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1.
Hum Reprod ; 36(10): 2732-2742, 2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34411244

RESUMO

STUDY QUESTION: How is the localisation of ovarian follicles affected by ageing and chronic diseases? SUMMARY ANSWER: Ovarian follicles shift deeper towards the medulla, due to thickening of the tunica albuginea (TA), with ageing and some major common chronic diseases. WHAT IS KNOWN ALREADY: The ovary undergoes morphological and functional changes with ageing. The follicular pool follows these changes with alterations in the amount and distribution of residual follicles. Diseases causing a chronic inflammatory process are associated with morphological changes and impaired ovarian function. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study, examining 90 ovaries from 90 female monkeys. The samples were collected from April 2018 to March 2019 at Tsukuba Primate Research Center in National Institutes of Biomedical Innovation, Health and Nutrition, Japan. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian samples were obtained from cynomolgus monkeys that died from natural causes or were euthanised. Ovarian sections were stained with haematoxylin and eosin (H&E) for histological analyses. In ovarian sections from 64 female macaques aged 0-25 years, a total of 13 743 follicles at different developmental stages (primordial, intermediary, primary, early secondary and late secondary) were assessed to determine the depth of each follicle from the outer surface of the ovarian cortex to the far end of the follicle, by using a digital imaging software. TA thickness was measured as sum of basal membrane and tunica collagen layer for each ovary under H&E staining. To explore the possibility of age-related trends in ovarian morphometric characteristics, samples were divided into four different age groups (0-3 years (pre-menarche), 4-9 years, 10-14 years and 15-20 years). To evaluate the effect of common chronic diseases on ovarian morphometric characteristics, macaques with diabetes mellitus (DM) (n = 10), endometriosis (n = 8) or inflammatory bowel disease (IBD) (n = 8) were compared to age-matched controls without chronic diseases. MAIN RESULTS AND THE ROLE OF CHANCE: Ovarian morphometric analysis revealed that the relative location of follicles became deeper in all age groups according to development of follicles (P < 0.05). Total follicle distance from the ovarian surface was increased with ageing (P < 0.05). In a sub-analysis according to developmental stage, only primordial and intermediary follicles were localised deeper with increasing age (P < 0.05). TA thickness was also increased with ageing (P < 0.05). The localisation of the total number of follicles became deeper in ovaries from monkeys with DM, endometriosis or IBD as compared to the control group (P < 0.05). With DM, analysis of follicles distance at almost each developmental stage was significantly deeper compared to controls (P < 0.05) with the exception of early secondary follicles. With endometriosis, follicles at primary and early and late secondary stages were significantly deeper compared to controls (P < 0.05). Also with IBD, follicles at primary and early and late secondary follicles were significantly deeper compared to controls (P < 0.001). The TA was thicker with DM and endometriosis compared to controls (P < 0.05), but not with IBD (P = 0.16). LARGE SCALE DATA: NA. LIMITATIONS, REASONS FOR CAUTION: Two-dimensional histology was used to assess follicle localisation. The possibility of minimal variations between the measured distance to the actual distance in a spherical structure cannot be excluded. Additionally, the severity of disease was not assessed. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first step towards enhancing our understanding of how ageing and chronic diseases affect the relative localisation of dormant and developing follicles. These observations, combined with possible future human studies, may have managerial implications in the field of fertility preservation and other conditions involving ovarian tissue cryopreservation. STUDY FUNDING/COMPETING INTEREST(S): The present work was supported by the Grant-in-Aid for Scientific Research B (19H03801) (to K.K.), Challenging Exploratory Research (18K19624), Japan Agency for Medical Research and Development, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Takeda Science Foundation and Naito Foundation (to K.K.). All authors have no conflicts of interest directly relevant to the content of this article.


Assuntos
Preservação da Fertilidade , Folículo Ovariano , Animais , Doença Crônica , Estudos Transversais , Feminino , Macaca fascicularis
2.
Cell Tissue Res ; 362(3): 623-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26202892

RESUMO

In most pre-clinical animal studies investigating stem cell therapy in acute myocardial infarction (AMI), the administered stem cells are isolated from healthy donors. In clinical practice, however, patients who suffer from AMI will receive autologous cells, for example using adipose-derived stem cells (ASC). During AMI, inflammation is induced and we hypothesized that this might affect characteristics of ASC. To investigate this, ASC were isolated from rat adipose tissue 1 day (1D group, n = 5) or 7 days (7D group, n = 6) post-AMI, and were compared with ASC from healthy control rats (Control group, n = 6) and sham-operated rats (Sham 1D group, n = 5). We found that significantly fewer ASC were present 1 day post-AMI in the stromal vascular fraction (SVF), determined by a colony-forming-unit assay (p < 0.001 vs. Control and 7D). These data were confirmed by flow cytometry, showing fewer CD90-positive cells in SVF of the 1D group. When cultured, no differences were found in proliferation rate and cell size between the groups in the first three passages. Also, no difference in the differentiation capacity of ASC was found. In conclusion, it was shown that significantly fewer stem cells were present in the SVF 1 day post-AMI; however, the stem cells that were present showed no functional differences.


Assuntos
Tecido Adiposo/citologia , Infarto do Miocárdio/patologia , Células-Tronco/citologia , Animais , Contagem de Células , Diferenciação Celular , Linhagem da Célula , Células Cultivadas , Masculino , Ratos Wistar , Células Estromais/citologia
4.
RSC Adv ; 14(23): 16445-16458, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38774611

RESUMO

Using DFT calculations, the structural and electronic properties of the ZZ7 p-PdSe2 nanoribbons (ZZ7) with the four kinds of vacancy defects, including ZZ7-VPd, ZZ7-VSe, ZZ7-VPd+Se, and ZZ7-V2Se are studied, in which their stability, diverse geometries, and altered electronic properties are determined through the formation energies, optimal structural parameters, electronic band structures, and DOSs. Specifically, the formation energies of all studied systems show significant negative values around -3.9 eV, evidencing their good thermal stability. The geometries of four defective structures exhibit different diversification, whereas only the ZZ7-V2Se structure possesses the highly enhanced feature, identified as the most effective substrate for the acetone and acetonitrile adsorption. On the electronic behaviors, the ZZ7 band structure displays the nonmagnetic metallic characteristics that become the ferromagnetic half-metallic band structures for the ZZ7-VPd and ZZ7-VSe and the ferromagnetic semi-metallic band structures for the ZZ7-VPd+Se and ZZ7-V2Se. For adsorption of the acetone and acetonitrile on the ZZ7-V2Se structure, the energetic stability, adsorption sites, adsorption distances, charge transfers, and electronic characteristics of the adsorbed systems are determined by the adsorption energies, optimal adsorption sites, adsorption distances, Mulliken populations, and DOSs. The adsorption energies of the acetone- and acetonitrile-adsorbed ZZ7-V2Se systems display significant values at -1.2 eV and -0.86 eV at the preferable sites of 8 and 11, respectively, indicating their great adsorption ability. The adsorption mechanism of the acetone- and acetonitrile-adsorbed systems belongs to the physisorption owing to absence of chemical bonds, in which the bond lengths of the ZZ7-V2Se substrate show a very small deviation. Under the acetone and acetonitrile adsorptions, the ferromagnetic semi-metallic DOSs of the ZZ7-V2Se become the ferromagnetic half-metallic DOSs for the ZZ7-V2Se-acetone-8 and the ferromagnetic semiconducting DOSs for the ZZ7-V2Se-acetonitrile-11. Our systematic results can provide a complete understanding of the acetone- and acetonitrile adsorptions on the potential ZZ7-V2Se structure, which is very useful for nanosensor application.

5.
Haemophilia ; 19(1): 71-5, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23005346

RESUMO

Heavy menstrual bleeding (HMB) is a frequent complaint in adolescence. Although HMB is often caused by immaturity of the hypothalamic-pituitary-ovarian axis, bleeding disorders are another common yet often unidentified cause. The aim of this study was to examine the bleeding patterns and prevalence of inherited bleeding disorders among females referred for HMB to a multidisciplinary adolescent haematology clinic. We retrospectively reviewed the first 105 patients (ages 8-18 years) referred to this specialty clinic from February 2009 to December 2011. Using menstrual bleeding questionnaires and medical records, data were extracted regarding demographics, bleeding patterns, frequency and types of bleeding disorders identified, and prescribed interventions. Sixty-two per cent of patients were diagnosed with a bleeding disorder, including platelet storage pool deficiency (36%), von Willebrand's disease (9%), other platelet function defect (8%), Ehlers-Danlos syndrome (7%) and combined bleeding disorders (2%). Comparison of the bleeding profiles for females with and without a bleeding disorder revealed only three factors that were significantly different, including the reported regularity of patients' periods (P = 0.02), description of period flow (P = 0.04) and number of days of each period that the bleeding was described as 'heavy' (P = 0.007). Bleeding disorders are prevalent in adolescent females presenting to a specialty clinic. Specifically, a relatively high proportion of adolescents were diagnosed with platelet storage pool deficiency. In our small population, menstrual bleeding profiles, as examined by a standardized questionnaire, could not identify females with an underlying bleeding disorder, demonstrating the important role of haemostasis testing in the evaluation of adolescents with HMB.


Assuntos
Transtornos Herdados da Coagulação Sanguínea/epidemiologia , Distúrbios Menstruais/epidemiologia , Menstruação , Adolescente , Criança , Feminino , Humanos , Menstruação/fisiologia , Distúrbios Menstruais/fisiopatologia , Ohio/epidemiologia , Deficiência do Pool Plaquetário/complicações , Prevalência , Estudos Retrospectivos
6.
AJNR Am J Neuroradiol ; 42(11): 2062-2069, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34556478

RESUMO

BACKGROUND AND PURPOSE: Asymmetries in the circle of Willis have been associated with several conditions, including migraines and stroke, but they may also be age-dependent. This study examined the impact of age and age-dependent changes in cerebral perfusion on circle of Willis anatomy in healthy children and adults. MATERIALS AND METHODS: We performed an observational, cross-sectional study of bright and black-blood imaging of the proximal cerebral vasculature using TOF-MRA and T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (T2-SPACE) imaging at the level of the circle of Willis in 23 healthy children and 43 healthy adults (4-74 years of age). We compared arterial diameters measured manually and cerebral perfusion via pseudocontinuous arterial spin-labeling between children and adults. RESULTS: We found that the summed cross-sectional area of the circle of Willis is larger in children than in adults, though the effect size was smaller with T2-SPACE-based measurements than with TOF-MRA. The circle of Willis is also more symmetric in children, and nonvisualized segments occur more frequently in adults than in children. Moreover, the size and symmetry of the circle of Willis correlate with cerebral perfusion. CONCLUSIONS: Our results demonstrate that the circle of Willis is different in size and symmetry in healthy children compared with adults, likely associated with developmental changes in cerebral perfusion. Further work is needed to understand why asymmetric vasculature develops in some but not all adults.


Assuntos
Círculo Arterial do Cérebro , Angiografia por Ressonância Magnética , Adulto , Criança , Círculo Arterial do Cérebro/diagnóstico por imagem , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética , Marcadores de Spin
7.
Mol Hum Reprod ; 15(10): 625-31, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19692421

RESUMO

Endometriosis is a common gynecologic disorder characterized by pain and infertility. In addition to estrogen dependence, progesterone resistance is an emerging feature of this disorder. Specifically, a delayed transition from the proliferative to secretory phase as evidenced by dysregulation of progesterone target genes and maintenance of a proliferative molecular fingerprint in the early secretory endometrium (ESE) has been reported. MicroRNAs (miRNAs) are small noncoding RNAs that collectively represent a novel class of regulators of gene expression. In an effort to investigate further the observed progesterone resistance in the ESE of women with endometriosis, we conducted array-based, global miRNA profiling. We report distinct miRNA expression profiles in the ESE of women with versus without endometriosis in a subset of samples previously used in global gene expression analysis. Specifically, the miR-9 and miR-34 miRNA families evidenced dysregulation. Integration of the miRNA and gene expression profiles provides unique insights into the molecular basis of this enigmatic disorder and, possibly, the regulation of the proliferative phenotype during the early secretory phase of the menstrual cycle in affected women.


Assuntos
Endometriose/genética , Endométrio/metabolismo , MicroRNAs/genética , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
8.
Clin Transl Sci ; 10(3): 201-207, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28181420

RESUMO

Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF-1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF-1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF-1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF-1a mRNA is of kidney origin, we examined colocalization of HIF-1a mRNA with two kidney specific markers in urine cells. We found that HIF-1a mRNA is readily quantifiable in urine pellets and its expression was significantly higher in CKD patients compared with healthy adults. We also showed that the urinary HIF-1a mRNA comes primarily from cells of renal origin. Our data suggest that urinary HIF-1a mRNA is a potential biomarker in CKD and can be noninvasively assessed in patients.


Assuntos
Biomarcadores/urina , Fator 1 Induzível por Hipóxia/urina , Insuficiência Renal Crônica/urina , Adulto , Idoso , Caderinas/metabolismo , Creatinina/sangue , Demografia , Feminino , Genes Essenciais , Receptor Celular 1 do Vírus da Hepatite A/genética , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Humanos , Fator 1 Induzível por Hipóxia/genética , Fator 1 Induzível por Hipóxia/metabolismo , Hibridização in Situ Fluorescente , Rim/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Padrões de Referência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/genética
9.
Endocrinology ; 147(3): 1097-121, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16306079

RESUMO

Histological evaluation of endometrium has been the gold standard for clinical diagnosis and management of women with endometrial disorders. However, several recent studies have questioned the accuracy and utility of such evaluation, mainly because of significant intra- and interobserver variations in histological interpretation. To examine the possibility that biochemical or molecular signatures of endometrium may prove to be more useful, we have investigated whole-genome molecular phenotyping (54,600 genes and expressed sequence tags) of this tissue sampled across the cycle in 28 normo-ovulatory women, using high-density oligonucleotide microarrays. Unsupervised principal component analysis of all samples revealed that samples self-cluster into four groups consistent with histological phenotypes of proliferative (PE), early-secretory (ESE), mid-secretory (MSE), and late-secretory (LSE) endometrium. Independent hierarchical clustering analysis revealed equivalent results, with two major dendrogram branches corresponding to PE/ESE and MSE/LSE and sub-branching into the four respective phases with heterogeneity among samples within each sub-branch. K-means clustering of genes revealed four major patterns of gene expression (high in PE, high in ESE, high in MSE, and high in LSE), and gene ontology analysis of these clusters demonstrated cycle-phase-specific biological processes and molecular functions. Six samples with ambiguous histology were identically assignable to a cycle phase by both principal component analysis and hierarchical clustering. Additionally, pairwise comparisons of relative gene expression across the cycle revealed genes/families that clearly distinguish the transitions of PE-->ESE, ESE-->MSE, and MSE-->LSE, including receptomes and signaling pathways. Select genes were validated by quantitative RT-PCR. Overall, the results demonstrate that endometrial samples obtained by two different sampling techniques (biopsy and curetting hysterectomy specimens) from subjects who are as normal as possible in a human study and including those with unknown histology, can be classified by their molecular signatures and correspond to known phases of the menstrual cycle with identical results using two independent analytical methods. Also, the results enable global identification of biological processes and molecular mechanisms that occur dynamically in the endometrium in the changing steroid hormone milieu across the menstrual cycle in normo-ovulatory women. The results underscore the potential of gene expression profiling for developing molecular diagnostics of endometrial normalcy and abnormalities and identifying molecular targets for therapeutic purposes in endometrial disorders.


Assuntos
Endométrio/metabolismo , Regulação da Expressão Gênica , Ciclo Menstrual/fisiologia , Modelos Biológicos , Ovulação , Doenças Uterinas/genética , Adulto , Algoritmos , Biópsia , Análise por Conglomerados , Regulação para Baixo , Neoplasias do Endométrio/metabolismo , Endométrio/fisiologia , Feminino , Perfilação da Expressão Gênica , Genoma , Humanos , Pessoa de Meia-Idade , Família Multigênica , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Análise de Componente Principal , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Esteroides/metabolismo , Regulação para Cima , Doenças Uterinas/patologia , Útero/metabolismo , Útero/fisiologia
10.
Cancer Res ; 58(14): 3111-5, 1998 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-9679979

RESUMO

The tumor-suppressing phenotype of p53 is thought to be due to its accumulation in response to DNA damage and resultant cell cycle arrest or apoptosis. scid/scid mice are defective in DNA double-strand break repair due to a mutation in DNA-dependent protein kinase (DNAPK). Treatment of scid/scid mice with gamma radiation or N-ethyl-N-nitrosourea resulted in approximately 86% incidence of T-cell lymphomas, compared with <6% in wild-type mice. The incidence of other tumor types was not increased in scid/scid mice, suggesting that the types of DNA double-strand break that are unrepaired in these mice are not strongly carcinogenic. To determine whether mutations in DNAPK and p53 interact, we examined mice deficient in both genes. Both scid/scid p53-/- and scid/scid p53+/- mice spontaneously developed lymphomas at shorter latency than did mice with either defect alone. Loss of the wild-type p53 allele was observed in 100% of tumors from scid/scid p53 +/- mice, indicating strong selection against p53. In contrast, p53 was not inactivated in lymphomas from scid/scid p53+/+ mice. Exposure of these tumor-bearing mice to gamma radiation resulted in p53 protein accumulation and high levels of apoptosis in all tumors that were not observed in tumors from scid/scid p53+/- mice. Thus, there was a bifurcation of molecular pathways to tumorigenesis. When p53 was heterozygous in the germ line, loss of the wild-type allele occurred, and the tumors became apoptosis resistant. When p53 was wild type in the germ line, p53 was not inactivated, and the tumors remained highly apoptosis sensitive.


Assuntos
Linfoma de Células T/genética , Proteína Supressora de Tumor p53/genética , Animais , Apoptose/efeitos da radiação , Carcinógenos , Dano ao DNA , Etilnitrosoureia , Raios gama , Linfoma de Células B/induzido quimicamente , Linfoma de Células B/genética , Linfoma de Células B/patologia , Linfoma de Células T/induzido quimicamente , Linfoma de Células T/patologia , Camundongos , Camundongos SCID , Neoplasias Induzidas por Radiação/genética , Proteína Supressora de Tumor p53/efeitos da radiação
11.
Oncogene ; 18(33): 4689-98, 1999 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-10467416

RESUMO

p27Kip1 and p21Cip1 are cyclin dependent kinase inhibitors which can arrest cell proliferation and p27 is a tumor suppressor gene. To address the mechanism of tumor suppression by p27 and to determine if p21 has a tumor suppressor phenotype, we utilized the two stage skin carcinogenesis model on p27 and p21 knockout mice. In this model, initiation, which involves mutation of H-ras induced by DMBA, can be distinguished from promotion induced by TPA, and progression to carcinoma. The mean number of papillomas did not differ between p27-/- and control littermates, but papilloma growth rate was increased and carcinomas developed earlier. Thus, p27 deficiency did not enhance initiation, but resulted in more rapid clonal expansion of initiated cells during promotion. TPA treatment reduced p27 expression in keratinocytes also supporting a role for p27 during promotion. Tumors from p27-/- mice contained mutant H-ras indicating that p27 deficiency did not substitute for mutant ras and further, that during ras driven tumor growth, p27 is partially antagonistic since its removal led to faster growth. The treated p27-/- mice also developed intestinal adenomas. p21-/- mice did not display a significant increase in tumor numbers, growth rate or progression to carcinomas and these tumors also had mutated H-ras. Carcinomas from p21-/- mice were more poorly differentiated with a high frequency of anaplastic spindle cell carcinomas. Thus p21 deficiency mainly resulted in higher grade undifferentiated tumors.


Assuntos
9,10-Dimetil-1,2-benzantraceno/farmacologia , Proteínas de Ciclo Celular , Transformação Celular Neoplásica , Ciclinas/genética , Proteínas Associadas aos Microtúbulos/genética , Neoplasias Cutâneas/induzido quimicamente , Proteínas Supressoras de Tumor , Adenoma , Animais , Carcinógenos/farmacologia , Carcinoma/induzido quimicamente , Inibidor de Quinase Dependente de Ciclina p21 , Inibidor de Quinase Dependente de Ciclina p27 , Quinases Ciclina-Dependentes/antagonistas & inibidores , Ciclinas/metabolismo , Genes Supressores de Tumor , Genes ras , Neoplasias Intestinais , Queratinócitos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Mutação , Papiloma/induzido quimicamente , Acetato de Tetradecanoilforbol/farmacologia
12.
Exp Hematol ; 24(5): 613-21, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8605966

RESUMO

The protein kinase C (PKC) activator bryostatin 1 (bryo) has substantial antileukemic and hematopoietic actions. Bryo promotes the in vitro growth of normal hematopoietic progenitors by inducing the release of growth factors from accessory cells. We have examined the effects of bryo on the expression and release of certain myeloid growth factors from fibroblastlike marrow stromal cells (MSC). Substantial release of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF). or interleukin-6 (IL-6) following bryo treatment was seen only in MSC cultures contaminated with macrophages. Bryo alone was ineffective in inducing release of the cytokines from MSC cultures containing only fibroblastlike stromal cells. When MSC were treated with IL-1alpha, substantial quantities of the cytokines (G-CSF, GM-CSF,IL-6) were released. Bryo acted synergistically with IL-1 alpha to significantly increase cytokine release to- to nine-fold compared to IL-1alpha alone (p < 0.016). Neither Il-1alpha nor bryo, alone or in combination, induced release of stem cell factor (scf) from MSC. The synergistic interaction between IL-1alpha and bryo was dose- and schedule-dependent, requiring simultaneous application of IL-1alpha and bryo for optimum effect. Bryo alone induced no G-CSF mRNA accumulation but increased the level seen with IL-1alpha treatment by 50%. The synergistic interaction of bryo and IL-1alpha required PKC, since it was antagonized by agents which depleted or inhibited PKC but not by a protein kinase A antagonist. The increase in G-CSF mRNA was associated with a marked increase in mRNA stability. Bryostatin may promote the release of cytokines from several accessory cell populations, including MSC, to accomplish its in vivo hematopoietic effects.


Assuntos
Células da Medula Óssea , Citocinas/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Interleucina-1/administração & dosagem , Lactonas/administração & dosagem , Medula Óssea/metabolismo , Briostatinas , Células Cultivadas , Ativação Enzimática , Expressão Gênica , Hematopoese , Humanos , Macrolídeos , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/fisiologia , RNA Mensageiro/genética
13.
AJNR Am J Neuroradiol ; 36(12): 2206-13, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26427831

RESUMO

In April 2015, the American Roentgen Ray Society and the American Society of Neuroradiology cosponsored a unique program designed to evaluate the state of the art in the imaging work-up of acute stroke. This topic has grown in importance because of the recent randomized controlled trials demonstrating the clear efficacy of endovascular stroke treatment. The authors, who were participants in that symposium, will highlight the points of emphasis in this article.


Assuntos
Imagem Multimodal/métodos , Acidente Vascular Cerebral/diagnóstico , Embolectomia/métodos , Procedimentos Endovasculares/métodos , Humanos , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/métodos
14.
Am J Cardiol ; 79(6): 742-7, 1997 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-9070552

RESUMO

Unstable angina occurs when atherosclerotic plaque ruptures. Recent evidence suggests a role for inflammation in this process. Leukocyte-endothelial cell interactions are important in inflammation and are regulated by cell adhesion molecules. This study was designed to examine the vascular expression of cell adhesion molecules and cytokines in patients with unstable angina. Directional coronary atherectomy was performed in patients with unstable and stable angina. Expression of the cell adhesion molecules P-selectin, E-selectin, and intercellular adhesion molecule-1 in the tissue obtained was examined using immunohistochemistry. In addition, expression of the cytokines tumor necrosis factor-alpha and interleukin-1beta, which participate in the regulation of cell adhesion molecule expression, was also examined. Atherectomy specimens had significantly greater P-selectin expression from patients with unstable angina than from patients with stable angina. P-selectin expression was observed primarily on endothelial cells. There were no differences in any of the other factors between patients with unstable and stable angina. In addition, other clinical and angiographic variables were not associated with differential expression of any of the cell adhesion molecules or cytokines. These results indicate a possible role for P-selectin in the process of unstable angina.


Assuntos
Angina Pectoris/metabolismo , Angina Instável/metabolismo , Aterectomia Coronária , Vasos Coronários/metabolismo , Selectina E/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Selectina-P/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/cirurgia , Angina Instável/cirurgia , Arteriosclerose/metabolismo , Arteriosclerose/cirurgia , Vasos Coronários/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Interleucina-1/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo
15.
AJNR Am J Neuroradiol ; 20(7): 1239-42, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10472978

RESUMO

A new technique for detecting vascular malformations, high-resolution BOLD venography (HRBV), is described. This technique relies on the BOLD principle for detecting deoxygenated blood in low-flow malformations. HRBV images are acquired using a modified 3D gradient-echo with voxel volumes of 0.5 x 0.5 x 2 mm3. The magnitude data are masked with the phase images to enhance visibility of the venous structures and are displayed using the minimum intensity projection. Preliminary results for 10 patients show that HRBV is more sensitive in detecting cavernomas than is T2-weighted imaging, and lesions that are presumed to be telangiectasias are detected only with this technique.


Assuntos
Neoplasias Encefálicas/diagnóstico , Encéfalo/irrigação sanguínea , Hemangioma Cavernoso/diagnóstico , Malformações Arteriovenosas Intracranianas/diagnóstico , Angiografia por Ressonância Magnética , Oxigênio/sangue , Circulação Cerebrovascular , Humanos , Telangiectasia/diagnóstico
16.
Neurotoxicology ; 19(1): 129-46, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9498229

RESUMO

The effects of subchronic exposure to carbon disulfide (CS2) on ventral caudal tail nerve compound nerve action potential (CNAP) amplitudes and latencies, and nerve conduction velocity (NCV) in rats were examined. Male and female Fischer 344 rats were exposed to 0, 50, 500, or 800 ppm CS2 for 6 hrs/day, 5 days/week. Using separate groups, exposure duration was 2, 4, 8, or 13 weeks. Exposure to 500 or 800 ppm CS2 for 13 weeks decreased NCV compared to the 50 ppm CS2 group. CNAP amplitudes were increased, and peak P1P2 interpeak latency decreased, after exposure to 500 or 800 ppm CS2 for 13 weeks. Most of the changes in NCV and CNAPs were not attributable to differences in tail or colonic temperature. However, the increases in peak P1 amplitude may relate to the proximity of the electrodes to the tail nerves. Assessment of tail nerve morphology after 13 weeks exposure to 800 ppm CS2 revealed only minor changes compared to the extent of axonal swelling and degeneration observed in the muscular branch of the tibial nerve and axonal swelling in the spinal cord. As anticipated, in older animals the NCV increased, the CNAP amplitudes increased, and the CNAP latencies decreased. The biological basis for the changes in CNAPs produced by CS2 is under investigation. Future studies will focus on electrophysiological evaluation of spinal nerve function, to allow better correlation with pathological and behavioral endpoints.


Assuntos
Dissulfeto de Carbono/toxicidade , Condução Nervosa/efeitos dos fármacos , Sistema Nervoso Periférico/efeitos dos fármacos , Sistema Nervoso Periférico/fisiopatologia , Cauda/inervação , Potenciais de Ação/efeitos dos fármacos , Administração por Inalação , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Axônios/ultraestrutura , Temperatura Corporal/efeitos dos fármacos , Dissulfeto de Carbono/administração & dosagem , Colo/efeitos dos fármacos , Colo/fisiopatologia , Relação Dose-Resposta a Droga , Eletrofisiologia , Feminino , Masculino , Sistema Nervoso Periférico/patologia , Ratos , Ratos Endogâmicos F344 , Cauda/efeitos dos fármacos , Cauda/fisiopatologia
17.
Physiol Behav ; 59(2): 325-40, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8838613

RESUMO

Flash evoked potentials (FEPs) undergo within- and between-session changes and are modified by auditory white noise (26). We examined whether an auditory potential produced by the "click" associated with the strobe discharge could be recorded, and if alterations in an auditory response could explain the within- and between-session changes in FEPs. We also examined differences between a frontal cortex or a nasal reference electrode location on FEPs and auditory potentials. An auditory potential associated with the strobe discharge could be clearly recorded. This response was eliminated by the presence of 80 dB SPL masking white noise. However, the within- and between-session changes in FEPs could not be explained by modifications of the auditory potential. Animals whose ear drums were ruptured did not exhibit an auditory response, and their FEPs were similar to those of controls tested in the presence of masking white noise. A nasal reference electrode decreased the impact of auditory potentials on FEPs, but allow visual potentials (electroretinogram and optic tract activity) to influence FEPs. The data show that auditory potentials associated with the strobe discharge can be recorded from the visual cortex of rats, and that these auditory responses represent a possible confounding factor in the interpretation of toxicological studies employing FEPs.


Assuntos
Estimulação Acústica , Atenção/fisiologia , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Visuais/fisiologia , Estimulação Luminosa , Animais , Artefatos , Masculino , Mascaramento Perceptivo/fisiologia , Ratos , Córtex Visual/fisiologia
18.
J Pharm Sci ; 84(8): 915-21, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7500273

RESUMO

In recent years there has been an increased interest in the use of oligonucleotides as therapeutic agents. Oligonucleotide therapeutics may have significant potential over traditional drugs due to their high degree of specificity and increased affinity. The major drawbacks to the use of oligonucleotide therapeutics are the problems associated with their delivery and their relative instability in serum. The serum instability problem has been partially overcome through the use of oligonucleotides with modified backbones. Transdermal electrotransport may be used to overcome the problems associated with delivery. Here we report the use of transdermal electrotransport in the delivery of oligonucleotides across hairless mouse skin. The effects of pH, salt concentration, current density, and oligonucleotide concentration, structure, and length have been investigated.


Assuntos
Oligonucleotídeos/administração & dosagem , Absorção Cutânea/fisiologia , Pele/metabolismo , Administração Cutânea , Animais , Densitometria , Eletroforese em Gel de Poliacrilamida , Concentração de Íons de Hidrogênio , Iontoforese , Camundongos , Camundongos Pelados , Oligonucleotídeos/química , Radioisótopos de Fósforo
19.
J Pediatr Surg ; 30(7): 983-6; discussion 986-7, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7472958

RESUMO

Infants with gastroschisis experience delayed intestinal motility and absorption for several weeks after birth. This intestinal dysfunction is believed to occur primarily in the third trimester and to be largely caused by the prolonged exposure of the intestine to amniotic fluid. Previous studies have shown that prenatal steroid administration will enhance mucosal disaccharidase activity and nutrient uptake. The present study evaluates the effects of dexamethasone on intestinal function in a rabbit fetal gastroschisis model. Thirty-four fetuses from 10 New Zealand white rabbits were divided into three groups: (1) gastroschisis group (GSC, n = 10), gastroschisis was created on gestational day (GD) 24 (term = 31 to 33 days); (2) dexamethasone group (GSD, n = 10), after the creation of gastroschisis, a small osmotic pump was placed into the rabbit doe for dexamethasone infusion into the fetal amniotic cavity for 7 days (0.2 microgram/g/d); (3) normal group (NF, n = 10), unoperated littermates from the GSC group. There were no maternal deaths, and fetal survival rate was 85%. The fetal small intestinal disaccharidase enzyme, lactase (UE/g protein), was markedly decreased in GSC fetuses. It was increased 70% in the GSD group but lower than in normal fetuses (GSC = 10.0 +/- 1.6; GSD = 17.3 +/- 1.6 [GSD versus GSC, P < .05]; NF = 48.0 +/- 6.7). Maltase activity in the GSD group was significantly increased (GSC = 7.2 +/- 1.1; GSD = 13.9 +/- 1.8 [GSD versus GSC, P < .05]; NF = 12.2 +/- 1.3).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Músculos Abdominais/anormalidades , Dexametasona/uso terapêutico , Doenças Fetais/fisiopatologia , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Músculos Abdominais/fisiopatologia , Âmnio , Animais , Dexametasona/administração & dosagem , Dissacaridases/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Idade Gestacional , Glucose/metabolismo , Hérnia Ventral/fisiopatologia , Bombas de Infusão Implantáveis , Injeções , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/enzimologia , Intestino Delgado/enzimologia , Lactase , Gravidez , Coelhos , Taxa de Sobrevida , alfa-Glucosidases/efeitos dos fármacos , beta-Galactosidase/efeitos dos fármacos
20.
Poult Sci ; 57(2): 542-4, 1978 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-674033

RESUMO

In two trials, S. C. White Leghorns were subjected to constant ambient temperatures of 21.1, 29.4 and 35.0 C from 2 to 33 or 2 to 31 weeks of age. Blood samples were obtained 4 days prior to termination of the trial. In trial 1, blood electrolytes Na, K, Ca, Mg and Cl were studied. In trial 2, the same blood electrolytes plus P were studied and the left femur was analyzed for Na, K, Ca, Mg, P, Cu, Zn, Fe, Mn and % ash. Results indicate that both males and females can maintain homeostasis of both blood and bone under the above temperature conditions.


Assuntos
Galinhas/metabolismo , Eletrólitos/sangue , Fêmur/metabolismo , Estresse Fisiológico/veterinária , Temperatura , Animais , Cálcio/sangue , Cálcio/metabolismo , Feminino , Magnésio/sangue , Masculino , Fósforo/metabolismo , Fatores Sexuais , Sódio/sangue , Estresse Fisiológico/metabolismo
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