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Magnetic refrigeration (MR) is a key technique for hydrogen liquefaction. Although the MR has ideally higher performance than the conventional gas compression technique around the hydrogen liquefaction temperature, the lack of MR materials with high magnetic entropy change in a wide temperature range required for the hydrogen liquefaction is a bottle-neck for practical applications of MR cooling systems. Here, we show a series of materials with a giant magnetocaloric effect (MCE) in magnetic entropy change (-∆Sm > 0.2 J cm-3K-1) in the Er(Ho)Co2-based compounds, suitable for operation in the full temperature range required for hydrogen liquefaction (20-77 K). We also demonstrate that the giant MCE becomes reversible, enabling sustainable use of the MR materials, by eliminating the magneto-structural phase transition that leads to deterioration of the MCE. This discovery can lead to the application of Er(Ho)Co2-based alloys for the hydrogen liquefaction using MR cooling technology for the future green fuel society.
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OBJECTIVE: Although the postoperative use of hormonal treatment for endometriosis is recommended in the European Society of Human Reproduction and Embryology guidelines to prevent the recurrence of endometriosis-associated dysmenorrhoea, hormonal treatment may not be necessary for all patients who undergo surgical treatment for endometriosis. The aim of this study was to clarify the determinant factors that predict the recurrence of endometriosis after surgery in order to develop personalized hormonal treatment recommendations. Factors associated with the recurrence of endometrioma and pain were investigated independently to identify the likelihood of recurrence in each individual patient. STUDY DESIGN: Between 2008 and 2013, 352 patients underwent surgery and were diagnosed with endometriosis based on pathological findings at the study hospital. Among these patients, 191 experienced a recurrence of endometrioma in the absence of pre- or postoperative hormonal treatment. Various clinical factors such as pre-operative pain, intra-operative findings and postoperative improvement of pain were compared between patients who experienced recurrence after surgery and those who did not. RESULTS: The cumulative 5-year recurrence rate of endometrioma was 28.7% among the 191 patients who did not undergo pre- or postoperative hormonal treatment. Significant differences were detected in maximum tumour diameter, revised American Society for Reproductive Medicine score (r-ASRM score), operative time and operative blood loss between patients in the recurrent endometrioma group and the non-recurrent endometrioma group; only the r-ASRM score was significantly correlated with recurrence of endometrioma in the multivariate analysis. The cumulative 5-year rate of persistent/recurrent pain was 33.4%. There were significant differences in the postoperative improvement of pain between the persistent/recurrent pain group and the non-recurrent pain group according to the univariate and multivariate analyses. CONCLUSION: This study suggests that the risk factors for recurrence of endometrioma differ from the risk factors for recurrence of pain. The use of postoperative hormonal treatment should be considered based on the dominant risk factors and needs of each patient.
Assuntos
Endometriose/cirurgia , Laparoscopia , Doenças Ovarianas/cirurgia , Dor/diagnóstico , Adulto , Fatores Etários , Endometriose/diagnóstico , Feminino , Humanos , Doenças Ovarianas/diagnóstico , Período Pós-Operatório , Recidiva , Fatores de Risco , Resultado do TratamentoRESUMO
It is known that solid food is transported to the pharynx actively in parallel to it being crushed by chewing and mixed with saliva in the oral cavity. Therefore, food bolus formation should be considered to take place from the oral cavity to the pharynx. In previous studies, the chewed food was evaluated after the food had been removed from the oral cavity. However, it has been pointed out that spitting food out of the oral cavity interferes with natural food bolus formation. Therefore, we observed food boluses immediately before swallowing using an endoscope to establish a method to evaluate the food bolus-forming function, and simultaneously performed endoscopic evaluation of food bolus formation and its relationship with the number of chewing cycles. The subject was inserted the endoscope nasally and instructed to eat two coloured samples of boiled rice simultaneously in two ingestion conditions ('as usual' and 'chewing well'). The condition of the food bolus was graded into three categories for each item of grinding, mixing and aggregation and scored 2, 1 and 0. The score of aggregation was high under both ingestion conditions. The scores of grinding and mixing tended to be higher in subjects with a high number of chewing cycles, and the score of aggregation was high regardless of the number of chewing cycles. It was suggested that food has to be aggregated, even though the number of chewing cycles is low and the food is not ground or mixed for a food bolus to reach the swallowing threshold.
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Deglutição/fisiologia , Alimentos , Mastigação/fisiologia , Faringe , Adulto , Endoscopia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Conventional superconductivity follows Bardeen-Cooper-Schrieffer(BCS) theory of electrons-pairing in momentum-space, while superfluidity is the Bose-Einstein condensation(BEC) of atoms paired in real-space. These properties of solid metals and ultra-cold gases, respectively, are connected by the BCS-BEC crossover. Here we investigate the band dispersions in FeTe(0.6)Se(0.4)(Tc = 14.5 K ~ 1.2 meV) in an accessible range below and above the Fermi level(EF) using ultra-high resolution laser angle-resolved photoemission spectroscopy. We uncover an electron band lying just 0.7 meV (~8 K) above EF at the Γ-point, which shows a sharp superconducting coherence peak with gap formation below Tc. The estimated superconducting gap Δ and Fermi energy [Symbol: see text]F indicate composite superconductivity in an iron-based superconductor, consisting of strong-coupling BEC in the electron band and weak-coupling BCS-like superconductivity in the hole band. The study identifies the possible route to BCS-BEC superconductivity.
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Disuse atrophy of swallowing-related organs due to an excessive decrease in swallowing frequency is suspected to occur in patients with poor oral intake, especially elderly people. However, swallowing frequency in daily life has not previously been examined in the elderly. This study examined swallowing frequency in elderly people and compared these findings to those in a younger population and differences in the degree of activity in daily life. (i) We compared swallowing frequency in 20 elderly people (82·0 ± 8·3 year) and 15 healthy young people (26·5 ± 3·5 year). (ii) 20 elderly people were divided into two groups according to the degree of activity in daily life: a semi-bedridden group and bedridden group; the swallowing frequency was compared between these groups. (i) The swallowing frequency in the elderly people was 2-19 times per hour and the mean was 9·4 ± 4·9, and that in the healthy young people was 16-76 times per hour and the mean was 40·7 ± 19·5. Swallowing frequency in elderly people was significantly lower than that in young healthy people (P < 0·0001). (ii) The swallowing frequency in bedridden group was 2-11 times per hour and the mean was 6·8 ± 3·3, and that in semi-bedridden group was 3-19 times per hour and the mean was 11·9 ± 5·1. Swallowing frequency in bedridden group was significantly lower than that in semi-bedridden group (P < 0·05). These results indicate that in daily life, elderly people tend to swallow less frequently than young people. In addition, swallowing frequency was lower in elderly subjects with a low degree of activity in daily life.
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Atividades Cotidianas , Repouso em Cama/efeitos adversos , Deglutição/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Fatores de Tempo , Adulto JovemRESUMO
The hyoid bone moves during swallowing due to contraction of suprahyoid muscles, which are critical components of normal swallowing function. It has been reported that the muscle force and shortening velocity decline gradually with age. Reduced hyoid velocities may delay the sealing of the laryngeal vestibule and opening of the cricopharyngeal muscle. We hypothesised that the hyoid velocity could be a factor influencing aspiration. This study evaluated effects of bolus volume changes on the hyoid distance and velocity in normal swallowing. The subjects were 21 healthy young adults. Lateral projection videofluorography was recorded while each subject swallowed 2·5, 5·0, 10 and 20 mL of liquid barium. We evaluated the maximum hyoid distance (Max d), anterior and superior distance (Max ad, Max sd). And, we evaluated the maximum velocity (Max v), anterior and superior velocity (Max av, Max sv). Two-way anova test revealed that Max d, Max ad and Max sd for different bolus volumes are not significantly different. But, two-way anova test showed statistically significant difference in Max v, Max av and Max sv among different bolus volume (P < 0·01). Tukey's test showed that there are significant differences in Max v between 2·5 and 20 mL, 5·0 and 20 mL, 10 and 20 mL, and 2·5 and 10 mL swallowing. And, Tukey's test showed significant differences in Max av and Max sv between 2·5 and 20 mL, 5·0 and 20 mL, and 10 and 20 mL swallowing. It is possible that a larger bolus volume requires greater maximum hyoid velocity. We plan to study hyoid velocity in elderly subjects and in those with dysphagia.
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Deglutição/fisiologia , Osso Hioide/fisiologia , Movimento/fisiologia , Adulto , Análise de Variância , Bário , Feminino , Fluoroscopia/métodos , Humanos , Osso Hioide/anatomia & histologia , Masculino , Gravação em Vídeo , Adulto JovemRESUMO
In order to examine to what extent the rigid-band-like electron doping scenario is applicable to the transition metal-substituted Fe-based superconductors, we have performed angle-resolved photoemission spectroscopy studies of Ba(Fe(1-x)Ni(x))(2)As(2) (Ni-122) and Ba(Fe(1-x)Cu(x))(2)As(2) (Cu-122), and compared the results with Ba(Fe(1-x)Co(x))(2)As(2) (Co-122). We find that Ni 3d-derived features are formed below the Fe 3d band and that Cu 3d-derived ones further below it. The electron and hole Fermi surface (FS) volumes are found to increase and decrease with substitution, respectively, qualitatively consistent with the rigid-band model. However, the total extra electron number estimated from the FS volumes (the total electron FS volume minus the total hole FS volume) is found to decrease in going from Co-, Ni-, to Cu-122 for a fixed nominal extra electron number, that is, the number of electrons that participate in the formation of FS decreases with increasing impurity potential. We find that the Néel temperature T(N) and the critical temperature T(c) maximum are determined by the FS volumes rather than the nominal extra electron concentration or the substituted atom concentration.
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In iron-pnictide superconductivity, the interband interaction between the hole and electron Fermi surfaces (FSs) is believed to play an important role. However, KFe(2)As(2) has three zone-centered hole FSs and no electron FS but still exhibits superconductivity. Our ultrahigh-resolution laser angle-resolved photoemission spectroscopy unveils that KFe(2)As(2) is a nodal s-wave superconductor with highly unusual FS-selective multi-gap structure: a nodeless gap on the inner FS, an unconventional gap with "octet-line nodes" on the middle FS, and an almost-zero gap on the outer FS. This gap structure may arise from the frustration between competing pairing interactions on the hole FSs causing the eightfold sign reversal. Our results suggest that the A(1g) superconducting symmetry is universal in iron-pnictides, in spite of the variety of gap functions.
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INTRODUCTION: Laparoscopic surgery has become a standard surgical method for benign gynecological diseases, but the technique can still be accompanied, albeit infrequently, by intraoperative or postoperative complications. It has been postulated that the frequency of complications differs according to patient body habitus or surgical challenge level. We evaluated the relationship between the complication rate at different levels of surgery and BMI in patients with benign gynecological diseases who have undergone laparoscopic surgery at our hospital. METHODS: A total of 3231 patients who underwent laparoscopic surgery between 1989 and 2010 were enrolled in this study retrospectively. They were classified into four groups by surgery level (diagnostic laparoscopy or minor, major, or advanced laparoscopic surgery). At each challenge level, patients were classified into three groups based on BMI (as defined by the WHO): A group (underweight), BMI < 18.5; B group (healthy), BMI ≥ 18.5 and < 25; and C group (overweight), BMI ≥ 25. We compared the complication rates between the groups at each level of surgical challenge. RESULTS: There was no difference in the complication rate between groups A, B and C at any of the surgical challenge levels. However, at the higher surgical difficulty levels, a higher incidence of overall complications was observed. CONCLUSION: The complication rate differs between surgical levels, and complications can occur in any type of surgery, irrespective of the body habitus of the patient. The complication rate is higher when difficult surgical methods are employed, and extra caution is needed.
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Índice de Massa Corporal , Doenças dos Genitais Femininos/cirurgia , Complicações Intraoperatórias/etiologia , Laparoscopia/métodos , Sobrepeso/complicações , Complicações Pós-Operatórias/etiologia , Feminino , Doenças dos Genitais Femininos/diagnóstico , Humanos , Incidência , Complicações Intraoperatórias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Uterine myoma and uterine adenomyosis frequently occur in sexually mature women. Total hysterectomy is the treatment of choice when the symptoms are severe. To select an operative procedure from abdominal, vaginal, and laparoscopic methods, precise estimation of the preoperative uterine weight is desired. In this study, we estimated the preoperative uterine weight with preoperative images in cases of uterine myoma and uterine adenomyosis. METHODS: We evaluated 403 patients with uterine myoma or uterine adenomyosis (uterus < 1000 g) between 1996 and 2010. All patients underwent a preoperative MRI and received a hysterectomy with the uterine weight recorded. Based on MR images, we measured (in centimeters) the maximum longitudinal diameter in the sagittal section (a), the maximum lateral diameter (b) and the maximum longitudinal diameter in the transverse section (c) of each uterus. A correlation coefficient was calculated between the weight of the removed uterus and the value of a × b × c for each individual uterus. Also, a regression analysis was performed between x (the value of a × b × c) and y (weight of the removed uterus). RESULTS: A strong correlation was shown between the weight of the removed uterus and the value of a × b × c (r = 0.81, P < 0.01). As a result of the regression analysis, the regression equation y = 0.35x + 107 (R(2) = 0.66, P < 0.01) was obtained. CONCLUSION: In this study, the estimated weight of the uterus was calculated by the formula y = 0.35x + 107 (x = a × b × c), and this could be the determining factor in choosing a surgical method for hysterectomy.
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Adenomiose/patologia , Leiomioma/patologia , Neoplasias Uterinas/patologia , Útero/patologia , Adenomiose/cirurgia , Feminino , Humanos , Histerectomia Vaginal , Leiomioma/cirurgia , Imageamento por Ressonância Magnética , Tamanho do Órgão , Período Pré-Operatório , Neoplasias Uterinas/cirurgiaRESUMO
Disuse atrophy of swallowing-related organs is suspected when decreased swallowing frequency is seen in the elderly. However, swallowing frequency has not been examined in elderly people during daily life. We developed a swallowing frequency meter containing a laryngeal microphone that does not restrict the subject's ability to perform daily activities. In this study, the utility of the meter was assessed. Experiment 1: The ability of the meter to detect swallowing was examined. The subject was instructed to swallow saliva or foods at a voluntarily pace. During these procedures, swallowing events were simultaneously recorded by the meter, self-enumeration and videofluorography. As a result, all of the swallowing events identified by the meter coincided with the swallowing events identified by self-enumeration and videofluorography. Experiment 2: Swallowing sounds display various patterns both between and within individuals. Therefore, we examined the concordance rate between the number of swallowing events counted by the meter and that counted by self-enumeration in 15 subjects over a longer period than in experiment 1. The concordance rates calculated by two examiners between the meter and self-enumeration were 96·8 ± 4·5% and 98·9 ± 3·3% at rest and 95·2 ± 4·5% and 96·1 ± 4·1% during meals, respectively. Our findings indicate that this meter is useful for measuring the frequency of swallowing during daily situations.
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Deglutição/fisiologia , Laringe , Monitorização Ambulatorial/instrumentação , Som , Adulto , Feminino , Fluoroscopia/métodos , Humanos , MP3-Player , Masculino , Reprodutibilidade dos Testes , Autorrelato , Gravação em Vídeo , Adulto JovemRESUMO
We study the superconducting-gap anisotropy of the Γ-centered hole Fermi surface in optimally doped FeTe(0.6)Se(0.4) (T(c)=14.5 K), using laser-excited angle-resolved photoemission spectroscopy. We observe sharp superconducting (SC) coherence peaks at T=2.5 K. In contrast to earlier angle-resolved photoemission spectroscopy studies but consistent with thermodynamic results, the momentum dependence shows a cos(4φ) modulation of the SC-gap anisotropy. The observed SC-gap anisotropy strongly indicates that the pairing interaction is not a conventional phonon-mediated isotropic one. Instead, the results suggest the importance of second-nearest-neighbor electronic interactions between the iron sites in the framework of s(±)-wave superconductivity.
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INTRODUCTION: While total abdominal hysterectomy (TAH) and total vaginal hysterectomy (TVH) are conventional procedures, we have actively introduced laparoscopically-assisted vaginal hysterectomy (LAVH) since its advent. This study was the first attempt to retrospectively compare the surgical results, including invasiveness, among the three methods of performing a hysterectomy. METHODS: The subjects included 1181 patients who underwent total hysterectomies (TAH, n=465; LAVH, n=629; TVH, n=87) due to uterine fibroids or uterine adenomyosis at our hospital between January 1995 and December 2009. The mean age, parity, weight of the removed uterus, operative time, blood loss, rates of intra- and post-operative complications, length of post-operative hospital stay, leukocyte count, and CRP and hemoglobin levels were compared. RESULTS: The operative time was significantly longer in the LAVH group than the other two groups. Blood loss was significantly greater in the TAH group than the LAVH and TVA groups. The rates of intra- and post-operative complications were significantly higher in the TAH group than the LAVH group. The CRP level and leukocyte count were significantly lower in the LAVH group than the TAH and TVH groups. CONCLUSION: LAVH can be applied to nulligravidas or patients with relatively large uteri and it is proved less invasive than TAH and TVH in this study. We recommend active application of LAVH.
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Endometriose/cirurgia , Histerectomia/métodos , Laparoscopia , Leiomioma/cirurgia , Neoplasias Uterinas/cirurgia , Adulto , Idoso , Feminino , Humanos , Histerectomia Vaginal/métodos , Complicações Intraoperatórias/epidemiologia , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Doenças Uterinas/cirurgiaRESUMO
Immunoglobulins (Igs) play important immunomodulatory effects on allergic asthma. Among these, IgG has been reported to regulate allergic inflammation in previous studies about immunotherapy and intravenous immunoglobulin therapy. In this study, to examine the immunomodulatory mechanisms of IgG and FcRs we evaluated the effects of intravenous (i.v.) rabbit IgG administration (IVIgG) on allergic airway inflammation and lung antigen-presenting cells (APCs) in a murine model of ovalbumin (OVA) sensitization and challenge. In OVA-challenged mice, IVIgG attenuated airway eosinophilia, airway hyperresponsiveness and goblet cell hyperplasia and also inhibited the local T helper type (Th) 2 cytokine levels. Additionally, IVIgG attenuated the proliferation of OVA-specific CD4(+) T cells transplanted into OVA-challenged mice. Ex vivo co-culture with OVA-specific CD4(+) cells and lung CD11c(+) APCs from mice with IVIgG revealed the attenuated transcription level of Th2 cytokines, suggesting an inhibitory effect of IVIgG on CD11c(+) APCs to induce Th2 response. Next, to analyse the effects on Fcγ receptor IIb and dendritic cells (DCs), asthmatic features in Fcγ receptor IIb-deficient mice were analysed. IVIgG failed to attenuate airway eosinophilia, airway inflammation and goblet cell hyperplasia. However, the lacking effects of IVIgG on airway eosinophilia in Fcγ receptor IIb deficiency were restored by i.v. transplantation of wild-type bone marrow-derived CD11c(+) DCs. These results demonstrate that IVIgG attenuates asthmatic features and the function of lung CD11c(+) DCs via Fcγ receptor IIb in allergic airway inflammation. Targeting Fc portions of IgG and Fcγ receptor IIb on CD11c(+) DCs in allergic asthma is a promising therapeutic strategy.
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Asma/terapia , Antígeno CD11c/metabolismo , Células Dendríticas/efeitos dos fármacos , Imunoglobulina G/farmacologia , Imunoglobulinas Intravenosas/farmacologia , Receptores de IgG/genética , Transferência Adotiva , Animais , Apresentação de Antígeno/efeitos dos fármacos , Apresentação de Antígeno/imunologia , Asma/imunologia , Asma/patologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/fisiopatologia , Hiper-Reatividade Brônquica/prevenção & controle , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Proliferação de Células , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/transplante , Modelos Animais de Doenças , Eosinófilos/citologia , Feminino , Imunoglobulina E/sangue , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Inflamação/imunologia , Inflamação/patologia , Inflamação/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Organismos Livres de Patógenos Específicos , Células Th2/imunologiaRESUMO
It has been reported that the levator veli palatini muscles of speakers with velopharyngeal incompetence tend to demonstrate muscle fatigue during speech. This study examined whether a speech aid prosthesis might reduce levator muscle fatigue in such speakers. Eight individuals with post-surgical cleft palates, and who wore a speech aid prosthesis, were studied. Each person was asked to pronounce the syllable [pu] more than 50 times. Mean power frequency (MPF) of one syllable was obtained from electromyographic data from the levator muscle. The MPF regression line was calculated during the course of syllable repetition. The absolute values of the slopes of the regression lines with the prosthesis were significantly smaller than those without the prosthesis. It was shown that the prosthesis reduced the decrease in MPF during speech. These results suggested that speech aid prostheses reduce levator muscle fatigue during speech in persons with velopharyngeal incompetence.
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Fadiga Muscular/fisiologia , Músculos Palatinos/fisiologia , Fonoterapia/instrumentação , Adolescente , Criança , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Eletromiografia , Feminino , Humanos , Masculino , Nasofaringe/fisiologia , Fibras Ópticas , Fonação/fisiologia , Fonética , Fala/fisiologia , Fatores de Tempo , Insuficiência Velofaríngea/fisiopatologiaRESUMO
The authors report the cases of 3 patients with tuberculous spondylodiscitis. All patients suffered from severe back or low back pain. Posterolateral endoscopic debridement and irrigation were performed followed by retention of a drainage tube at the affected sites. Additional puncture and drainage were conducted at the same time when extensive cold abscesses were identified around the paravertebral muscle. All patients experienced immediate pain relief postoperatively. This technique is effective for rapid pain relief and in obtaining neurological resolution for patients in the early stages of tuberculous spondylodiscitis and may also be a good method for preventing further vertebral collapse and kyphotic spinal deformity such as Gibbus vertebrae.
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Discite/microbiologia , Discite/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Tuberculose/complicações , Adulto , Discite/diagnóstico , Feminino , Humanos , Disco Intervertebral/microbiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mycobacterium/isolamento & purificaçãoRESUMO
An eosinophilic substance (ES) is usually observed in the mouse nasal septum and increases in volume with aging. It has been described as amyloid in textbooks and one report. However, it has been described as "not amyloid" in other reports because there was a negative reaction to Congo red. In this study, the ES was investigated histopathologically and electron microscopically to determine whether it was amyloid or not. The ES was only observed at the interstitium of clear HE-stained nasal glands in the septum, in which 2 kinds of glands were present (dark and clear stained by HE). The volume of the ES was small in young mice and large in older ones. Neither nasal gland degeneration nor inflammation resulted, even if a large amount of the ES was observed. The ES reacted negatively to Congo red but was strongly positive to periodic acid-Schiff reaction with prior diastase treatment. In the electron microscope observation, the ES consisted of amorphous material and collagen, but no nonbranching fibrils. Similar amorphous material was also observed in the nasal gland epithelial cells and was connected to the material in the rough endoplasmic reticulum. The above-mentioned findings indicated that the ES was not amyloid and suggested the ES might consist of not only collagen but also complex carbohydrate, which was produced by the nasal gland epithelial cells.
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Amiloide/química , Eosinófilos , Septo Nasal/química , Septo Nasal/ultraestrutura , Envelhecimento , Animais , Feminino , Masculino , Camundongos , Septo Nasal/metabolismoRESUMO
(2S)-1-(4-Amino-2,3,5-trimethylphenoxy)-3-{4-[4-(4-fluorobenzyl) phenyl]-1-piperazinyl}-2-propanol dimethanesulfonate (SUN N8075) is a novel antioxidant with neuroprotective properties. We examined whether SUN N8075 inhibited the neuronal damage resulting from permanent focal cerebral ischemia, and examined its neuroprotective properties in vivo and in vitro mechanism. Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion in mice, and the resulting infarction, brain swelling, and neurological deficits were evaluated after 24 h or 72 h. Brain damage was assessed histochemically using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and antibody recognizing 4-hydroxynonenal histidine adduct (4-HNE). In the in vitro study, we examined the effects of SUN N8075 on 1) lipid peroxidation in mouse brain homogenates and 2) cell viability and caspase-3 protease activity under a hypoxic insult or FeSO(4) in rat cultured cerebrocortical neurons. SUN N8075 administered either 10 min before or at 1 h after the occlusion reduced both infarction size and neurological deficits. SUN N8075 reduced brain swelling when administered 10 min before, 1 h, or 3 h after occlusion. Furthermore, only pretreatment (administered 10 min before) decreased infarct volume and brain swelling at 72 h after middle cerebral artery occlusion. SUN N8075 reduced the number of TUNEL-positive cells and decreased the level of oxidative damage, as assessed by immunopositive staining to 4-HNE. SUN N8075 inhibited lipid peroxidation, leakage of lactate dehydrogenase, caspase-3 activation induced by in vitro hypoxia, and the neuronal damage induced by in vitro FeSO(4) exposure. These findings indicate that SUN N8075 has neuroprotective effects against acute ischemic neuronal damage in mice and may prove promising as a therapeutic drug for stroke.
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Compostos de Anilina/uso terapêutico , Infarto Encefálico/prevenção & controle , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Piperazinas/uso terapêutico , Aldeídos/metabolismo , Análise de Variância , Animais , Infarto Encefálico/etiologia , Isquemia Encefálica/complicações , Caspase 3/metabolismo , Contagem de Células/métodos , Morte Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Marcação In Situ das Extremidades Cortadas/métodos , Técnicas In Vitro , Ferro/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Camundongos , Neurônios/fisiologia , Fatores de TempoRESUMO
This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. A total of 221 Japanese patients who received gefitinib (250 mg day(-1)) were examined retrospectively and potential predictive factors analysed. Overall response rate (ORR) was 24.4% and median survival time (MST) was 8.0 months. In a log-rank test, survival was significantly better in females, patients with adenocarcinoma, never-smokers, favourable performance status (PS) and patients with epidermal growth factor receptor (EGFR) mutation. The lower the smoking exposure (Brinkman Index (BI)=cigarettes per day x years smoked), the better the MST (BI 0: 14.5 months, BI <500: 9.5 months, BI 500 to <1000: 6.9 months, BI > or =1000: 4.0 months). Positive-EGFR mutation status and PS 0-1 were independent predictors of favourable prognosis by multivariate analysis. Prognosis was significantly different according to EGFR mutation status (with the same smoking status), but not according to smoking status (with the same EGFR mutation status). EGFR mutation status is the most important independent predictor of survival benefit with gefitinib treatment. Although differences in prognosis were observed according to relative smoking status and smoking exposure, the results suggested that smoking is not a direct predictor of prognosis, yet is a surrogate marker of EGFR mutation status.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/genética , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Quinazolinas/efeitos adversos , Estudos Retrospectivos , Fumar/efeitos adversosRESUMO
Cell-surface oxytocinase inactivates oxytocin and regulates oxytocin stimulation. We reported that oxytocinase in human endometrial epithelial cells was secreted from the cell membrane in the mid-secretory phase and disappeared from the cell surface. On the other hand, the production in human endometrium of prostaglandins, which play important roles in the reproductive process, has been reported to be upregulated by oxytocin. We investigated whether progesterone affects cell-surface oxytocinase and oxytocin-induced prostaglandin E2 (PGE2) production in vitro. Progesterone induced secretion of oxytocinase into the culture medium, which resulted in a decrease in cell-surface oxytocinase. Production of PGE2 was increased slightly by oxytocin without progesterone, and significantly with progesterone. The inhibition of oxytocinase activity by amastatin had a similar effect to the loss of cell-surface oxytocinase caused by progesterone. It is therefore likely that the cell-surface oxytocinase of endometrial epithelial cells modified by progesterone plays an important role in the function of the human endometrium through PGE2.