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The recent implementation of attosecond and few-femtosecond X-ray pump/X-ray probe schemes in large-scale free-electron laser facilities has opened the way to visualize fast nuclear dynamics in molecules with unprecedented temporal and spatial resolution. Here, we present the results of theoretical calculations showing how polarization-averaged molecular-frame photoelectron angular distributions (PA-MFPADs) can be used to visualize the dynamics of hydrogen migration in methanol, ethanol, propanol, and isopropyl alcohol dications generated by X-ray irradiation of the corresponding neutral species. We show that changes in the PA-MFPADs with the pump-probe delay as a result of intramolecular photoelectron diffraction carry information on the dynamics of hydrogen migration in real space. Although visualization of this dynamics is more straightforward in the smaller systems, methanol and ethanol, one can still recognize the signature of that motion in propanol and isopropyl alcohol and assign a tentative path to it. A possible pathway for a corresponding experiment requires an angularly resolved detection of photoelectrons in coincidence with molecular fragment ions used to define a molecular frame of reference. Such studies have become, in principle, possible since the first XFELs with sufficiently high repetition rates have emerged. To further support our findings, we provide experimental evidence of H migration in ethanol-OD from ion-ion coincidence measurements performed with synchrotron radiation.
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The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2's Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu's surface age.
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Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3-4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibits lung fibrosis by direct administration into the lung by intranasal route. Pulmonary fibrosis was induced with bleomycin and RNA therapeutics was administered during both acute and chronic phases of the disease. The levels of periostin and transforming growth factor-ß1 in airway fluid and lung tissue, the deposition of collagen in lung tissue and the lung fibrosis score were significantly reduced in mice treated with siRNA and antisense against periostin compared to control mice. These findings suggest that direct administration of siRNA or antisense oligonucleotides against periostin into the lungs is a promising alternative therapeutic approach for the management of pulmonary fibrosis.
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Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/fisiología , Fibrosis Pulmonar/terapia , Administración Intranasal/métodos , Animales , Bleomicina/farmacología , Colágeno/análisis , Femenino , Fibroblastos/metabolismo , Fibrosis , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/terapia , Pulmón/metabolismo , Ratones , Ratones Endogámicos C57BL , Oligonucleótidos , Oligonucleótidos Antisentido/metabolismo , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/farmacología , Factor de Crecimiento Transformador beta/análisisRESUMEN
The aim of this study was to determine whether l-methyl-[11C]-methionine (MET) positron emission tomography (PET) allows the prediction of outcomes in patients with head and neck mucosal malignant melanoma treated with carbon ion radiation therapy (CIRT). This was a retrospective cohort study involving 85 patients who underwent a MET-PET or MET-PET/computed tomography (CT) examination before and after CIRT. MET uptake in the tumour was evaluated semi-quantitatively using the tumour-to-normal tissue ratio (TNR). Local recurrence, metastasis, and outcome predictions were studied in terms of TNR before CIRT (TNRpre), TNR after CIRT (TNRpost), and the TNR change ratio. Kaplan-Meier curves revealed significant differences between patients with higher TNRpre values and those with lower TNRpre values in regard to local recurrence, metastasis, and outcome (log-rank test P<0.0001 for all three). There were also significant differences in metastasis rates and outcomes between patients with higher and lower TNRpost values (log-rank test P=0.0105 and P=0.027, respectively). The Cox proportional hazards model revealed TNRpre to be a factor significantly influencing the risk of local recurrence (hazard ratio (HR) 29.0, P<0.001), risk of metastasis (HR 2.67, P=0.024), and the outcome (HR 6.3, P<0.001). MET-PET or MET-PET/CT is useful for predicting the outcomes of patients with head and neck mucosal malignant melanoma treated with CIRT.
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Neoplasias de Cabeza y Cuello/radioterapia , Radioterapia de Iones Pesados/métodos , Melanoma/radioterapia , Neoplasias Nasales/radioterapia , Tomografía de Emisión de Positrones , Adulto , Anciano , Anciano de 80 o más Años , Radioisótopos de Carbono , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Melanoma/patología , Metionina , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Nasales/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Pronóstico , Radiofármacos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Studies have revealed that patients who undergo preemptive kidney transplantation (PKT) have favorable prognoses compared with those who undergo kidney transplantation after the initiation of dialysis. The number of PKT cases performed worldwide has been increasing. The goal of this study was to determine the clinical characteristics of patients who may successfully receive PKT. METHODS: A single-center, case-control study was conducted to determine the clinical factors that lead to referral for PKT. RESULTS: Between April 1, 2009, and August 1, 2015, a total of 118 patients underwent living donor kidney transplantation. Thirty of these patients had not undergone dialysis before their initial visit to the study hospital. Of these, 20 received kidney transplantation before and after dialysis initiation, respectively (group PKT+, successful PKT; group PKT-, failed PKT). The baseline characteristics at the primary visit were compared between groups. The median duration from the first visit to the study institution to PKT was 5.6 ± 0.7 months. Serum creatinine (Cr) levels differed significantly between groups (PKT+ vs PKT-, 6.0 ± 0.3 mg/dL vs 7.5 ± 0.5 mg/dL; P = .03). The receiver-operating characteristic curves revealed that a serum Cr level >5.7 mg/dL at the initial visit to the unit was a cutoff point for predicting the success of PKT (area under the curve, 0.721; P = .02). CONCLUSIONS: Our results indicate that PKT should be performed within â¼6 months of the initial visit to the transplant center. Serum Cr levels <5.7 mg/dL predict successful PKT.
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Supervivencia de Injerto , Trasplante de Riñón , Adulto , Estudios de Casos y Controles , Creatinina/sangre , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Pronóstico , Diálisis RenalRESUMEN
Differential Scanning Calorimetry (DSC) and optical polarization microscopy of a mixture of the liquid crystalline material (N-(4-methoxybenzylidene)-4-butylaniline, MBBA) and a Fe-based room temperature ionic liquid 1-ethyl-3-methylimidazolium tetrachloroferrate ([Emim](+) [FeCl4](-), EMIF) indicate a decrease in the nematic-isotropic (N-I) phase transition temperature (T(NI)) with an increase in EMIF concentration, explained by a proposed model of Coulomb "screening" of MBBA quadrupoles by the EMIF ions along with ionic "self screening." DSC studies of EMIF-MBBA and pure EMIF and comparison with pure MBBA results show that the major transitions in pure EMIF have Arrhenius behaviour, but more importantly the previously found convex Arrhenius behaviour of the pristine MBBA [K. Dan et al., Europhys. Lett. 108, 36007 (2014)] becomes Arrhenius in the mixture, indicating a conversion of the entropic N-I activation barrier to an enthalpic one. In presence of EMIF, a drastic decrease in the intensity of out-of-plane distortions of benzene rings in MBBA is found from Fourier transform infrared spectroscopy, consistent with significant reduction in the conformational states of MBBA. This suppression of large amplitude motion is again consistent with a Coulomb screening and gives a molecular basis for the entropic-to-enthalpic conversion of the N-I activation barrier.
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BACKGROUND AND OBJECTIVE: Previous studies have shown that cigarette smoke (CS) and periodontal pathogens could alter wound healing responses of gingival epithelial cells. To elucidate molecular mechanisms leading to these epithelial changes, we studied the signaling pathway involved in the modulation of cell migration by CS condensate (CSC) and the infection by a prominent periodontal pathogen, Porphyromonas gingivalis. MATERIAL AND METHODS: Human gingival epithelial cells (Ca9-22) were treated with CSC or vehicle control for 24 h. Activation of mitogen-activated protein kinases (MAPK) in cells with or without infection by P. gingivalis was assessed by polymerase chain reaction array and immunoblotting using phospho-specific antibodies. Cell migration was assessed using in vitro wound closure model, and specific pharmacologic inhibitors of MAPK pathways were used to characterize further the extent of involvement of the MAPK pathways. RESULTS: Polymerase chain reaction array showed that gene expression of several members of the MAPK, particularly p38 and JNK, was upregulated more than twofold in Ca9-22 cells stimulated with 10 µg/mL CSC. Coincubation with P. gingivalis induced a different pattern of gene expression for MAPK pathways, but it did not suppress the MAPK-related genes upregulated by CSC. A significant phosphorylation of ERK1/2 and p38 was observed in cells stimulated with 10 µg/mL CSC (p < 0.05), whereas coincubation with a higher concentration of CSC (250 µg/mL) evoked no such activation. P. gingivalis infection resulted in a tendency to reduce the phosphorylation of ERK1/2 and p38, which had been enhanced by stimulation with 10 µg/mL CSC. Incubation with ERK1/2 and p38 inhibitors significantly reduced the wound closure of CSC-stimulated cells, by approximately 43% and 46%, respectively (p < 0.05). CONCLUSION: CSC exerts effects on the migration of human gingival epithelial cells through the activation of the MAPK ERK1/2 and p38 signaling pathways. P. gingivalis infection attenuates the CSC-induced migration at least partly by suppressing the phosphorylation of ERK1/2 and p38, but other pathways are likely to be involved in this modulatory process.
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Movimiento Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Encía/citología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/fisiología , Nicotiana , Porphyromonas gingivalis/fisiología , Humo , Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Línea Celular , Células Cultivadas , Células Epiteliales/microbiología , Células Epiteliales/fisiología , Regulación de la Expresión Génica , Encía/efectos de los fármacos , Encía/microbiología , Interacciones Huésped-Patógeno/fisiología , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/farmacología , Nicotina/efectos adversos , Fosforilación , Porphyromonas gingivalis/patogenicidad , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba , Cicatrización de Heridas , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Most catalytic micro/nanomotors that have been developed so far use hydrogen peroxide as fuel, while some use hydrazine. These fuels are difficult to apply because they can cause skin irritation, and often form and store disruptive bubbles. In this paper, we demonstrate a novel catalytic Pt micromotor that does not produce bubbles, and is driven by the oxidation of stable, non-toxic primary alcohols and aldehydes with dissolved oxygen. This use of organic oxidation mirrors living systems, and lends this new motor essentially the same characteristics, including decreased motility in low oxygen environments and the direct isothermal conversion of chemical energy into mechanical energy. Interestingly, the motility direction is reversed by replacing the reducing fuels with hydrogen peroxide. Therefore, these micromotors not only provide a novel system in nanotechnology, but also help in further revealing the underlining mechanisms of motility of living organisms.
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Peróxido de Hidrógeno/química , Nanotecnología , Oxígeno/química , Agua/químicaRESUMEN
Age-related macular degeneration (AMD) is a vision-threatening disease characterized by choroidal fibrovascular membrane (FVM) formation, choroidal neovascularization (CNV) and choroidal fibrosis. No safe and effective therapeutic method has been developed for the choroidal fibrosis, although anti-vascular endothelial growth factor therapy can partially shrink the CNV. We recently reported that periostin (POSTN), which is produced by retinal pigment epithelial cells, has an important role in the formation of preretinal FVMs, but its role in choroidal FVMs has not been determined. In this study, we used Postn knockout mice to investigate the role played by POSTN in choroidal FVM formation. In addition, we used a new class of RNA interference (RNAi) agent (NK0144) that targets POSTN and determined its effect on choroidal FVM development. Genetic ablation of Postn had an inhibitory effect not only on CNV formation but also on choroidal fibrosis in a mouse CNV model. NK0144 also had a greater inhibitory effect on both the CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between POSTN and choroidal FVM formation, and also a potential therapeutic role of intravitreal NK0144 for AMD.
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Moléculas de Adhesión Celular/genética , Neovascularización Coroidal/terapia , Degeneración Macular/terapia , Interferencia de ARN , Animales , Secuencia de Bases , Adhesión Celular , Moléculas de Adhesión Celular/metabolismo , Movimiento Celular , Proliferación Celular , Células Cultivadas , Coroides/irrigación sanguínea , Coroides/patología , Técnicas de Silenciamiento del Gen , Terapia Genética , Humanos , Inyecciones Intravítreas , Ratones Endogámicos C57BL , Ratones Noqueados , Datos de Secuencia Molecular , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/fisiología , Receptor Toll-Like 3/metabolismoRESUMEN
Previously, we have demonstrated that prostamide/PGF synthase, which catalyzes the reduction of prostaglandin (PG) H2 to PGF2α, is constitutively expressed in myelin sheaths and cultured oligodendrocytes, suggesting that PGF2α has functional significance in myelin-forming oligodendrocytes. To investigate the effects of PGF2α/FP receptor signaling on demyelination, we administrated FP receptor agonist and antagonist to cuprizone-exposed mice, a model of multiple sclerosis. Mice were fed a diet containing 0.2% cuprizone for 5 weeks, which induces severe demyelination, glial activation, proinflammatory cytokine expression, and motor dysfunction. Administration of the FP receptor antagonist AL-8810 attenuated cuprizone-induced demyelination, glial activation, and TNFα expression in the corpus callosum, and also improved the motor function. These data suggest that during cuprizone-induced demyelination, PGF2α/FP receptor signaling contributes to glial activation, neuroinflammation, and demyelination, resulting in motor dysfunction. Thus, FP receptor inhibition may be a useful symptomatic treatment in multiple sclerosis.
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Enfermedades Desmielinizantes/metabolismo , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/metabolismo , Receptores de Prostaglandina/metabolismo , Animales , Cuerpo Calloso/efectos de los fármacos , Cuerpo Calloso/metabolismo , Cuerpo Calloso/patología , Cuprizona/toxicidad , Enfermedades Desmielinizantes/patología , Dinoprost/administración & dosificación , Dinoprost/análogos & derivados , Modelos Animales de Enfermedad , Humanos , Ratones , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Esclerosis Múltiple/inducido químicamente , Esclerosis Múltiple/patología , Vaina de Mielina/metabolismo , Oligodendroglía/metabolismo , Prostaglandina H2/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
We recently reported that (11)C-methionine positron-emission tomography (PET) is clinically useful for the evaluation of the pancreatic function of the living donor. The objective of this study was to evaluate the postoperative insulin independence in 10 living donor (LD) and 10 brain-dead donor (BD) pancreas transplantations for 20 patients with type I diabetes mellitus by using (11)C-methionine PET. After 6 months, PET/computed tomography was performed 30 minutes after (11)C-methionine (370-740 MBq) injection. The uptake in the pancreas was expressed as the standardized uptake value (SUV). Patient survival rates were 100% at 5 years for LD transplantations and at 2 years for BD transplantations. Insulin independence was 60% for LD transplantations at 5 years and 75% for BD transplantations at 2 years. There were no major surgical complications such as vascular thrombosis, intra-abdominal abscess, and graft pancreatitis. The SUVs for LD and BD pancreas transplantations with insulin independence were 7.2 ± 1.8 and 10.4 ± 2.3, respectively. The SUVs for LD pancreas transplantations with insulin dependence and BD pancreas transplantations with graft failure were 3.6 ± 1.1 and 2.9 ± 1.0, respectively. At 5 years after transplantation, for the LD transplants, the insulin-independent rate was 100% for the graft recipients with an SUV higher than 5, and the median insulin independence duration of the graft recipients with an SUV less than 5 was 7 months (P < .01). The (11)C-methionine PET may be a potent modality to predict long-term insulin independence and the avoidance of pancreas graft failure.
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Diabetes Mellitus Tipo 1/cirugía , Trasplante de Páncreas , Páncreas/diagnóstico por imagen , Adulto , Muerte Encefálica , Péptido C/sangre , Radioisótopos de Carbono , Femenino , Hemoglobina Glucada/análisis , Humanos , Donadores Vivos , Masculino , Metionina , Páncreas/fisiología , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Cisplatin and other anticancer drugs are important in the treatment of head and neck squamous cell carcinoma; however, some tumours develop drug resistance. If chemoresistance could be determined before treatment, unnecessary drug administration would be avoided. Here, we investigated chemoresistance factors by comprehensive analyses at the protein level. METHODS: Four human carcinoma cell lines were used: cisplatin-sensitive UM-SCC-23, UM-SCC-23-CDDPR with acquired cisplatin resistance, naturally cisplatin-resistant UM-SCC-81B, and UM-SCC-23/WR with acquired 5-fluorouracil resistance. Extracted proteins were labelled with iTRAQ and analysed by tandem mass spectrometry to identify resistance. Protein expression was confirmed by western blotting and functional analysis was carried out using siRNA. RESULTS: Thirteen multiple-drug resistance proteins were identified, as well as seven proteins with specific resistance to cisplatin, including α-enolase. Differential expression of these proteins in cisplatin-resistant and -sensitive cell lines was confirmed by western blotting. Functional analysis for α-enolase by siRNA showed that cisplatin sensitivity significantly was increased in UM-SCC-81B and slightly in UM-SCC-23-CDDPR but not in UM-SCC-23/WR cells. CONCLUSIONS: We identified proteins thought to mediate anticancer drug resistance using recent proteome technology and identified α-enolase as a true cisplatin chemoresistance factor. Such proteins could be used as biomarkers for anticancer agent resistance and as targets of cancer therapy.
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Antineoplásicos/farmacología , Carcinoma de Células Escamosas/metabolismo , Cisplatino/farmacología , Resistencia a Antineoplásicos , Fluorouracilo/farmacología , Neoplasias de Cabeza y Cuello/metabolismo , Proteoma/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/metabolismo , ARN Interferente Pequeño/genética , Receptor Notch1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Coloración y Etiquetado , Espectrometría de Masas en TándemRESUMEN
BACKGROUND AND PURPOSE: Several studies have reported moyamoya syndrome associated with thyroid disease, and the mechanism involved in this relationship is unknown. This study aimed to clarify the involvement of thyroid antibodies and thyroid function in intracranial arterial stenosis. METHODS: The study included 30 patients <65 years of age with intracranial arterial steno-occlusion. Patients with definitive moyamoya disease were excluded. Thyroid function and thyroid antibody levels were evaluated. The steno-occlusive site and the presence of moyamoya vessels were evaluated using digital subtraction angiography. The characteristics of intracranial arterial lesions were compared between patients with and without elevated thyroid antibody levels, and between patients with increased thyroid function and those with normal thyroid function. RESULTS: Five patients had increased thyroid function and seven had elevated thyroid antibody levels. Four were diagnosed with Graves' disease, 13 with atherosclerotic intracranial stenosis, two with intracranial arterial dissection, one with vasculitis syndrome and 10 with intracranial stenosis of unknown cause. All patients with Graves' disease and patients with elevated antithyroid peroxidase antibody levels had steno-occlusion in the terminal portion of the internal carotid arteries, whereas most of the patients with normal thyroid function or without elevated thyroid antibody levels had stenosis in the middle cerebral arteries. CONCLUSIONS: In young and middle-aged patients, a lesion in the terminal portion of the internal carotid artery was associated with elevated thyroid antibody levels and increased thyroid function. Stenoses found in the terminal portion of the internal carotid artery and immune-mediated thyroid diseases may share a common background.
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Autoanticuerpos/sangre , Arteria Carótida Interna/patología , Estenosis Carotídea/inmunología , Enfermedad de Moyamoya/inmunología , Enfermedades de la Tiroides/inmunología , Adulto , Estenosis Carotídea/sangre , Estenosis Carotídea/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Moyamoya/sangre , Enfermedad de Moyamoya/patología , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/patologíaRESUMEN
BACKGROUND: We evaluated the efficacy and safety of superselective embolization with assistance of colonoscopy for acute colonic hemorrhage. METHODS: Of 92 cases of acute colonic hemorrhage requiring colonoscopic intervention, 11 (12 %) could not be successfully treated. Of these, 10 patients (9 men, mean age 65.5 years, range 39-75 years) underwent superselective embolization. Hemorrhage was caused by diverticular disease (n = 8), polypectomy (n = 1), and vascular malformation (n = 1). In all 10 cases, the radiopaque clips were placed at the bleeding point via colonoscopy. Microcatheters were used in all procedures, and embolization was performed at the level of the vasa recta leading to or near the clips with Gelfoam particles, microcoils, or both. RESULTS: Immediate hemostasis was achieved in all patients. In 6 of 10 patients (60 %), selective angiograms showed no active extravasation at the time of the procedure and the embolization was performed using clips as a landmark. In the remaining four patients, selective angiograms showed active extravasation from the vasa recta leading to the clips. The mean number of embolized vessels with no active extravasation and with active extravasation was 1.83 (range 1-3) and 1.25 (range 1-2), respectively. The mean duration of clinical follow-up was 11.6 months (range 1-29 months). One patient (10 %) bled from a different site than the treated site a month after embolization, but the bleeding ceased after endoscopic intervention. All the patients (100 %) were evaluated for objective evidence of ischemia by colonoscopy. Four of the 10 patients (40 %) were found endoscopically to have small areas of ischemia involving only the mucosa, but they remained asymptomatic. There was no bowel infarction or stricture. CONCLUSIONS: Colonoscopy-assisted superselective embolization may be a safe and useful procedure for acute colonic hemorrhage without active extravasation on angiogram.
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Enfermedades del Colon/terapia , Colonoscopía/métodos , Embolización Terapéutica/métodos , Hemorragia Gastrointestinal/terapia , Enfermedad Aguda , Adulto , Angiografía/métodos , Estudios de Cohortes , Colectomía/métodos , Enfermedades del Colon/diagnóstico por imagen , Enfermedades del Colon/mortalidad , Femenino , Estudios de Seguimiento , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/mortalidad , Humanos , Japón , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Leucemia Mielomonocítica Juvenil/tratamiento farmacológico , Leucemia Mielomonocítica Juvenil/genética , Mercaptopurina/farmacología , Mercaptopurina/uso terapéutico , Mutación , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Preescolar , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Lactante , Leucemia Mielomonocítica Juvenil/metabolismo , Masculino , Transducción de Señal , Resultado del TratamientoRESUMEN
INTRODUCTION: Micafungin (MCFG) is used for the prophylaxis of invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, the safety, efficacy, or optimal dosage/blood levels as prophylaxis is uncertain in pediatric HSCT-patients. METHODS: We prophylactically administered MCFG at 2 mg/kg once daily to 38 children and adolescents undergoing allogeneic HSCT. RESULTS: During MCFG prophylaxis, infusion reactions or adverse events (grades 2-5) related to MCFG use were not found in all the patients. Thus, MCFG prophylaxis was not discontinued and other antifungal agents were not added except for 2 patients in whom probable or possible IFDs developed (completion rate, 94.7 %). To elucidate the influence of HSCT-related complications/drugs on blood concentration of MCFG, we determined the plasma trough and peak levels in 13 and 10 among 38 patients, respectively. The mean trough and peak levels were 3.04 ± 1.21 µg/mL (569 samples) and 9.63 ± 3.62 µg/mL (44 samples), respectively. The peak levels were moderately correlated to the trough levels (R (2) = 0.466). In a patient, the trough level of MCFG transiently increased up to 10.21 µg/mL during hepatic dysfunction due to acute graft-versus-host disease. The MCFG trough levels strongly correlated with T-Bil value (R (2) = 0.894). There was no relationship between the trough levels of MCFG and the circulating concentrations of tacrolimus (R (2) = 0.040). Additionally, MCFG levels were not influenced by treatment with cyclophosphamide or corticosteroids. CONCLUSIONS: Prophylaxis with MCFG at 2 mg/kg once daily may be safe, tolerable, and feasible in pediatric HSCT-patients.
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Antifúngicos/administración & dosificación , Quimioprevención/métodos , Equinocandinas/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Lipopéptidos/administración & dosificación , Micosis/prevención & control , Adolescente , Antifúngicos/efectos adversos , Antifúngicos/farmacocinética , Quimioprevención/efectos adversos , Niño , Preescolar , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Equinocandinas/efectos adversos , Equinocandinas/farmacocinética , Femenino , Humanos , Lactante , Lipopéptidos/efectos adversos , Lipopéptidos/farmacocinética , Masculino , Micafungina , Plasma/químicaRESUMEN
Chemical communication is widely used among various organisms to obtain essential information from their environment required for life. Although a large variety of molecules have been shown to act as chemical cues, the molecular and neural basis underlying the behaviors elicited by these molecules has been revealed for only a limited number of molecules. Here, we review the current knowledge regarding the signaling molecules whose flow from receptor to specific behavior has been characterized. Discussing the molecules utilized by mice, insects, and the worm, we focus on how each organism has optimized its reception system to suit its living style. We also highlight how the production of these signaling molecules is regulated, an area in which considerable progress has been recently made.
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Células Quimiorreceptoras/fisiología , Nervio Olfatorio/fisiología , Vías Olfatorias/fisiología , Transducción de Señal/fisiología , Olfato/fisiología , Animales , Humanos , Órgano Vomeronasal/fisiologíaRESUMEN
In general, bio-macromolecules are composed of hydrophilic and hydrophobic moieties and are confined within small cavities, such as cell membranes and intracellular organelles. Here, we studied the self-organization of macromolecules having groups with different affinities to solvents under spherical nano-scale confinement by means of computer modeling. It is shown that depending on the interaction parameters of monomer units composed of side- and main-chain monomer groups along a single linear macromolecule and on cavity size, such amphiphilic polymers undergo the conformational transitions between hollow nanospheres, rod-like and folded cylindrical structures, and a necklace conformation with and without a particular ordering of beads. The diagram of the conformations in the variables the incompatibility parameter of monomer units and the cavity radius is constructed.
Asunto(s)
Interacciones Hidrofóbicas e Hidrofílicas , Sustancias Macromoleculares/química , Nanopartículas/química , Modelos Moleculares , Conformación Molecular , TermodinámicaRESUMEN
Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at <37-week gestational age, including 10 small for gestational age (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P < 0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P < 0.001), and negatively with log TG (r = -0.484, P = 0.002) and log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level.