RESUMO
A rhizomatous Dioscorea crop 'Edo-dokoro' was described in old records of Japan, but its botanical identity has not been characterized. We found that Edo-dokoro is still produced by four farmers in Tohoku-machi of the Aomori prefecture, Japan. The rhizomes of Edo-dokoro are a delicacy to the local people and are sold in the markets. Morphological characters of Edo-dokoro suggest its hybrid origin between the two species, Dioscorea tokoro and Dioscorea tenuipes. Genome analysis revealed that Edo-dokoro likely originated by hybridization of a male D. tokoro to a female D. tenuipes, followed by a backcross with a male plant of D. tokoro. Edo-dokoro is a typical minor crop possibly maintained for more than 300 years but now almost forgotten by the public. We hypothesize that there are many such uncharacterized genetic heritages passed over generations by small-scale farmers that await serious scientific investigation for future use and improvement by using modern genomics information.
Assuntos
Dioscorea , Dioscorea/genética , Genoma de Planta/genética , Genômica , Hibridização Genética , Plantas/genéticaRESUMO
Metabolomics of human biological fluids or tissues is used to discover markers for diseases by comparing the metabolome of the patients against healthy individuals. Ultimately, these markers can be used in drug discovery to determine how medications normalize (at least in part) the human metabolome at specific disease stages to homeostatic. Likewise, the health effects of food can be studied. Even metabolomics of the food can be combined with metabolomics of the treated patients to correlate compounds from food with measurable health effects from clinical studies. Various chemometric analyses of these metabolomics data are used to identify markers for diseases and to obtain evidence for health effects. This review discusses recent researches (published from 2013 to 2021) on whether specific dietary intervention to humans suffering from metabolic disorders may improve their pathological status. The scope is limited to those associated with major lifestyle diseases such as diabetes, obesity, and cardiovascular diseases, for which food is thought may have detrimental as well as beneficial effects on human health. It includes metabolites characterization of different biological samples such as the human serum/plasma, urine, saliva, feces, or ileal fluid. Whether the study results supported the claimed health benefits and whether the research was conducted with appropriate study design, was criticized.
Assuntos
Líquidos Corporais , Metabolômica , Biomarcadores/metabolismo , Líquidos Corporais/metabolismo , Alimentos , Humanos , Metaboloma , Metabolômica/métodosRESUMO
Because ceramide-like lipo-amino acid cholesteryl derivatives can exert a bound water-holding function due to their lamellae-forming properties, in this study, we determined if topical application of those derivatives to atopic dry skin would elicit an ameliorative effect on skin symptoms, at least on its water-holding function. In this clinical study, daily treatment with a nano-emulsion containing 10% phytosteryl/octyldodecyl lauroyl glutamate (POLG) significantly (p < 0.0001) improved skin symptoms, including dryness/scaling, itchiness and stimulus sensations, in the non-lesional skin of patients with atopic dermatitis (AD) at 3 and at 6 weeks compared with week 0. Those significant improvements in skin symptoms were accompanied by a significantly enhanced water content (conductance) and a significant improvement of roughness (SESC) and smoothness (SESM) values measured using a Visioscan at 3 and 6 weeks. Those effects appeared concomitant with a significantly increased corneocyte size, a significantly down-regulated degree of thick abrasions, and a significant impairment of the corneocyte lipid envelope at 6 weeks. Thus, our clinical study suggests, for the first time, that topical application of the POLG nano-emulsion has the distinct potential to ameliorate atopic dry skin symptoms, particularly scaling and itchiness, in the skin of patients with AD. Those effects result from alleviation of the disrupted water-holding function probably due to the increased supply of lamellae structures into the stratum corneum despite the failure to improve barrier function.
Assuntos
Dermatite Atópica , Dermatopatias , Humanos , Dermatite Atópica/etiologia , Ceramidas/metabolismo , Água/metabolismo , Epiderme/metabolismo , Pele/metabolismo , Dermatopatias/metabolismo , Emulsões/metabolismo , Compostos Orgânicos/metabolismo , Aminoácidos/metabolismoRESUMO
BACKGROUND: Clinical evidence is required about the long-term efficacy and safety of melatonin treatment for sleep problems in children with neurodevelopmental disorders (NDDs) who underwent adequate sleep hygiene interventions. METHODS: We conducted a 26-week, multicenter, collaborative, uncontrolled, open-label, phase III clinical trial of melatonin granules in children 6 to 15 years of age who had NDDs and sleep problems. The study consisted of the 2-week screening phase, the 26-week medication phases I and II, and the 2-week follow-up phase. Children received 1, 2, or 4 mg melatonin granules orally in the medication phases. Variables of sleep status including sleep onset latency (SOL), aberrant behaviors listed on the Aberrant Behavior Check List-Japanese version (ABC-J), and safety were examined. The primary endpoint was SOL in the medication phase I. RESULTS: Between June 2016 and July 2018, 99 children (80 males and 19 females, 10.4 years in mean age) were enrolled at 17 medical institutions in Japan-74, 60, 22, 9, 6, and 1 of whom had autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disabilities, motor disorders, specific learning disorder, and communication disorders, respectively, at baseline. Fifteen children received the maximal dose of 4 mg among the prespecified dose levels. SOL recorded with the electronic sleep diary shortened significantly (mean ± standard deviation [SD], - 36.7 ± 46.1 min; 95% confidence interval [CI], - 45.9 to - 27.5; P < 0.0001) in the medication phase I from baseline, and the SOL-shortening effect of melatonin persisted in the medication phase II and the follow-up phase. Temper upon wakening and sleepiness after awakening improved significantly (P < 0.0001 each) in the medication phase I from baseline and persisted in the follow-up phase. The following subscales of the ABC-J improved significantly: stereotypic behavior (P = 0.0322) in the medication phase I; and irritability, hyperactivity, and inappropriate speech (P < 0.0001) in the medication phase II. Treatment-emergent adverse events did not occur subsequent to week 16 after medication onset, and NDDs did not deteriorate in the follow-up phase. CONCLUSIONS: Long-term melatonin treatment in combination with adequate sleep hygiene interventions may afford clinical benefits to children with NDDs and potentially elevates their well-being. TRIAL REGISTRATION: ClinicalTrils.gov , NCT02757066 . Registered April 27, 2016.
Assuntos
Transtorno do Espectro Autista , Melatonina , Transtornos do Neurodesenvolvimento , Transtornos do Sono-Vigília , Adolescente , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/tratamento farmacológico , Criança , Feminino , Humanos , Japão , Masculino , Melatonina/uso terapêutico , Transtornos do Neurodesenvolvimento/complicações , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Sono , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/tratamento farmacológicoRESUMO
Our previous study revealed that gamma-aminobutyric acid (GABA) in Earl's muskmelon is more concentrated in the inner than the outer parts of the fruit. Here, the GABA and antioxidant capacity of the placental tissue of muskmelon, which is considered waste, were evaluated for possible use as a source of bioactive compounds. The concentrations of GABA and related substances in the placental tissue were significantly higher than in the fleshed pulp, whereas glutamic acid and sugar levels were significantly lower. The two sites showed no difference in GAD activity. Furthermore, the placental site showed high antioxidant capacities based on 2,2-diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity for hydrophilic compounds assays compared with the fleshed pulp, because of the higher levels of total phenolic and L-ascorbic acids. Therefore, the placental tissue of muskmelons may be useful for developing functional foods, which would also reduce the amount of residues during muskmelon processing.
Assuntos
Antioxidantes/análise , Cucumis melo/química , Frutas/química , Ácido gama-Aminobutírico/análise , Antioxidantes/química , Ácido Ascórbico/análise , Glutamato Descarboxilase/análise , Glutamato Descarboxilase/química , Ácido Glutâmico/análise , Hidroxibenzoatos/análise , Açúcares/análise , Ácido gama-Aminobutírico/químicaRESUMO
Objectives. Although deuterium oxide (D2O) has preservative property on the extracted organ, whether D2O also protects the in situ myocardial injury remains unknown. Using cardiac microdialysis, local administration of D2O through dialysis probe was applied in situ rat heart. We examined the effect of the D2O on the myocardial injury induced ischemia, reperfusion, and chemical hypoxia. Methodology. We measured dialysate myoglobin levels during 30 min of coronary occlusion and reperfusion in the absence and presence of D2O. Furthermore, to confirm the effect of D2O on NaCN induced myocardial injury, we measured the dialysate myoglobin levels with local perfusion of NaCN in the absence and presence of D2O. Results. The dialysate myoglobin levels increased from 177 ± 45 ng/mL at baseline to 3030 ± 1523 ng/mL during 15-30 min of coronary occlusion and further increased to 8588 ± 1684ng/mL at 0-15 min of reperfusion. The dialysate myoglobin levels with 60 min local perfusion of NaCN increased to 1214 ± 279 ng/mL. D2O attenuated myocardial myoglobin release during 15-30 min of coronary occlusion and 0-30 min of reperfusion and 15-60 min of local perfusion of NaCN. Conclusions. D2O might have a beneficial effect of myocardium against ischemia, reperfusion and chemical hypoxia.
Assuntos
Óxido de Deutério/farmacologia , Cardiopatias/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Animais , Modelos Animais de Doenças , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Mioglobina/metabolismo , Ratos Sprague-Dawley , Cianeto de Sódio , Fatores de TempoRESUMO
PURPOSE: To determine whether the presence of intact cumulus cells during the preincubation period for ICSI should be considered as a critical factor in fertilization and embryonic development. METHODS: The cohort of this prospective randomized study was limited to infertile women younger than 39 years of age who underwent controlled ovarian stimulation for ICSI between October 2013 and May 2015 and whose embryos were to be incubated until day 5. Women with estradiol levels of <2000 pmol/L on the day of HCG injection were excluded. Cumulus cells were removed immediately after OPU in Group A and at 120 minutes after OPU in Group B. ICSI was performed with all mature oocytes, and fertilized oocytes were cultured to the blastocyst stage. Maturation, fertilization, blastocyst, good quality blastocyst, pregnancy, live birth, and miscarriage rates were compared. RESULTS: There were no significant differences in maturation, fertilization, blastocyst, pregnancy, live birth, or miscarriage rates between Groups A and B. However, the percentage of good quality blastocysts was significantly higher in Group B than Group A (52.0% vs 33.1%). CONCLUSIONS: Intact cumulus cells should be maintained during the preincubation period, as they are important to embryonic development after fertilization.
RESUMO
Preferential attention to living creatures is believed to be an intrinsic capacity of the visual system of several species, with perception of biological motion often studied and, in humans, it correlates with social cognitive performance. Although domestic dogs are exceptionally attentive to human social cues, it is unknown whether their sociability is associated with sensitivity to conspecific and heterospecific biological motion cues of different social relevance. We recorded video clips of point-light displays depicting a human or dog walking in either frontal or lateral view. In a preferential looking paradigm, dogs spontaneously viewed 16 paired point-light displays showing combinations of normal/inverted (control condition), human/dog and frontal/lateral views. Overall, dogs looked significantly longer at frontal human point-light display versus the inverted control, probably due to its clearer social/biological relevance. Dogs' sociability, assessed through owner-completed questionnaires, further revealed that low-sociability dogs preferred the lateral point-light display view, whereas high-sociability dogs preferred the frontal view. Clearly, dogs can recognize biological motion, but their preference is influenced by their sociability and the stimulus salience, implying biological motion perception may reflect aspects of dogs' social cognition.
Assuntos
Comportamento Animal , Cães/fisiologia , Percepção de Movimento , Personalidade , Animais , Atenção , Feminino , Humanos , Masculino , Comportamento Social , CaminhadaRESUMO
The mechanisms regulating the maintenance of quiescent adult stem cells in teeth remain to be fully elucidated. Our aim is to clarify the relationship between BrdU label-retaining cells (LRCs) and sonic hedgehog (Shh) signaling in murine teeth. After prenatal BrdU labeling, mouse pups were analyzed during postnatal day 1 (P1) to week 5 (P5W). Paraffin sections were processed for immunohistochemistry for BrdU, Sox2, Gli1, Shh, Patched1 (Ptch1) and Ki67 and for in situ hybridization for Shh and Ptch1. Dense LRCs, Gli1-(+) cells and Ptch1-(+) cells were co-localized in the outer enamel epithelium of the apical bud and apical dental papilla of incisors. In developing molars, dense LRCs were numerous at P1 but then decreased in number over the course of odontogenesis and were maintained in the center of pulp tissue. Gli1-(+) cells were maintained in the pulp horn during the examined stages, while they increased in number and were maintained in the center of pulp tissue during P2-5W. Ptch1-(+) cells were localized in the pulp horn at P1 and increased in number in the center of the pulp after P3W. Shh mRNA was first expressed in the enamel epithelium and then shifted to odontoblasts and other pulp cells. Shh protein was distributed in the epithelial and mesenchymal tissues of incisors and molars. These findings suggest that quiescent dental stem cells are regulated by Shh signaling, and that Shh signaling plays a crucial role in the differentiation and integrity of odontoblasts during epithelial-mesenchymal interactions and dentinogenesis.
Assuntos
Células-Tronco Adultas/citologia , Células-Tronco Adultas/metabolismo , Ciclo Celular , Proteínas Hedgehog/metabolismo , Dente/citologia , Animais , Animais Recém-Nascidos , Bromodesoxiuridina/metabolismo , Feminino , Proteínas Hedgehog/genética , Antígeno Ki-67/metabolismo , Camundongos Endogâmicos ICR , Mucosa Bucal/metabolismo , Receptor Patched-1/genética , Receptor Patched-1/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Dente/crescimento & desenvolvimento , Proteína GLI1 em Dedos de Zinco/metabolismoRESUMO
This study aimed to characterize the inactivation kinetics of cytochrome P450 3A4 (CYP3A4) by erythromycin, which involves mechanism-based inhibition (MBI), in detail. In addition to an MBI assay based on the conventional method in which erythromycin and recombinant CYP3A4 were pre-incubated for 15 min, the study also evaluated the long-term MBI kinetics of this reaction by pre-incubation for 120 min. Mechanism-based inhibition profiles were obtained using three typical substrates, testosterone, midazolam and nifedipine. In the long-term assay, erythromycin evoked a time-dependent biphasic reduction in enzyme activity, but some residual activity (α) was detected in the terminal phase. The inactivation rate constant obtained in the presence of 30 µm erythromycin using nifedipine as a substrate was 1.44-fold higher than that acquired using testosterone, while there was no difference among the α values obtained with the three substrates. In the short-term assay, time-dependent monophasic inactivation was observed. To extrapolate these data to in vivo, the extent of the increase in the area under the curve (AUC ratio) induced by erythromycin was estimated from the results of the conventional short-term experiment and the long-term experiment examining residual activity. The AUC ratio estimated from the long-term kinetics (2.92) was closer to the clinically reported values (3.3-4.42). In conclusion, the relatively long-term evaluation of the kinetics of CYP3A4 inactivation revealed that the enzyme was not fully inactivated by erythromycin. To improve the estimation of the extent of the drug-drug interactions induced by MBI from in vitro data, longer-term investigations of the target enzyme's inactivation profile might be necessary.
Assuntos
Antibacterianos/farmacologia , Inibidores do Citocromo P-450 CYP3A/farmacologia , Citocromo P-450 CYP3A/metabolismo , Eritromicina/farmacologia , Citocromo P-450 CYP3A/genética , Interações Medicamentosas , Cinética , Midazolam/metabolismo , Nifedipino/metabolismo , Testosterona/metabolismoRESUMO
Two cultivars of Japanese parsley were harvested in different seasons; their antioxidant capacities were evaluated by oxygen radical absorbance capacity (ORAC) methods, and the contents of hydrophilic and lipophilic antioxidants were compared. Japanese parsley possessed potent antioxidant capacities both in hydrophilic and lipophilic extracts when evaluated by ORAC methods. LC/MS/MS analyses revealed that chlorogenic acid and four kinds of quercetin glycosides were major antioxidants in the hydrophilic extract. Lutein was the main contributor to the antioxidant capacity of the lipophilic extract. Antioxidant capacities of the hydrophilic extracts of both cultivars tended to be higher in winter because of the increase in the contents of chlorogenic acid and quercetin glycosides. An obvious trend in the lipophilic antioxidant capacities or lutein contents was not observed irrespective of the cultivar.
Assuntos
Antioxidantes/análise , Ácido Clorogênico/análise , Glicosídeos/análise , Luteína/análise , Oenanthe/química , Componentes Aéreos da Planta/química , Quercetina/análise , Antioxidantes/química , Antioxidantes/isolamento & purificação , Ácido Clorogênico/química , Ácido Clorogênico/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Sequestradores de Radicais Livres/análise , Sequestradores de Radicais Livres/química , Glicosídeos/química , Glicosídeos/isolamento & purificação , Interações Hidrofóbicas e Hidrofílicas , Japão , Luteína/química , Luteína/isolamento & purificação , Oenanthe/crescimento & desenvolvimento , Quercetina/química , Quercetina/isolamento & purificação , Estações do Ano , Solventes/química , Especificidade da Espécie , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , alfa-Tocoferol/análise , alfa-Tocoferol/química , alfa-Tocoferol/isolamento & purificação , gama-Tocoferol/análise , gama-Tocoferol/química , gama-Tocoferol/isolamento & purificaçãoRESUMO
BACKGROUND: Epidemiologic studies have shown that the consumption of whole grains can reduce the risk of type 2 diabetes mellitus, cardiovascular disease, and all-cause mortality. However, the underlying mechanisms remain a matter of debate. OBJECTIVE: We aimed to determine the effects of wheat bran-derived alkylresorcinols on diet-induced metabolic disorders in mice. METHODS: We fed C57BL/6J mice a normal refined diet or a high-fat, high-sucrose diet [29.1% fat, 20.7% protein, 34.0% carbohydrates containing 20.0% sucrose (w/w)] alone (FS) or containing 0.4% (wt:wt) alkylresorcinols (FS-AR) for 10 wk. RESULTS: The alkylresorcinols suppressed FS-induced increases in body weight by 31.0% as well as FS-induced hepatic triglyceride accumulation (means ± SEMs: 29.6 ± 3.18 and 19.8 ± 2.42 mg/g tissue in the FS and FS-AR groups, respectively), without affecting energy intake. We measured circadian changes in blood metabolic hormones and found that FS-induced hyperinsulinemia (5.1 and 2.1 µg/L at night in the FS and FS-AR groups, respectively) and hyperleptinemia (21.6 and 10.8 µg/L at night in the FS and FS-AR groups, respectively) were suppressed by alkylresorcinols. Glucose and insulin tolerance tests showed that alkylresorcinols significantly reduced fasting blood glucose concentrations (190 ± 3.62 and 160 ± 8.98 mg/dL in the FS and FS-AR groups, respectively) and suppressed glucose intolerance as well as insulin resistance induced by the FS diet. Furthermore, alkylresorcinols significantly increased insulin-stimulated hepatic serine/threonine protein kinase B phosphorylation compared to the FS diet (+81.3% and +57.4% for Ser473 and Thr308, respectively). On the other hand, pyruvate and starch tolerance tests suggested that alkylresorcinols did not affect gluconeogenesis and carbohydrate digestion, respectively. Alkylresorcinols significantly increased fecal cholesterol excretion by 39.6% and reduced blood cholesterol concentrations by 30.4%, while upregulating the expression of hepatic cholesterol synthetic genes such as sterol regulatory element binding protein 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1). CONCLUSIONS: These findings suggest that wheat alkylresorcinols increase glucose tolerance and insulin sensitivity by suppressing hepatic lipid accumulation and intestinal cholesterol absorption, which subsequently suppresses diet-induced obesity in mice.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/tratamento farmacológico , Obesidade/tratamento farmacológico , Resorcinóis/farmacologia , Sacarose/administração & dosagem , Triticum/química , Animais , Glicemia/metabolismo , Colesterol/sangue , Carboidratos da Dieta/administração & dosagem , Fibras na Dieta/farmacologia , Ingestão de Energia , Fezes/química , Hiperinsulinismo/tratamento farmacológico , Insulina/sangue , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triglicerídeos/sangueRESUMO
Procyanidins, which are flavonoids that are found in a variety of plant species, reduce or prevent immune disorders, such as allergy and autoimmune diseases, through an unknown mechanism. In the present study, we investigated the effects of procyanidins on the T cell receptor (TCR)-mediated responses of CD4⺠T cells in vitro. Apple procyanidins strongly suppressed the proliferation of splenic CD4⺠T cells that were stimulated by an anti-CD3ε antibody, as well as splenocytes stimulated by antigen, but did not alter interleukin (IL)-2 secretion from these cells. Furthermore, we found that oligomeric procyanidins strongly suppressed, in a degree of polymerization dependent manner, the proliferation of activated CD4⺠T cells, as well as their production of effector cytokines, including glycolysis associated-cytokines, without affecting IL-2 secretion. Additionally, we investigated the inhibitory effects of oligomeric procyanidins on the glycolytic activity of activated CD4⺠T cells. We show that pentameric procyanidin suppressed L-lactate production and glucose uptake in activated CD4⺠T cells. These results suggest that oligomeric procyanidins suppress the functions of activated CD4⺠T cells by interfering with glycolysis.
Assuntos
Antioxidantes/farmacologia , Biflavonoides/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Catequina/farmacologia , Glicólise/efeitos dos fármacos , Malus/química , Proantocianidinas/farmacologia , Animais , Antioxidantes/química , Biflavonoides/química , Linfócitos T CD4-Positivos/citologia , Catequina/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Interleucina-2/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Proantocianidinas/química , Receptores de Antígenos de Linfócitos T , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologiaRESUMO
Acute zoster-associated pain develops in most patients with herpes zoster. Nonopioid analgesics are usually used to treat acute zoster-associated pain but are frequently ineffective. We administered intravenous fosphenytoin, the prodrug of phenytoin, to patients with acute zoster-associated pain to examine its analgesic efficacy and safety. At 13 medical institutions in Japan, we conducted a phase II, double-blind, placebo-controlled, randomized trial of intravenous fosphenytoin in Japanese inpatients with acute zoster-associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect. The patients were randomly assigned (1:1:1) to receive a single intravenous dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or placebo. The primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min after dosing. Seventeen patients were randomly assigned to the low-dose fosphenytoin group (n = 6, median age 62.5 years, range 39-75 years), high-dose fosphenytoin group (n = 5, median age 69.0 years, range 22-75 years), and placebo group (n = 5, median age 52.0 years, range 38-72 years). One patient was excluded because of investigational drug dilution failure. This study was discontinued because of the influences of coronavirus disease 2019. The slope was significantly lower in the high- and low-dose fosphenytoin groups than in the placebo group (P < 0.001 and P = 0.016, respectively). Responsiveness to intravenous fosphenytoin (≥2-point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10-15 µg/mL. Treatment-emergent adverse events caused no safety concerns in the clinical setting and intravenous fosphenytoin was well tolerated. Intravenous fosphenytoin appears to be an effective and promising alternative treatment for acute zoster-associated pain. Trial Registration: ClinicalTrials.gov NCT04139330.
Assuntos
Herpes Zoster , Dor , Fenitoína , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Analgésicos , Analgésicos não Narcóticos/farmacologia , Método Duplo-Cego , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3 , Dor/tratamento farmacológico , Dor/etiologia , Fenitoína/efeitos adversosRESUMO
We improved the procedure for lipophilic-oxygen radical absorbance capacity (L-ORAC) measurement for better repeatability and intermediate precision. A sealing film was placed on the assay plate, and glass vials and microdispensers equipped with glass capillaries were used. The antioxidant capacities of food extracts can be evaluated by this method with nearly the same precision as antioxidant solutions.
Assuntos
Sequestradores de Radicais Livres/química , Interações Hidrofóbicas e Hidrofílicas , Laboratórios , Espectrometria de Fluorescência/métodos , Radicais Livres/química , Reprodutibilidade dos TestesRESUMO
LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) is an endothelial scavenger receptor that is important for the uptake of OxLDL (oxidized low-density lipoprotein) and contributes to the pathogenesis of atherosclerosis. However, the precise structural motifs of OxLDL that are recognized by LOX-1 are unknown. In the present study, we have identified products of lipid peroxidation of OxLDL that serve as ligands for LOX-1. We used CHO (Chinese-hamster ovary) cells that stably express LOX-1 to evaluate the ability of BSA modified by lipid peroxidation to compete with AcLDL (acetylated low-density lipoprotein). We found that HNE (4-hydroxy-2-nonenal)-modified proteins most potently inhibited the uptake of AcLDL. On the basis of the findings that HNE-modified BSA and oxidation of LDL resulted in the formation of HNE-histidine Michael adducts, we examined whether the HNE-histidine adducts could serve as ligands for LOX-1. The authentic HNE-histidine adduct inhibited the uptake of AcLDL in a dose-dependent manner. Furthermore, we found the interaction of LOX-1 with the HNE-histidine adduct to have a dissociation constant of 1.22×10(-8) M using a surface plasmon resonance assay. Finally, we showed that the HNE-histidine adduct stimulated the formation of reactive oxygen species and activated extracellular-signal-regulated kinase 1/2 and NF-κB (nuclear factor κB) in HAECs (human aortic endothelial cells); these signals initiate endothelial dysfunction and lead to atherosclerosis. The present study provides intriguing insights into the molecular details of LOX-1 recognition of OxLDL.
Assuntos
Aldeídos/metabolismo , Histidina/análogos & derivados , Receptores Depuradores Classe E/metabolismo , Aldeídos/farmacologia , Animais , Aorta/metabolismo , Células CHO , Cricetinae , Endotélio Vascular/citologia , Histidina/metabolismo , Histidina/farmacologia , Humanos , Ligantes , Lipoproteínas LDL/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) inhalation may alleviate pulmonary inflammation caused by viral pneumonia. To investigate this, we evaluated its efficacy on COVID-19 pneumonia. METHODS: This double-blind, randomised, placebo-controlled study (ClinicalTrials.gov: NCT04642950) evaluated patients in the first half of 2021 at seven Japanese hospitals. Hospitalised patients with COVID-19 pneumonia with moderate hypoxaemia inhaled sargramostim or placebo for 5 days. The primary endpoint was days to achieve a ≥ 2-category improvement from baseline on a modified 7-category ordinal scale. Secondary endpoints included degree of oxygenation, defined by amount of oxygen supply, and serum CCL17 level. RESULTS: Seventy-five patients were randomly assigned in a 2:1 ratio to receive sargramostim or placebo, of which 47 and 23 were analysed, respectively. No difference was observed between groups regarding the primary endpoint (8.0 and 7.0 days for sargramostim and placebo, respectively) or in the secondary endpoints, except for CCL17. A post hoc sub-analysis indicated that endpoint assessments were influenced by concomitant corticosteroid therapy. When the cumulative corticosteroid dose was ≤500 mg during Days 1-5, recovery and oxygenation were faster in the sargramostim group than for placebo. Bolus dose corticosteroids were associated with temporarily impaired oxygenation and delayed clinical recovery. The increase in serum CCL17, a candidate prognostic factor, reflected improvement with sargramostim inhalation. The number of adverse events was similar between groups. Two serious adverse events were observed in the sargramostim group without causal relation. CONCLUSIONS: Inhaled sargramostim was likely to be effective for COVID-19 pneumonia unless the concomitant corticosteroid dose was high.
Assuntos
COVID-19 , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Corticosteroides/uso terapêutico , Esteroides , Método Duplo-Cego , Resultado do TratamentoRESUMO
Human dental pulp contains adult stem cells. Our recent study demonstrated the localization of putative dental pulp stem/progenitor cells in the rat developing molar by chasing 5-bromo-2'-deoxyuridine (BrdU)-labeling. However, there are no available data on the localization of putative dental pulp stem/progenitor cells in the mouse molar. This study focuses on the mapping of putative dental pulp stem/progenitor cells in addition to the relationship between cell proliferation and differentiation in the developing molar using BrdU-labeling. Numerous proliferating cells appeared in the tooth germ and the most active cell proliferation in the mesenchymal cells occurred in the prenatal stages, especially on embryonic Day 15 (E15). Cell proliferation in the pulp tissue dramatically decreased in number by postnatal Day 3 (P3) when nestin-positive odontoblasts were arranged in the cusped areas and disappeared after postnatal Week 1 (P1W). Root dental papilla included numerous proliferating cells during P5 to P2W. Three to four intraperitoneal injections of BrdU were given to pregnant ICR mice and revealed slow-cycling long-term label-retaining cells (LRCs) in the mature tissues of postnatal animals. Numerous dense LRCs postnatally decreased in number and reached a plateau after P1W when they mainly resided in the center of the dental pulp, associating with blood vessels. Furthermore, numerous dense LRCs co-expressed mesenchymal stem cell markers such as STRO-1 and CD146. Thus, dense LRCs in mature pulp tissues were believed to be dental pulp stem/progenitor cells harboring in the perivascular niche surrounding the endothelium.
Assuntos
Bromodesoxiuridina/metabolismo , Diferenciação Celular , Polpa Dentária/citologia , Dente Molar/citologia , Dente Molar/crescimento & desenvolvimento , Coloração e Rotulagem , Células-Tronco/citologia , Animais , Contagem de Células , Proliferação de Células , Polpa Dentária/crescimento & desenvolvimento , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Microscopia Confocal , Modelos Biológicos , Proteínas do Tecido Nervoso/metabolismo , Nestina , Ratos , Células-Tronco/metabolismoRESUMO
Robust clinical evidence has not been available for melatonin, a drug commonly administered for treating sleep problems of children with autism spectrum disorder (ASD). In a phase 3 randomized, placebo-controlled clinical trial, we administered 1-mg melatonin (n = 65), 4-mg melatonin (n = 65), or placebo (n = 66) to196 children with ASD once daily before bedtime under adequate sleep hygiene interventions. The primary outcome was sleep onset latency (SOL) assessed with the electronic sleep diary. SOL shortened significantly in the 1- and 4-mg melatonin groups compared to the placebo group (- 22.0, - 28.0, and - 5.0 min, respectively; p < 0.0001 each). This therapeutic regimen of melatonin is a reasonable clinical approach to cope with ASD-emergent difficulties in children with ASD.
Assuntos
Transtorno do Espectro Autista , Melatonina , Transtornos do Sono-Vigília , Transtorno do Espectro Autista/tratamento farmacológico , Criança , Humanos , Sono , Higiene do Sono , Transtornos do Sono-Vigília/tratamento farmacológicoRESUMO
To reveal heterogeneous properties of triple-negative (TN) breast cancers (estrogen receptor negative, progesterone receptor negative and HER2 negative) and to clarify whether the developmental pathways to TN breast cancer are single or multiple, we conducted clinicopathological and immunohistochemical studies on TN breast cancers, with special reference to comparison of the invasive component (iIC) and the ductal component (dcIC) of invasive TN breast cancer and pure TN ductal carcinoma in situ (TNDCIS). Tumor tissues were obtained from 97 patients with TN invasive carcinoma and 10 patients with TNDCIS. Two histological subclassifications, "atypical" medullary carcinoma (type A, n=16) and carcinoma with a central acellular zone (type B, n=11), were distinguished from conventional ductal carcinoma. Other invasive ductal carcinomas were classified as type C (n=64) and special types were classified as type D (n=5). The follow-up period for the 96 patients ranged from 5 to 147.8 months (mean, 47.6 months). Out of 97 cases, dcIC was present in 29 (30%) cases and type A and B had significantly few ductal components, 0% and 18%, respectively. There were only six (6%) cases with non-TN cells in dcIC and TN cells in iIC and five of them were type C. In 13 (13%) cases, epidermal growth factor receptor (EGFR) expression existed only in iIC. Therefore, most of the TN carcinoma develops originally and rapidly invades at the early stage, especially in types A and B. The relapse rate of type B was the highest (36.4%) and the overall survival of patients with type B was the shortest (P=0.02), which indicates that the prognosis of type B is significantly worse than the other types.