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BACKGROUND: The purpose of the present study was to evaluate the accuracy of the measurements associated with leg alignment on a teleoroentgenogram and an orthoroentgenogram. METHODS: The models being irradiated were manufactured and represented 10° varus and 15° varus leg alignment, in which the true values of hip-knee-ankle angle (HKAA), mechanical axis (MA) length, and percentage of MA (%MA) were already known. HKAA, MA length, and %MA were measured in various radiographic conditions of the teleoroentgenogram and orthoroentgenogram. Then, the differences between the radiographic measurement values and the corresponding true values were analyzed. RESULTS: Regarding HKAA, the teleoroentgenogram provided accurate angular measurements with minimal differences between the measurement and true value in both the 10° and 15° varus models, irrespective of the radiographic condition. In the orthoroentgenogram, the modified method measured accurate HKAA; however, the standard method showed significant angular measurement errors with a 0.6° and 1.0° difference from the true value in the 10° and 15° varus models, respectively. This angular measurement error of HKAA in the standard orthoroentgenogram became significantly larger with object-to-image distance. Regarding MA length, the orthoroentgenogram exhibited accurate length measurements. In contrast, the teleoroentgenogram showed a significant length measurement error for the MA length. Regarding %MA, significant differences from the true values of 2.0% and 2.4% were observed in the modified orthoroentgenograms of the 10° and 15° varus models, respectively. The teleoroentgenogram and standard orthoroentgenogram reproduced the accurate measurement value of %MA in the 10° and 15° varus models. CONCLUSION: A teleoroentgenogram is a reliable modality for accurate angular measurements such as HKAA and %MA. An orthoroentgenogram has the potential to measure both HKAA and length accurately if the radiographic condition was modified; however, measurement error in %MA may occur.
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Articulación de la Rodilla , Pierna , Humanos , Extremidad Inferior , Radiografía , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. METHODS: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. RESULTS: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. CONCLUSIONS: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.
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Anticuerpos , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anticuerpos/sangre , Isquemia Encefálica/diagnóstico , Estudios de Casos y Controles , Factor de Especificidad de Desdoblamiento y Poliadenilación/inmunología , Proteínas de Unión al ADN/inmunología , Factores de Transcripción Forkhead/inmunología , Humanos , Accidente Cerebrovascular/diagnósticoRESUMEN
BACKGROUND AND OBJECTIVES: Red yeast rice contains monacolin K, an inhibitor of cholesterol synthesis, and gamma-aminobutyric acid, a neurotransmitter. The daily dose of red yeast rice and monacolin K in previous studies was relatively high; therefore, there were safety concerns. We aimed to examine the effects of low daily dose red yeast rice on arteriosclerosis in patients with mild dyslipidemia. METHODS AND STUDY DESIGN: Eighteen patients without known cardiovascular disease and unsatisfactory low-density lipoprotein cholesterol (3.96±0.19 mmol/L) controlled only by diet therapy were randomly allocated to receive low dose red yeast rice (200 mg/day) containing 2 mg monacolin K or diet therapy alone for 8 weeks. The primary outcome was the absolute change in low-density lipoprotein cholesterol. Secondary outcomes included total cholesterol, apolipoprotein B, and blood pressure. RESULTS: Low-density lipoprotein cholesterol decreased significantly in the red yeast rice group than in the diet therapy group (median [interquartile range]: control -0.20 [-0.62, 1.19] mmol/L vs. red yeast rice -0.96 [-1.05, -0.34] mmol/L, p=0.030). The red yeast rice group also exhibited significant decreases in total cholesterol, apolipoprotein B, and blood pressure. No severe treatment-related adverse effects on muscles, liver, or renal function were observed. CONCLUSIONS: We found that patients in the red yeast rice group exhibited significant reductions in lowdensity lipoprotein cholesterol, total cholesterol, apolipoprotein B, and blood pressure without any recognised adverse effect. This suggests that low daily dose red yeast rice could reduce cardiovascular risk in patients with dyslipidemia.
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Dislipidemias , Hipercolesterolemia , Productos Biológicos , Presión Sanguínea , LDL-Colesterol , Suplementos Dietéticos , Dislipidemias/tratamiento farmacológico , Humanos , Japón , LovastatinaRESUMEN
A prospective, multicentre, open-label, blinded-endpoint, randomized controlled study was conducted to evaluate the efficacy of treatment with ipragliflozin (sodium-dependent glucose transporter-2 inhibitor) versus metformin for visceral fat reduction and glycaemic control among Japanese patients with type 2 diabetes treated with sitagliptin, HbA1c levels of 7%-10%, and body mass index (BMI) ≥ 22 kg/m2 . Patients were randomly assigned (1:1) to receive ipragliflozin 50 mg or metformin 1000-1500 mg daily. The primary outcome was change in visceral fat area as measured by computed tomography after 24 weeks of therapy. The secondary outcomes were effects on glucose metabolism and lipid metabolism. Mean percentage reduction in visceral fat area was significantly greater in the ipragliflozin group than in the metformin group (-12.06% vs. -3.65%, P = 0.040). Ipragliflozin also significantly reduced BMI, subcutaneous fat area, waist circumference, fasting insulin, and homeostatic model assessment (HOMA)-resistance, and increased HDL-cholesterol levels. Metformin significantly reduced HbA1c and LDL-cholesterol levels and increased HOMA-beta. There were no severe adverse events. The use of ipragliflozin or metformin in combination with dipeptidyl peptidase-4 inhibitors, widely used in Japan, may have beneficial effects in ameliorating multiple cardiovascular risk factors.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Grasa Intraabdominal/efectos de los fármacos , Metformina/administración & dosificación , Tiofenos/administración & dosificación , Adulto , Anciano , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/efectos de los fármacos , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Fosfato de Sitagliptina/administración & dosificación , Resultado del TratamientoRESUMEN
The purpose of this study was to investigate whether patients can be identified by using biological fingerprints extracted from bedside chest radiographs and template matching techniques for preventing filing mistakes in a picture archiving and communication system (PACS) server. A total of 400 bedside chest radiographs from 100 male and 100 female patients with current and previous images were used for evaluating patient identification performance. Five biological fingerprints were extracted from 200 previous images using the averaged bedside chest radiographs, produced for each sex and detector size. The correlation values of 200 same patients and 39,800 different patients were calculated as a similarity index, and used for the receiver operating characteristic (ROC) analysis. The patient identification performance was examined by using the correlation index calculated by the summation of correlation values obtained from five biological fingerprints. The sensitivity at 90.0% specificity was calculated using the correlation index. The correlation index for same patients was higher than that for different patients. The area under the ROC curve was 0.974. The patient identification performance was 76.0% (152/200), and the sensitivity at 90.0% specificity was 93.4% (37168/39800). Our results suggest that the proposed method may potentially be useful for preventing filing mistakes in bedside chest radiographs on a PACS server.
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Sistemas de Identificación de Pacientes , Radiografía Torácica , Sistemas de Información Radiológica , Femenino , Archivo , Humanos , Masculino , Sistemas de Atención de Punto , Curva ROC , RadiografíaRESUMEN
BACKGROUND: The prevalence of, and mortality from, colorectal cancer is increasing worldwide, and new strategies for prevention are needed to reduce the burden of this disease. The oral diabetes medicine metformin might have chemopreventive effects against cancer, including colorectal cancer. However, no clinical trial data exist for the use of metformin for colorectal cancer chemoprevention. Therefore, we devised a 1-year clinical trial to assess the safety and chemopreventive effects of metformin on sporadic colorectal cancer (assessed by adenoma and polyp recurrence) in patients with a high risk of adenoma recurrence. METHODS: This trial was a multicentre, double-blind, placebo-controlled, randomised phase 3 trial. Non-diabetic adult patients who had previously had single or multiple colorectal adenomas or polyps resected by endoscopy were enrolled into the study from five hospitals in Japan. Eligible patients were randomly assigned (1:1) to receive oral metformin (250 mg daily) or identical placebo tablets by a stratified computer-based randomisation method, with stratification by institute, age, sex, and body-mass index. All patients, endoscopists, doctors, and investigators were masked to drug allocation until the end of the trial. After 1 year of administration of metformin or placebo, colonoscopies were done to assess the co-primary endpoints: the number and prevalence of adenomas or polyps. Our analysis included all participants who underwent random allocation, according to the intention-to-treat principle. This trial is registered with University Hospital Medical Information Network (UMIN), number UMIN000006254. FINDINGS: Between Sept 1, 2011, and Dec 30, 2014, 498 patients who had had single or multiple colorectal adenomas resected by endoscopy were enrolled into the study. After exclusions for ineligibility, 151 patients underwent randomisation: 79 were assigned to the metformin group and 72 to the placebo group. 71 patients in the metformin group and 62 in the placebo group underwent 1-year follow-up colonoscopy. The prevalence of total polyps (hyperplastic polyps plus adenomas) and of adenomas in the metformin group was significantly lower than that in the placebo group (total polyps: metformin group 27 [38·0%; 95% CI 26·7-49·3] of 71 patients, placebo group 35 [56·5%; 95% CI 44·1-68·8] of 62; p=0·034, risk ratio [RR] 0·67 [95% CI 0·47-0·97]; adenomas: metformin group 22 [30·6%; 95% CI 19·9-41·2] of 71 patients, placebo group 32 [51·6%; 95% CI 39·2-64·1] of 62; p=0·016, RR 0·60 [95% CI 0·39-0·92]). The median number of polyps was zero (IQR 0-1) in the metformin group and one (0-1) in the placebo group (p=0·041). The median number of adenomas was zero (0-1) in the metformin group and zero (0-1) in the placebo group (p=0·037). 15 (11%) of patients had adverse events, all of which were grade 1. We recorded no serious adverse events during the 1-year trial. INTERPRETATION: The administration of low-dose metformin for 1 year to patients without diabetes was safe. Low-dose metformin reduced the prevalence and number of metachronous adenomas or polyps after polypectomy. Metformin has a potential role in the chemoprevention of colorectal cancer. However, further large, long-term trials are needed to provide definitive conclusions. FUNDING: Ministry of Health, Labour and Welfare, Japan.
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Adenoma/tratamiento farmacológico , Pólipos del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Metformina/administración & dosificación , Neoplasias Primarias Secundarias/tratamiento farmacológico , Adenoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Quimioprevención , Pólipos del Colon/patología , Colonoscopía , Neoplasias Colorrectales/patología , Método Doble Ciego , Femenino , Humanos , Japón , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Secundarias/patologíaRESUMEN
Workloads of radiological technologists under different conditions of heights of radiographic table and/or X-ray tube assembly were calculated using a software for preventing musculoskeletal complaint to investigate optimal working environment for general X-ray examinations. In the patient positioning, compressive force of lumbar disc decreased at higher radiographic table within the range of 45-90 cm. On the other hand, workload of the shoulder joint increased with increase in the height of radiographic table. Load of the shoulder joint similarly increased as the height of the X-ray tube assembly increased. Compressive force of lumbar disc reduced by approximately 10-30% as the height ratio of the radiographic table to body height increased by approximately 40%, compared to the lowest table of 45 cm. Muscle load of a 50-years-old woman was approximately double compared to a 30-year-old man, even in the same workload. It is important to keep suitable height of radiographic table for reduction of the workloads of lumbar rather than shoulder joint, because floating-type radiographic table is generally used.
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Mesas de Exámenes , Radiografía/instrumentación , Tecnología Radiológica , Carga de Trabajo , Adulto , Femenino , Humanos , Región Lumbosacra/fisiología , Masculino , Persona de Mediana EdadRESUMEN
Eusocial insects exhibit various morphological castes associated with the division of labor within a colony. Termite soldiers possess defensive traits including mandibles that are greatly exaggerated and enlarged, as compared to termite reproductives and workers. The enlarged mandibles of soldiers are known to result from dynamic morphogenesis during soldier differentiation that can be induced by juvenile hormone and its analogs. However, the detailed developmental mechanisms still remain unresolved. Because the insulin/insulin-like growth factor signaling (IIS) pathway has been shown to regulate the relative sizes of organs (i.e., allometry) in other insects, we examined the expression profiles of major IIS factors in the damp-wood termite Hodotermopsis sjostedti, during soldier differentiation. The relative expression patterns of orthologs for termite InR (HsjInR), PKB/Akt (HsjPKB/Akt), and FOXO (HsjFOXO) suggest that HsjInR and HsjPKB/Akt were up-regulated in the period of elongation of mandibles during soldier development. In situ hybridization showed that HsjInR was strongly expressed in the mandibular epithelial tissues, and RNA interference (RNAi) for HsjInR disrupted soldier-specific morphogenesis including mandibular elongation. These results suggest that signaling through the IIS pathway is required for soldier-specific morphogenesis. In addition, up-regulation of the IIS pathway in other body tissues occurred at earlier stages of development, indicating that there is tissue-specific IIS regulation. Because the IIS pathway is generally thought to act upstream of JH in insects, our results suggest the damp-wood termite may have evolved a novel feedback loop between JH and IIS that enables social interactions, rather than nutrition, to regulate caste determination.
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Insulina/metabolismo , Isópteros/crecimiento & desarrollo , Morfogénesis , Animales , Hibridación in Situ , Hormonas Juveniles/metabolismo , Transducción de Señal , Madera/químicaRESUMEN
Detecting genotoxicity in the liver is considered an effective approach for predicting hepatocarcinogenicity, as many genotoxic chemicals in vivo may act as hepatocarcinogens in rodents. Here, a genotoxic rodent hepatocarcinogen, 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), and a genotoxic (Ames positive) noncarcinogen, 2,6-diaminotolunene (2,6-DAT), were administered orally to rats for up to 28 days, and liver samples were then examined in a repeated-dose liver micronucleus (MN) assay, and additionally tested in the bone marrow (BM) MN assay concurrently. We recently established a simple method to isolate hepatocytes without in situ liver perfusion procedures, and applied this method in the liver MN assay. As a result, 1,2-DMH increased the proportion of micronucleated hepatocytes in both a dose- and duration-dependent manner at relatively low-dose levels that are routinely used in repeated-dose toxicity studies. In contrast to 1,2-DMH, 2,6-DAT did not have a detectable effect. In addition to these two chemicals, two genotoxic rodent hepatocarcinogens, diethylnitrosamine and 2,4-diaminotoluene, which gave positive responses in the liver MN assay in our previous investigation [Narumi et al., Mutat. Res. 747 (2012) 234-239], were subjected to the BM MN assay and histopathological evaluation. All four test chemicals gave negative responses in the BM MN assay. Furthermore, the three hepatocarcinogens displayed hepatotoxicity, including hepatocellular hypertrophy and anisokaryosis, but no abnormal findings were observed in the liver of rats treated with 2,6-DAT. Taken together, the present results indicate that the liver MN assay is effective for predicting hepatocarcinogenicity and may be integrated into repeated-dose toxicity studies without disturbing routine examinations, such as histopathology. Furthermore, with repeat-dose treatment protocols, our findings indicate that the liver MN assay is superior to the BM MN assay for detecting genotoxic or carcinogenic chemicals in rats.
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1,2-Dimetilhidrazina/toxicidad , Carcinógenos/toxicidad , Hígado/efectos de los fármacos , Pruebas de Micronúcleos/métodos , Mutágenos/toxicidad , Fenilendiaminas/toxicidad , Animales , Médula Ósea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Hígado/patología , Masculino , RatasRESUMEN
STUDY OBJECTIVE: The effects of the sodium-dependent glucose transporter-2 inhibitor ipragliflozin were compared with metformin in a previous study, which revealed that ipragliflozin reduced visceral fat content by 12%; however, the underlying mechanism was unclear. Therefore, this sub-analysis aimed to compare metabolomic changes associated with ipragliflozin and metformin that may contribute to their biological effects. DESIGN: A sub-analysis of a randomized controlled study. SETTING: Chiba University Hospital and ten hospitals in Japan. PATIENTS: Fifteen patients with type 2 diabetes in the ipragliflozin group and 15 patients with type 2 diabetes in the metformin group with matching characteristics, such as age, sex, baseline A1C, baseline visceral fat area, smoking status, and concomitant medication. INTERVENTIONS: Ipragliflozin 50 mg or metformin 1000 mg daily. MEASUREMENTS: The clinical data were reanalyzed, and metabolomic analysis of serum samples collected before and 24 weeks after drug administration was performed using capillary electrophoresis time-of-flight mass spectrometry. MAIN RESULTS: The reduction in the mean visceral fat area after 24 weeks of treatment was significantly larger (p = 0.002) in the ipragliflozin group (-19.8%) than in the metformin group (-2.5%), as were the subcutaneous fat area and body weight. The A1C and blood glucose levels decreased in both groups. Glutamic pyruvic oxaloacetic transaminase, γ-glutamyl transferase, uric acid, and triglyceride levels decreased in the ipragliflozin group. Low-density lipoprotein cholesterol levels decreased in the metformin group. After ipragliflozin administration, N2-phenylacetylglutamine, inosine, guanosine, and 1-methyladenosine levels increased, whereas galactosamine, glucosamine, 11-aminoundecanoic acid, morpholine, and choline levels decreased. After metformin administration, metformin, hypotaurine, methionine, methyl-2-oxovaleric acid, 3-nitrotyrosine, and cyclohexylamine levels increased, whereas citrulline, octanoic acid, indole-3-acetaldehyde, and hexanoic acid levels decreased. CONCLUSIONS: Metabolites that may affect visceral fat reduction were detected in the ipragliflozin group. Studies are required to further elucidate the underlying mechanisms.
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Diabetes Mellitus Tipo 2 , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/uso terapéutico , Hipoglucemiantes/efectos adversos , Japón , Hemoglobina Glucada , Grasa Intraabdominal/metabolismo , Glucemia , Quimioterapia Combinada , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
CONTEXT: Pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGLs), catecholamine-producing tumors, represent an emerging cause of secondary osteoporosis. However, despite decreased bone mineral density (BMD), vertebral fracture (VF) is not associated with BMD in PPGLs. OBJECTIVE: To evaluate whether deteriorated bone quality is involved in the development of osteoporosis in PPGLs. PARTICIPANTS: Trabecular bone score (TBS), used to assess trabecular bone quality, was examined in 56 patients with PPGLs and 52 with non-functional adrenal tumors (AT). Radiograph of the spine was carried out in 35 patients with PPGLs, and TBS was analyzed in 18 patients with PPGLs at follow-up. MAIN OUTCOME MEASURE: TBS and BMD at the lumbar spine in patients with PPGLs with and without VF. RESULTS: PPGLs had a lower TBS (n = 56, 1.338 [1.294-1.420]) than non-functional AT (n = 52, 1.394 [1.342-1.444]; p = 0.033). Among those with PPGLs, patients with VF (n = 14, 1.314 [1.289-1.346]) had a lower TBS than those without VF (n = 21, 1.383 [1.324-1.426]; p = 0.046), despite no significant difference in BMD at the lumbar spine between the two groups (p = 0.501). An optimal cut-off level of TBS for diagnosing VF in PPGLs was 1.323, and its area under the curve was 0.702. The severity of catecholamine excess and maximal size of tumor were associated with decreased TBS in PPGLs patients (p = 0.016 and p = 0.020, respectively). Surgical resection of PPGLs improved TBS at follow-up, with 2.5% increase (p = 0.007). CONCLUSIONS: This study provides evidence for the importance of deteriorated bone quality rather than decreased bone mass in the development of VF in PPGLs.
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Neoplasias de las Glándulas Suprarrenales , Osteoporosis , Fracturas Osteoporóticas , Paraganglioma , Feocromocitoma , Absorciometría de Fotón , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Densidad Ósea , Hueso Esponjoso/diagnóstico por imagen , Humanos , Vértebras Lumbares/diagnóstico por imagen , Osteoporosis/diagnóstico por imagen , Paraganglioma/complicaciones , Paraganglioma/diagnóstico por imagen , Feocromocitoma/diagnóstico por imagenRESUMEN
AIMS/INTRODUCTION: Recent randomized clinical trials have suggested that sodium-glucose cotransporter 2 inhibitors might reduce cardiovascular events and heart failure, and have renal protective effects. Despite these remarkable benefits, the effects of sodium-glucose cotransporter 2 inhibitors on bone and muscle are unclear. MATERIALS AND METHODS: A subanalysis of a randomized controlled study was carried out to evaluate the effects of the sodium-glucose cotransporter 2 inhibitor, ipragliflozin, versus metformin on bone and muscle in Japanese patients with type 2 diabetes mellitus (baseline body mass index ≥22 kg/m2 and hemoglobin A1c 7-10%) who were already receiving sitagliptin. These patients were randomly administered ipragliflozin 50 mg or metformin 1,000-1,500 mg daily. The effects of these medications on the bone formation marker, bone alkali phosphatase; the bone resorption marker, tartrate-resistant acid phosphatase 5b (TRACP-5b); handgrip strength; abdominal cross-sectional muscle area; and bone density of the fourth lumbar vertebra were evaluated. RESULTS: After 24 weeks of treatment, the changes in bone density of the fourth lumbar vertebra, handgrip strength and abdominal cross-sectional muscle area were not significantly different between the two groups. However, TRACP-5b levels increased in patients treated with ipragliflozin compared with patients treated with metformin (median 11.94 vs -10.30%, P < 0.0001), showing that ipragliflozin can promote bone resorption. CONCLUSIONS: There were no adverse effects on bone or muscle when sitagliptin was used in combination with either ipragliflozin or metformin. However, ipragliflozin combination increased the levels of TRACP-5b. A long-term study is required to further understand the effects of this TRACP-5b increase caused by ipragliflozin.
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Huesos/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Metformina/uso terapéutico , Músculos/efectos de los fármacos , Fosfato de Sitagliptina/uso terapéutico , Tiofenos/uso terapéutico , Adulto , Anciano , Biomarcadores/análisis , Glucemia/análisis , Huesos/patología , Estudios Transversales , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Músculos/patología , Pronóstico , Estudios Prospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Adulto JovenRESUMEN
Immunoglobulin (Ig)A nephropathy is the most common cause of primary glomerulonephritis worldwide. While IgA nephropathy has been associated with a variety of other diseases, pulmonary complications are extremely rare. A 58-year-old man presented with a 2-week history of fever and exertional dyspnoea. A chest imaging revealed bilateral consolidation predominantly in upper lungs. Laboratory findings showed elevated serum creatinine with proteinuria and haematuria. Flexible bronchoscopy revealed diffuse alveolar haemorrhage, and IgA nephropathy was confirmed on a renal biopsy. He received prednisone with good effect. This case highlights the need to consider IgA nephropathy in the differential diagnosis of pulmonary renal syndrome.
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Glomerulonefritis por IGA/complicaciones , Hemorragia/inmunología , Enfermedades Pulmonares/inmunología , Biopsia , Glomerulonefritis por IGA/patología , Hemorragia/patología , Humanos , Riñón/inmunología , Riñón/patología , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Alveolos Pulmonares/inmunología , Alveolos Pulmonares/patologíaRESUMEN
BACKGROUND: Recessive inherited disorder lecithin-cholesterol acyltransferase (LCAT) deficiency causes severe hypocholesterolemia and nephrotic syndrome. Characteristic lipoprotein subfractions have been observed in familial LCAT deficiency (FLD) with renal damage. OBJECTIVE: We described a case of acquired LCAT deficiencies with literature review. METHODS: The lipoprotein profiles examined by gel permeation-high-performance liquid chromatography (GP-HPLC) and native 2-dimensional electrophoresis before and after prednisolone (PSL) treatment. RESULTS: Here we describe the case of a 67-year-old man with severely low levels of cholesterol. The serum LCAT activity was undetectable, and autoantibodies against it were detected. The patient developed nephrotic syndrome at the age of 70 years. Renal biopsy revealed not only membranous glomerulonephritis but also lesions similar to those seen in FLD. We initiated PSL treatment, which resulted in remission of the nephrotic syndrome. In GP-HPLC analysis, lipoprotein profile was similar to that of FLD although lipoprotein X level was low. Acquired LCAT deficiencies are extremely rare with only 7 known cases including ours. Patients with undetectable LCAT activity levels develop nephrotic syndrome that requires PSL treatment; cases whose LCAT activity levels can be determined may also develop nephrotic syndrome, but spontaneously recover. CONCLUSION: Lipoprotein X may play a role in the development of renal impairment in individuals with FLD. However, the effect might be less significant in individuals with acquired LCAT deficiency.
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Deficiencia de la Lecitina Colesterol Aciltransferasa/diagnóstico , Fosfatidilcolina-Esterol O-Aciltransferasa/inmunología , Anciano , Antiinflamatorios/uso terapéutico , Autoanticuerpos/sangre , Cromatografía Líquida de Alta Presión , Electroforesis en Gel Bidimensional , Humanos , Riñón/patología , Deficiencia de la Lecitina Colesterol Aciltransferasa/tratamiento farmacológico , Deficiencia de la Lecitina Colesterol Aciltransferasa/inmunología , Lipoproteína X/sangre , Lipoproteínas/sangre , Masculino , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Prednisolona/uso terapéuticoRESUMEN
AIMS: Dipeptidyl peptidase-4 inhibitor (DPP-4i) is commonly used worldwide for the treatment of type 2 diabetes mellitus. In addition to its hypoglycemic activity, DPP-4i might have anti-inflammatory effects. In this study we examined the effects of DPP-4i on the serum levels of soluble CD163 (sCD163), a marker for activated macrophages, in individuals with type 2 diabetes mellitus. We compared these anti-inflammatory effects with those of α glucosidase inhibitor (αGI). METHODS: Japanese patients with type 2 diabetes mellitus who were stably maintained on ≤2mg/day glimepiride alone were recruited and randomly assigned to receive additional sitagliptin (n=37) or αGI (n=37). Levels of sCD163 were measured before the addition and after a 24-week treatment period. RESULTS: Addition of sitagliptin significantly reduced the serum sCD163 (632 vs. 575ng/mL, p<0.05), while αGI did not display this effect (624 vs. 607ng/mL). The changes in levels of sCD163 were not related to changes in either HbA1c or body mass index (BMI). CONCLUSIONS: Our results suggested that DPP-4i might exert anti-inflammatory effects in individuals with type 2 diabetes mellitus, which are independent of its effects on glycemia and BMI.
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Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Diabetes Mellitus Tipo 2/sangre , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Hipoglucemiantes/uso terapéutico , Macrófagos/efectos de los fármacos , Receptores de Superficie Celular/sangre , Fosfato de Sitagliptina/uso terapéutico , Anciano , Antígenos CD/efectos de los fármacos , Antígenos de Diferenciación Mielomonocítica/efectos de los fármacos , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Receptores de Superficie Celular/efectos de los fármacos , Compuestos de Sulfonilurea/uso terapéuticoRESUMEN
Podocytes are essential for maintaining kidney glomerular functions. Injuries to podocyte are closely related to the pathological process of proteinuria. However, a treatment for podocyte injury has still not been established. Cilostazol (CSZ) and probucol (PBC) have been shown to possess renoprotective effects. Therefore, we evaluated these drugs in a lipopolysaccharide (LPS)-induced podocyte injury model. 7-week-old female C57BL/6J mice were fed a normal diet or a diet containing 0.3% CSZ, 0.5% PBC, or both for 10 days. Then, mice were intraperitoneally injected with 13 µg g-1 body weight LPS. Both CSZ and PBC decreased LPS-induced albuminuria and co-administration was found to be most effective. These treatments ameliorated the upregulation of monocyte chemoattractant protein 1. In cultured podocytes, CSZ suppressed LPS-induced activation of nuclear factor-kappa B (NF-κB) and phosphorylation of p44/42 mitogen-activated protein kinase (MAPK). PBC reduced LPS-induced activation of NF-κB and reactive oxygen species production. Furthermore, PBC decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase4 expression. Our findings suggest that CSZ and PBC are able to inhibit podocyte-injury through different mechanisms, indicating that a combination of these two old drugs is a good treatment option to protect podocytes from injury.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Enfermedades Renales/prevención & control , Estrés Oxidativo/efectos de los fármacos , Podocitos/efectos de los fármacos , Probucol/farmacología , Tetrazoles/farmacología , Albuminuria/inducido químicamente , Albuminuria/metabolismo , Albuminuria/prevención & control , Animales , Células Cultivadas , Quimiocina CCL2/metabolismo , Cilostazol , Citoprotección , Modelos Animales de Enfermedad , Femenino , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Lipopolisacáridos , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , NADPH Oxidasa 4/metabolismo , FN-kappa B/metabolismo , Fosforilación , Podocitos/metabolismo , Podocitos/patología , Transducción de Señal/efectos de los fármacosRESUMEN
Vibrio parahaemolyticus RIMD2210633 has two sets of type IV-A pilus genes. One set is similar to that found in other Gram-negative bacteria, such as Pseudomonas aeruginosa, Vibrio cholerae (chitin-regulated pilus; ChiRP), and Vibrio vulnificus. The other is homologous to the genes for the mannose-sensitive hemagglutinin (MSHA) pilus. In this study, we analyzed the effects of the deletions in the pilin genes for each type IV pilus (the ChiRP and the MSHA pilus) on biofilm formation. Although the MSHA pilin mutant formed aggregates, the number of bacteria that attached directly to the coverslip was reduced, suggesting that this pilus contributes to the bacterial attachment to the surface of the coverslip. In contrast, the ChiRP mutant attached to the surface of the coverslip, but did not form aggregates, suggesting that ChiRP plays a role in bacterial agglutination during biofilm formation. These results suggest that the two type IV pili of V. parahaemolyticus contribute to biofilm formation in different ways. Both mutants showed a lower fitness for adsorption onto chitin particles than that of the wild type. Collectively, these data suggest that the use of two type IV pili is a refined strategy of V. parahaemolyticus for survival in natural environments.
Asunto(s)
Biopelículas/crecimiento & desarrollo , Proteínas Fimbrias/fisiología , Vibrio parahaemolyticus/fisiología , Adhesión Bacteriana/genética , Quitina/metabolismo , Proteínas Fimbrias/genética , Fimbrias Bacterianas/ultraestructura , Eliminación de Gen , Genoma Bacteriano , Hemaglutininas/metabolismo , Manosa/metabolismo , Vibrio parahaemolyticus/citología , Vibrio parahaemolyticus/genéticaRESUMEN
As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative International Validation Study of an in vivo rat alkaline comet assay, we examined 1,2-dibromoethane (DBE), p-anisidine (ASD), and o-anthranilic acid (ANT) to investigate the effectiveness of the comet assay in detecting genotoxic carcinogens. Each of the three test chemicals was administered to 5 male Sprague-Dawley rats per group by oral gavage at 48, 24, and 3h before specimen preparation. Single cells were collected from the liver and glandular stomach at 3h after the final dosing, and the specimens prepared from these two organs were subjected to electrophoresis under alkaline conditions (pH>13). The percentage of DNA intensity in the comet tail was then assessed using an image analysis system. A micronucleus (MN) assay was also conducted using these three test chemicals with the bone marrow (BM) cells collected from the same animals simultaneously used in the comet assay, i.e., combination study of the comet assay and BM MN assay. A genotoxic (Ames positive) rodent carcinogen, DBE gave a positive result in the comet assay in the present study, while a genotoxic (Ames positive) non-carcinogen, ASD and a non-genotoxic (Ames negative) non-carcinogen, ANT showed negative results in the comet assay. All three chemicals produced negative results in the BM MN assay. While the comet assay findings in the present study were consistent with those obtained from the rodent carcinogenicity studies for the three test chemicals, we consider the positive result in the comet assay for DBE to be particularly meaningful, given that this chemical produced a negative result in the BM MN assay. Therefore, the combination study of the comet assay and BM MN assay is a useful method to detect genotoxic carcinogens that are undetectable with the BM MN assay alone.
Asunto(s)
Compuestos de Anilina/toxicidad , Ensayo Cometa/métodos , Daño del ADN/efectos de los fármacos , Dibromuro de Etileno/toxicidad , ortoaminobenzoatos/toxicidad , Administración Oral , Animales , Médula Ósea/efectos de los fármacos , Carcinógenos/toxicidad , Relación Dosis-Respuesta a Droga , Hígado/efectos de los fármacos , Masculino , Pruebas de Micronúcleos/métodos , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Estómago/efectos de los fármacosRESUMEN
The liver micronucleus (MN) assay is useful for predicting genotoxic rodent hepatocarcinogenicity. We have recently established the repeated-dose liver MN (RDLMN) assay in rats for integration into general toxicity studies. To investigate the effectiveness of the RDLMN assay, the genotoxic rodent hepatocarcinogen, monocrotaline (MCT), was administered by oral gavage to 6-week old male rats once daily for 14 days at 0.5 and 1.5mg/kg/day, and for 28 days at 0.15, 0.5, 1.5, 3.75, 7.5 and 15mg/kg/day. Then, MN induction was measured in the liver and bone marrow (BM), and histopathological hepatotoxicity was examined. Additionally, in order to evaluate the effects of repeated dosing periods on MN inducibility, a double-dose examination of MCT at doses of 15, 30 and 60mg/kg/day in juvenile (26-days old) and young adult (7-weeks old) rats was also conducted, as an acute dose MN assay. The peripheral blood (PB) and liver were sampled at 48h and 4 days after the second dosing, respectively. In the repeated-dose MN assay, MCT produced a positive result in the liver at a non-hepatotoxic lower dose level, but not in the BM at any dose level. In contrast, in the double-dose MN assay, MCT showed a negative result in the young adult rat livers, although it gave positive responses in the livers of juvenile rats and in the PB with both age groups. The maximum dose used in the repeated-dose assay was considerably lower than that used in the acute dose assay. These results suggest that a repeated dosing regimen is more suitable for the liver MN assay using young adult rats than an acute dose regimen, and the RDLMN assay might be capable of detecting genotoxic rodent hepatocarcinogens at dose levels that are typically undetectable in BM MN assays.