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1.
J Nutr Health Aging ; 26(5): 515-520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35587765

RESUMO

OBJECTIVES: Muscle health plays an important role in maintaining function and independence in the elderly, and some nutrients provide protection against the age-related decline of muscle strength and function. Minerals are important nutrients that may contribute to the prevention and treatment of sarcopenia, but they have not been well-studied. This study investigated whether hair mineral concentrations differ between subjects with low muscle mass (LMM) and subjects with normal muscle mass. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 232 adults ≥ 20 years of age who visited the Health Promotion Center of the University Hospital in Gyeonggi-do, Republic of Korea. MEASUREMENTS: The data from 232 subjects were analyzed and divided into LMM and normal groups based on the appendicular skeletal muscle mass index (ASMI) (LMM was defined as ASMI < 7.0 kg/m2 in men and < 5.7 kg/m2 in women). Skeletal muscle mass was estimated using a multi-frequency bioelectrical impedance analysis (BIA) device with a body composition analyzer. RESULTS: Overall mean age of participants was 50.4±11.6 years (29.7% women). Subjects with LMM showed significantly lower triglyceride levels, greater high-density lipoprotein cholesterol levels, and lower body mass index (BMI), compared with subjects who had normal muscle mass. No significant differences in hair mineral concentrations were observed between subjects with LMM and subjects with normal muscle mass, with the exception of copper. Hair copper concentrations were significantly greater in subjects with LMM than in subjects with normal muscle mass after adjustment for covariates and factors (65.7±14.2 vs 33.1±4.3 µg/g, P = 0.035). CONCLUSION: These results suggest that hair mineral status may play a role in the development of LMM. Therefore, further studies with larger numbers of subjects are required to identify the effects of mineral imbalances, their relationships with sarcopenia, and the differences between subjects with LMM and subjects with normal muscle mass.


Assuntos
Sarcopenia , Idoso , Cobre , Estudos Transversais , Feminino , Cabelo , Humanos , Masculino , Minerais , Músculo Esquelético/fisiologia , República da Coreia
2.
Lupus ; 28(7): 898-902, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31042127

RESUMO

Headaches are common in patients with systemic lupus erythematosus (SLE). It is important to identify the exact cause of headaches in SLE to avoid unnecessary steroid or immunosuppressive therapy like in neuropsychiatric SLE. A 35-year-old woman with SLE suddenly developed severe headache. Magnetic resonance angiography showed multifocal segmental narrowing of cerebral arteries, suggestive of central nervous system vasculitis. However, lack of abnormal enhancement in vessel wall imaging indicated reversible cerebral vasoconstriction syndrome (RCVS) rather than central nervous system vasculitis. The patient was treated with oral nimodipine and she recovered over a period of two months. Following magnetic resonance angiography on day 90 was normal. Herein we report a case of reversible cerebral vasoconstriction syndrome in an SLE patient with literature review.


Assuntos
Transtornos da Cefaleia Primários/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasoconstrição , Vasoespasmo Intracraniano/complicações , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/patologia , Diagnóstico Diferencial , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Angiografia por Ressonância Magnética , Síndrome , Vasoespasmo Intracraniano/diagnóstico por imagem
3.
Clin Exp Allergy ; 47(2): 217-223, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27883235

RESUMO

BACKGROUND: Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genomewide association study (GWAS) has been published. OBJECTIVE: To identify genetic variants associated with challenge-proven peanut allergy. METHODS: We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. RESULTS: We identified 21 independent associations at P ≤ 5 × 10-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2 × 10-4 ). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.


Assuntos
Substituição de Aminoácidos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Cadeias HLA-DRB1/genética , Hipersensibilidade a Amendoim/genética , Hipersensibilidade a Amendoim/imunologia , Polimorfismo Genético , Alelos , Genótipo , Cadeias HLA-DRB1/química , Cadeias HLA-DRB1/imunologia , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único
4.
Eur J Pain ; 21(2): 374-384, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27633925

RESUMO

BACKGROUND: Patients with fibromyalgia (FM) exhibit significant clinical heterogeneity, in terms of physical, social and psychological functions, as well as therapeutic responses. Here, we examined FM patients in terms of pain, physical, social and psychological variables to identify clinical subgroups that may be predictive of treatment patterns. METHODS: A total of 313 FM patients were interviewed using a structured questionnaire that included sociodemographic data, current or past FM symptoms and current use of relevant medications. A K-means cluster analysis was conducted using variables reflecting tender points, the Fibromyalgia Impact Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventor and Social Support Scale. RESULTS: Four distinct clusters were identified in these patients. Group 1 was characterized by high pain levels, severe physical and mental impairment and low social support. Group 2 had moderate pain and physical impairment, mild mental impairment and moderate social support. Group 3 had moderate pain, low physical and moderate mental impairment and low social support. Group 4 had low pain levels, nearly normal physical and mental function and high social support. Group 1 was more often a current or past smoker, more likely to have a variety of symptoms, including swelling, cognitive dysfunction, dizziness, syncope, oesophageal dysmotility, dyspepsia, irritable bladder, vulvodynia and restless leg syndrome. CONCLUSIONS: We identified four subgroups of FM patients based on pain, physical, social and psychological function. These subgroups had different clinical symptoms and medication profiles, suggesting that FM may be better managed using a more comprehensive assessment of an individual patient's symptoms. SIGNIFICANCE: FM patients can be clustered into four distinct subgroups based on clinically measurable variables - pain, physical involvement, psychological function and social support. These subgroups had different clinical symptoms and medication profiles.


Assuntos
Ansiedade/diagnóstico , Depressão/diagnóstico , Fibromialgia/diagnóstico , Adulto , Ansiedade/fisiopatologia , Ansiedade/psicologia , Análise por Conglomerados , Estudos Transversais , Depressão/fisiopatologia , Depressão/psicologia , Feminino , Fibromialgia/fisiopatologia , Fibromialgia/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Clínicas de Dor , Exame Físico , Escalas de Graduação Psiquiátrica , Apoio Social , Inquéritos e Questionários , Avaliação de Sintomas
5.
Eur J Pain ; 20(7): 1131-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26849490

RESUMO

BACKGROUND: Although polymorphisms of the catechol-O-methyl transferase (COMT) gene have been implicated in altered pain sensitivity, results concerning the association between COMT gene polymorphisms and fibromyalgia (FM) are equivocal. We assessed the associations between COMT single-nucleotide polymorphisms (SNP) and FM risk and symptom severity. METHODS: In total, 409 FM patients and 423 controls were enrolled. Alleles and genotypes at five positions [rs6269 (A>G), rs4633 (C>T), rs4818 (C>G), rs4680 (C>G) and rs165599 (A>G)] in the COMT gene were genotyped from peripheral blood DNA. RESULTS: Alleles and genotypes of the rs4818 COMT gene polymorphism were significantly associated with increased susceptibility to FM. The rs4818 GG genotype was more strongly associated with FM compared to the CC genotype (OR = 1.680, 95% CI: 1.057, 2.672, p = 0.027). Although allele and genotype frequencies did not differ among groups, the rs4633 CT genotype was not associated with the presence of FM following adjustment for age and sex (OR = 0.745; 95% CI: 0.558, 0.995; p = 0.046). However, no association was observed between clinical measures and individual COMT SNPs. In haplotype analysis, there was a significant association between ACG haplotype and FM susceptibility sex (OR = 2.960, 95% CI: 1.447, 6.056, p = 0.003) and the number of tender points (p = 0.046). CONCLUSIONS: This large-scale study suggests that polymorphisms of the COMT gene may be associated with FM risk and pain sensitivity in Korean FM patients. However, our results differed to those of previous studies, suggesting ethnic variation in COMT gene polymorphisms in FM. WHAT DOES THIS STUDY ADD: By contrast to Caucasian and Latin-American populations, the COMT gene polymorphisms are associated with FM risk and pain sensitivity in Korean FM patients, suggesting ethnic variation in COMT gene polymorphisms.


Assuntos
Povo Asiático/genética , Catecol O-Metiltransferase/genética , Fibromialgia/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Limiar da Dor , República da Coreia
6.
J Anim Sci ; 92(3): 984-95, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24504041

RESUMO

Spermatogonial stem cells provide the foundation for continued adult spermatogenesis and their manipulation can facilitate assisted reproductive technologies or the development of transgenic animals. Because the pig is an important agricultural and biomedical research animal, the development of practical application techniques to manipulate the pig Spermatogonial stem cell is needed. The ability to preserve porcine Spermatogonial stem cell or testis tissue long term is one of these fundamental techniques. The objective of this study was to optimize methods to cryopreserve porcine Spermatogonial stem cell when freezing testis cells or testis tissue. To identify the most efficient cryopreservation technique, porcine testis cells (cell freezing) or testis tissue (tissue freezing) were frozen in medium containing dimethyl sulfoxide (DMSO) and fetal bovine serum (FBS) or DMSO, FBS, and various concentrations of trehalose (50, 100, or 200 mM). After thawing, undifferentiated germ cells were enriched and treatments were evaluated for cryopreservation efficiency. The tissue freezing method resulted in significantly greater germ cell recovery (P = 0.041) and proliferation capacity (P < 0.001) compared to the cell freezing treatment. Regardless of freezing method (cell vs. tissue), addition of 200 mM trehalose to freezing medium increased germ cell recovery and proliferation capacity compared to cells frozen using the same freezing method without trehalose. Interestingly, addition of trehalose to the tissue freezing medium significantly increased germ cell recovery (P = 0.012) and proliferation capacity (P = 0.004) compared to the cell freezing treatment supplemented with trehalose. To confirm that cryopreservation in trehalose improves the survival of Spermatogonial stem cell, testis cells enriched for undifferentiated germ cells were xenotransplanted into recipient mouse testes. Germ cells recovered from tissue frozen with 200 mM trehalose generated significantly more (P < 0.001) donor derived colonies than tissue frozen without trehalose. Regardless of cryopreservation medium or freezing method, testis cell recovery, viability, and proliferation capacity of germ cells after thawing were significantly lower compared to those of untreated fresh control. Nevertheless, these data demonstrate that undifferentiated porcine germ cells can be efficiently cryopreserved in the presence of 200 mM trehalose.


Assuntos
Células-Tronco Adultas/fisiologia , Criopreservação/veterinária , Suínos/fisiologia , Testículo/fisiologia , Trealose/farmacologia , Animais , Proliferação de Células , Sobrevivência Celular , Criopreservação/métodos , Congelamento , Masculino
7.
J Anim Sci ; 92(1): 106-18, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24166994

RESUMO

Undifferentiated germ cells have the capacity to develop into sperm capable of fertilizing oocytes and contributing genetic material to subsequent generations. The most primitive prepubertal undifferentiated germ cells include gonocytes and undifferentiated spermatogonia, including spermatogonial stem cells (SSC). Gonocytes, present in the testis at birth, differentiate into SSC, which maintain spermatogenesis for the remainder of the male's life. Because of their capacity to contribute to lifelong spermatogenesis, undifferentiated germ cells are attractive targets for genetic modification to produce transgenic animals, including cattle. To maximize the efficiency of genetic modification of bovine gonocytes and SSC, effective enrichment techniques need to be developed. Selection of bovine gonocytes using differential plating was improved 8-fold (P < 0.001) when using a combination of extracellular matrix proteins, including laminin, fibronectin, collagen type IV, and gelatin, compared to using laminin and gelatin alone. Selected cells labeled with PKH26 formed colonies of donor-derived germ cells after transplantation into recipient mouse testes, indicating putative stem cell function. Significantly more colonies (P < 0.001) per 1 × 10(5) viable transplanted cells were formed from isolated nonadherent cells (203 ± 23.2) compared to adherent (20 ± 2.7) or Percoll (45.5 ± 4.5) selected cells. After selection, some gonocytes were transduced using a lentiviral vector containing the transgene for the enhanced green fluorescent protein. Transduction efficiency was 17%. Collectively, these data demonstrate effective methods for the selection and genetic modification of bovine undifferentiated germ cells.


Assuntos
Bovinos , Separação Celular/métodos , Lentivirus , Espermatogônias/metabolismo , Células-Tronco/metabolismo , Transdução Genética/métodos , Animais , Animais Geneticamente Modificados , Vetores Genéticos , Proteínas de Fluorescência Verde/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Espermatogônias/citologia , Células-Tronco/citologia , Transdução Genética/veterinária
8.
J Anim Sci ; 91(7): 3143-54, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23572256

RESUMO

The objective of this study was to use fluorescence-activated cell sorting (FACS) and spermatogonial stem cell (SSC) xenotransplantation to identify cell surface markers of putative porcine SSC. Analysis of porcine testis cells enriched for spermatogonia using FACS indicated that nearly half of stage-specific embryonic antigen-1 (SSEA-1) expressing testis cells expressed the undifferentiated spermatogonia marker protein gene product 9.5 (PGP 9.5) whereas significantly fewer (P < 0.05) cells selected for thymus cell antigen-1 (Thy-1), also known as cluster of differentiation 90 (CD90), cluster of differentiation 9 (CD9), or other SSC markers expressed PGP 9.5. Immunocytochemical analysis indicated that promyelocytic leukemia zinc finger (PLZF) protein and germ cell lineage marker VASA homolog (VASA), also known as DEAD box protein 4 (DDX4), were expressed by SSEA-1 expressing germ cells. Spermatogonial stem cell xenotransplantation of testis cell populations enriched for cells expressing SSEA-1 generated significantly (P < 0.05; greater than 15-fold) more colonies of donor derived germ cells than unselected testis cells. In conclusion, these data indicate that SSC markers identified in rodents are likely not entirely conserved in pigs and that SSEA-1 is a marker for porcine undifferentiated spermatogonia including SSC in prepubertal boars and its expression may serve as a target for the further study of porcine germ cells.


Assuntos
Células-Tronco Adultas/metabolismo , Regulação da Expressão Gênica , Antígenos CD15/genética , Sus scrofa/genética , Testículo/metabolismo , Células-Tronco Adultas/citologia , Animais , Biomarcadores , Citometria de Fluxo , Antígenos CD15/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/metabolismo , Testículo/citologia , Testículo/crescimento & desenvolvimento , Transplante Heterólogo
9.
Transplant Proc ; 45(1): 108-14, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23375283

RESUMO

BACKGROUND: Growth retardation is a common problem for children with chronic kidney disease. Although renal transplantation (RTx) resolves endocrine metabolic and uremic disturbances, growth continues to be suboptimal. This study aims to describe changes in height from diagnosis to final adult height (FAH) in Korean renal allograft recipients and determine factors associated with posttransplantation growth. METHODS: We retrospectively reviewed 63 renal allograft recipients who underwent RTx at <15 years of age with regular follow-up for >3 years afterwards. Pre- and post-RTx growth was analyzed by height Z scores (Ht_Z) at RTx, 2 and 5 years follow-up, and at FAH. RESULTS: Ht_Z decreased from diagnosis to dialysis by -0.8 (P = .009) and from dialysis to RTx by -0.46 (P < .001). The mean baseline Ht_Z at RTx was -1.62 ± 1.36. The change in Ht_Z at 2 and 5 years after transplantation was 0.68 ± 0.88 and 0.48 ± 0.86, respectively. Both variables were negatively correlated with baseline age at RTx. Mean FAH was -1.22 ± 1.11 and was positively correlated with baseline height at RTx. Height at start of dialysis and dialysis duration were significant determinants of baseline height at RTx (P < .001). CONCLUSIONS: Although there is significant posttransplant catch-up growth among younger recipients and among those with greater baseline height deficit, catch-up growth is not sustained and greater FAH is attained in those who are taller at RTx. Achieving greater height before dialysis and decreasing dialysis duration leads to maximal height at RTx as well as greater FAH.


Assuntos
Estatura , Transplante de Rim/métodos , Insuficiência Renal Crônica/cirurgia , Adolescente , Criança , Desenvolvimento Infantil , Pré-Escolar , Sistema Endócrino , Feminino , Transtornos do Crescimento/etiologia , Humanos , Lactente , Coreia (Geográfico) , Modelos Lineares , Masculino , Período Pós-Operatório , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Transplante Homólogo
10.
Osteoporos Int ; 23(7): 1921-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22057549

RESUMO

SUMMARY: We measured bone mineral densities in 28 intracranial germ cell tumor long-term survivors. There was the high prevalence of osteoporosis and osteopenia, 25.0% and 42.9%, respectively, and three additional risk factors, male sex, a low lean mass, and adult growth hormone replacement, were identified. INTRODUCTION: Intracranial germ cell tumor long-term survivors (iGCTLS) have many risk factors for osteoporosis, including irradiation from cancer therapy and multiple hormone deficiencies. However, no study of bone mineral density (BMD) has been conducted in iGCTLS because these tumors are rare. The aims of this study were to evaluate the prevalence of osteoporosis and to identify risk factors associated with reduced bone mass in iGCTLS. METHODS: We evaluated BMD and body composition of 28 iGCTLS (10.9 ± 5.2 years after cancer treatment; 13 males) using dual-energy X-ray absorptiometry. To determine risk factors, we analyzed the medical history, including the nature of the tumor, treatment modality, endocrine status, hormone replacement therapy, lifestyle, and biochemical parameters. RESULTS: Twenty-five percent of iGCTLS were diagnosed with osteoporosis and 42.9% with osteopenia. Most males (92.3%) had low BMD. Lean mass (LM) was positively correlated with BMD in all regions of interest, and the starting age of adult growth hormone (GH) replacement was negatively correlated with the BMD Z-score at the femur neck. In logistic regression analysis, male sex and low LM were related to low BMD. CONCLUSIONS: The iGCTLS had a high prevalence of low BMD. We found that male sex, low LM, and delayed start of adult GH replacement were risk factors for osteoporosis. Therefore, the BMD of all iGCTLS should be evaluated, and if it is low, proper management should be started early.


Assuntos
Neoplasias Encefálicas/terapia , Neoplasias Embrionárias de Células Germinativas/terapia , Osteoporose/etiologia , Sobreviventes , Adolescente , Adulto , Composição Corporal/fisiologia , Índice de Massa Corporal , Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Criança , Esquema de Medicação , Feminino , Colo do Fêmur/fisiopatologia , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Osteoporose/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Fatores de Risco , Fatores Sexuais , Magreza/complicações , Adulto Jovem
11.
Parasite Immunol ; 33(7): 390-400, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21535020

RESUMO

Naegleria fowleri, a free-living amoeba, is the causative pathogen of primary amoebic meningoencephalitis in humans and experimental mice. N. fowleri is capable of destroying tissues and host cells through lytic necrosis. However, the mechanism by which N. fowleri induces host cell death is unknown. Electron microscopy indicated that incubation of Jurkat T cells with N. fowleri trophozoites induced necrotic morphology of the Jurkat T cells. N. fowleri also induced cytoskeletal protein cleavage, extensive poly (ADP-ribose) polymerase hydrolysis and lactate dehydrogenase (LDH) release. Although no activation of caspase-3 was observed in Jurkat T cells co-incubated with amoebae, intracellular reactive oxygen species (ROS) were strongly generated by NADPH oxidase (NOX). Pretreating cells with necroptosis inhibitor necrostatin-1 or NOX inhibitor diphenyleneiodonium chloride (DPI) strongly inhibited amoeba-induced ROS generation and Jurkat cell death, whereas pan-caspase inhibitor z-VAD-fmk did not. N. fowleri-derived secretory products (NfSP) strongly induced intracellular ROS generation and cell death. Necroptotic effects of NfSP were effectively inhibited by pretreating NfSP with proteinase K. Moreover, NfSP-induced LDH release and intracellular ROS accumulation were inhibited by pretreating Jurkat T cells with DPI or necrostatin-1. These results suggest that N. fowleri induces ROS-dependent necroptosis in Jurkat T cells.


Assuntos
Morte Celular , Naegleria fowleri/patogenicidade , Espécies Reativas de Oxigênio/toxicidade , Linfócitos T/imunologia , Linfócitos T/parasitologia , Proteínas do Citoesqueleto/metabolismo , Humanos , Células Jurkat , L-Lactato Desidrogenase/metabolismo , NADPH Oxidases , Poli(ADP-Ribose) Polimerases/metabolismo
12.
Parasite Immunol ; 33(6): 349-56, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21426360

RESUMO

Entamoeba histolytica is known to induce host cell death via activation of calpain and caspases. In this study, we investigated the specific proteases involved in the degradation of cytoskeletal proteins during Jurkat T-cell death induced by E. histolytica. Amoebic trophozoites induced marked degradation of paxillin, Cas, vimentin, vinculin and talin, as well as α- or ß-spectrin, in Jurkat T cells. The cleavage effects of E. histolytica were strongly retarded by pretreatment with a calpain inhibitor, but not with a pan-caspase inhibitor. In addition, calpain knockdown with siRNA in Jurkat T cells effectively inhibited E. histolytica-induced PARP, paxillin, α-spectrin, ß-spectrin and talin degradation, as compared to scrambled siRNA. These results suggest that calpain plays a crucial role in the cleavage of cytoskeletal proteins during cell death induced by E. histolytica.


Assuntos
Calpaína/metabolismo , Morte Celular , Proteínas do Citoesqueleto/metabolismo , Entamoeba histolytica/imunologia , Entamoeba histolytica/patogenicidade , Células Jurkat/metabolismo , Humanos
13.
Neuroscience ; 183: 108-20, 2011 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-21440605

RESUMO

Chronic stress causes neuronal adaptation and maladaptation in the widespread brain regions including the prefrontal cortex (PFC) and limbic structures, resulting in cognitive and affective dysfunctions. In this study, we examined the impacts of chronic stress on functional interaction between the medial PFC and limbic structures in rats. In vivo electrophysiological recordings in rats exposed to chronic stress unveiled disturbance of correlated local field potential activity between the PFC and limbic structures as well as impairment of synaptic plasticity induction in the limbic-PFC pathways. However, these stress-induced alterations in limbic-PFC interaction were distinct along with the dorsal-ventral axis within the PFC, with greater stress vulnerability in the dorsal than the ventral PFC, such that alterations in the dorsal PFC became evident with much shorter duration of repeated stress exposure than those occurring in the ventral PFC. In agreement with the stress-induced alterations in limbic-PFC interaction, spike firing patterns of neurons in the dorsal and ventral PFC were also differently modulated by chronic stress. These results suggest that chronic stress produces heterogeneous cellular and neural network adaptation and maladaptation within the PFC that affect limbic information integration mechanisms.


Assuntos
Ondas Encefálicas/fisiologia , Fenômenos Eletrofisiológicos/fisiologia , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Estresse Psicológico/patologia , Potenciais de Ação/fisiologia , Análise de Variância , Animais , Modelos Animais de Doenças , Estimulação Elétrica/métodos , Potenciais Evocados/fisiologia , Potenciação de Longa Duração/fisiologia , Masculino , Córtex Pré-Frontal/patologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Vigília
14.
Drug Discov Ther ; 5(3): 109-18, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22466239

RESUMO

Senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence, shows age-related deficits in learning and memory. The oral administration of oligomers improved spatial and object recognition impairment in SAMP8. The expression of phosphorylated neurofilament-H was significantly elevated in the hippocampal CA1. This indicates that oligomers induce an increase in the density of axons. To investigate the protective mechanisms of oligomers against brain dysfunction with aging, we carried out a receptor tyrosine kinase phosphorylation antibody array, and clarified that the administration of oligomers led to an increase in the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2, suggesting the neuroprotective role of oligomers. The phosphorylation of VEGFR-2 was more markedly increased in the hypothalamus and choroid plexus than in other brain regions of SAMP8. Memory in oligomer-treated mice was impaired by SU1498, a VEGFR-2-specific antagonist. Elucidating the relationship between memory impairment with aging and VEGFR-2 signaling may provide new suggestions for protection against memory deficit in the aging brain. In addition, we revealed that the administration of oligomers extended the life span of SAMP8. Oligomers elevated SIRT1 expression, which is recognized as an essential factor for life span extension in the brain. However, the administration of oligomers did not induce stereotypical behaviors such as rearing, jumping, or hanging from the lid of a cage, while food restriction increased these frequencies without a significant change in motor function. The present study suggests the promising role of oligomers as an anti-aging agent to extend life span.

15.
Parasite Immunol ; 32(3): 176-83, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20398180

RESUMO

Host cell death induced by Entamoeba histolytica is an important mechanism for both host defence and microbial immune evasion during human amoebiasis. However, the signalling pathways underlying cell death induced by E. histolytica are not fully understood. This study investigated the involvement of the protein tyrosine phosphatases (PTPs) SHP-1 and SHP-2 in the dephosphorylation associated with E. histolytica-induced host cell death. Incubation with E. histolytica resulted in a marked decrease in protein tyrosine phosphorylation levels and degradation of SHP-1 or SHP-2 in Jurkat cells. Pre-treatment of cells with a calpain inhibitor, calpeptin, impeded the amoeba-induced dephosporylation and cleavage of SHP-1 or SHP-2. Additionally, inhibition of PTPs with phenylarsine oxide (PAO) attenuated Entamoeba-induced dephosphorylation and DNA fragmentation in Jurkat T cells. These results suggest that calpain-dependent cleavage of SHP-1 and SHP-2 may contribute to protein tyrosine dephosphorylation in Jurkat T cell death induced by E. histolytica.


Assuntos
Calpaína/metabolismo , Entamoeba histolytica/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Linfócitos T/metabolismo , Linfócitos T/parasitologia , Arsenicais/farmacologia , Calpaína/antagonistas & inibidores , Morte Celular , Dipeptídeos/farmacologia , Entamoeba histolytica/patogenicidade , Inibidores Enzimáticos/farmacologia , Humanos , Células Jurkat
16.
J Investig Allergol Clin Immunol ; 19(3): 188-94, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19610261

RESUMO

BACKGROUND: Eosinophils are important effector cells in the pathogenesis of allergic diseases such as bronchial asthma. Oxidative stress in the form of cellular reactive oxygen species (ROS) has been implicated in the pathogenesis of several allergic diseases. Recently, it has become evident that mitochondrial-derived ROS are important transducers of apoptosis and intracellular signaling. In this study, we investigated the role of mitochondrial ROS in the activation of extracellular signal-regulated kinases (ERK) 1 and 2-mitogen-activated protein kinase (MAPK) and caspase-3 in human eosinophils stimulated with H2O2. METHODS: Human eosinophils were purified using immunomagnetic negative selection and then stimulated with H2O. H2O2-induced eosinophil apoptosis was measured by staining cells with annexin V. Activation of ERK1/2 MAPK and caspases was assessed by Western blotting. Eosinophils were pretreated with rotenone, an inhibitor of the mitochondrial electron transport chain, before H2O2 was added. RESULTS: Treatment with 1 mM H2O2 induced externalization of phosphatidylserine (PS) and activation of caspases in eosinophils. H2O2-triggered PS externalization and cleavage of caspase-3 were markedly inhibited by pretreatment with the mitochondrial ROS scavenger N-acetyl-L-cysteine. In addition, H2O2 strongly induced phosphorylation of ERK1/2, but not ERK5, in eosinophils. Hydrogen peroxide-triggered activation of caspase-3 and ERK1/2 was attenuated by pretreatment with rotenone. CONCLUSIONS: These results suggest that mitochondrial respiration is essential for activation of ERK1/2 and caspase-3 in human eosinophils stimulated with H2O2.


Assuntos
Caspase 3/metabolismo , Eosinófilos/imunologia , Mitocôndrias/imunologia , Proteína Quinase 1 Ativada por Mitógeno/biossíntese , Proteína Quinase 3 Ativada por Mitógeno/biossíntese , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Caspase 3/efeitos dos fármacos , Caspase 3/imunologia , Ativação Enzimática , Eosinófilos/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Rotenona/farmacologia
17.
Eye (Lond) ; 23(3): 645-51, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18292791

RESUMO

PURPOSE: To evaluate the therapeutic effect of photodynamic therapy (PDT) combined with posterior subtenon injection of triamcinolone acetonide (PSTA) in the treatment of choroidal neovascularization (CNV). METHODS: In this retrospective case-control study, treatment outcomes at 12 months of patients with CNV were reviewed. One hundred and two consecutive patients (102 eyes) with subfoveal CNV of various causes were included. Patients in the study group (n=46) received PDT followed within 2 days by 40 mg of PSTA. Patients in the control group (n=56) received PDT alone. Patients were retreated 3 months later or more if fluorescein angiography showed residual membrane leakage. Treatment outcomes were compared between the two groups and among different CNV subgroups. RESULTS: Gain in mean best-corrected visual acuity (BCVA) was significantly higher in the study group (+0.78 lines) than in the control group (-1.86 lines) (P<0.0001). The number of treatments within 1 year was significantly less in the study group (1.26 vs 1.63, P=0.008). The mean BCVA change for myopic CNV and age-related predominantly classic CNV subgroups was significantly higher in the study group (+2.82 vs -0.91 lines, P=0.0005 for myopic CNV; +0.6 vs -1.79 lines, P=0.01 for age-related predominantly classic CNV). The main side effect in the study group was increased intraocular pressure (8.7%). CONCLUSION: Compared with PDT alone, PDT combined with PSTA has a better therapeutic effect for both myopic and age-related predominantly classic CNV; the myopic CNV subgroup shows the best response.


Assuntos
Neovascularização de Coroide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Fotoquimioterapia/métodos , Triancinolona Acetonida/uso terapêutico , Adulto , Idoso , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/fisiopatologia , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Injeções Intraoculares , Masculino , Pessoa de Meia-Idade , Miopia/complicações , Estudos Retrospectivos , Resultado do Tratamento , Triancinolona Acetonida/administração & dosagem , Acuidade Visual/efeitos dos fármacos
18.
Scand J Rheumatol ; 36(4): 299-306, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17763208

RESUMO

OBJECTIVE: To investigate the possible association between polymorphisms [the -2510A/G promoter polymorphism (rs1024611) and the Cys35Cys coding polymorphism (rs4586) in exon 2] of the chemokine (C-C motif) ligand 2 (CCL2) gene and knee osteoarthritis (OA) in a Korean population. METHODS: DNA was obtained from 153 Korean primary knee OA patients and 270 healthy controls. CCL2 genomic variants (-2510A/G and Cys35Cys polymorphisms) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In additional, the effect of -2510A/G on CCL2 transcription was examined, using a luciferase reporter gene construct transfected into HMC-1 cells. RESULTS: The -2510A/G promoter polymorphism was associated with OA [genotype frequency, p = 0.041; allele frequency, p = 0.017, odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.07-1.96]. Significant association was observed between the G carrier of the -2510A/G promoter polymorphism and primary knee OA patients (p = 0.021, OR = 2.25, 95% CI = 1.12-4.52). The G carrier of the -2510A/G promoter polymorphism was also associated with both clinically subtyped OA patients (OA patients with functionally poor index and radiographically severe OA patients). However, no significant difference was found in the Cys35Cys polymorphism. Haplotype frequency analysis revealed a significant difference (chi(2) = 8.98, p = 0.030). The CCL2 serum level of subjects with the G carrier (290.0+/-87.5 pg/mL) of the -2510A/G promoter polymorphism was statistically higher than that of subjects with the non-G carrier (161.5+/-48.3 pg/mL). The luciferase activity was significantly greater from interleukin (IL)-1beta-induced cells transfected with constructs containing G at position -2510. CONCLUSIONS: The G carrier of the -2510A/G promoter polymorphism was found to be associated with primary knee OA, and could be a susceptibility factor in the development of primary knee OA in the Korean population.


Assuntos
Quimiocinas C/genética , Osteoartrite do Joelho/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Portador Sadio , Quimiocina CCL2/genética , Cisteína , Primers do DNA , Feminino , Frequência do Gene , Genótipo , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/epidemiologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Regiões Promotoras Genéticas
19.
Plant Dis ; 88(8): 910, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30812538

RESUMO

Leaf blight symptoms on coriander (Coriandrum sativum) were observed during the summers of 2000 to 2002 in fields at the Beidou and Sijhou townships, Changhua County, Taiwan. Symptoms first appeared as small spots on the lower sides of leaves and stems. The centers of the spots quickly turned brown and were surrounded by whitish yellow halos. The brown spots and halos enlarged rapidly and coalesced into irregular, yellowish or brownish dry dead areas on the leaf. V-shaped and chlorotic blotch symptoms were also found at the margins of leaves. Isolations from diseased leaves consistently yielded bacterial colonies that were yellow and glistening on nutrient and potato dextrose agar media. Five representative strains were chosen for further characterization. All strains were gram-negative rods, aerobic, and produced yellow, nonwater soluble, xanthomonadin pigments identified by thin-layer chromatography (1). The strains were positive for catalase and ß-galactosidase and negative for oxidase, nitrate reductase, urease, and tryptophanase (indole production) and hydrolyzed starch, gelatin, and esculin. Hydrogen sulfide was produced from cysteine. L-asparagine was not sufficient as a sole carbon source for growth. In Dye's medium C, acids were produced from metabolizing arabinose, glucose, and sucrose but not from rhamnose, cellobiose, lactose, dulcitol, mannitol, and sorbitol. The bacterium was identified as Xanthomonas campestris. Almost complete 16S rDNA sequence of strain TC3 (1,502 bp; GenBank Accession No. AY604178) was determined and compared with available 16S rDNA sequences in GenBank. The sequence was highly identical (99%) to those of Xanthomonas campestris pathovars. Coriander plants were inoculated by spraying bacterial suspensions (108 CFU/ml) on leaves, enclosed in a plastic bag to maintain high humidity for 2 days, and kept in a growth chamber at 28°C. Typical symptoms were observed in 2 to 6 days in all four inoculated plants and appeared to be identical to those observed in the fields. Control plants were inoculated with sterile distilled water and showed no symptoms. The bacterium was readily reisolated from diseased leaves. Bacterial leaf blight of coriander was first reported in India, and the pathogen was identified as X. campestris pv. coriandri (2). To our knowledge, this is the first occurrence of this bacterium on coriander in Taiwan. References: (1) N. W. Schaad et al. Laboratory Guide for Identification of Plant Pathogenic Bacteria. 3rd ed. The American Phytopathological Society, St. Paul, MN, 2001. (2) M. C. Srinivasan et al. Proc. Indian Acad. Sci. Sect. B 53:298, 1961.

20.
Arch Dis Child ; 88(2): 162-4, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12538326

RESUMO

We report an unusual presentation of ganglioneuroblastoma with features of dilated cardiomyopathy in a 22 month old girl. She was admitted with cardiomegaly; during echocardiography a suspicious abdominal mass was detected by chance. Further imaging studies, including abdominal ultrasonography and spiral computed tomography, revealed a solid mass originating in the right adrenal gland. Metabolic studies and pathological findings were compatible with ganglioneuroblastoma. Following tumour removal and supportive therapy for cardiomyopathy, her clinical condition and laboratory findings improved. Although ganglioneuroblastoma with features of dilated cardiomyopathy is rare, because neurogenic tumours may be involved in its development, measurement of catecholamines in children with dilated cardiomyopathy is strongly recommended.


Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Cardiomiopatia Dilatada/etiologia , Ganglioneuroblastoma/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Feminino , Ganglioneuroblastoma/diagnóstico por imagem , Humanos , Lactente , Tomografia Computadorizada por Raios X , Ultrassonografia
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