Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 423
Filtrar
1.
Climacteric ; 27(2): 187-192, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38108204

RESUMO

OBJECTIVE: Autoimmunity seems to be present in a large proportion of women with spontaneous premature ovarian insufficiency (POI). Whether these women are at increased risk for autoimmune disease has not been determined to date. Therefore, the aim of this study was to investigate a large series of antibodies in order to shed more light into the autoimmune risk of POI women. METHODS: In a prospective case-control study, blood samples from 66 patients with spontaneous POI and 66 healthy controls were analyzed for a series of autoimmune antibodies. RESULTS: POI women revealed significantly increased thyroglobulin antibodies (TGAb) (p = 0.045) and thyroid peroxidase antibodies (TPOAb) (p = 0.002). At least one abnormal autoimmune parameter was present in 37.9% of POI women, compared to 18.2% in healthy controls (p = 0.045). A strong association between POI and increased TGAb (adjusted odds ratio 3.586, p = 0.028), increased TPOAb (adjusted odds ratio 7.496, p = 0.003) and any increased autoimmune parameter (adjusted odds ratio 3.189, p = 0.008) could be demonstrated in a binary logistic regression model. CONCLUSION: A high prevalence of autoimmunity in POI women compared to a healthy young collective could be demonstrated. Thyroid antibodies were significantly increased in POI women. Our data highlight the increased risk for autoimmune diseases, especially for thyroid disorders.


Assuntos
Doenças Autoimunes , Menopausa Precoce , Insuficiência Ovariana Primária , Humanos , Feminino , Estudos de Casos e Controles , Autoanticorpos , Autoimunidade
2.
Biophys Rep (N Y) ; 2(2): None, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-36299769

RESUMO

Cellular functions rely on proper actions of organelles such as peroxisomes. These organelles rely on the import of proteins from the cytosol. The peroxisomal import receptor PEX5 takes up target proteins in the cytosol and transports them to the peroxisomal matrix. However, its cytosolic molecular interactions have so far not directly been disclosed. Here, we combined advanced optical microscopy and spectroscopy techniques such as fluorescence correlation spectroscopy and stimulated emission depletion microscopy with biochemical tools to present a detailed characterization of the cytosolic diffusion and interaction dynamics of PEX5. Among other features, we highlight a slow diffusion of PEX5, independent of aggregation or target binding, but associated with cytosolic interaction partners via its N-terminal domain. This sheds new light on the functionality of the receptor in the cytosol as well as highlighting the potential of using complementary microscopy tools to decipher molecular interactions in the cytosol by studying their diffusion dynamics.

3.
Eur Rev Med Pharmacol Sci ; 26(24): 9275-9310, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36591839

RESUMO

Modern industrial agricultural processes expose human beings to multifactorial environmental pollution including heightened levels of heavy metals. The effects of acute heavy metal exposures at toxic levels are usually known; they are tested for and treated promptly. The effects of low/moderate-level chronic heavy metal exposures are less known as they may be subclinical, and pathogenic effects may only manifest clinically over time under the disguise of a diagnosable disease or miscellaneous symptoms attributed to aging. Consequently, the health impact of low-moderate heavy metal exposure is unlikely to be identified. Furthermore, established heavy metal safety levels often fail to recognize the potential toxic effects on humans. We report in this review what is known about the sub-chronic and chronic effects of exposure to heavy metals, particularly lead, mercury, cadmium, arsenic, and nickel, and we highlight their possible effects in the brain, cardiovascular and endocrine-metabolic systems, and on reproduction.


Assuntos
Arsênio , Metais Pesados , Humanos , Teorema de Bayes , Metais Pesados/toxicidade , Cádmio/toxicidade , Arsênio/toxicidade , Fatores de Risco
4.
J Ovarian Res ; 14(1): 170, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872604

RESUMO

BACKGROUND: Vitrification has superseded the slow freezing method for cryopreservation of oocytes, embryos, and sperm, but there are as yet no standard protocols for its use in ovarian tissue cryopreservation (OTC). Published protocols diverge mainly with regard to the extent of supplementation of dimethyl sulfoxide (DMSO) to the vitrification medium, and to the use of an open or closed vitrification system. We investigated the viability of cells after vitrification/warming, using ovarian tissue of transgender patients, by means of Fluorescence Activated Cells Sorting (FACS), and histomorphological analyses using a DMSO-containing (P1) and a DMSO-free protocol (P2) in an open or closed vitrification setting. RESULTS: Twelve ovarian samples were donated from female-to-male transgender patients: 6 were vitrified according to protocol 1, the other 6 according to protocol 2. The amount of viable cells was 90.1% (P1) and 88.4% (P2) before vitrification. After vitrification and subsequent warming, viable cells were reduced to 82.9% (P1, p = 0.093) and 72.4% (P2, p = 0.019). When comparing the closed and the open systems, the decline in cell viability from pre- to post-vitrification was significant only for the latter (p = 0.037). Histological examination reveals no significant differences with respect to degenerated follicles before or after vitrification. CONCLUSION: These results led us to conclude that a protocol containing DMSO results in a higher viability of ovarian cells than a protocol that uses ethylene glycol as cryoprotective agent in vitrification. The use of an open vitrification system led to significant decline in the rate of viable cells. TRIAL REGISTRATION: NCT03649087 , retrospectively registered 28.08.2018.


Assuntos
Criopreservação/métodos , Ovário , Vitrificação , Adolescente , Adulto , Sobrevivência Celular/efeitos dos fármacos , Dimetil Sulfóxido/farmacologia , Feminino , Humanos , Projetos Piloto , Adulto Jovem
5.
Sci Rep ; 11(1): 11607, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078953

RESUMO

Atom Probe Tomography (APT) is currently a well-established technique to analyse the composition of solid materials including metals, semiconductors and ceramics with up to near-atomic resolution. Using an aqueous glucose solution, we now extended the technique to frozen solutions. While the mass signals of the common glucose fragments CxHy and CxOyHz overlap with (H2O)nH from water, we achieved stoichiometrically correct values via signal deconvolution. Density functional theory (DFT) calculations were performed to investigate the stability of the detected pyranose fragments. This paper demonstrates APT's capabilities to achieve sub-nanometre resolution in tracing whole glucose molecules in a frozen solution by using cryogenic workflows. We use a solution of defined concentration to investigate the chemical resolution capabilities as a step toward the measurement of biological molecules. Due to the evaporation of nearly intact glucose molecules, their position within the measured 3D volume of the solution can be determined with sub-nanometre resolution. Our analyses take analytical techniques to a new level, since chemical characterization methods for cryogenically-frozen solutions or biological materials are limited.

6.
Pharmazie ; 75(1): 27-31, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-32033630

RESUMO

The passive surveillance system is an important tool in pharmacovigilance of vaccines. However, reporting of adverse events following immunization (AEFI) post-marketing has limitations regarding under-reporting, biased reports and lack of exposure data resulting in imprecise estimates. New mobile application technology may provide an opportunity for an enhanced surveillance. A pre-requisite for the use of new app-based technology is to identify practical challenges and end users' preferences for design of app-features. The objectives were (i) to investigate the recruitment and feasibility of an app-based study in Germany, (ii) to assess individuals' motivation to participate in such a study and (iii) to identify app-features for reporting AEFI. We conducted a cross-sectional study among employees of a financial institution who attended the occupational health office during the seasonal influenza vaccination in November 2017. Participants tested feasibility and assessed an app prototype for AEFI reporting by using a case vignette and a questionnaire. Of the 153 attending employees, 65 (42%) agreed to participate and returned the questionnaire. Twenty-three (63%) rated the experience of reporting AEFI with the app prototype to be positive. Among three features offered for gamification, collecting points was most frequently chosen (n=22, 34%). The main reason for declining participation was the apprehension about data protection (n=28, 43%). Results suggest that the app-based technology was well accepted and is a suitable supplement for AEFI reporting and in our study. A convincing data protection concept is likely to enhance acceptability of such a system.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Vacinas contra Influenza/efeitos adversos , Aplicativos Móveis , Vacinação/efeitos adversos , Adolescente , Adulto , Estudos Transversais , Estudos de Viabilidade , Feminino , Alemanha , Humanos , Vacinas contra Influenza/administração & dosagem , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Vigilância da População/métodos , Inquéritos e Questionários , Adulto Jovem
7.
J Opt Soc Am A Opt Image Sci Vis ; 35(6): 1063-1073, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29877322

RESUMO

Photonic wire bonds, i.e., freeform waveguides written by 3D direct laser writing, emerge as a technology to connect different optical chips in fully integrated photonic devices. With the long-term vision of scaling up this technology to a large-scale fabrication process, the in situ optimization of the trajectory of photonic wire bonds is at stake. A prerequisite for the real-time optimization is the availability of a fast loss estimator for single-mode waveguides of arbitrary trajectory. Losses occur because of the bending of the waveguides and at transitions among sections of the waveguide with different curvatures. Here, we present an approach that resides on the fundamental mode approximation, i.e., the assumption that the photonic wire bonds predominantly carry their energy in a single mode. It allows us to predict in a quick and reliable way the pertinent losses from pre-computed modal properties of the waveguide, enabling fast design of optimum paths.

8.
Epidemiol Infect ; 146(3): 372-378, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29357958

RESUMO

Sex differences in the incidence of infections may indicate different risk factors and behaviour but have not been analysed across pathogens. Based on 3.96 million records of 33 pathogens in Germany, notified from 2001 to 2013, we applied Poisson regression to generate age-standardised incidence rate ratios and assessed their distribution across age and sex. The following trends became apparent: (a) pathogens with male incidence preponderance at infant and child age (meningococcal disease (incidence rate ratio (IRR) = 1.19, 95% CI 1.03-1.38, age = 0-4); influenza (IRR = 1.09, 95% CI 1.06-1.13, age = 0-4)), (b) pathogens with sex-switch in incidence preponderance at puberty (e.g. norovirus (IRR = 1.10, 95% CI 1.02-1.19 in age = 5-14, IRR = 0.96, 95% CI 0.93-0.99, age ⩾ 60), (c) pathogens with general male incidence preponderance (bacterial/parasitic infections with campylobacter, Yersinia and Giardia), (d) pathogens with male incidence preponderance at juvenile and adult age (sexually transmitted or vector-borne infections (combined-IRR = 2.53, 95% CI 2.36-2.71, age = 15-59), (e) pathogens with male preponderance at older age (tick-borne encephalitis - IRR = 2.75, 95% CI 1.21-6.24, listeriosis - IRR = 2.06, 95% CI 1.38-3.06, age ⩾ 60). Risk factor concepts only partly serve to interpret similarities of grouped infections, i.e. transmission-related explanations and sex-specific exposures not consistently explain the pattern of food-borne infections (b). Sex-specific differences in infectious disease incidence are well acknowledged regarding the sexually transmitted diseases. This has led to designing gender-specific prevention strategies. Our data suggest that for infections with other transmission routes, gender-specific approaches can also be of benefit and importance.


Assuntos
Doenças Transmissíveis/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/parasitologia , Doenças Transmissíveis/virologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Adulto Jovem
9.
Astron Astrophys ; 6022017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29151605

RESUMO

AIMS: Extragalactic observations of water emission can provide valuable insights into the excitation of the interstellar medium. In particular they allow us to investigate the excitation mechanisms in obscured nuclei, i.e. whether an active galactic nucleus or a starburst dominate. METHODS: We use sub-arcsecond resolution observations to tackle the nature of the water emission in Arp 220. ALMA Band 5 science verification observations of the 183 GHz H2O 313-220 line, in conjunction with new ALMA Band 7 H2O 515-422 data at 325 GHz, and supplementary 22 GHz H2O 616 - 523 VLA observations, are used to better constrain the parameter space in the excitation modelling of the water lines. RESULTS: We detect 183 GHz H2O and 325 GHz water emission towards the two compact nuclei at the center of Arp 220, being brighter in Arp 220 West. The emission at these two frequencies is compared to previous single-dish data and does not show evidence of variability. The 183 and 325 GHz lines show similar spectra and kinematics, but the 22 GHz profile is significantly different in both nuclei due to a blend with an NH3 absorption line. CONCLUSIONS: Our findings suggest that the most likely scenario to cause the observed water emission in Arp 220 is a large number of independent masers originating from numerous star-forming regions.

10.
Comput Biol Chem ; 69: 171-177, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28391977

RESUMO

Construction of phylogenetic trees has traditionally focused on binary trees where all species appear on leaves, a problem for which numerous efficient solutions have been developed. Certain application domains though, such as viral evolution and transmission, paleontology, linguistics, and phylogenetic stemmatics, often require phylogeny inference that involves placing input species on ancestral tree nodes (live phylogeny), and polytomies. These requirements, despite their prevalence, lead to computationally harder algorithmic solutions and have been sparsely examined in the literature to date. In this article we prove some unique properties of most parsimonious live phylogenetic trees with polytomies, and their mapping to traditional binary phylogenetic trees. We show that our problem reduces to finding the most compact parsimonious tree for n species, and describe a novel efficient algorithm to find such trees without resorting to exhaustive enumeration of all possible tree topologies.


Assuntos
Algoritmos , Filogenia
11.
Osteoarthritis Cartilage ; 24(4): 655-63, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26603474

RESUMO

OBJECTIVE: The aim of the study was to identify genetic variants predisposing to primary hip and knee osteoarthritis (OA) in a sample of Finnish families. METHODS: Genome wide analysis was performed using 15 independent families (279 individuals) originating from Central Finland identified as having multiple individuals with primary hip and/or knee OA. Targeted re-sequencing was performed for three samples from one 33-member, four-generation family contributing most significantly to the LOD score. In addition, exome sequencing was performed in three family members from the same family. RESULTS: Genome wide linkage analysis identified a susceptibility locus on chromosome 2q21 with a multipoint LOD score of 3.91. Targeted re-sequencing and subsequent linkage analysis revealed a susceptibility insertion variant rs11446594. It locates in a predicted strong enhancer element region with maximum LOD score 3.42 under dominant model of inheritance. Insertion creates a recognition sequence for ELF3 and HMGA1 transcription factors. Their DNA-binding affinity is highly increased in the presence of A-allele compared to wild type null allele. CONCLUSION: A potentially novel functional OA susceptibility variant was identified by targeted re-sequencing. This variant locates in a predicted regulatory site and creates a recognition sequence for ELF3 and HMGA1 transcription factors that are predicted to play a significant role in articular cartilage homeostasis.


Assuntos
Cromossomos Humanos Par 2/genética , Ligação Genética , Osteoartrite do Quadril/genética , Osteoartrite do Joelho/genética , Exoma/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Linhagem
12.
Psychol Med ; 46(1): 117-23, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26347209

RESUMO

BACKGROUND: Neurological soft signs (NSS) have long been considered potential endophenotypes for schizophrenia. However, few studies have investigated the heritability and familiality of NSS. The present study examined the heritability and familiality of NSS in healthy twins and patient-relative pairs. METHOD: The abridged version of the Cambridge Neurological Inventory was administered to 267 pairs of monozygotic twins, 124 pairs of dizygotic twins, and 75 pairs of patients with schizophrenia and their non-psychotic first-degree relatives. RESULTS: NSS were found to have moderate but significant heritability in the healthy twin sample. Moreover, patients with schizophrenia correlated closely with their first-degree relatives on NSS. CONCLUSIONS: Taken together, the findings provide evidence on the heritability and familiality of NSS in the Han Chinese population.


Assuntos
Doenças em Gêmeos/fisiopatologia , Endofenótipos , Transtornos das Habilidades Motoras/fisiopatologia , Esquizofrenia/fisiopatologia , Transtornos de Sensação/fisiopatologia , Adolescente , Adulto , Suscetibilidade a Doenças , Doenças em Gêmeos/complicações , Família , Feminino , Humanos , Masculino , Transtornos das Habilidades Motoras/etiologia , Esquizofrenia/complicações , Transtornos de Sensação/etiologia , Adulto Jovem
13.
Phys Med ; 31(8): 823-843, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26459319

RESUMO

Evaluation of image quality (IQ) in Computed Tomography (CT) is important to ensure that diagnostic questions are correctly answered, whilst keeping radiation dose to the patient as low as is reasonably possible. The assessment of individual aspects of IQ is already a key component of routine quality control of medical x-ray devices. These values together with standard dose indicators can be used to give rise to 'figures of merit' (FOM) to characterise the dose efficiency of the CT scanners operating in certain modes. The demand for clinically relevant IQ characterisation has naturally increased with the development of CT technology (detectors efficiency, image reconstruction and processing), resulting in the adaptation and evolution of assessment methods. The purpose of this review is to present the spectrum of various methods that have been used to characterise image quality in CT: from objective measurements of physical parameters to clinically task-based approaches (i.e. model observer (MO) approach) including pure human observer approach. When combined together with a dose indicator, a generalised dose efficiency index can be explored in a framework of system and patient dose optimisation. We will focus on the IQ methodologies that are required for dealing with standard reconstruction, but also for iterative reconstruction algorithms. With this concept the previously used FOM will be presented with a proposal to update them in order to make them relevant and up to date with technological progress. The MO that objectively assesses IQ for clinically relevant tasks represents the most promising method in terms of radiologist sensitivity performance and therefore of most relevance in the clinical environment.


Assuntos
Garantia da Qualidade dos Cuidados de Saúde/métodos , Tomografia Computadorizada por Raios X , Humanos , Processamento de Imagem Assistida por Computador , Variações Dependentes do Observador
14.
J Dent Res ; 94(9): 1196-201, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26124221

RESUMO

Mandibular prognathism is a facial skeletal malocclusion. Until now, the genetic mechanism has been unclear. The goal of this study was to identify candidate genes or genomic regions directly associated with mandibular prognathism development, by employing whole genome sequencing. A large Chinese family was recruited, composed of 9 affected and 12 unaffected individuals, and the inheritance pattern of this family tends to be autosomal dominant. A single-nucleotide missense mutation in the ADAMTS1 gene (c. 742I>T) was found to segregate in the family, given that the affected individuals must be heterozygous for the mutation. For mutation validation, we screened this candidate mutation and 15 tag single-nucleotide polymorphisms in the coding sequence of ADAMTS1 among 230 unrelated cases and 196 unrelated controls using Sequenom Massarray and found that 3 in 230 cases carried this mutation and none of the controls did. Final results suggested that 2 single-nucleotide polymorphisms (rs2738, rs229038) of ADAMTS1 were significantly associated with mandibular prognathism.


Assuntos
Proteínas ADAM/genética , Polimorfismo de Nucleotídeo Único , Prognatismo/genética , Proteína ADAMTS1 , Adolescente , Adulto , Idoso , Povo Asiático , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Adulto Jovem
15.
Ann Cardiol Angeiol (Paris) ; 64(3): 205-9, 2015 Jun.
Artigo em Francês | MEDLINE | ID: mdl-26047874

RESUMO

While physical activity (PA) is recommended for high blood pressure management, the level of PA practice of hypertensive patients remains unclear. We aimed to assess the association between the level of both PA and blood pressure of individuals consulting in 9 hypertension specialist centres. Eighty-five hypertensive patients were included (59 ± 14 years, 61% men, 12% smokers, 29% with diabetes). Following their consultation, they performed home blood pressure measurement (HBPM) over 7 days (2 in the morning+2 in the evening), they wrote in a dedicated form their daily activities to estimate the additional caloric expenditure using Acti-MET device (built from International physical Activity Questionnaire [IPAQ]). Thus, patients completed a self-administered questionnaire "score of Dijon" (distinguishing active subjects with a score>20/30, from sedentary<10/30). Subjects with normal HBPM value (<135/85 mm Hg) (55% of them) compared to those with high HBPM were older, had a non-significant trend towards higher weekly caloric expenditure (4959 ± 5045 kcal/week vs. 4048 ± 4199 kcal/week, P=0.3755) and score of Dijon (19.44 ± 5.81 vs. 18.00 ± 4.32, P=0.2094) with a higher proportion of "active" subjects (48.9% vs. 34.2%, P=0.1773). In conclusion, our results demonstrate a "tendency" to a higher level of reported PA for subjects whose hypertension was controlled. This encourages us to continue with a study that would include more subjects, which would assess PA level using an objective method such as wearing an accelerometer sensor.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Hipertensão/diagnóstico , Hipertensão/terapia , Atividade Motora , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e Questionários
16.
Reprod Biomed Online ; 30(4): 408-14, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25691449

RESUMO

Fertiloscopy represents an alternative to laparoscopy in the diagnostic evaluation of unexplained infertility or for the purpose of ovarian drilling. The learning curve of fertiloscopy in an experienced laparoscopic surgeon was evaluated in a prospective multicentre observational trial. A total of 110 fertiloscopies were carried out. At Centre 1, a beginner, and at Centre 2, an expert in fertiloscopy, performed the procedures. In three cases in Centre 1, and in 0 cases in Centre 2, the procedure was converted to transabdominal laparoscopy owing to intraoperative complications. Median operating time was longer at Centre 1 during the first 40 procedures (P < 0.001) and equal thereafter. Analyzing fertiloscopies with and without ovarian drilling separately, operating time was only longer for the first 20 procedures in each group (P < 0.001 and P = 0.002). In a multivariate analysis, intraoperative complications and fertiloscopy with ovarian drilling (compared with diagnostic fertiloscopy) were associated with longer duration of surgery (P < 0.001 for both parameters). An increasing consecutive number of fertiloscopies was associated with shorter duration of surgery (P < 0.001). Experienced laparoscopists should consider a transition towards fertiloscopy in the diagnostic workup of unexplained infertility or for the purpose of ovarian drilling.


Assuntos
Histerossalpingografia/métodos , Infertilidade Feminina/diagnóstico , Adulto , Feminino , Humanos , Laparoscopia/métodos , Curva de Aprendizado , Estudos Prospectivos
17.
Neuroscience ; 285: 34-46, 2015 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-25446355

RESUMO

Abuse and addiction to prescription opioids such as oxycodone (a short-acting Mu opioid receptor (MOP-r) agonist) in adolescence is a pressing public health issue. We have previously shown differences in oxycodone self-administration behaviors between adolescent and adult C57BL/6J mice and expression of striatal neurotransmitter receptor genes, in areas involved in reward. In this study, we aimed to determine whether oxycodone self-administration differentially affects genes regulating synaptic plasticity in the hippocampus of adolescent compared to adult mice, since the hippocampus may be involved in learning aspects associated with chronic drug self administration. Hippocampus was isolated for mRNA analysis from mice that had self administered oxycodone (0.25 mg/kg/infusion) 2h/day for 14 consecutive days or from yoked saline controls. Gene expression was analyzed with real-time polymerase chain reaction (PCR) using a commercially available "synaptic plasticity" PCR array containing 84 genes. We found that adolescent and adult control mice significantly differed in the expression of several genes in the absence of oxycodone exposure, including those coding for mitogen-activated protein kinase, calcium/calmodulin-dependent protein kinase II gamma subunit, glutamate receptor, ionotropic AMPA2 and metabotropic 5. Chronic oxycodone self administration increased proviral integration site 1 (Pim1) and thymoma viral proto-oncogene 1 mRNA levels compared to controls in both age groups. Both Pim1 and cadherin 2 mRNAs showed a significant combined effect of Drug Condition and Age × Drug Condition. Furthermore, the mRNA levels of both cadherin 2 and cAMP response element modulators showed an experiment-wise significant difference between oxycodone and saline control in adult but not in adolescent mice. Overall, this study demonstrates for the first time that chronic oxycodone self-administration differentially alters synaptic plasticity gene expression in the hippocampus of adolescent and adult mice.


Assuntos
Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/metabolismo , Oxicodona/administração & dosagem , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Caderinas/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Modulador de Elemento de Resposta do AMP Cíclico/metabolismo , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , RNA Mensageiro/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptores de AMPA/metabolismo , Autoadministração
18.
Psychoneuroendocrinology ; 45: 67-76, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24845178

RESUMO

BACKGROUND: Stress is a critical risk factor affecting both the development of and the relapse to drug addictions. Drug addictions are caused by genetic, environmental and drug-induced factors. The objective of this hypothesis-driven association study was to determine if genetic variants in stress-related genes are associated with heroin addiction. METHODS: 112 selected genetic variants in 26 stress-related genes were genotyped in 852 case subjects and 238 controls of predominantly European ancestry. The case subjects are former heroin addicts with a history of at least one year of daily multiple uses of heroin, treated at a methadone maintenance treatment program (MMTP). The two most promising SNPs were subsequently tested in an African-American sample comprising of 314 cases and 208 control individuals. RESULTS: Nineteen single nucleotide polymorphisms (SNPs) in 9 genes (AVP, AVPR1A, CRHR1, CRHR2, FKBP5, GAL, GLRA1, NPY1R and NR3C2) showed nominally significant association with heroin addiction. The associations of two FKBP5 SNPs that are part of one haplotype block, rs1360780 (intron 2) and rs3800373 (the 3' untranslated region), remained significant after correction for multiple testing (Pcorrected=0.03; OR=2.35, Pcorrected=0.0018; OR=2.85, respectively). The two SNPs also showed nominally significant association (P<0.05) with heroin addiction in an independent African-American cohort. FKBP5 is a co-chaperone that regulates glucocorticoid sensitivity. These FKBP5 SNPs were previously associated with diverse affective disorders and showed functional differences in gene expression and stress response. This study also supports our and others' previous reports of association of the GAL SNP rs694066 and the AVPR1A SNPs rs11174811, rs1587097 and rs10784339 with heroin and general drug addiction, respectively. CONCLUSIONS: This study suggests that variations in the FKBP5 gene contribute to the development of opiate addiction by modulating the stress response. These findings may enhance the understanding of the interaction between stress and heroin addiction.


Assuntos
Dependência de Heroína/genética , Estresse Psicológico/genética , Proteínas de Ligação a Tacrolimo/fisiologia , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Dependência de Heroína/epidemiologia , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estresse Psicológico/epidemiologia , Proteínas de Ligação a Tacrolimo/genética
19.
Vet J ; 200(1): 22-30, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24559744

RESUMO

Meniscal injury is a common cause of osteoarthritis, pain, and disability in dogs and humans, but tissue-engineered bioscaffolds could be a treatment option for meniscal deficiency. The objective of this study was to compare meniscus-like matrix histology, composition, and biomechanical properties of autologous tensioned synoviocyte neotissues (TSN) treated with fetal bovine serum (TSNfbs) or three chondrogenic growth factors (TSNgf). Fourth passage canine synoviocytes from 10 dogs were grown in hyperconfluent monolayer culture, formed into TSN, and then cultured for 3 weeks with 17.7% FBS or three human recombinant TSNgf (bFGF, TGF-ß1, and IGF-1). Cell viability was determined with laser microscopy. Histological architecture and the composition of fibrocartilage matrix were evaluated in TSN by staining tissues for glycosaminoglycan (GAG), α-smooth muscle actin, and collagen 1 and 2; quantifying the content of GAG, DNA, and hydroxyproline; and measuring the gene expression of collagens type 1α and 2α, the GAG aggrecan, and transcription factor Sry-type Homeobox Protein-9 (SOX9). Biomechanical properties were determined by materials testing force-deformation curves. The TSN contained components and histological features of mensical fibrocartilage extracellular matrix. Growth factor-treated TSN had higher DNA content but lower cell viability than TSNfbs. TSNgf had greater fibrocartilage-like matrix content (collagen 2 and GAG content with increased collagen 2α and SOX9 gene expression). Additionally, TSNgf collagen was more organized histologically and so had greater tensile biomechanical properties. The results indicate the potential of TSN when cultured with growth factors as implantable bioscaffolds for the treatment of canine meniscal deficiency.


Assuntos
Fibrocartilagem/fisiologia , Meniscos Tibiais/fisiologia , Membrana Sinovial/citologia , Técnicas de Cultura de Tecidos/veterinária , Engenharia Tecidual/veterinária , Alicerces Teciduais/veterinária , Animais , Bovinos , Sobrevivência Celular , Células Cultivadas , Cães , Fatores de Crescimento de Fibroblastos/farmacologia , Fibrocartilagem/citologia , Osteoartrite/terapia , Osteoartrite/veterinária , Soroalbumina Bovina/farmacologia , Membrana Sinovial/metabolismo , Engenharia Tecidual/métodos
20.
Climacteric ; 17(1): 92-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23647522

RESUMO

We evaluated dehydroepiandrosterone sulfate (DHEAS) levels in premature ovarian failure (POF) patients with and without Hashimoto's thyroiditis, and the impact of DHEA supplementation on thyroid autoantibodies. In a retrospective case series, we included 67 women with spontaneous POF who received estrogen/gestagen replacement with or without DHEA (30 mg/day) for 3 months. Women who were seropositive for thyroglobulin antibodies and/or thyroperoxidase autoantibodies (n = 30) revealed lower pretherapeutic DHEAS levels (1.2 µg/ml, range 0.4-2.9 µg/ml vs. 1.9 µg/ml, range 0.2-3.9 µg/ml; p < 0.001). DHEAS showed an inverse correlation with both thyroglobulin antibodies (r = -0.426, p < 0.001) and thyroperoxidase autoantibodies (r = -0.362, p = 0.002). When treated with additional DHEA, significant decreases were found for thyroperoxidase autoantibodies (median 85.0 IU/ml, range 41-600 IU/ml vs. median 51.0 IU/ml, range 20-589 IU/ml; p = 0.005) but not for thyroglobulin antibodies.


Assuntos
Sulfato de Desidroepiandrosterona/sangue , Desidroepiandrosterona/administração & dosagem , Doença de Hashimoto/sangue , Insuficiência Ovariana Primária/sangue , Insuficiência Ovariana Primária/imunologia , Adolescente , Adulto , Autoanticorpos/sangue , Terapia de Reposição de Estrogênios , Feminino , Doença de Hashimoto/tratamento farmacológico , Doença de Hashimoto/imunologia , Humanos , Iodeto Peroxidase/imunologia , Insuficiência Ovariana Primária/tratamento farmacológico , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA