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1.
Nat Commun ; 15(1): 4581, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811546

RESUMEN

The anomalous strange metal phase found in high-Tc cuprates does not follow the conventional condensed-matter principles enshrined in the Fermi liquid and presents a great challenge for theory. Highly precise experimental determination of the electronic self-energy can provide a test bed for theoretical models of strange metals, and angle-resolved photoemission can provide this as a function of frequency, momentum, temperature and doping. Here we show that constant energy cuts through the nodal spectral function in (Pb,Bi)2Sr2-xLaxCuO6+δ have a non-Lorentzian lineshape, consistent with a self-energy that is k dependent. This provides a new test for aspiring theories. Here we show that the experimental data are captured remarkably well by a power law with a k-dependent scaling exponent smoothly evolving with doping, a description that emerges naturally from anti-de Sitter/conformal-field-theory based semi-holography. This puts a spotlight on holographic methods for the quantitative modelling of strongly interacting quantum materials like the cuprate strange metals.

2.
AJNR Am J Neuroradiol ; 43(10): 1502-1507, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36137665

RESUMEN

BACKGROUND AND PURPOSE: West syndrome is a developmental and epileptic encephalopathy characterized by epileptic spasms, neurodevelopmental regression, and a specific EEG pattern called hypsarrhythmia. Our aim was to investigate the brain activities related to hypsarrhythmia at onset and focal epileptiform discharges in the remote period in children with West syndrome using simultaneous electroencephalography and fMRI recordings. MATERIALS AND METHODS: Fourteen children with West syndrome underwent simultaneous electroencephalography and fMRI at the onset of West syndrome. Statistically significant blood oxygen level-dependent responses related to hypsarrhythmia were analyzed using an event-related design of 4 hemodynamic response functions with peaks at 3, 5, 7, and 9 seconds after the onset of each event. Six of 14 children had focal epileptiform discharges after treatment and underwent simultaneous electroencephalography and fMRI from 12 to 25 months of age. RESULTS: At onset, positive blood oxygen level-dependent responses were seen in the brainstem (14/14 patients), thalami (13/14), basal ganglia (13/14), and hippocampi (13/14), in addition to multiple cerebral cortices. Group analysis using hemodynamic response functions with peaks at 3, 5, and 7 seconds showed positive blood oxygen level-dependent responses in the brainstem, thalamus, and hippocampus, while positive blood oxygen level-dependent responses in multiple cerebral cortices were seen using hemodynamic response functions with peaks at 5 and 7 seconds. In the remote period, 3 of 6 children had focal epileptiform discharge-related positive blood oxygen level-dependent responses in the thalamus, hippocampus, and brainstem. CONCLUSIONS: Positive blood oxygen level-dependent responses with hypsarrhythmia appeared in the brainstem, thalamus, and hippocampus on earlier hemodynamic response functions than the cerebral cortices, suggesting the propagation of epileptogenic activities from the deep brain structures to the neocortices. Activation of the hippocampus, thalamus, and brainstem was still seen in half of the patients with focal epileptiform discharges after adrenocorticotropic hormone therapy.


Asunto(s)
Espasmos Infantiles , Niño , Humanos , Espasmos Infantiles/diagnóstico por imagen , Imagen por Resonancia Magnética , Electroencefalografía , Tronco Encefálico/diagnóstico por imagen , Encéfalo , Hipocampo/diagnóstico por imagen , Tálamo/diagnóstico por imagen
3.
J Small Anim Pract ; 63(1): 45-51, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34585398

RESUMEN

OBJECTIVES: To characterise the clinical signs of suspected cerebrovascular disease in dogs. MATERIALS AND METHODS: Medical records of one hospital were searched from November 2009 to December 2016 for dogs that suffered of cerebrovascular disease. We diagnosed cerebrovascular disease based on acute onset, clinical signs and magnetic resonance imaging findings. The medical history, clinical signs, concurrent disease, area of infarction, cerebrospinal fluid results, month at onset and outcome were investigated in the cerebrovascular disease group and in a control group (dogs with brain disorders other than cerebrovascular disease). RESULTS: A total of 122 CVD cases were extracted from the 5312 patients that visited during the study period. Of these 122 cases, 66 (1.2%) matched the subject selection criteria of our study and were included in the analysis. Forebrain infarction was observed in 51 of 66 cases, of which 24 (47.1%) suffered from seizures. The number of dogs diagnosed with cerebrovascular disease was disproportionately high in August (nine of 59 cases) and December (13 of 59 cases). In the outcome survey, deterioration was observed in 11 of 55 cases. CLINICAL SIGNIFICANCE: Seizure is an important clinical sign of cerebrovascular disease in dogs. There was a significant seasonal variation in the number of dogs diagnosed with cerebrovascular disease in Japan. Clinical features observed in this report differ from those of previous reports and highlight the need for additional research in this area.


Asunto(s)
Trastornos Cerebrovasculares , Enfermedades de los Perros , Animales , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/patología , Perros , Imagen por Resonancia Magnética/veterinaria , Estudios Retrospectivos , Convulsiones/veterinaria
4.
Nature ; 595(7869): 661-666, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34321672

RESUMEN

Strange metals possess highly unconventional electrical properties, such as a linear-in-temperature resistivity1-6, an inverse Hall angle that varies as temperature squared7-9 and a linear-in-field magnetoresistance10-13. Identifying the origin of these collective anomalies has proved fundamentally challenging, even in materials such as the hole-doped cuprates that possess a simple bandstructure. The prevailing consensus is that strange metallicity in the cuprates is tied to a quantum critical point at a doping p* inside the superconducting dome14,15. Here we study the high-field in-plane magnetoresistance of two superconducting cuprate families at doping levels beyond p*. At all dopings, the magnetoresistance exhibits quadrature scaling and becomes linear at high values of the ratio of the field and the temperature, indicating that the strange-metal regime extends well beyond p*. Moreover, the magnitude of the magnetoresistance is found to be much larger than predicted by conventional theory and is insensitive to both impurity scattering and magnetic field orientation. These observations, coupled with analysis of the zero-field and Hall resistivities, suggest that despite having a single band, the cuprate strange-metal region hosts two charge sectors, one containing coherent quasiparticles, the other scale-invariant 'Planckian' dissipators.

5.
Diabet Med ; 37(1): 105-113, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31621107

RESUMEN

AIM: To evaluate the association between sarcopenic obesity and the decline in estimated GFR in people with type 2 diabetes. METHODS: We enrolled 745 people with type 2 diabetes (mean age 64.6 years, 53.6% men). Body composition was evaluated using dual-energy X-ray absorptiometry. Skeletal muscle index, calculated as appendicular non-fat mass (kg) divided by height squared (m2 ), was used to determine sarcopenia. Sarcopenic obesity was defined as the coexistence of sarcopenia and a ratio of android to gynoid fat mass greater than the median values in each gender. The association of sarcopenic obesity both with the annual rate of decline in estimated GFR and a >30% decline in estimated GFR was evaluated using multivariate linear regression models and Cox proportional hazard models, respectively. RESULTS: Participants with sarcopenic obesity were at an increased risk of a high annual rate of decline in estimated GFR, even after adjustment for the confounding variables (standardized ß = -0.228, P <0.001). Sarcopenic obesity was also significantly associated with risk of a >30% decline in estimated GFR (hazard ratio 4.52, 95% CI 2.16-9.47; P < 0.01) in multivariate model. CONCLUSIONS: Sarcopenic obesity evaluated by dual energy X-ray absorptiometry is associated with a faster decline in renal function in people with type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Riñón/fisiopatología , Obesidad/epidemiología , Insuficiencia Renal Crónica/epidemiología , Sarcopenia/epidemiología , Anciano , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Reino Unido
6.
Mitochondrial DNA A DNA Mapp Seq Anal ; 30(3): 434-439, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30489182

RESUMEN

The native distribution of the yellow-legged hornet, Vespa velutina, is throughout East Asia. Around 15 years ago this species was accidentally introduced into South Korea and France, where it became established and then spread into neighbouring countries. Previous mitochondrial DNA studies showed that the South Korean, Japanese, and French populations all originated from Eastern China. Recently, the hornet has invaded Iki Island, Japan and Jersey Island, UK. In this study, we analyze the complete mitochondrial DNA sequence of V. velutina to trace the origin of these two populations. The mitochondrial DNA haplotypes (COI, Cytb, and 16S rRNA) of V. velutina in Iki Island matched the unique haplotype present in China, South Korea, and Japan, while the haplotype from Jersey Island matched that of V. velutina found in France and China. These findings were supported by data from the complete mitochondrial DNA sequence of V. velutina from Iki Island, which was consistent with the sequence from South Korea and Tsushima, whereas V. velutina in Jersey was most similar to the French population.


Asunto(s)
ADN Mitocondrial/genética , Islas , Avispas/genética , Migración Animal , Animales , Haplotipos , Japón , Reino Unido
7.
Lupus ; 27(14): 2245-2252, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30394835

RESUMEN

OBJECTIVES: We investigated the efficacy and safety of tacrolimus (TAC) by monitoring its serum concentration for mothers and infants in pregnant patients with systemic lupus erythematosus (SLE). METHODS: We measured trough concentrations of TAC in 25 pregnant patients with SLE to assess influence of TAC on the disease activity. Additionally, we measured the concentrations of TAC in umbilical arterial blood, breast milk, and breastfed infants to investigate the safety of TAC for the mothers and infants. RESULTS: The trough concentrations of TAC in the mothers significantly decreased in the second trimester as compared with those before pregnancy. However, the decrease in the trough concentrations of TAC did not lead to the deterioration of SLE. When examined, the doses of TAC were significantly lower in the second trimester and postpartum in the deteriorating group than those in the non-deteriorating group. There were no adverse events by TAC in mothers and fetuses. The concentrations of TAC in the umbilical cord blood were lower than those in the maternal blood. The relative infant dose in breastfed infants of TAC was < 1%. The level of TAC in infant bloods was below detectable limits. CONCLUSION: These findings suggest that TAC is one of the most effective and safest immunosuppressive drugs for use in pregnant patients with SLE.


Asunto(s)
Inmunosupresores/uso terapéutico , Lactancia , Lupus Eritematoso Sistémico/tratamiento farmacológico , Tacrolimus/uso terapéutico , Adulto , Lactancia Materna , Femenino , Sangre Fetal/química , Humanos , Inmunosupresores/sangre , Lactante , Recién Nacido , Japón , Leche Humana/química , Embarazo , Índice de Severidad de la Enfermedad , Tacrolimus/sangre
8.
Lupus ; 27(10): 1636-1643, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29954283

RESUMEN

Objective The objective of this study is to investigate the effectiveness of discontinuation of risedronate for patients with systemic lupus erythematosus (SLE) treated with glucocorticoid (GC). Methods The participants were patients with SLE treated with prednisolone (PSL) ≥ 2 mg/day and risedronate for at least three years. Lumbar spine and total hip bone mineral density (BMD) measurements were taken at baseline and 24 and 48 weeks after discontinuation of risedronate, and bone turnover markers were evaluated at baseline, 12, 24, 36, and 48 weeks. Results A total of 36 patients were enrolled, 25 of whom discontinued risedronate. The mean age was 46.8 ± 11.2 years, and 23 were female. The mean duration of GC treatment was 14.8 ± 11.4 years, the mean dose of PSL was 7.8 ± 3.9 mg/day, and the mean duration of risedronate was 5.8 ± 2.4 years. Seventeen patients showed decreased lumbar spine BMD at 48 weeks after discontinuation of risedronate, with a mean lumbar spine lumbar decrease of 1.42% ± 3.20% ( p = 0.034); 17 patients (71%) showed a decreased total hip BMD at 48 weeks after discontinuation of risedronate, with a mean total hip BMD decrease of 0.99% ± 2.10% ( p = 0.021). Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) ≥ 309 mU/dl at baseline was a risk factor for decreased total hip BMD at 48 weeks compared with serum TRACP-5b < 309 mU/dl (56% vs 0%, p = 0.0098). One patient developed a clinical fracture of the lumbar spine at 20 weeks. Conclusions Discontinuation of risedronate treatment in patients with SLE who had received GC therapy led to decreases in lumbar spine and total hip BMD, particularly in patients with high baseline serum TRACP-5b levels.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Densidad Ósea/efectos de los fármacos , Glucocorticoides/administración & dosificación , Vértebras Lumbares/efectos de los fármacos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Huesos Pélvicos/efectos de los fármacos , Prednisolona/administración & dosificación , Ácido Risedrónico/administración & dosificación , Adulto , Biomarcadores/sangre , Esquema de Medicación , Femenino , Glucocorticoides/efectos adversos , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiopatología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Osteoporosis/sangre , Osteoporosis/inducido químicamente , Osteoporosis/diagnóstico por imagen , Osteoporosis/fisiopatología , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/fisiopatología , Prednisolona/efectos adversos , Factores Protectores , Factores de Riesgo , Fosfatasa Ácida Tartratorresistente/sangre , Factores de Tiempo , Resultado del Tratamiento
9.
Chem Commun (Camb) ; 54(36): 4557-4560, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29662978

RESUMEN

Size-dependent uptake behaviors of electrically neutral amphipathic polymeric nanoparticles in cell-sized liposomes and living cells were investigated. Kinetic analyses and the particle size distribution suggested a size-dependent penetration mechanism (size threshold: 3.1 nm). The definite size-dependent uptake provides a new insight into the interactions between nanomaterials and living cells.


Asunto(s)
Resinas Acrílicas/metabolismo , Membrana Celular/metabolismo , Liposomas/metabolismo , Nanopartículas/metabolismo , Tamaño de la Partícula , 1,2-Dipalmitoilfosfatidilcolina/química , Resinas Acrílicas/química , Animales , Membrana Celular/química , Colesterol/química , Fluoresceínas/química , Liposomas/química , Microdominios de Membrana/química , Microdominios de Membrana/metabolismo , Ratones , Microscopía Confocal , Células 3T3 NIH , Nanopartículas/química , Fosfatidilcolinas/química
10.
Neurogastroenterol Motil ; 30(7): e13319, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29498457

RESUMEN

BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.


Asunto(s)
Ansiedad/diagnóstico , Ansiedad/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Dispepsia/diagnóstico , Dispepsia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/epidemiología , Método Doble Ciego , Dispepsia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego , Resultado del Tratamiento , Adulto Joven
11.
Scand J Rheumatol ; 47(4): 276-281, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29458278

RESUMEN

OBJECTIVE: To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors. METHOD: This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years. RESULTS: ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies. CONCLUSIONS: Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados , Artritis Reumatoide/inmunología , Artritis Reumatoide/fisiopatología , Proteína C-Reactiva/inmunología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia del Tratamiento , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
12.
Nat Commun ; 9(1): 154, 2018 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-29323126

RESUMEN

Superconductivity is ubiquitous as evidenced by the observation in many crystals including carrier-doped oxides and diamond. Amorphous solids are no exception. However, it remains to be discovered in quasicrystals, in which atoms are ordered over long distances but not in a periodically repeating arrangement. Here we report electrical resistivity, magnetization, and specific-heat measurements of Al-Zn-Mg quasicrystal, presenting convincing evidence for the emergence of bulk superconductivity at a very low transition temperature of [Formula: see text] K. We also find superconductivity in its approximant crystals, structures that are periodic, but that are very similar to quasicrystals. These observations demonstrate that the effective interaction between electrons remains attractive under variation of the atomic arrangement from periodic to quasiperiodic one. The discovery of the superconducting quasicrystal, in which the fractal geometry interplays with superconductivity, opens the door to a new type of superconductivity, fractal superconductivity.

14.
J Physiol Pharmacol ; 68(1): 79-90, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28456772

RESUMEN

Intestinal mucositis accompanied by severe diarrhea is one of the most common side effects during cancer chemotherapy. Lafutidine, a histamine H2 receptor antagonist with mucosal protective properties via sensory afferent neurons, is used for the treatment of upper gastrointestinal diseases. The present study investigated the effects of lafutidine on 5-fluorouracil (5-FU)-induced intestinal mucositis induced in mice. Male C57BL/6 wild-type (WT), sensory deafferented mice, and transient receptor potential vanilloid subfamily 1 knockout (TRPV1KO) mice were used. Animals were administered 5-FU once daily, while lafutidine and famotidine were administered twice daily for 6 days. Repeated administration of 5-FU caused severe intestinal mucositis, characterized by shortening of villi and destruction of crypts and was accompanied by diarrhea and body weight loss. Daily administration of lafutidine reduced the severity of intestinal mucositis, diarrhea and body weight loss in a dose-dependent manner, while famotidine had no effect on intestinal mucositis. The preventive effects of lafutidine were completely abolished in sensory deafferented and TRPV1-KO mice. Lafutidine significantly suppressed 5-FU-increased MPO activity and inflammatory cytokine expression on day 6, but not apoptosis induction in intestinal crypts on day 1. Lafutidine induced Alcian Blue and PAS-positive mucus production in the small intestine. These findings suggest that lafutidine attenuates 5-FU-induced intestinal mucositis, most likely by increasing mucus production via activation of sensory afferent neurons. Furthermore, intact TRPV1 signaling is essential for the activation of sensory afferent neurons induced by lafutidine. Therefore, lafutidine is more useful than other common antacids for the treatment of intestinal mucositis during cancer chemotherapy.


Asunto(s)
Acetamidas/uso terapéutico , Diarrea/tratamiento farmacológico , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Mucositis/tratamiento farmacológico , Piperidinas/uso terapéutico , Piridinas/uso terapéutico , Acetamidas/farmacología , Animales , Antimetabolitos Antineoplásicos , Diarrea/metabolismo , Diarrea/patología , Famotidina/uso terapéutico , Fluorouracilo , Antagonistas de los Receptores H2 de la Histamina/farmacología , Interleucina-1beta/genética , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Intestinos/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Mucositis/inducido químicamente , Mucositis/patología , Peroxidasa/metabolismo , Piperidinas/farmacología , Piridinas/farmacología , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/genética
15.
Pharmazie ; 72(2): 95-97, 2017 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-29441860

RESUMEN

In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enrolled a total of 10 Japanese adult patients with RA who were treated with infliximab concomitantly with methotrexate or azathioprine. Serum concentrations of infliximab and ATI of these patients were measured. The mean serum infliximab concentrations was 1.6±1.3 µg/ml in patients with methotrexate and 1.0±0.5 µg/ml in patients with azathioprine. Serum ATI concentrations were below the limit of quantitation in 4 of 5 patients in each group. The results from the present study suggest that azathioprine suppresses ATI production.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Azatioprina/farmacología , Infliximab/inmunología , Metotrexato/farmacología , Adulto , Anticuerpos/sangre , Anticuerpos/inmunología , Azatioprina/administración & dosificación , Quimioterapia Combinada , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacología , Infliximab/administración & dosificación , Metotrexato/administración & dosificación
16.
Pharmazie ; 72(1): 22-28, 2017 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-29441893

RESUMEN

Azathioprine (AZA) is increasingly being prescribed to rheumatoid arthritis (RA) patients. Following oral administration, AZA is converted into its active form. Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) patients with low thiopurine (S)-methyltransferase (TPMT) activity tend to respond well to AZA therapy. In a previous study of Japanese SLE patients under low-dose AZA therapy, the group with the 94C>A mutation in inosine triphosphatase (ITPA) showed greater improvement in their disease activity index. However, it is not yet clear how genotypes relate to responsiveness to RA treatment. The genotypes ITPA 94C>A, TPMT*3C, NUDT15 595C>T, GST-M1, GST-T1 and MRP4/ABCC4 2269G>A of Japanese patients with RA were determined. The relationship between these genotypes and response to AZA therapy was evaluated using the Disease Activity Score 28 (DAS28) and various medical data. Of the 22 patients 15 had the ITPA 94C/C genotype, 7 had the ITPA 94C/A genotype, none had the TPMT*3C mutation, 4 had the NUDT15 595C>T mutation, 8 had the GST-M1 and T1 null genotypes and 9 had the MRP4/ABCC4 2269G>A mutation. Changes in DAS28 at 6 months after baseline were similar in both ITPA genotype groups. However, the maintenance dose of AZA was significantly lower in the C/A group than in the C/C group (0.85±0.30 mg/kg/day vs. 1.2±0.46 mg/kg/day, respectively; p = 0.043). The ITPA 94C/A group showed the same response to RA treatment as the C/C group, but at a lower dose. This demonstrates that RA patients with the ITPA 94C>A mutation are more responsive to AZA.


Asunto(s)
Antirreumáticos/metabolismo , Artritis Reumatoide/enzimología , Artritis Reumatoide/genética , Azatioprina/metabolismo , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Pueblo Asiatico , Azatioprina/uso terapéutico , Femenino , Eliminación de Gen , Frecuencia de los Genes , Genotipo , Humanos , Japón , Masculino , Persona de Mediana Edad , Mutación/genética , Polimorfismo Genético , Estudios Retrospectivos
17.
Lupus ; 26(6): 656-660, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27831538

RESUMEN

Objectives The selectivity index has been proposed in predicting the response to immunosuppressive therapy in nephrotic syndrome and other primary kidney disorders. The aim of this study was to elucidate the predictive value of the selectivity index for the treatment response and renal outcome in patients with lupus nephritis. Methods Forty-four patients with lupus nephritis with selectivity index available at the time of renal biopsy were divided into two groups according to the cut-off value of the selectivity index determined by a receiver operating characteristics curve to differentiate treatment responders from non-responders. The baseline characteristics, overall response rate and renal functional outcome were studied retrospectively, and compared between the two groups. Prognostic factors for achieving remission were identified. Results The cut-off value of the selectivity index was 0.167. The low selectivity index (<0.167) and the high selectivity index (≥0.167) group included 24 and 20 patients, respectively. The overall response rate was significantly higher (88% vs. 50%, P = 0.007) and the rate of progression to end-stage renal disease was lower in the low selectivity index group (0% vs. 15%, P = 0.049). More patients in the high selectivity index group had chronic lesions on renal biopsy ( P = 0.002). The selectivity index was the prognostic factor for achieving overall response based on a multivariate analysis ( P = 0.020). Conclusions A selectivity index ≥0.167 was a strong predictor for a poor treatment response and the presence of chronic lesions on renal biopsy. Further exploration with a larger cohort and longer follow-up period is warranted.


Asunto(s)
Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Proteinuria/epidemiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Resultado del Tratamiento
18.
Epidemiol Infect ; 145(2): 272-284, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27682641

RESUMEN

In temperate zones, human respiratory syncytial virus (HRSV) outbreaks typically occur in cold weather, i.e. in late autumn and winter. However, recent outbreaks in Japan have tended to start during summer and autumn. This study examined associations of meteorological conditions with the numbers of HRSV cases reported in summer in Japan. Using data from the HRSV national surveillance system and national meteorological data for summer during the period 2007-2014, we utilized negative binomial logistic regression analysis to identify associations between meteorological conditions and reported cases of HRSV. HRSV cases increased when summer temperatures rose and when relative humidity increased. Consideration of the interaction term temperature × relative humidity enabled us to show synergistic effects of high temperature with HRSV occurrence. In particular, HRSV cases synergistically increased when relative humidity increased while the temperature was ⩾28·2 °C. Seasonal-trend decomposition analysis using the HRSV national surveillance data divided by 11 climate divisions showed that summer HRSV cases occurred in South Japan (Okinawa Island), Kyushu, and Nankai climate divisions, which are located in southwest Japan. Higher temperature and higher relative humidity were necessary conditions for HRSV occurrence in summer in Japan. Paediatricians in temperate zones should be mindful of possible HRSV cases in summer, when suitable conditions are present.


Asunto(s)
Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Humanos , Humedad , Incidencia , Japón/epidemiología , Conceptos Meteorológicos , Estaciones del Año , Temperatura
19.
Pharmacopsychiatry ; 50(2): 69-73, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27595297

RESUMEN

Introduction: Very few studies have explored the adverse effect of psychotropic drugs worldwide. Methods: This study analyzed 1 813 suicide-related drug reports involving 553 patients collected from the Japanese National Adverse Drug Report Database between October 2001 and January 2012 to investigate psychotropic drugs associated with completed suicide vs. other suicide-related behaviors, including ideation and self-injury. The drugs investigated included antidepressants, antipsychotics, benzodiazepines, non-benzodiazepine hypnotic agents, noradrenergic and specific serotonergic antidepressants, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and other drugs. Results: These reports referenced 300 (54.2%) individuals who completed suicide. Adjusting for age, sex, and drugs used, the multivariate model revealed that participants who took antipsychotics were 1.70 times (95% CI, 1.11-2.61) more likely to complete suicide compared with those who did not. All other drugs became non-significant. Compared with those who took only one medication, those prescribed more than 4 drugs were more likely to complete suicide (OR 4.44, 95% CI, 2.40-8.20). Discussion: Antipsychotic drugs and polypharmacy may be regarded as predictors of completed suicide.


Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Psicotrópicos/efectos adversos , Conducta Autodestructiva/inducido químicamente , Conducta Autodestructiva/epidemiología , Ideación Suicida , Suicidio/estadística & datos numéricos , Adulto , Anciano , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polifarmacia , Conducta Autodestructiva/psicología , Adulto Joven
20.
Rev Sci Instrum ; 87(4): 043503, 2016 04.
Artículo en Inglés | MEDLINE | ID: mdl-27131670

RESUMEN

In TST-2 Ohmic discharges, local current is measured using a Rogowski probe by changing the angle between the local magnetic field and the direction of the hole of the Rogowski probe. The angular dependence shows a peak when the direction of the hole is almost parallel to the local magnetic field. The obtained width of the peak was broader than that of the theoretical curve expected from the probe geometry. In order to explain this disagreement, we consider the effect of sheath in the vicinity of the Rogowski probe. A sheath model was constructed and electron orbits were numerically calculated. From the calculation, it was found that the electron orbit is affected by E × B drift due to the sheath electric field. Such orbit causes the broadening of the peak in the angular dependence and the dependence agrees with the experimental results. The dependence of the broadening on various plasma parameters was studied numerically and explained qualitatively by a simplified analytical model.

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