dysfunction and heart disease. We assessed if genetic variants of the SNARE genes are associated with IHD.SNAP25 rs363050, Stx-1A rs4717806, rs2293489, and VAMP2 26bp ins/del genetic polymorphisms were analyzed in a cohort of 100 participants who underwent heart surgery; 56 of them were affected by IHD, while 44 were not. A statistical association of plasma glycemia and insulin resistance, calculated as Triglyceride glucose (TyG) index, was observed in IHD (P < .001 and P = .03, respectively) after binomial logistic stepwise regression analysis, adjusted by age, gender, diabetes positivity, waist circumference, and cholesterol plasma level. Among genetic polymorphisms, rs4717806(A) and rs2293489(T), as well as the rs4717806 - rs2293489 (A-T) haplotype were associated with higher risk for IHD (Pc = .02; Pc = .02; P = .04, respectively). Finally, a statistical association of rs4717806(AA) genotype with higher TyG index in IHD patients (P = .03) was highlighted by multiple regression analysis considering log-transformed biochemical parameters as dependent variable and presence of coronary artery disease, age, gender, waist circumference, presence of diabetes as predictors. These results point to a role of the Stx-1A rs4717806 SNP in IHD, possibly due to its influence on Stx-1A expression and, as a consequence, on insulin secretion and glucose metabolism.


Asunto(s)
Estudios de Asociación Genética/métodos , Isquemia Miocárdica/genética , Isquemia Miocárdica/cirugía , Polimorfismo de Nucleótido Simple , Sintaxina 1/genética , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Cardíacos , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Mutación INDEL , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteína 25 Asociada a Sinaptosomas/genética , Proteína 2 de Membrana Asociada a Vesículas/genética
13.
Brain Behav Immun ; 79: 314-318, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30763769

RESUMEN

Recent results show that in mainland Italian children with Autism spectrum disorder (ASD), HLA-G coding alleles distribution is skewed and an association between HLA-G*01:05N and ASD is present. Herein, in an independent cohort of Sardinian ASD (sASD) children and their relatives, we verify whether HLA-G allele association with ASD could be confirmed in this genetically peculiar insular population. One hundred children with a diagnosis of ASD, born in Sardinia and of Sardinian descent, 91 of their mothers, and 40 of their healthy siblings were enrolled. DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies. Alleles distribution was compared with that of continental ASD children and with a control group of Caucasoid couples of multiparous women and their partners from Brazil and Denmark. Skewing of HLA-G allele distribution was replicated in sASD children; in particular, the HLA-G*01:03 allele, associated with reduced fetal tolerogenicity and development of myeloid leukemia, was more common in both ASD groups compared to controls (pc = 1 × 10-3; OR:3.5, 95%CI: 1.8-6.8). However, given the lack of data on HLA-G*01:03 allelic distribution among Sardinian healthy subjects, we cannot exclude a population effect. These data confirm an association of HLA-G locus with ASD development, particularly with those alleles linked to a lower expression of tolerogenic HLA-G protein, thus warranting further studies on HLA-G polymorphism distribution in different ASD populations.


Asunto(s)
Trastorno del Espectro Autista/genética , Antígenos HLA-G/genética , Adulto , Alelos , Trastorno del Espectro Autista/inmunología , Niño , Estudios de Cohortes , Etnicidad/genética , Exones/genética , Femenino , Frecuencia de los Genes/genética , Genes MHC Clase I/genética , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA-G/inmunología , Haplotipos , Humanos , Italia , Masculino , Polimorfismo Genético/genética
14.
Mol Neurobiol ; 56(8): 5792-5798, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30680692

RESUMEN

A loss of synaptic density and connectivity is observed in multiple brain regions of Alzheimer's disease (AD) patients, resulting in a reduced expression of synaptic proteins such as SNAP-25 (synaptosomal-associated-protein-25). SNAP-25 alterations thus could be an index of the degree of synaptic degeneration in the central nervous system (CNS). We isolated from serum of both AD patients and healthy controls (HC) a population of neuron-derived exosomes (NDEs) and measured the concentrations of SNAP-25 contained in such NDEs. The levels of SNAP-25 carried by NDEs were reduced in AD patients (mean 459.05 ng/ml, SD 146.35 ng/ml) compared to HC (mean 686.42 ng/ml, SD 204.08 ng/ml) (p < 0.001). As a further confirmation of these results, ROC (receiver operating characteristic) analyses indicated that the level of SNAP-25 carried by NDEs has the power to discriminate between AD and HC (AUC = 0.826, sensitivity = 87.5%, specificity = 70.6%, p < 0.0001, cut-off value 587.07 ng/ml). Notably, a correlation between the levels of SNAP-25 carried by NDEs and levels and cognitive status measured by MMSE score (r = 0.465, 95% CI 0.11 to 0.714, p = 0.01) was detected. This is the first report of SNAP-25 measurement in serum. These data suggest that NDE-carried SNAP-25 could be an effective and accessible biomarker that reflects synapses integrity in the brain.


Asunto(s)
Enfermedad de Alzheimer/sangre , Exosomas/metabolismo , Neuronas/metabolismo , Proteína 25 Asociada a Sinaptosomas/sangre , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Curva ROC
17.
J Transl Med ; 16(1): 80, 2018 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-29587799

RESUMEN

BACKGROUND: The etiopathology of multiple sclerosis (MS) is believed to include genetic and environmental factors. Human leukocyte antigen (HLA) alleles, in particular,  are associated with disease susceptibility, whereas Epstein Barr Virus (EBV) infection has long been suspected to play a role in disease pathogenesis. The aim of the present study is to evaluate correlations between HLA alleles and EBV infection in MS. METHODS: HLA alleles, EBV viral load (VL) and serum anti-EBV antibody titers were evaluated in EBV-seropositive MS patients (N = 117) and age- and sex-matched healthy controls (HC; N = 89). RESULTS: Significantly higher DNA viral loads (p = 0.048) and EBNA-1 antibody titer (p = 0.0004) were seen in MS compared to HC. EBV VL was higher in HLA-B*07+ (p = 0.02) and HLA-DRB1*15+ (p = 0.02) MS patients, whereas it was lower in HLA-A*02+ (p = 0.04) subjects. EBV VL was highest in HLA-A*02-/B*07+/DRB1*15+ patients and lowest in HLA-A*A02+/B*07-/DRB1*15- individuals (p < 0.0001). HLA-B*07 resulted the most associated allele to EBV VL after multiple regression analysis considering altogether the three alleles, (p = 0.0001). No differences were observed in anti-EBV antibody titers in relationship with HLA distribution. CONCLUSIONS: Host HLA-B*07 allele influence EBV VL in MS. As HLA-class I molecules present antigens to T lymphocytes and initiate immune response against viruses, these results could support a role for EBV in MS.


Asunto(s)
Alelos , Antígenos HLA/genética , Herpesvirus Humano 4/fisiología , Esclerosis Múltiple/genética , Esclerosis Múltiple/virología , Carga Viral , Adulto , Estudios de Casos y Controles , Citomegalovirus/fisiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Estudios Seroepidemiológicos
18.
Brain Behav Immun ; 67: 308-313, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28923404

RESUMEN

Different isoforms of HLA-G protein are endowed with a differential ability to induce allogenic tolerance during pregnancy. As prenatal immune activation is suggested to play a role in the onset of autistic spectrum disorders (ASD), we evaluated HLA G*01:01-*01:06 allelic polymorphism in a cohort of Italian children affected by ASD (N=111) their mothers (N=81), and their healthy siblings (N=39). DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies; alleles distribution was compared with that of two control groups of Caucasoid couples of multiparous women and their partners from Brazil and Denmark. HLA-G distribution was significantly different in ASD children compared to both control groups (Brazilian pc=1×10-4; Danish pc=1×10-3). Since HLA-G distribution was similar in the two control groups, their data were pooled. Results indicated that HLA-G*01:01 was significantly less frequent (pc=1×10-4; OR:0.5, 95%CI: 0.3-0.7) whereas HLA-G*01:05N was significantly more frequent (pc=2×10-3; OR:7.3, 95%CI: 2.4-26.6) in ASD children compared to combined controls. Finally, no clear pattern emerged when HLA-G allelic distribution was analyzed in healthy sibs. Notably, HLA-G allelic distribution found in ASD mothers was similar to that observed in the control subgroup of women with recurrent miscarriages, whilst it was significantly different compared to women without miscarriages (pc=6×10-4 df=12). Since HLA-G*01:01 is associated with the elicitation of KIR-mediated tolerogenic responses and HLA-G*01:05N correlates with NK cells activation, results herein indicate that an immune activating milieu during pregnancy is more likely observed in association with the development of ASD, similarly to what occurs in women with recurrent miscarriages.


Asunto(s)
Trastorno del Espectro Autista/genética , Antígenos HLA-G/genética , Niño , Femenino , Frecuencia de los Genes , Humanos , Masculino , Polimorfismo Genético
19.
Neuroscience ; 370: 163-169, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28627421

RESUMEN

Activating KIR-HLA-C ligand complexes and HLA-G∗14bp insertion/deletion (+/-) polymorphism were associated to Autism Spectrum Disorders (ASD) and were suggested to correlate with inflammation during fetal development. We evaluated whether HLA-G∗14bp(+/-) and KIR-HLA-C complexes are associated with cognitive and behavioral scores and EEG profile in 119 ASD children (58 from Sardinia, 61 from Peninsular Italy). KIR2DS1-C2; KIR2DS2-C1; KIR2DL1-C2; KIR2DL2-C1; KIR2DL3-C1 and HLA-G∗14bp(+/-) were molecularly genotyped by Single Specific Primer PCR and gel electrophoresis. Univariate linear model analysis adjusted for age, gender and provenience showed statistically higher scores of Childhood Autism Rating Scale (CARS) and Autistic Core Behavior in KIR2DS1-C2+/HLA-G∗14bp+ASD children (43.7±1.5, p=0.03; 3.3±0.1, p=0.03, respectively). These results suggested a synergistic polygenic association of KIR2DS1-HLAC2+/HLA-G∗14bp+ pattern with behavioral impairment in ASD children.


Asunto(s)
Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/psicología , Antígenos HLA-C/genética , Antígenos HLA-G/genética , Mutación INDEL , Receptores KIR/genética , Trastorno del Espectro Autista/fisiopatología , Encéfalo/fisiopatología , Niño , Estudios de Cohortes , Electroencefalografía , Femenino , Humanos , Masculino , Herencia Multifactorial , Escalas de Valoración Psiquiátrica , Población Blanca/genética
20.
Water Sci Technol ; 76(5-6): 1188-1195, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28876260

RESUMEN

Treatment of the highly polluting and variable textile industry wastewater using aerobic granular sludge (AGS) sequencing batch reactors (SBRs) has been recently suggested. Aiming to develop this technology application, two feeding strategies were compared regarding the capacity of anaerobic-aerobic SBRs to deal with disturbances in the composition of the simulated textile wastewater feed. Both a statically fed, anaerobic-aerobic SBR and an anaerobic plug-flow fed, anaerobic-aerobic SBR could cope with shocks of high azo dye concentration and organic load, the overall chemical oxygen demand and color removal yields being rapidly restored to 80%. Yet, subsequent azo dye metabolite bioconversion was not observed, along the 315-day run. Moreover, switching from a starch-based substrate to acetate in the feed composition deteriorated AGS stability. Overall, the plug-flow fed SBR recovered more rapidly from the imposed disturbances. Further research is needed towards guaranteeing long-term AGS stability during the treatment of textile wastewater.


Asunto(s)
Reactores Biológicos , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , Aerobiosis , Compuestos Azo , Análisis de la Demanda Biológica de Oxígeno , Residuos Industriales , Industria Textil , Textiles
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