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The aims of the present study were to determine whether high-density lipoprotein (HDL) functionality-mediated cholesterol efflux is altered in Alzheimer's disease and to investigate the role and effect of amyloid-beta (Aß) in the regulation of the anti-atherogenic activity of HDL. Eighty-seven elderly subjects were recruited, of whom 27 were healthy, 27 had mild cognitive impairment (MCI), and 33 had mild Alzheimer's disease (mAD). Our results showed that total cholesterol levels are negatively correlated with the Mini-Mental State Examination (MMSE) score (r = -0.2602, p = 0.0182). HDL from the mAD patients was less efficient at mediating cholesterol efflux from J774 macrophages (p < 0.05) than HDL from the healthy subjects and MCI patients. While HDL from the MCI patients was also less efficient at mediating cholesterol efflux than HDL from the healthy subjects, the difference was not significant. Interestingly, the difference between the healthy subjects and the MCI and mAD patients with respect to the capacity of HDL to mediate cholesterol efflux disappeared when ATP-binding cassette transporter A1 (ABCA1)-enriched J774 macrophages were used. HDL fluidity was significantly inversely correlated with the MMSE scores (r = -0.4137, p < 0.009). In vitro measurements of cholesterol efflux using J774 macrophages showed that neither Aß1-40 nor Aß1-42 stimulate cholesterol efflux from unenriched J774 macrophages in basal or ABCA1-enriched J774 macrophages.
Assuntos
Doença de Alzheimer/sangue , Lipoproteínas HDL/sangue , Idoso , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/sangue , Transporte Biológico , Colesterol/metabolismo , Feminino , Humanos , Masculino , Fragmentos de Peptídeos/sangueRESUMO
The objective of this study was to compare the course of parturitions induced with sole oxytocin with those induced with the combination of intracervical prostaglandin E2 jelly and oxytocin. For this purpose 13 mares in advanced pregnancy were allocated to the groups pretreated with either intracervical PGE2 (experimental group) or saline (control group) two hours before intravenous oxytocin (5 IU) administration. The mares were compared with respect to cervical dilation diameter (CDD) 20 min. after oxytocin injection. Time intervals from the first oxytocin dose to: the first external signs of parturition, the chorioallantois rupture, the delivery of a foal and time interval from the delivery of a foal to the placenta separation were measured. Cervical dilatation diameter as well as proportion of mares with cervical dilatation > 20 cm were significantly higher in the group of PGE2 treated mares comparing with control group (p = 0.0115 and p = 0.0490, respectively). All time intervals measured were statistically insignificant for both groups of mares, however time intervals from the first oxytocin dose to the first external signs of parturition, to the allantochorion rupture and to the delivery of a foal, were very close to the significance level (alpha = 0.05). To conclude, PGE/oxytocin combination has positive influence on the preparation of the uterine cervix to parturition. Moreover, it seems that PGE2 pretreatment reduced total oxytocin dose for successful parturition induction and shortened time elapsing between the first oxytocin dose and the delivery of a foal what is crucial for foal's safety.
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Dinoprostona/farmacologia , Cavalos/fisiologia , Trabalho de Parto Induzido/veterinária , Ocitocina/farmacologia , Parto/efeitos dos fármacos , Animais , Dinoprostona/administração & dosagem , Quimioterapia Combinada , Feminino , Ocitócicos/administração & dosagem , Ocitócicos/farmacologia , Ocitocina/administração & dosagem , Parto/fisiologia , GravidezRESUMO
In this paper, we present the results of experiments on samples of ß-Ga2O3 single crystals under a project aimed at assessing and improving the scintillation performance of this material by studying scintillation and radioluminescence mechanism and its limitations. In addition to standard experiments, such as scintillation light yields and time profiles, radio-, and thermoluminescence, we developed and tested a new and promising two-beam experiment, in which a sample is excited by an X-ray beam and additionally stimulated by an IR laser diode. Fe and Mg doping compensate for the inherent n-type conductivity of ß-Ga2O3 to obtain semi-insulating single crystals for large-area substrates and wafers. At the same time, residual Fe and Ir are ubiquitous uncontrolled impurities leached from the Ir crucibles used to grow large bulk crystals by the Czochralski method. For these experiments, we selected four samples cut from the Czochralski grown 2-cm diameter ß-Ga2O3 single crystal boules; one with a reduced Fe content, two unintentionally Fe- and Ir-doped (UID) with lower and higher Fe content, and one doped with Mg. We find that steady-state radioluminescence spectra measured at temperatures between 10 and 350 K are dominated by the UV emission peaking at about 350-370 nm. Unfortunately, even for the best sample with a reduced Fe-content, the intensity of this emission drops precipitously with the temperature down to about 10 % at 300 K. From the two-beam experiments, we conclude that recombination via inadvertent Fe impurity involving three charge states (2+, 3+, and 4+) may reduce a steady-state UV emission of ß-Ga2O3 under X-ray excitation by as much as 60-70 %, one-third to one-half of which is due to the recombination (specific for Fe-doped ß-Ga2O3) involving the 4+ and 3+ charge states of Fe and the remaining 50-70 % being due to a more familiar route typical of other oxides, involving the 2+ and 3+ charge states of Fe. These losses are at higher temperatures enhanced by a thermally activated redistribution of self-trapped holes (STHs). In addition, the trapping of electrons by Fe and holes by Mg, Fe, and Ir may be responsible for scintillation light loss and reduction of the zero-time amplitude essential for the fast timing scintillation applications. Despite indirect evidence of competitive recombination in ß-Ga2O3 involving a deep Ir3+/4+ donor level, we could not quantitatively assess losses of the UV steady state radioluminescence light due to the inadvertent Ir impurity.
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Endometrosis is a periglandular fibrosis associated with dysfunction of affected glandular epithelial cells that is the most common cause of reduced fertility in mares, although it is not fully understood. The etiology of the disease is still partially unknown. This study focuses on understanding the genetic mechanisms potentially underlying endometrosis in mares using the Next Generation Sequencing (NGS) technique. Endometrial samples, used in the study, were obtained in the anestrus phase both from healthy mares and those diagnosed with endometrosis. The NGS data were analyzed for gene involvement in biological processes and pathways (e.g. STAR, KOBAS-I, STRING, and ClustVis software). Bioinformatic analysis revealed differential expression of 55 transcripts. In tissues with endometrosis, most genes displayed upregulated expression. The protein-protein interaction analysis disclosed a substantial transcript network including transcripts related to metabolism e.g. sulfur metabolism (SELENBP1), ovarian steroidogenesis, steroid hormone biosynthesis, and chemical carcinogenesis (CYP1B1), COXs (COX4I1, COX3, UQCRFS1) as well as transcripts related to immune response e.g. MMP7, JCHAIN, PIGR, CALR, B2M, FCGRT. Interestingly, the latter has been previously linked with various pathologies including cancers in the female reproductive system. In conclusion, this study evaluated genes that are not directly impacted by sex hormone feedback, but that create a metabolic and immune environment in tissues, thus influencing fertility and pregnancy in mares with endometrosis. Moreover, some of the identified genes may be implicated in tumorigenesis of endometrial lesions. These data may be useful as a starting point in further research, such as the development of targeted strategies for rapid diagnosis and/or prevention of this pathology based on gene and protein-protein interactions.
Assuntos
Endometriose , Doenças dos Cavalos , Animais , Carcinogênese/metabolismo , Carcinogênese/patologia , Endometriose/veterinária , Endométrio/metabolismo , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Doenças dos Cavalos/patologia , Cavalos , GravidezRESUMO
BACKGROUND: The equine colic, which is caused by the presence of enteroliths that are most often found in the small or large colon, is typical for certain geographical regions (dry and hot climate). A diet rich in alfalfa is one of the highest risk factors. The earliest symptoms include weight loss and repeated episodes of colic pain. Aims: To present the results of operative treatment of 15 horses with enteroliths in Saudi Arabia. METHODS: Fifteen purebred Arabian horses in Saudi Arabia, aged between 2 and 18 years, were treated. Decision about the surgery was based on clinical exam, ultrasound and rectal examination. The surgery was done on recumbent position in every case, under general inhalation anesthesia performed with izofluran. RESULTS: Midline laparotomy was performed in all cases. Additional left flank laparotomy was performed in one horse, in which the stone was located in the proximal part of the small colon and parainguinal laparotomy was performed in 1 horse, in which the stone was located distally in the small colon. In each case, pelvic flexure enterotomy was performed in order to empty the large colon. Additionally, four horses underwent ventral colon enterotomy due to the presence of large stones. Small colon enterotomy was performed in 9 horses. In 12 cases treatment outcome was good and in 3 - poor. Chemical analysis of the stones showed similar results: calcium, calcium oxalate, ammonium, phosphates, and magnesium (Mg) were obtained in all these cases but there were quantitative differences accounting for 15 to 30%, 10 to 20%, 10%, 20 to 40%, and 10 to 15%, respectively. CONCLUSION: The results of surgery are generally good if stones are located in the large colon, but the prognosis is worse if they are located in the small colon, particularly in its proximal part. There is a huge importance of X-ray examination, which allows accurate diagnosis for locating the enteroliths and making a decision about surgery.
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Direct brain control of advanced robotic systems promises substantial improvements in health care, for example, to restore intuitive control of hand movements required for activities of daily living in quadriplegics, like holding a cup and drinking, eating with cutlery, or manipulating different objects. However, such integrated, brain- or neural-controlled robotic systems have yet to enter broader clinical use or daily life environments. We demonstrate full restoration of independent daily living activities, such as eating and drinking, in an everyday life scenario across six paraplegic individuals (five males, 30 ± 14 years) who used a noninvasive, hybrid brain/neural hand exoskeleton (B/NHE) to open and close their paralyzed hand. The results broadly suggest that brain/neural-assistive technology can restore autonomy and independence in quadriplegic individuals' everyday life.
Assuntos
Interfaces Cérebro-Computador , Exoesqueleto Energizado , Quadriplegia/reabilitação , Atividades Cotidianas , Adolescente , Adulto , Eletroencefalografia/estatística & dados numéricos , Eletroculografia/estatística & dados numéricos , Exoesqueleto Energizado/estatística & dados numéricos , Feminino , Mãos , Força da Mão/fisiologia , Humanos , Masculino , Destreza Motora/fisiologia , Quadriplegia/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Adulto JovemRESUMO
Activating NOTCH1 mutations occur in ~60% of human T-cell acute lymphoblastic leukemias (T-ALLs), and mutations disrupting the transcription factor IKZF1 (IKAROS) occur in ~5% of cases. To investigate the regulatory interplay between these driver genes, we have used a novel transgenic RNA interference mouse model to produce primary T-ALLs driven by reversible Ikaros knockdown. Restoring endogenous Ikaros expression in established T-ALL in vivo acutely represses Notch1 and its oncogenic target genes including Myc, and in multiple primary leukemias causes disease regression. In contrast, leukemias expressing high levels of endogenous or engineered forms of activated intracellular Notch1 (ICN1) resembling those found in human T-ALL rapidly relapse following Ikaros restoration, indicating that ICN1 functionally antagonizes Ikaros in established disease. Furthermore, we find that IKAROS mRNA expression is significantly reduced in a cohort of primary human T-ALL patient samples with activating NOTCH1/FBXW7 mutations, but is upregulated upon acute inhibition of aberrant NOTCH signaling across a panel of human T-ALL cell lines. These results demonstrate for the first time that aberrant NOTCH activity compromises IKAROS function in mouse and human T-ALL, and provide a potential explanation for the relative infrequency of IKAROS gene mutations in human T-ALL.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas F-Box/metabolismo , Fator de Transcrição Ikaros/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Receptores Notch/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Biomarcadores Tumorais/genética , Western Blotting , Proteínas de Ciclo Celular/genética , Imunoprecipitação da Cromatina , Proteínas F-Box/genética , Proteína 7 com Repetições F-Box-WD , Citometria de Fluxo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fator de Transcrição Ikaros/antagonistas & inibidores , Fator de Transcrição Ikaros/genética , Camundongos , Camundongos Transgênicos , Mutação/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Receptores Notch/genética , Transdução de Sinais , Ubiquitina-Proteína Ligases/genéticaRESUMO
Next to the sex steroid hormone T, PRL has been shown to influence prostatic function and development. Transgenic mice overexpressing the rat PRL gene develop dramatic enlargements of the prostate gland. Proliferation and secretory activities of epithelial cells are stimulated by PRL in rodents and men. Low concentrations of human PRL (hPRL) and hPRL receptors have been observed in human prostatic epithelial cells (ECs). The aim of this study was to compare regulation of the in vitro hPRL secretion in prostatic ECs and stromal smooth muscle cells (SMCs) after stimulation with seminal plasma (SMP), containing a variety of prostatic factors. SMCs released up to 1 ng hPRL/ml (i.e., approximately 500-fold more than unstimulated SMCs and ECs). Quantification of PRL mRNA by highly sensitive quantitative RT-PCR revealed that hPRL gene expression increased 5-fold within 24 h of SMP incubation. Sex steroids (dihydrotestosterone, progesterone, 17beta-estradiol), prostaglandins (PGE-1, PGE-2), and cAMP-stimulating substances (forskolin) were not responsible for induction of hPRL. Compared with endometrial SMCs, regulation of prostatic hPRL secretion was independent of progesterone and cAMP. HPLC analysis of human SMP revealed that the common action of at least two different proteins and a low molecular cofactor is required. We concluded that prostatic ECs secrete proteins acting synergistically with low-molecular-weight cofactors to induce differentiation and hPRL release in SMCs. Age-related increases in SMC-derived hPRL might contribute to the development of benign hyperplasia of the prostate.
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Músculo Liso Vascular/metabolismo , Prolactina/metabolismo , Próstata/metabolismo , Sêmen/fisiologia , Adulto , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Imunofluorescência , Regulação da Expressão Gênica , Hormônios Esteroides Gonadais/metabolismo , Hormônios Esteroides Gonadais/fisiologia , Humanos , Masculino , Peso Molecular , Músculo Liso Vascular/citologia , Próstata/citologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estimulação Química , Células Estromais/metabolismoAssuntos
Abscesso/etiologia , Branquioma/complicações , Fístula/diagnóstico , Dermatopatias/diagnóstico , Adulto , Criança , Erros de Diagnóstico , Face , Feminino , Fístula/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , PescoçoRESUMO
We describe the method allowing quantitative interpretation of absorptive images of mixtures of Bose-Einstein condensate and thermal atoms which reduces possible systematic errors associated with evaluation of the contribution of each fraction and eliminates arbitrariness of most of the previous approaches. By using known temperature dependence of the BEC fraction, the analysis allows precise calibration of the fitting results. The developed method is verified in two different measurements and compares well with theoretical calculations and with measurements performed by another group.
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The aim of the present study was to determine the effect of prolonged photoperiod during late pregnancy on subsequent ovarian activity and fertility in mares. Pregnant mares (n=13) due to give birth in January and February were stimulated by a fixed photoperiod (16 h light: 8 h dark) from 15 November (during the last 2-3 months of gestation) until up to 1 month after parturition. A control group of mares (n=9) due to give birth at the same time were kept in the same stable and management regimen, but under natural light conditions. Light-treated mares ovulated during foal oestrus approximately 3 days earlier than did the control mares (P < 0.05). The incidence of winter ovarian inactivity in foaling mares was 7.6% in the treatment group and 33% in the control mares. The processes of involution and uterine fluid expulsion were similar in both groups. The final pregnancy rate was high in both the experimental and control groups, being 92 and 89%, respectively. However, the duration of the open period (period from parturition to next pregnancy) was significantly shorter in the mares that received the light treatment compared with the untreated control mares.
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Ciclo Estral/fisiologia , Cavalos/fisiologia , Parto/fisiologia , Fotoperíodo , Reprodução/fisiologia , Animais , Feminino , GravidezRESUMO
The case of acute alcoholic pancreatitis, complicated by internal pancreatic fistula is being reported. The general patients symptom in initial illness period was ascites in peritoneal cavity. Biochemical investigation of ascites has shown elevated activity of amylase and protein which is typical for pancreatic ascites. The late diagnosis of ascites cause (in 3rd week of the illness) and complications decreased efficacy of the treatment used (parenteral nutrition and somatostatin). Thus worse the course of the illness.
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Ascite/etiologia , Fístula Pancreática/complicações , Pancreatite Alcoólica/complicações , Doença Aguda , Adulto , Amilases/análise , Líquido Ascítico/química , Humanos , Masculino , Pancreatite Alcoólica/diagnóstico , Proteínas/análiseRESUMO
One of the complications of femoral artery synthetic prostheses are anastomotic aneurysms. In 1985-1993, 38 patients were treated for anastomotic aneurysms. Diagnosis was based on clinical and ultrasound examinations. A retrospective analysis has shown an occurrence of fever in 12 patients, and superficial pus oozing in 10 patients. Bacteriological cultures of intra-operatively collected specimens were positive in 25 patients. An infection with staphylococci was predominating. Repeated reconstructive surgery was performed within 6 months to 5 years after the primary one, mean 1.6 years. Aneurysm with the segment of prosthesis was excised and replaced by a fragment of new prosthesis (26 patients) or the vessel after excision of aneurysm was sutured with additional sutures on the whole anastomosis circumference (6 patients). On 7 patients bypass grafting was performed with ligation of vessels supplying anastomotic aneurysm. In all patients flow drainage was used. Positive result of re-operation was achieved in 21 (68.4%) patients. Limb was amputated in 10 cases (26.3%), and 2 patients (5.3%) died. An analysis of the treated patients showed an important role of the anastomotic infection in the anastomotic aneurysms formation. The treatment should include prolonged antibiotic therapy prior to the operation. In case of reoperation possible infection should always be considered.
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Falso Aneurisma/etiologia , Prótese Vascular/efeitos adversos , Artéria Femoral/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus/isolamento & purificaçãoRESUMO
Prostate epithelial cells contain the highest levels of zinc among all organs and tissues in the human body. Zinc is accumulated primarily in the mitochondria, where it is responsible for inhibition of mitochondrial aconitase activity, thereby increasing citrate production. The present study was designed to clarify the role of zinc for human prostate epithelial cell growth and apoptosis. Apoptosis of in vitro cultivated human prostate epithelial cells exposed to ZnCl(2) was analyzed by determination of phospholipid membrane asymmetry, nuclear fragmentation, DNA strand breaks, changes of mitochondrial potential and cellular pro/antiapoptotic proteins. Zinc induced apoptosis without involvement of p53 by decreasing mitochondrial transmembrane potential (DeltaPsi(m)) and Bcl-2 protein levels in proliferating epithelial cells. Thus, the high local concentrations of zinc ions in the prostatic lumen seem to be necessary to regulate proliferative activities and to enforce epithelial differentiation processes.
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Cloretos/farmacologia , Dano ao DNA , Células Epiteliais/fisiologia , Membranas Intracelulares/fisiologia , Mitocôndrias/fisiologia , Próstata/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Compostos de Zinco/farmacologia , Actinas/metabolismo , Apoptose , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/ultraestrutura , DNA/efeitos dos fármacos , DNA/metabolismo , Células Epiteliais/citologia , Humanos , Membranas Intracelulares/efeitos dos fármacos , Cinética , Masculino , Lipídeos de Membrana/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Fosfolipídeos/metabolismo , Próstata/citologia , Zinco/fisiologiaRESUMO
41 heifers of 260-440 kg body weight used in an experiment were polyovulated with PGF2 alpha and PMSG (1000 IU). Animals were slaughtered during luteal phase of ovarian cycle (day 12-15). Shortly before slaughter ovarian structures were defined by rectal palpation und ultrasonographical examination. Post mortem ovaries were collected to compare their structures with previously performed in vivo diagnosis. More follicular structures were detected sonographically (109%) than could be found by morphologic examination (100%). Concerning corpora lutea a right diagnosis was made by palpation in 94% of cases, whereas the rate was only 85% for ultrasonographical examination. Main reasons for false diagnoses of ultrasonographical examination are as follows: multiple ovarian structures, corpora lutea with holes inside, atypical shape of ovaries, atypical ultrasonographical pictures and irregular shape of follicles.