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The prevalence of azole-resistant Aspergillus fumigatus is increasing worldwide and is speculated to be related to the use of azole pesticides. Aspergillus spp., the causative agent of aspergillosis, could be brought into domestic dwellings through food. However, studies on azole-resistant Aspergillus spp. in food products are limited. Therefore, we aimed to isolate Aspergillus spp. from processed foods and commercial agricultural products and performed drug susceptibility tests for azoles. Among 692 food samples, we isolated 99 strains of Aspergillus spp. from 50 food samples, including vegetables (22.9%), citrus fruits (26.3%), cereals (25.5%), and processed foods (1.8%). The isolates belonged to 18 species across eight sections: Aspergillus, Candidi, Clavati, Flavi, Fumigati, Nidulantes, Nigri, and Terrei. The most frequently isolated section was Fumigati with 39 strains, followed by Nigri with 28 strains. Aspergillus fumigatus and A. welwitschiae were the predominant species. Ten A. fumigatus and four cryptic strains, four A. niger cryptic strains, two A. flavus, and four A. terreus strains exceeded epidemiological cutoff values for azoles. Aspergillus tubingensis, A. pseudoviridinutans, A. lentulus, A. terreus, and N. hiratsukae showed low susceptibility to multi-azoles. Foods containing agricultural products were found to be contaminated with Aspergillus spp., with 65.3% of isolates having minimal inhibitory concentrations below epidemiological cutoff values. Additionally, some samples harbored azole-resistant strains of Aspergillus spp. Our study serves as a basis for elucidating the relationship between food, environment, and clinically important Aspergillus spp.
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INTRODUCTION: In nurturing systems, the oxytocin (Oxt)-oxytocin receptor (Oxtr) system is important for parturition, and essential for lactation and parental behavior. Among the nerve nuclei that express Oxtr, the lateral septal nucleus (LS) and medial preoptic area (MPOA) are representative regions that control maternal behavior. METHODS: We investigated the role of Oxtr- and Oxtr-expressing neurons, located in the LS and MPOA, in regulating maternal behavior by regulating Oxtr expression in a region-specific manner using recombinant mice and adeno-associated viruses. We quantified the prolactin (Prl) concentrations in the pituitary gland and plasma when Oxtr expression in the MPOA was reduced. RESULTS: The endogenous Oxtr gene in the neurons of the LS did not seem to play an essential role in maternal behavior. Conversely, decreased Oxtr expression in the MPOA increased the frequency of pups being left outside the nest and reduced their survival rate. Deletion of Oxtr in MPOA neurons prevented elevation of Prl levels in plasma and pituitary at postpartum day 2. DISCUSSION/CONCLUSION: Oxtr-expressing neurons in the MPOA are involved in the postpartum production of Prl. We confirmed the essential functions of Oxtr-expressing neurons and the Oxtr gene itself in the MPOA for the sustainability of maternal behavior, which involved Oxtr-dependent induction of Prl.
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Two novel endornaviruses, Phytophthora endornavirus 2 (PEV2) and Phytophthora endornavirus 3 (PEV3) were found in isolates of a Phytophthora pathogen of asparagus collected in Japan. A molecular phylogenetic analysis indicated that PEV2 and PEV3 belong to the genus Alphaendornavirus. The PEV2 and PEV3 genomes consist of 14,345 and 13,810 bp, and they contain single open reading frames of 4,640 and 4,603 codons, respectively. Their polyproteins contain the conserved domains of an RNA helicase, a UDP-glycosyltransferase, and an RNA-dependent RNA polymerase, which are conserved in other alphaendornaviruses. PEV2 is closely related to Brown algae endornavirus 2, whereas PEV3 is closely related to Phytophthora endornavirus 1 (PEV1), which infects a Phytophthora sp. specific to Douglas fir. PEV2 and PEV3 were detected at high titers in two original Phytophthora sp. isolates, and we found a sub-isolate with low titers of the viruses during subculture. We used the high- and low-titer isolates to evaluate the effects of the viruses on the growth, development, and fungicide sensitivities of the Phytophthora sp. host. The high-titer isolates produced smaller mycelial colonies and much higher numbers of zoosporangia than the low-titer isolate. These results suggest that PEV2 and PEV3 inhibited hyphal growth and stimulated zoosporangium formation. The high-titer isolates were more sensitive than the low-titer isolate to the fungicides benthiavalicarb-isopropyl, famoxadone, and chlorothalonil. In contrast, the high-titer isolates displayed lower sensitivity to the fungicide metalaxyl (an inhibitor of RNA polymerase I) when compared with the low-titer isolate. These results indicate that persistent infection with PEV2 and PEV3 may potentially affect the fungicide sensitivities of the host oomycete.
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Ventricular arrhythmia (VA) is the major cause of death in patients with left ventricular (LV) hypertrophy and/or acute ischemia. We hypothesized that apamin, a blocker of small-conductance Ca2+-activated K+ (SK) channels, alters Ca2+ handling and exhibits anti-arrhythmic effects in ventricular myocardium. Spontaneous hypertensive rats were used as a model of LV hypertrophy. A dual optical mapping of membrane potential (Vm) and intracellular calcium (Cai) was performed during global hypoxia (GH) on the Langendorff perfusion system. The majority of pacing-induced VAs during GH were initiated by triggered activities. Pretreatment of apamin (100 nmol/L) significantly inhibited the VA inducibility. Compared with SK channel blockers (apamin and NS8593), non-SK channel blockers (glibenclamide and 4-AP) did not exhibit anti-arrhythmic effects. Apamin prevented not only action potential duration (APD80) shortening (-18.7 [95% confidence interval, -35.2 to -6.05] ms vs. -2.75 [95% CI, -10.45 to 12.65] ms, P = 0.04) but also calcium transient duration (CaTD80) prolongation (14.52 [95% CI, 8.8-20.35] ms vs. 3.85 [95% CI, -3.3 to 12.1] ms, P < 0.01), thereby reducing CaTD80 - APD80, which denotes "Cai/Vm uncoupling" (33.22 [95% CI, 22-48.4] ms vs. 6.6 [95% CI, 0-14.85] ms, P < 0.01). The reduction of Cai/Vm uncoupling was attributable to less prolonged Ca2+ decay constant and suppression of diastolic Cai increase by apamin. The inhibition of VA inducibility and changes in APs/CaTs parameters caused by apamin was negated by the addition of ouabain, an inhibitor of Na+/K+ pump. Apamin attenuates APD shortening, Ca2+ handling abnormalities, and Cai/Vm uncoupling, leading to inhibition of VA occurrence in hypoxic hypertrophied hearts.NEW & NOTEWORTHY We demonstrated that hypoxia-induced ventricular arrhythmias were mainly initiated by Ca2+-loaded triggered activities in hypertrophied hearts. The blockades of small-conductance Ca2+-activated K+ channels, especially "apamin," showed anti-arrhythmic effects by alleviation of not only action potential duration shortening but also Ca2+ handling abnormalities, most notably the "Ca2+/voltage uncoupling."
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Antiarrítmicos/farmacologia , Arritmias Cardíacas/prevenção & controle , Sinalização do Cálcio/efeitos dos fármacos , Cardiomegalia/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Baixa/antagonistas & inibidores , 1-Naftilamina/análogos & derivados , 1-Naftilamina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Apamina/farmacologia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Estimulação Cardíaca Artificial , Cardiomegalia/complicações , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Preparação de Coração Isolado , Masculino , Ratos Endogâmicos SHR , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Fatores de TempoRESUMO
Recurrence of atrial tachyarrhythmias (ATA) following catheter ablation for atrial fibrillation (AF) is often associated with the recovery of conduction into previously isolated pulmonary veins (PVs). Little evidence concerning repeat PV isolation (PVI) and non-PV ATA ablation has been reported. This study aimed to explore the clinical outcome of recurrent ATA ablation after PVI and the difference between patients with and without non-PV ATA.A total of 49 patients without structural heart diseases who received catheter ablation for recurrent AF between January 2014 and December 2018 were recruited (prior ablation with PVI only 71.4% and PVI with cavotricuspid isthmus line ablation 28.6%). Patients were divided into two groups according to the presence or absence of non-PV ATA.Most patients (53.1%) experienced very late recurrence with a median duration of 15 months. A total of 15 patients had non-PV ATA and received non-PV ATA ablation whereas 34 patients received only repeat PVI for reconnected PVs. A higher pulmonary arterial systolic pressure (PASP) was associated with non-PV ATA (odds ratio: 1.161; 95% confidence interval: 1.021-1.321; P = 0.023). During 4.7 ± 1 months, 4/15 (26.7%) and 1/34 (2.9%) patients with and without non-PV ATA, respectively, had ATA recurrence (P = 0.011). The cumulative incidence of ATA recurrence after repeat ablation was significantly lower in patients without non-PV ATA (P = 0.013).In our study, a high PASP was associated with non-PV ATA in patients with recurrent AF. Repeat PVI had a high rate of maintenance of sinus rhythm in patients without non-PV ATA.
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Pressão Arterial , Fibrilação Atrial/cirurgia , Ablação por Cateter , Artéria Pulmonar/fisiopatologia , Veias Pulmonares/cirurgia , Taquicardia Atrial Ectópica/epidemiologia , Idoso , Fibrilação Atrial/epidemiologia , Flutter Atrial , Ecocardiografia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Recidiva , Fatores de Risco , Fatores SexuaisRESUMO
AIMS: Nonsustained ventricular tachycardia (NSVT) occurs frequently in patients with dilated cardiomyopathy (DCM), especially in high-risk patients. The role of rapid-rate NSVT (RR-NSVT) documented by an implantable cardioverter-defibrillator (ICD) in DCM patients has not been fully explored. This study aimed to determine the relationship between RR-NSVT and the occurrence of ventricular tachyarrhythmias (VTAs) in DCM patients with ICD. METHODS: From December 2000 to December 2017, 136 DCM patients received ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation for primary or secondary prevention of VTAs. Based on the occurrence of documented RR-NSVT, patients were classified into RR-NSVT (-) or RR-NSVT (+) groups. RESULT: During the median follow-up of 4.5 years, 50.0% (68/136) patients experienced ≥1 episode, and 25.0% (34/136) patients experienced ≥3 episodes of RR-NSVT. Event-free survival for VTAs was significantly higher in the RR-NSVT (-) group, whereas those for heart failure admission and cardiovascular mortality were comparable between groups. In the multivariate Cox regression analysis, any RR-NSVT showed a positive association with the occurrence of VTAs (hazard ratio: 5.087; 95% confidence interval: 2.374-10.900; P < .001). In RR-NSVT (+) patients, a cluster (≥3 times/6 months) and frequent pattern (≥3 runs/day) of RR-NSVT were observed in 42.6% (29/68) and 30.9% (21/68) patients, respectively, who showed further increased incidence of VTAs. CONCLUSION: In DCM patients with ICD/CRT-D, 50.0% patients experienced at least one episode of RR-NSVT. RR-NSVT documentation showed a positive association with subsequent occurrence of VTAs, suggesting the importance of constructive arrhythmia management for patients with RR-NSVT.
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Cardiomiopatia Dilatada/complicações , Desfibriladores Implantáveis , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/prevenção & controle , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taquicardia Ventricular/fisiopatologiaRESUMO
Hypertrophic cardiomyopathy (HCM) with apical aneurysm (AA) is rare, but has been reported to be associated with refractory ventricular tachycardias (VTs). Majority of such cases had a central isthmus of the reentry circuit on the border zone of AA. In this report, we describe a rare case of the successful epicardial ablation for a refractory VT originating from a true apex of the aneurysm in a HCM patient. Mid-diastolic potential during sustained VT was recorded at the isolated epicardial myocardium surround by the gross unexcitable scar in AA, and radiofrequency current application rendered VT non-inducible.
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Aneurisma , Cardiomiopatia Hipertrófica , Ablação por Cateter , Taquicardia Ventricular , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/cirurgia , Eletrocardiografia , Humanos , Taquicardia Ventricular/cirurgiaRESUMO
OBJECTIVE: Alzheimer's disease (AD) is characterized by a slow progressive impairment of episodic memory. Many studies have shown that AD exhibits deterioration of semantic memory during the course of disease progression. We previously reported that AD patients exhibited severe access disorders in the semantic memory system, using the Momentary Presentation Task (20 or 300 ms). In this study, we studied access disorder in patients with AD by the use of object difference (pictures vs words) methods. METHODS: 56 patients with probable AD (NINCDS-ADRDA, mean age 79.0 years) and 11 healthy controls (HC) (mean age 67.0 years) were studied. Ten pictures and 10 corresponding Japanese Hiragana words were presented arbitrarily for 20 and 300 ms on the monitor screen which were correctly named at the usual confrontation setting (i.e., semantic memory preserved). They were asked to name the pictures or to read the words or nonsense syllables aloud. RESULTS: The AD group showed significantly lower scores than the HC group, especially for the 20 ms condition. For the type of stimuli, the AD patients had better performances for words > pictures > nonsense syllables, although no differences for the HC group. The effect of AD severity was noted, moderate > severe stage. CONCLUSIONS: Our results suggested that the processing speed in AD patients may have reduced, even if the semantic memory were preserved. These data indicated that the difference in the processing speeds by the type of stimuli (pictures, words, and nonsense syllables) may be a character of AD patients.
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Audição/fisiologia , Transtornos da Memória/fisiopatologia , Visão Ocular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Percepção Auditiva/fisiologia , Cognição/fisiologia , Feminino , Humanos , Masculino , Memória Episódica , Testes Neuropsicológicos , Leitura , Semântica , Fala , Percepção Visual/fisiologiaRESUMO
BACKGROUND: Atrial fibrillation (AF) is an important prognostic determinant in heart failure (HF) with preserved ejection fraction (HFpEF). However, it is unclear which HFpEF phenotypes are affected by AF in terms of long-term clinical outcomes because HFpEF is a heterogeneous syndrome with comorbidities such as coronary artery disease (CAD). In this study we determined the differential prognostic significance of AF in HFpEF patients according to CAD status.MethodsâandâResults:Data for 408 hospitalized HFpEF patients enrolled in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Nationwide Multicenter Registry were analyzed. Patients were divided into 4 groups according to the presence of AF and CAD. The primary outcome was the composite of all-cause death and HF rehospitalization. The incidence of adverse events was higher in the AF-non-CAD than non-AF-non-CAD group (P=0.004). On multivariable Cox regression analysis with prespecified confounders, AF-non-CAD was significantly associated with an increased risk of adverse events than non-AF-non-CAD (adjusted HR, 1.91; 95% CI: 1.02-3.92) regardless of the type of AF. In contrast, risk was comparable between the AF-CAD and non-AF-CAD groups (adjusted HR, 1.24; 95% CI: 0.64-2.47). CONCLUSIONS: In HFpEF patients without CAD, AF was independently related to adverse events, indicating that intensive management of AF would have more beneficial effects particularly in HFpEF patients without CAD.
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Fibrilação Atrial/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Insuficiência Cardíaca/epidemiologia , Admissão do Paciente , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/terapia , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Frequência Cardíaca , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Função Ventricular EsquerdaRESUMO
Becker muscular dystrophy (BMD) carriers are at risk to developing cardiac dysfunction. The prevalence of female BMD carriers remains underestimated, and the disease progression varies. We herein report the case of a young female BMD carrier who developed dilated cardiomyopathy (DCM) and heart failure without any skeletal muscle signs. Her cardiac dysfunction progressed over a mere two months, resulting in the need for left ventricular assist device implantation. Her case demonstrates that progressive cardiomyopathy can be the only clinical manifestation in some BMD carriers, suggesting the need for a more aggressive implementation of genetic testing in female DCM patients.
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Cardiomiopatia Dilatada/etiologia , Insuficiência Cardíaca/etiologia , Distrofia Muscular de Duchenne/complicações , Adulto , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/terapia , Progressão da Doença , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Coração Auxiliar , Heterozigoto , Humanos , Distrofia Muscular de Duchenne/genéticaRESUMO
Although cardiac involvement is rare in polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, the clinical course becomes considerably worse on complication with cardiac lesions. The increased release of various cytokines has been observed in the pathogenesis of POEMS syndrome, and serum vascular endothelial growth factor (VEGF) levels are known to be associated with the disease activity. We herein report a patient with POEMS syndrome who showed left ventricular systolic dysfunction and was treated with lenalidmide therapy. Of note, the reduction in extracellular edema in the left ventricular wall was clearly visualized by changes in the native T1 values and extracellular volumes on cardiac magnetic resonance imaging.
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Edema/diagnóstico por imagem , Edema/fisiopatologia , Síndrome POEMS/diagnóstico por imagem , Síndrome POEMS/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Citocinas/sangue , Dexametasona/uso terapêutico , Quimioterapia Combinada , Edema/etiologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lenalidomida/uso terapêutico , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Síndrome POEMS/sangue , Síndrome POEMS/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/sangue , Fatores de Crescimento do Endotélio Vascular/sangue , Disfunção Ventricular Esquerda/tratamento farmacológicoRESUMO
Renal congestion is caused by elevated central venous pressure (CVP), and decreases glomerular filtration in patients with congestive heart failure. Since real-time contrast-enhanced ultrasonography (CEUS) using microbubble-based contrast agents can visualize the perfused microvascular bed, we sought to evaluate the impairment of renal perfusion during acute renal congestion with CEUS. In Wister rats, CEUS of kidney was performed with the direct monitoring of CVP and intra-renal pressure (IRP). When CVP was elevated to 10 and 15 mmHg after the bolus injection of normal saline via the femoral vein, peak intensity (PI, dB) and time to PI (TTP) in the renal cortex and medulla were compared with control rats. There was a strong correlation between IRP and CVP (r = 0.95, p < 0.0001). In the congestion model, more time was required for enhancement of the parenchyma, especially in the medulla compared to control; TTP of the medulla and cortex at 15 mmHg CVP (CVP15) was significantly prolonged compared with controls (medulla, 4351 ± 98 vs. 1415 ± 267 ms, p = 0.003; cortex, 3219 ± 106 vs. 1335 ± 264 ms, p = 0.005). In addition, medullary PI at CVP15 decreased, but not significantly, compared to those of controls and at 10 mmHg CVP (20.1 ± 0.9, 22.8 ± 1.6, 21.6 ± 0.2 dB). In contrast, cortical PIs at CVP15 were significantly lower than that of control (24.6 ± 1.0 vs. 31.4 ± 1.0 dB, p = 0.007). CEUS revealed that impaired renal parenchymal flow in an acute congestion model is accompanied with increased renal interstitial pressure.
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Síndrome Cardiorrenal/diagnóstico , Pressão Venosa Central/fisiologia , Meios de Contraste/farmacologia , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/complicações , Ultrassonografia/métodos , Animais , Síndrome Cardiorrenal/etiologia , Síndrome Cardiorrenal/fisiopatologia , Modelos Animais de Doenças , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Rim/diagnóstico por imagem , Masculino , Ratos , Ratos WistarRESUMO
Sterigmatocystin is a genotoxic and hepatocarcinogenic mycotoxin that contaminates foods and environments worldwide. Sterigmatocystin is produced as a precursor to aflatoxin B1 or as an end product by certain Aspergilli. Aspergillus section Versicolores is one of the major sections including sterigmatocystin-producing species and is thus a potential health and environmental hazard. Recently, the taxonomy of this section was revised and classified into 14 species on the basis of molecular phylogenetic analysis. However, investigation of the distribution and sterigmatocystin production of each species has been limited; in particular, its distribution in foods has been scarcely reported. In this study, we collected isolates of Aspergillus section Versicolores from various foods and environments in Japan and investigated their distribution and sterigmatocystin production. The isolates were classified into nine species or species groups, which revealed that A. creber, A. puulaauensis/tennesseensis and A. sydowii are the main species/species groups in Japan. In addition, A. versicolor sensu stricto was detected with some frequency, specifically in foods. Furthermore, the two species A. creber and A. versicolor sensu stricto frequently produced sterigmatocystin. It is therefore important for food safety to intensively monitor these two species and distinguish them from other species, especially A. sydowii, which is not considered to produce sterigmatocystin.
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The association between obesity and inflammation is well documented in epidemiological studies. Proteolysis of extracellular matrix (ECM) proteins is involved in adipose tissue enlargement, and matrix metalloproteinases (MMPs) collectively cleave all ECM proteins. Here, we examined the effects of C-reactive protein (CRP), an inflammatory biomarker, on the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs), which are natural inhibitors of MMPs, in adipocyte-differentiated 3T3-L1 cells. We analyzed the expression of Fcγ receptor (FcγR) IIb and FcγRIII, which are candidates for CRP receptors, and the effects of anti-CD16/CD32 antibodies, which can act as FcγRII and FcγRIII blockers on CRP-induced alteration of MMP and TIMP expression. Moreover, we examined the effects of CRP on the activation of mitogen-activated protein kinase (MAPK) signaling, which is involved in MMP and TIMP expression, in the presence or absence of anti-CD16/CD32 antibodies. Stimulation with CRP increased MMP-1, MMP-3, MMP-9, MMP-11, MMP-14, and TIMP-1 expression but did not affect MMP-2, TIMP-2, and TIMP-4 expression; TIMP-3 expression was not detected. Adipocyte-differentiated 3T3-L1cells expressed FcγRIIb and FcγRIII; this expression was upregulated on stimulation with CRP. Anti-CD16/CD32 antibodies inhibited CRP-induced expression of MMPs, except MMP-11, and TIMP-1. CRP induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK but did not affect SAPK/JNK phosphorylation, and Anti-CD16/CD32 attenuated the CRP-induced phosphorylation of p38 MAPK, but not that of ERK1/2. These results suggest that CRP facilitates ECM turnover in adipose tissue by increasing the production of multiple MMPs and TIMP-1 in adipocytes. Moreover, FcγRIIb and FcγRIII are involved in the CRP-induced expression of MMPs and TIMP-1 and the CRP-induced phosphorylation of p38, whereas the FcγR-independent pathway may regulate the CRP-induced MMP-11 expression and the CRP-induced ERK1/2 phosphorylation.
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Proteína C-Reativa/genética , Inflamação/genética , Obesidade/genética , Receptores de IgG/genética , Células 3T3-L1 , Tecido Adiposo/crescimento & desenvolvimento , Tecido Adiposo/metabolismo , Animais , Diferenciação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Inflamação/patologia , Metaloproteinases da Matriz/classificação , Metaloproteinases da Matriz/genética , Camundongos , Obesidade/patologia , Inibidor Tecidual de Metaloproteinase-1/genéticaRESUMO
BACKGROUND/AIMS: No previous studies have explored the relationship between physical activity (PA) and executive dysfunction. METHODS: We retrospectively evaluated the PA for 590 older participants in the Kurihara Project; 221 participants had a Clinical Dementia Rating (CDR) of 0 (healthy), 295 CDR 0.5 (very mild dementia), and 74 CDR 1+ (dementia). RESULTS: In the complicated task, whether the motor intensity was high (e.g. farming) or low (e.g. shopping), PA exhibited an inverse relationship with the CDR level. By contrast, for simple tasks with high intensity (e.g. walking), no CDR group differences were noted. For PA with low intensity (e.g. cleaning), the CDR 1+ group exhibited decreased levels. CONCLUSION: PA was related to the burden of executive function in patients with mild cognitive impairment; however, in patients with dementia, PA was related to both the burden of executive function and motor intensity.
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With the approval of pegfilgrastim, the use of dose-dense epirubicin and cyclophosphamide (EC) for breast cancer has become acceptable in Japan. Thus, we aimed to evaluate its safety and tolerability in Japanese patients. Nine breast cancer patients with a high risk of preoperative or postoperative recurrence received EC therapy(epirubicin 90 mg/m(2) and cyclo- phosphamide 600 mg/m(2))for 4 cycles every 2 weeks in combination with a subcutaneous injection of pegfilgrastim (3.6 mg) on day 2 of each cycle. Treatment was discontinued in 1 and extended in 1 of the 9 patients, and the mean relative dose intensity(RDI)was good at 0.93. No serious adverse events were observed, indicating good tolerability. The regimen has potential for use in cases in which the treatment dose needs to be increased. grade 4 neutropenia was observed in all the 9 patients on day 8, with 6 patients developing febrile neutropenia. In Japan, data on changes in neutrophil count associated with pegfilgrastim administration under anthracycline-based chemotherapy are currently insufficient, and further study is required.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/cirurgia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Tolerância a Medicamentos , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Pessoa de Meia-Idade , Polietilenoglicóis , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversosRESUMO
Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medical amino acid widely used as an anti-inflammatory and a whitening agent. This study examined the effect of tranexamic acid administration in wrinkle formation following skin dryness. We administered tranexamic acid (750mg/kg/day) orally for 20 consecutive days to Naruto Research Institute Otsuka Atrichia (NOA) mice, which naturally develop skin dryness. In these NOA mice, deterioration of transepidermal water loss (TEWL), generation of wrinkles, decrease of collagen type I, and increases in mast cell proliferation and tryptase and matrix metalloproteinase (MMP-1) release were observed. However, these symptoms were improved by tranexamic acid treatment. Moreover, the increase in the ß-endorphin level in the blood and the expression of µ-opioid receptor on the surface of fibroblasts increased by tranexamic acid treatment. In addition, when the fibroblasts induced by tranexamic acid treatment were removed, the amelioration effect by tranexamic acid treatment was halved. On the other hand, tranexamic acid treated NOA mice and mast cell removal in tranexamic acid treated NOA mice did not result in changes in the wrinkle amelioration effect. Additionally, the amelioration effect of mast cell deficient NOA mice was half that of tranexamic acid treated NOA mice. These results indicate that tranexamic acid decreased the proliferation of mast cells and increases the proliferation of fibroblasts, subsequently improving wrinkles caused by skin dryness.
Assuntos
Envelhecimento da Pele/efeitos dos fármacos , Dermatopatias/tratamento farmacológico , Ácido Tranexâmico/uso terapêutico , Hormônio Adrenocorticotrópico/sangue , Aminoquinolinas/farmacologia , Animais , Anticorpos/farmacologia , Benzamidas/farmacologia , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cloroquina/farmacologia , Corticosterona/sangue , Imunoglobulina E/sangue , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Receptores Opioides mu/metabolismo , Dermatopatias/sangue , Fator de Células-Tronco/imunologia , Ácido Tranexâmico/farmacologia , Perda Insensível de Água/efeitos dos fármacos , beta-Endorfina/sangueRESUMO
Mouthparts of Leptotrombidium larvae (Acariformes: Trombiculidae), potential vectors of tsutsugamushi disease agents, were studied in detail using light microscopy, scanning electron microscopy, and transmission electron microscopy. The mouthparts incorporated within the pseudotagma gnathosoma are composed of the infracapitulum ventrally and the chelicerae dorsally. The ventral wall of the infracapitulum is formed by a wide mentum posteriorly and a narrowed malapophysis anteriorly. The malapophysis firmly envelops the distal cheliceral portions by its lateral walls. The lateral lips of the malapophysis are flexible structures hiding the cheliceral blades in inactive condition and turning back forming a type of temporary sucker closely applied to the host skin during feeding. The roof of the infracapitulum is formed by a weakly sclerotized labrum anteriorly and a cervix with the capitular apodemes extending posteriorly. The labral muscles are lacking. The capitular apodemes serve as origin for pharyngeal dilators running to the dorsal wall of the pharynx fused with the bottom of the infracapitulum. The basal cheliceral segments are separated from each other besides the very posterior portions where they are movably joined by the inner walls. The sigmoid pieces serve for insertion of the cheliceral elevators originating at the posterior portions of the basal segments. The movable digits reveal the solid basal sclerite and the cheliceral blade curved upward with a tricuspid cap on its tip. Dendrites of nerve cells run along the digits to their tips. The ganglia are placed within the basal segments just behind the movable digits. The chelicerae also reveal well developed flexible fixed digits overhanging the basal portions of the blades. The gnathosoma possesses several sets of extrinsic muscles originating at the scutum and at the soft cuticle behind it. Laterally, the gnathosoma bears five-segmented palps with a trifurcate palpal claw.
Assuntos
Boca/ultraestrutura , Trombiculidae/ultraestrutura , Animais , Feminino , Larva/fisiologia , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de TransmissãoRESUMO
We previously reported that the Montréal Cognitive Assessment (MoCA) was effective in the evaluation of cerebrovascular diseases. We also demonstrated that the test was effective for screening for very mild vascular dementia (VaD) in the community. Herein, we examined the effectiveness of MoCA in the assessment of patients with VaD in an outpatient clinic. Forty-four patients with VaD (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences [NINDS-AIREN] criteria) and 58 patients with Alzheimer's disease (AD) (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association [NINCDS-ADRDA] criteria) were compared with 67 non-demented control subjects. All were outpatients at the Tajiri Memory Clinic, Osaki-Tajiri, northern Japan. All underwent 1.5 Tesla MRI and ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) examinations. The SPECT images were used to classify the VaD patients into two subgroups, those with frontal hypoperfusion (F-VaD) and those without frontal hypoperfusion. The frontal hypoperfusion pattern was defined as the "P2" pattern of the Sliverman classification, with or without focal hypometabolism in other areas, based on the agreement of three neurologists who were blinded to the results of the neuropsychological examinations. Total scores and attention subscores on the MoCA were lower in the F-VaD group compared with other groups. Our results suggest that the MoCA attention subscale can detect VaD participants, particularly those with frontal hypoperfusion.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Cognição , Demência Vascular/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Estudos de Casos e Controles , Demência Vascular/diagnóstico , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND: Tranexamic acid has an inhibitory action on ultraviolet (UV) B-induced melanocyte activation. This study examined the sex differences in the inhibitory action of tranexamic acid on UVB-induced melanocyte activation. METHODS: We irradiated the eye and ear of male and female mice with UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp. We orally administered tranexamic acid (750 mg/kg/day) at 30 min before UVB exposure. RESULTS: Tranexamic acid inhibited the UVB-induced epidermal melanocyte activation, and the effect was more remarkable under UVB eye irradiation than under UVB ear irradiation. Furthermore, the melanocyte activity suppression effect was stronger in female mice than in male mice. Following the administration of tranexamic acid, the female displayed increased blood levels of ß-endorphin and µ-opioid receptor and estradiol receptor ß expression in comparison with the male. Furthermore, the effect of melanocyte activity suppression in the female mice was decreased by the administration of tamoxifen (antagonist of estrogen receptor) or naltrexone (antagonist of µ-opioid receptor). CONCLUSIONS: These results suggest that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and ß-endorphin play an important role in this sex difference.