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OBJECTIVES: The Kyoto classification of gastritis was established for diagnosing Helicobacter pylori (H. pylori) infection via endoscopic findings. We investigated the role of the Kyoto classification of gastritis in the diagnosis of H. pylori infection and histological gastritis in Japanese individuals. Moreover, the histological findings of gastritis in H. pylori infection were examined based on age and sex differences. METHODS: We selected 561 patients aged 20-79 years who underwent gastroduodenal endoscopy at our hospital between 2010 and 2018. Endoscopic biopsy specimens from the antrum and corpus were used to investigate H. pylori infection and histology. Endoscopic findings were based on the Kyoto classification of gastritis, and histological findings were based on the updated Sydney System. RESULTS: Endoscopic findings based on the Kyoto classification of gastritis (H. pylori positive, 303 patients; H. pylori negative, 258 patients, based on endoscopic findings) had 98.7% sensitivity and 98.4% specificity for histological gastritis. In addition, endoscopic findings in the three age groups (20-39, 40-59, and 60-79 years) had high sensitivity and specificity. Atrophy and intestinal metaplasia were found only in the H. pylori-positive group and progressed with age. Histological inflammation of pyloric mucosa in the younger age group of H. pylori-positive patients was significantly higher than that in the elderly group. Significant inflammation was observed in young women. CONCLUSIONS: The Kyoto classification of gastritis can not only diagnose H. pylori infection but also detect histological gastritis. Histological gastritis has varying characteristics of inflammation, atrophy, and intestinal metaplasia, depending on age and sex.
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Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Adulto , Factores de Edad , Anciano , Femenino , Mucosa Gástrica/patología , Gastritis/diagnóstico , Gastritis/patología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/patología , Humanos , Japón , Masculino , Metaplasia/patología , Persona de Mediana Edad , Factores Sexuales , Adulto JovenRESUMEN
INTRODUCTION: Since inflammatory cells, such as lymphocytes and plasma cells, normally inhabit the stomach, the border between normal and mild inflammation is difficult to visually determine using the updated Sydney system scale of gastritis. Additionally, eosinophils in the gastric mucosa must be counted to diagnose eosinophilic gastritis. We aimed to determine the normal number of inflammatory cells in patients with endoscopically normal mucosa and without Helicobacter pylori infections. METHODS: We assessed patients aged 20-79 years, who had undergone upper gastrointestinal endoscopy at Kawasaki Medical School Hospital between January 2010 and December 2014. Inflammatory cells were counted in 1,000 µm2 fields of pyloric and fundic gland mucosal biopsy specimens. We finally included 325 (male, n = 141; female, n = 184; average age = 49.3 years) patients without inflammation who had H. pylori-negative endoscopic results and negative histological findings interpreted based on the updated Sydney System and the Kyoto classification of gastritis. RESULTS: The average numbers of nucleated cells were 83.3 ± 14.2 and 65.4 ± 12.6/mm2 in the pyloric and fundic gland mucosae, respectively. Inflammatory cells were significantly more abundant in the pyloric mucosa than in the fundic gland mucosa (p < 0.05). Age and sex distribution did not significantly differ. Eosinophils were absent or scanty in the gastric mucosae of both glands in all patients. CONCLUSION: We determined the absolute values of inflammatory cells, including eosinophils, in normal mucosae of pyloric and fundic glands. These findings could be important in defining gastric mucosal inflammation, including eosinophilic gastritis diagnosis.
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Infecciones por Helicobacter , Helicobacter pylori , Biopsia , Recuento de Células , Femenino , Mucosa Gástrica , Infecciones por Helicobacter/diagnóstico , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , EstómagoRESUMEN
Several studies showed that H. pylori infection is significantly lower in reflux esophagitis (RE) patients than in elder asymptomatic controls in Japan. It is well known that H. pylori infection induces corporal atrophic gastritis, and suppresses gastric acid secretion. In the other words, H. pylori infection shows a negative association with the development of RE. The relative lack of corpus gastritis might play a role in the pathogenesis of RE through preservation of the acid secretion area. Meanwhile, the occurrence of RE after H. pylori eradication was first report;e' in Europe in 1997. However, no consensus has been reached on whether H. pylori eradication leads to the onset of a de-novo RE. Eradication of H. pylori infection may be a risk factor for de-novo RE, especially in Asian populations. The presence of hiatal hernia and corpus gas- tritis are closely related to the development of RE after H. pylori eradication. RE, which develops after H. pylori eradication, rarely becomes a long-term clinical problem among patients who complete therapy successfully.
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Esofagitis Péptica , Reflujo Gastroesofágico , Infecciones por Helicobacter , Esofagitis Péptica/tratamiento farmacológico , Esofagitis Péptica/microbiología , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/microbiología , Reflujo Gastroesofágico/tratamiento farmacológico , Reflujo Gastroesofágico/microbiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Hernia Hiatal/complicaciones , HumanosRESUMEN
Recent studies have identified that high glucose-induced renal tubular cell damage. We previously demonstrated that high glucose treatment induced oxidative stress in human renal proximal tubular epithelial cells (RPTECs), and angiotensin II type 1 (AT1) receptor blockers reduce high glucose-induced oxidative stress in RPTEC possibly via blockade of intracellular as well as extracellular AT1 receptor. However, exact roles of tumor necrosis factor (TNF)-α and AT1 receptor on high glucose-induced renal tubular function remain unclear. N-acetyl-beta-glucosaminidase (NAG), concentrations of TNF-α/angiotensin II and p22(phox) protein levels after high glucose treatment with or without AT1 receptor blocker or thalidomide, an inhibitor of TNF-α protein synthesis, were measured in immortalized human renal proximal tubular epithelial cells (HK2 cells). AT1 receptor knockdown was performed with AT1 receptor small interfering RNA (siRNA). High glucose treatment (30 mM) significantly increased NAG release, TNF-α/angiotensin II concentrations in cell media and p22(phox) protein levels compared with those in regular glucose medium (5.6 mM). Candesartan, an AT1R blocker, showed a significant reduction on high glucose-induced NAG release, TNF-α concentrations and p22(phox) protein levels in HK2 cells. In addition, significant decreases of NAG release, TNF-α concentrations and p22(phox) protein levels in HK2 cells were observed in high glucose-treated group with thalidomide. AT1R knockdown with siRNA markedly reversed high glucose, angiotensin II or TNF-α-induced p22(phox) protein levels in HK2 cells. TNF-α may be involved in high glucose-induced renal tubular damage in HK2 cells possibly via AT1 receptor signaling.
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Células Epiteliales , Glucosa , Túbulos Renales Proximales , Receptor de Angiotensina Tipo 1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Acetilglucosaminidasa/metabolismo , Angiotensina II/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Glucosa/efectos adversos , Glucosa/metabolismo , Humanos , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
A 61-year-old female patient underwent upper gastrointestinal endoscopy, which confirmed the presence of Helicobacter pylori (H. pylori)-positive nodular gastritis (NG). Routine upper gastrointestinal endoscopy after H. pylori eradication revealed atrophic changes of the corpus, having gradually progressed over the 10 years after successful eradication. Serological and biopsy specimen examination showed hypergastrinemia (1200 pg/mL), positive anti-parietal cell antibody (with a titer of more 160), and endocrine cell micronests after 11 years of H. pylori eradication. The patient was diagnosed with autoimmune gastritis (AIG) based on endoscopic, serological, and histological findings. This is the first report of AIG diagnosed in a patient with NG over a long period of time after H. pylori eradication.
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Gastritis Atrófica , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Femenino , Humanos , Persona de Mediana Edad , Gastritis Atrófica/complicaciones , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/patología , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , AtrofiaRESUMEN
Objective Esophageal cancer is a gastrointestinal cancer with a poor prognosis. However, it is curable and can be treated endoscopically if it is detected at an early stage. The objective of this study was to identify the factors that contribute to early detection. Methods From April 2011 to December 2019, we retrospectively investigated consecutive patients diagnosed with esophageal squamous cell carcinoma (ESCC) through upper gastrointestinal endoscopy at two hospitals of Kawasaki Medical University based on medical records. The factors contributing to the early detection of ESCC were investigated by comparing patients with ESCC with those undergoing health checkups in whom no organic lesions were found in the upper gastrointestinal tract on endoscopy (controls). Patients Factors contributing to early detection were examined in 402 ESCC cases and 391 sex- and age-matched controls, and early and advanced cancers were compared along with the risk factors for ESCC. Results A multivariate analysis showed that alcohol consumption and smoking, concomitant cancer of other organs, and a low body mass index (BMI) were factors associated with ESCC (odds ratio [OR], 4.65; 95% confidence interval [CI], 2.880-7.520, OR,3.63; 95% CI, 2.380-5.540, OR, 2.09; 95% CI, 1.330-3.270, OR, 6.38; 95% CI, 3.780-10.800), whereas dyslipidemia was significantly less common in patients with ESCC (OR, 0.545; 95% CI, 0.348-0.853). Comparing early and advanced cancers, a history of endoscopic screening was the only factor involved in early detection (OR, 7.93; 95% CI, 4.480-14.00). Conclusion The factors associated with ESCC include alcohol consumption, smoking, concomitant cancer of other organs, and a low BMI. Endoscopy in subjects with these factors may therefore be recommended for the early detection of ESCC.
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Objective Gastrointestinal (GI) disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and inflammatory bowel disease (IBD) can exhibit overlapping GI symptoms, including abdominal pain and alterations in bowel habits. The symptoms of GI disorders are commonly considered to be triggered and exacerbated by fatty food intake. Therefore, this study aimed to compare the food preferences of patients with GI disorders. Methods Forty food images (including fatty and light foods) and 20 animal images were selected to evaluate food preferences. The preference score was assessed using a visual analog scale ranging from 1 to 100. GI symptoms were evaluated using the GI Symptom Rating Scale (GSRS), and correlations between the GSRS and preference scores were investigated. Results Overall, 22 healthy controls and 23, 29, 27, and 20 patients with FD, IBS, GERD, and IBD, respectively, were enrolled. The preference score for all foods in patients with FD was significantly lower than that in healthy controls and those with IBS, GERD, and IBD (52.9 vs. 66.5 vs. 68.5 vs. 69.1 vs. 70.7, p<0.01). The score of fatty foods was lower in patients with FD than in healthy controls and those with IBS, GERD, and IBD (43.8 vs. 72.3 vs. 77.5 vs. 77.4 vs. 80.7, p<0.01), whereas that of light foods and animal images was not different among the groups. No significant correlation was found between the preference score and symptom severity. Conclusions Patients with FD had a negative preference for foods, particularly fatty foods, independent of the severity of GI symptoms.
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A 61-year-old man presented with epigastric pain and underwent upper gastrointestinal endoscopy. A strongly erythematous area was found in the short segment of the Barrett's esophagus, and a biopsy revealed well-differentiated adenocarcinoma. Linear furrows were observed in the lower esophagus, and a biopsy of the lesion revealed eosinophil infiltration of 30 eosinophils per high-power field. Therefore, a diagnosis of Barrett's adenocarcinoma with eosinophilic esophagitis was made. Although rare, the incidence of Barrett's adenocarcinoma and eosinophilic esophagitis has been increasing in Japan in recent years, and the number of cases may increase in the future.
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BACKGROUND: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are caused and exacerbated by consumption of fatty foods. However, no study has evaluated brain activity in response to food images in patients with disorders of gut-brain interaction (DGBI). This study aimed to compare food preference and brain activity when viewing food images between patients with DGBI and healthy controls. METHODS: FD and IBS were diagnosed using the ROME IV criteria. Food preference was assessed using a visual analog scale (VAS). Brain activity in the prefrontal cortex (PFC) in response to food images was investigated using functional near-infrared spectroscopy (fNIRS). RESULTS: Forty-one patients were enrolled, including 25 with DGBI. The mean VAS scores for all foods (controls vs. FD vs. IBS: 69.1 ± 3.3 vs. 54.8 ± 3.8 vs. 62.8 ± 3.7, p = 0.02), including fatty foods (78.1 ± 5.4 vs. 43.4 ± 6.3 vs. 64.7 ± 6.1, p < 0.01), were the lowest in patients with FD among all groups. Patients with FD had significantly higher brain activity in the left PFC than those with IBS and healthy controls (mean z-scores in controls vs. FD vs. IBS: - 0.077 ± 0.03 vs. 0.125 ± 0.04 vs. - 0.002 ± 0.03, p < 0.001). CONCLUSIONS: Patients with DGBI, particularly those with FD, disliked fatty foods. The brain activity in patients with DGBI differed from that in healthy controls. Increased activity in the PFC of patients with FD was confirmed.
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Dispepsia , Síndrome del Colon Irritable , Humanos , Dispepsia/diagnóstico por imagen , Síndrome del Colon Irritable/diagnóstico por imagen , Alimentos , Dimensión del Dolor , Encéfalo/diagnóstico por imagenRESUMEN
Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. To determine the signaling pathway of aldosterone in relation to fibrosis and inflammation in mesangial cells, we investigated the effects of aldosterone on expression and activation of serum- and glucocorticoid-inducible protein kinase-1 (SGK1), the activation of nuclear factor-kappa B (NF-κB activation, and the expressions of intercellular adhesion molecule-1 (ICAM-1) and connective tissue growth factor (CTGF). Aldosterone stimulated SGK1 expression, phosphorylation (Ser-256), and kinase activity. The increments of phosphorylation and expression of SGK1 induced by aldosterone were inhibited by mineralocorticoid receptor (MR) inhibitor (eplerenone). Aldosterone stimulated NF-κB activity measured by NF-κB responsive elements, luciferase assay, and the levels of inhibitor of kappa B (IκB) phosphorylation. This aldosterone-induced activation of NF-κB was inhibited by the transfection of dominant-negative SGK1. Furthermore, aldosterone augmented the promoter activities and protein expressions of ICAM-1 and CTGF. The effects of aldosterone on ICAM-1 and CTGF promoter activities and protein expressions were inhibited by the transfection of dominant-negative SGK1 and dominant-negative IκBα. We also found that the MR antagonist significantly ameliorated the glomerular injury and enhancements in SGK1, ICAM-1, and CTGF expressions induced by 1% sodium chloride and aldosterone in vivo. In conclusion, our findings suggest that aldosterone stimulates ICAM-1 and CTGF transcription via activation of SGK1 and NF-κB, which may be involved in the progression of aldosterone-induced mesangial fibrosis and inflammation. MR antagonists may serve as useful therapeutic targets for the treatment of glomerular inflammatory disease.
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Aldosterona/farmacología , Factor de Crecimiento del Tejido Conjuntivo/biosíntesis , Proteínas Inmediatas-Precoces/fisiología , Molécula 1 de Adhesión Intercelular/biosíntesis , Células Mesangiales/metabolismo , FN-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas/fisiología , Animales , Eplerenona , Glomerulonefritis/inducido químicamente , Proteínas I-kappa B/metabolismo , Riñón/patología , MAP Quinasa Quinasa 1/metabolismo , Células Mesangiales/efectos de los fármacos , Antagonistas de Receptores de Mineralocorticoides , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Espironolactona/análogos & derivados , Espironolactona/farmacologíaRESUMEN
The objective of this investigation was to examine the stress and coping styles in Japanese nursing students. The principal measures of the stress and coping styles were the General Health Questionnaire (GHQ)-12 and Brief Coping Orientations to Problems Experienced scale. In a cross-sectional analysis, 1324 students completed the anonymous self-administered questionnaires including the scales earlier. Feeling stress, living with family, not eating breakfast every day, having no regular exercise and poor sleep were associated with GHQ responder (psychological distressed group). The most commonly reported source of stress was taking examinations, followed by relationships with friends, engaging in clinical practice and presenting reports. The three most common coping styles adopted by the nursing students were acceptance, self-distraction and using instrumental support. By logistic regression analysis of coping styles with GHQ responder, self-blame, active coping, acceptance and behavioural disengagement were highly associated with GHQ responder. The nursing school educators as well as students should be aware of stress management strategies (e.g. using active coping and avoiding self-blame) that may help prevent depression.
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Adaptación Psicológica , Estrés Psicológico/etiología , Estrés Psicológico/prevención & control , Estudiantes de Enfermería/psicología , Adolescente , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Modelos Logísticos , Masculino , Factores de Riesgo , Privación de Sueño/epidemiología , Apoyo Social , Estrés Psicológico/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Psychological well-being has been associated with reduced mortality rates in both healthy and diseased populations. However, there is considerably less evidence on the effect of lifestyle behaviours on positive health outcomes such as well-being. This study examines the association between lifestyle behaviours and optimal well-being. METHODS: From a total of 4324 Japanese individuals who participated in an annual health check-up in 2017, this study recruited 2295 participants (mean age: 49.3 ± 8.4 years; female: 54.3%) without a history of cerebrovascular, cardiovascular, or chronic renal disease and not on medication for hypertension, diabetes, or dyslipidaemia. The World Health Organization-Five Well-Being Index (WHO-5) scores were compared to self-reported scores on each of the following items: dietary habits, physical activity, smoking, alcohol consumption, and sleep quality. Logistic regression analysis was used to examine the association between optimal well-being (the top quartile of WHO-5 scores) and individual lifestyle behaviours. The association between change in dietary habits and physical activity from 2016 to 2017 and optimal well-being was also investigated. RESULTS: Good dietary habits and regular physical activity were associated with higher raw WHO-5 scores and were positively associated with optimal well-being after adjusting for age, sex, body mass index (BMI), and sleep quality. Raw WHO-5 scores were significantly higher in those who maintained good dietary and physical activity behaviours than in those who did not. Furthermore, maintaining regular physical activity for two years was positively associated with optimal well-being, after adjusting for age, sex, BMI, and sleep quality. CONCLUSION: These results demonstrate that not only currently practising good dietary and physical activity behaviours but also maintaining such behaviours over time is associated with optimal well-being. Maintaining good lifestyle behaviours, particularly regarding physical activity, could potentially improve people's well-being.
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A 55-year-old woman with signs of acromegaly was referred to our hospital. Endocrinological examinations showed that she had high levels of growth hormone (GH; 5.54 ng ml(-1); normal range: 0.66-3.68 ng ml(-1)) and insulin-like growth factor-I (IGF-I; 508 ng ml(-1); normal range: 37-266 ng ml(-1)) levels, incomplete suppression of serum GH following a 75-gram oral glucose tolerance test (oGTT; trough GH 3.66 ng ml(-1)), and paradoxical GH responses to a TRH provocation test (peak GH 38.9 ng ml(-1)). Dynamic magnetic resonance imaging (MRI) suggested the presence of an intrasellar mass lesion (5.9 x 2.8 mm) in the left part of her pituitary gland (Fig. 1a, upper panel). F-18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging clearly showed focal but remarkable FDG uptake (Fig. 1a, lower panel), consistent with the localization of the tumor suspected on MRI. The tumor was removed by transsphenoidal surgery. Subsequent histological analysis confirmed the diagnosis of a GH-producing pituitary adenoma. After removal, serum IGF-I levels decreased to a normal range (178 ng ml(-1)), and serum GH was appropriately suppressed during oGTT (trough GH 0.30 ng ml(-1)), suggesting that complete resection was obtained [1]. While postsurgical changes made it difficult to detect any residual lesion on MRI (Fig. 1b, upper panel), abnormal FDG uptake was not seen on FDG-PET after surgery (Fig. 1b, lower panel). PET scans are reported to be a valuable tool for the detection of pituitary adenomas [2-4]. This case clearly showed that FDG-PET is also useful for re-evaluation of the disease after surgery. PET scans are recommended for patients with equivocal pituitary mass lesions on conventional MRI, and for follow-up examinations after surgery.
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Dihidroxifenilalanina , Radioisótopos de Flúor , Adenoma Hipofisario Secretor de Hormona del Crecimiento/diagnóstico , Tomografía de Emisión de Positrones/métodos , Dihidroxifenilalanina/farmacocinética , Femenino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/cirugía , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía de Emisión de Positrones/normasRESUMEN
BACKGROUND: Autophagy is an intracellular bulk degradation process induced by cell starvation. Autophagy was recently reported to be induced by various stresses such as hypoxia, ischemia/reperfusion, toxins, and denatured proteins, and to affect cell survival and death. Light chain 3-II (LC3-II) is specifically located on double membrane-bound autophagosomes that envelop disused proteins or organelles. METHOD: Transgenic mice in which green fluorescent protein (GFP) was fused to LC3 (LC3-GFP) were administered cisplatin (20 mg/kg). After euthanasia at times between 0 and 72 h, kidneys were excised for immunohistochemical analyses. Microscopic examinations of the generated NRK-52E cell lines stably transfected with LC3-GFP, and Western blot analyses of NRK-52E cells, were undertaken after cisplatin treatment with or without autophagy inhibitors and beclin 1 small interfering RNA (siRNA). RESULTS: Autophagosomes increased in the proximal tubular cells of transgenic mice from 12 h after cisplatin injection (20 mg/kg). The time course for this was faster than those for tubular necrosis and apoptosis. Autophagosomes also increased in NRK-52E cells after cisplatin treatment, with the time course for this being faster than that for apoptosis. When autophagy was suppressed by autophagy inhibitors or beclin 1 siRNA, the level of apoptosis was also suppressed. CONCLUSION: Autophagy occurs in proximal tubular cells after cisplatin treatment and is involved in cell death in renal tubular injury. Our data suggest that autophagy is a kind of cell damage index and that cells with activated autophagy will be scavenged by apoptosis.
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Autofagia/fisiología , Cisplatino/farmacología , Túbulos Renales Proximales/metabolismo , Lesión Renal Aguda/fisiopatología , Animales , Apoptosis/fisiología , Autofagia/efectos de los fármacos , Masculino , Ratones , Ratones TransgénicosRESUMEN
A 55-year-old man with lumbago and polyarthralgia was admitted to our hospital. Laboratory data showed elevated levels of anti-streptolysin O and C-reactive protein. Throat swab culture revealed beta-hemolytic streptococcal infection. Magnetic resonance imaging detected effusion of the lumbar bone and the left hip joint. Positron emission tomography-computed tomography (PET-CT) demonstrated increased fluorodeoxyglucose activity in the bilateral shoulder and hip joints and the interspinal ligament between L2 and L3. He was diagnosed as having post-streptococcal reactive arthritis (PSReA) and treated with amoxicillin hydrate. Polyarthralgia improved and did not relapse. To our knowledge, no results of PET-CT have previously been reported in patients with PSReA. We propose that PET-CT might be a useful tool for diagnosing PSReA.
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Artritis Reactiva/diagnóstico por imagen , Infecciones Estreptocócicas/diagnóstico por imagen , Artritis Reactiva/fisiopatología , Fluorodesoxiglucosa F18 , Articulación de la Cadera/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiografía , Cintigrafía , Articulación del Hombro/fisiopatología , Infecciones Estreptocócicas/fisiopatologíaRESUMEN
BACKGROUND/AIMS: Proteinuria is not merely a marker of chronic nephropathies, but may also be involved in the progression to end-stage renal failure. We investigated the effect of angiotensin II type 1 receptor blockers (ARBs) on albumin-induced cell damage in human renal proximal tubular epithelial cells (RPTEC). METHODS: The N-acetyl-beta-D-glucosaminidase (NAG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the medium after albumin treatment with ARBs were determined by commercially available kits. The levels of p22(phox) protein in RPTEC were measured using Western blotting after albumin treatment with ARBs. Angiotensin II concentrations in cell media and cell lysates were assayed with a commercially available kit. RESULTS: Human albumin (0.1-10 mg/ml) dose-dependently increased NAG release and olmesartan or valsartan (10(-9)-10(-7) mol/l) showed a significant reduction on albumin (1 mg/ml)-induced NAG release in RPTEC. Albumin treatment (1 mg/ml) showed significant increases in p22(phox) protein levels in RPTEC and ARBs significantly decreased albumin-induced p22(phox) protein levels. Significant increases in 8-OHdG levels were observed in the albumin (1 mg/ml)-treated group and ARBs markedly reduced albumin-induced 8-OHdG levels in RPTEC. Human albumin dose-dependently increased angiotensin II concentrations in both cell media and lysates. CONCLUSION: These observations suggest renal tubular cell-protective properties of ARBs related to decreased oxidative stress during proteinuria.
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Albuminuria/tratamiento farmacológico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Imidazoles/farmacología , Túbulos Renales Proximales/efectos de los fármacos , Tetrazoles/farmacología , Valina/análogos & derivados , 8-Hidroxi-2'-Desoxicoguanosina , Acetilglucosaminidasa/metabolismo , Albúminas/farmacología , Albuminuria/metabolismo , Albuminuria/patología , Angiotensina II/metabolismo , Células Cultivadas , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , NADPH Oxidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Valina/farmacología , ValsartánRESUMEN
BACKGROUND: The objective of this investigation was to examine depression in, and the lifestyles of, 260 college students of a nursing school in nonclinical settings. METHODS: The principal measure of depressive symptoms was the 9-item depression module from the Patient Health Questionnaire (PHQ-9). Additional questions were focused on current stress levels and sleeping, eating, and exercising habits. RESULTS: One hundred and fifty-two college students finally participated. Overall, the average PHQ-9 score was 7.7 +/- 5.1 (SD). The students with PHQ-9 scores of 15 or higher were 9.2%. The average PHQ-9 scores in the 1st school year were significantly higher than those of the 4th school year. The students feeling stressed had significantly higher PHQ-9 scores than those that felt no stress. PHQ-9 scores in the students who had unsatisfactory sleeping habits were significantly higher than those in the students who felt they had satisfactory sleep. The students who slept less than 5 hours and more than 8 hours had significantly higher PHQ-9 scores than those who slept 6-7 hours. PHQ-9 scores in the students who never ate breakfast were higher than those who ate breakfast everyday. Moreover, the students who never ate 3 meals daily had higher PHQ-9 scores than those who did. CONCLUSIONS: The results suggest that there is a strong relationship between the severity of depressive symptoms and the lifestyles of college students. This underscores the need to provide effective mental health outreach and treatment, including lifestyle modification, at an early stage in college life.
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Depresión/diagnóstico , Estilo de Vida , Estudiantes de Enfermería/psicología , Depresión/epidemiología , Femenino , Encuestas Epidemiológicas , Humanos , Japón/epidemiología , Masculino , Prevalencia , Estrés Psicológico , Adulto JovenRESUMEN
While lipopolysaccharides (LPS) are known to activate the hypothalamo-pituitary-adrenal axis, their direct effects on proopiomelanocortin (POMC) and adrenocorticotropin (ACTH) expression at the pituitary level through Toll-like receptors (TLRs) remain unclear. In this study, we examined the effects of LPS on ACTH secretion and the transcription of the POMC gene in the AtT20 mouse pituitary corticotroph cell line. RT-PCR analysis showed that TLR1-4 and 6 subtype mRNAs were expressed in AtT20 cells. When the cells were treated with LPS, a significant increase in the 5'-promoter activity of POMC gene was observed at 24 h, without any stimulatory effect on ACTH secretion. LPS also stimulated the expression of c-Fos gene and protein, and AP1-, but not NF-kappaB-, mediated transcription. Overall, our data show the expression of TLRs in the pituitary corticotroph cells, and suggest the direct stimulatory effect of LPS on POMC gene expression via TLR (probably TLR4), although the intracellular signaling pathways in the corticotroph may be different from those in immune cells.
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Corticotrofos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/farmacología , Proopiomelanocortina/genética , Proopiomelanocortina/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Animales , Línea Celular , Corticotrofos/citología , Sistema Hipotálamo-Hipofisario/fisiología , Ratones , FN-kappa B/metabolismo , Sistema Hipófiso-Suprarrenal/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismo , ARN Mensajero/metabolismo , Transducción de Señal/fisiología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Receptores Toll-Like/metabolismo , Factor de Transcripción AP-1/metabolismoRESUMEN
Erdheim-Chester disease (ECD) is a form of non-Langerhans histiocytosis. In this report, we show a case of ECD presenting diabetes insipidus and multiple xanthogranulomas received glucocorticoid treatment over a year. During this period, xanthogranulomas improved in response to the glucocorticoid therapy. Furthermore, the expression of osteopontin in xanthogranulomatous tissues significantly decreased following the treatment. Our data show the expression of osteopontin in xanthogranulomatous tissues of ECD. Furthermore, the osteopontin mRNA decreased following glucocorticoid therapy with xanthogranuloma regression, suggesting that the expression level of osteopontin could be a marker of the disease activity of ECD.
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Enfermedad de Erdheim-Chester/tratamiento farmacológico , Enfermedad de Erdheim-Chester/genética , Granuloma/tratamiento farmacológico , Proteínas Asociadas a Microtúbulos/genética , Proteínas de Neoplasias/genética , Osteopontina/genética , Prednisolona/uso terapéutico , Xantomatosis/tratamiento farmacológico , Adulto , Femenino , Estudios de Seguimiento , Expresión Génica/efectos de los fármacos , Glucocorticoides/uso terapéutico , Granuloma/genética , Humanos , Proteínas Inhibidoras de la Apoptosis , Reacción en Cadena de la Polimerasa , Survivin , Xantomatosis/genéticaRESUMEN
An 81-year-old man was admitted to our hospital because of general fatigue. Hormonal examination showed that he had panhypopituitarism and central diabetes insipidus. MRI imaging revealed the presence of large cystic mass with suprasellar extension in his hypothalamo-pituitary region. Interestingly, the cystic mass shrank following the start of glucocorticoid replacement, and since then relatively high doses of cortisol administration were needed to prevent the re-enlargement of cystic size. Because of the concern over possible side effects of supraphysiological doses of glucocorticoid replacement, surgical treatment was eventually carried out, confirming the pathological feature of Rathke's cleft cyst. The present case suggests that the inflammatory nature of Rathke's cleft cyst may explain the observed short-term size changes in response to glucocorticoid administration.