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Adsorption of a biofouling layer on the surface of biosensors decreases the electrochemical activity and hence shortens the service life of biosensors, particularly implantable and wearable biosensors. Real-time quantification of the loss of activity is important for in situ assessment of performance while presenting an opportunity to compensate for the loss of activity and recalibrate the sensor to extend the service life. Here, we introduce an electrochemical noise measurement technique as a tool for the quantification of the formation of a biofouling layer on the surface of gold. The technique uniquely affords thermodynamic and kinetic information without applying an external bias (potential and/or current), hence allowing the system to be appraised in its innate state. The technique relies on the analysis of non-faradaic current and potential fluctuations that are intrinsically generated by the interaction of charged species at the electrode surface, i.e., gold. An analytical model is extended to explain the significance of parameters drawn from statistical analysis of the noise signal. This concept is then examined in buffered media in the presence of albumin, a common protein in the blood and a known source of a fouling layer in biological systems. Results indicate that the statistical analysis of the noise signal can quantify the loss of electrochemical activity, which is also corroborated by impedance spectroscopy as a complementary technique.
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Incrustação Biológica , Técnicas Eletroquímicas , Ouro , Ouro/química , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais , Propriedades de Superfície , Eletrodos , AdsorçãoRESUMO
The addition of nanomaterials to improve product properties has become a matter of course for many commodities: e.g., detergents, cosmetics, and food products. While this practice improves product characteristics, the increasing exposure and potential impact of nanomaterials (<100 nm) raise concerns regarding both the human body and the environment. Special attention should be taken for vulnerable individuals such as those who are ill, elder, or newborns. But detecting and quantifying nanoparticles in complex food matrices like early life nutrition (ELN) poses a significant challenge due to the presence of additional particles, emulsion-droplets, or micelles. There is a pressing demand for standardized protocols for nanoparticle quantification and the specification of "nanoparticle-free" formulations. To address this, silica nanoparticles (SiNPs), commonly used as anticaking agents (AA) in processed food, were employed as a model system to establish characterization methods with different levels of accuracy and sensitivity versus speed, sample handling, and automatization. Different acid treatments were applied for sample digestion, followed by size exclusion chromatography. Morphology, size, and number of NPs were measured by transmission electron microscopy, and the amount of Si was determined by microwave plasma atomic emission spectrometry. This successfully enabled distinguishing SiNP content in ELN food formulations with 2-4% AA from AA-free formulations and sorting SiNPs with diameters of 20, 50, and 80 nm. Moreover, the study revealed the significant influence of the ELN matrix on sample preparation, separation, and characterization steps, necessitating method adaptations compared to the reference (SiNP in water). In the future, we expect these methods to be implemented in standard quality control of formulation processes, which demand high-throughput analysis and automated evaluation.
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AIM: To investigate the role of the deep-learning (DL) method in the generation of dual-energy computed tomography (DECT) images from single-energy images for precise diagnosis of kidney stone type. MATERIALS AND METHODS: DECT of 23 patients was acquired, and the stone types were investigated based on the DECT software suggestions. The data were divided into two paired groups:120 kVp input and 80 kVp target and 120 kVp input and 135 kVp targets, p2p-UNet-GAN was exploited to generate the different energy images based on the common CT protocols. RESULTS: The images generated of the generative adversarial network (GAN) network were evaluated based on the SSIM, PSNR, and MSE metrics, and the values were estimated as 0.85-0.95, 28-32, and 0.85-0.89 respectively. The attenuation ratio of test patient images were estimated and compared with real patient reports. The network achieved high accuracy in stone region localisation and resulted in accurate stone type predictions. CONCLUSION: This study presents a useful method based on the DL technique to reduce patient radiation dose and facilitate the prediction of urinary stone types using single-energy CT imaging.
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Cálculos Renais , Urolitíase , Humanos , Tomografia Computadorizada por Raios X/métodos , Cálculos Renais/diagnóstico por imagem , CintilografiaRESUMO
OBJECTIVES: This study evaluated whether a novel standardized heparin dosing protocol used during atrial fibrillation catheter ablation resulted in a higher percentage of therapeutic activated clotting time (ACT) values compared to historic nonstandardized procedures. DESIGN: A retrospective cohort study SETTING: This study was conducted at Ochsner Medical Center, the largest tertiary-care teaching hospital in New Orleans, LA PARTICIPANTS: Patients undergoing catheter-based atrial fibrillation ablation INTERVENTIONS: The authors implemented a standardized heparin protocol, and enrolled 202 patients between November 2020 and March 2021. The historic controls consisted of 173 patients who underwent atrial fibrillation ablation between April 2020 and September 2020. Heparin administration in the control group was based on physician preference and was nonstandardized. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the percentage of intraprocedural ACTs in therapeutic range (≥300 to <450 s). Secondary endpoints included first measured ACT at ≥300 s and percent of measured ACTs in the supratherapeutic range (>450 s). Comparisons were performed using chi-squared tests or Fisher exact tests. Patients in the intervention group had a higher mean percentage of ACTs in the therapeutic range compared to the control group (84.9% vs. 75.8%, p<0.001). More patients in the intervention group reached therapeutic ACT on the first measurement compared to the control group (70.3% vs. 31.2%, p<0.001). CONCLUSION: During catheter-based cardiac ablation procedures, a novel standardized unfractionated heparin dosing protocol resulted in a higher percentage of ACTs in the target range, and a higher proportion of initial ACTs in the therapeutic range compared with baseline nonstandardized heparin dosing.
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Fibrilação Atrial , Ablação por Cateter , Humanos , Heparina , Anticoagulantes , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Ablação por Cateter/métodosRESUMO
The Indonesian island of Sulawesi has a unique geology and geography, which have produced an astoundingly diverse and endemic flora and fauna and a fascinating biogeographic history. Much biodiversity research has focused on the regional endemism in the island's Central Core and on its four peninsulas, but the biodiversity of the island's many upland regions is still poorly understood for most taxa, including amphibians and reptiles. Here, we report the first of several planned full-mountain checklists from a series of herpetological surveys of Sulawesi's mountains conducted by our team. In more than 3 weeks of work on Gunung Galang, a 2,254 m peak west of the city of Tolitoli, Sulawesi Tengah Province, on Sulawesi's Northern Peninsula, we recovered nearly fifty species of reptiles and amphibians, more than a dozen of which are either new to science or known but undescribed. The incompleteness of our sampling suggests that many more species remain to be discovered on and around this mountain.
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Biodiversidade , Lista de Checagem , Indonésia , Geografia , GeologiaRESUMO
The American Society of Bone and Mineral Research (ASBMR) Professional Practice Committee charged an ASBMR Task Force on Clinical Algorithms for Fracture Risk to review the evidence on whether current approaches for differentiating fracture risk based on race and ethnicity are necessary and valid. To help address these charges, we performed a systematic literature review investigating performance of calculators for predicting incident fractures within and across race and ethnicity groups in middle-aged and older US adults. We included English-language, controlled or prospective cohort studies that enrolled US adults aged >40 years and reported tool performance predicting incident fractures within individual race and ethnicity groups for up to 10 years. From 4838 identified references, six reports met eligibility criteria, all in women. Just three, all from one study, included results in non-white individuals. In these three reports, non-white women experienced relatively few major osteoporotic fractures (MOFs), especially hip fractures, and risk thresholds for predicting fractures in non-white women were derived from risks in the overall, predominantly white study population. One report suggested the Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD) overestimated hip fracture similarly across race and ethnicity groups (black, Hispanic, American Indian, Asian, white) but overestimated MOF more in non-white than White women. However, these three reports were inconclusive regarding whether discrimination of FRAX or the Garvan calculator without BMD or of FRAX with BMD for MOF or hip fracture differed between white versus black women. This uncertainty was at least partly due to imprecise hip fracture estimates in black women. No reports examined whether ratios of observed to predicted hip fracture risks within each race or ethnicity group varied across levels of predicted hip fracture risk. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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Fraturas do Quadril , Fraturas por Osteoporose , Adulto , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Etnicidade , Estudos Prospectivos , Medição de Risco/métodos , Fraturas por Osteoporose/epidemiologia , Fraturas do Quadril/epidemiologia , Densidade Óssea , Algoritmos , Minerais , Fatores de RiscoRESUMO
Positron emission tomography-computed tomography (PET-CT) with internal administration of the FDG-18 is characterized as a widespread functional imaging modality in diagnostic radiation medicine, which increases the patient effective doses owing to the presence of internal and external radiation sources. Hence, patient effective dose estimation has been pinpointed as a significant factor in radiation protection assessment. A large number of studies have been published in this regard, and various dosimetry methods have been surveyed. According to our previous research, 10 patients had participated in PET-CT scans with three static time sequences imaging. PET effective doses were estimated using a simple method derived from Anderson et al. and Kaushik et al. coefficients, and the CT effective doses were surveyed with a CTDI phantom and cylindrical ionization chamber. The CT dose was tripled owing to the three static time-sequences imaging. The effective doses were calculated using different coefficients and the results of the PET effective doses were compared. The PET-CT effective dose was varied from 17.14 to 18.42 mSv based on Kaushik et al. coefficients which were measured for one low-dose CT scan. This study aimed to survey simple PET-CT effective dose estimation using three static-time imaging approaches which increases the total patient effective doses.
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Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Doses de Radiação , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Imagem Corporal TotalRESUMO
BACKGROUND: It is well established that females and persons of racial and ethnic minorities are frequently underrepresented in clinical trials. These disparities are potentially important aspects of evidence-based formulary management and drug utilization review (DUR) processes. OBJECTIVE: The purpose of this study was to review the demographic composition of pivotal trials and post-approval study requirements for recent FDA-approved drugs, analyzing the representation of minority groups and its generalizability to the US population or corresponding disease state. METHODS: Drugs approved between July 2019 and June 2020 were identified and demographic data including race, ethnicity, and sex was extracted from their pivotal trials. Demographic data was compared to US demographics and/or the disease state demographics for the respective approved drug. RESULTS: There were a total of 85 drugs and 142 pivotal trials included in the study. Compared to the estimated US population, the minority groups with a statistically significant underrepresentation across all pivotal trials included Black or African Americans and American Indian or Alaska Natives. The Hispanic/Latinx population had a statistically significant underrepresentation in 55.4% of trials. Females had a statistically significant underrepresentation in 21.2% of trials when compared to the disease state demographics of the respective approved drug. CONCLUSION AND RELEVANCE: Persons of minorities are underrepresented in the generation of evidence of safety and efficacy for many new drugs. Formulary management and DUR offer an integrated strategic opportunity for the clinical community to formally and carefully consider the data on sex, race, and ethnicity to address disparities in health care.
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Etnicidade , Preparações Farmacêuticas , Minorias Étnicas e Raciais , Feminino , Hispânico ou Latino , Humanos , Grupos Minoritários , Estados UnidosRESUMO
Introduction: DSM-5 presented a revised conceptualization of specific learning disorders (LD). Contrary to former versions, the various types of LD-i.e., mathematics disorder, reading disorder, and writing disorder-are not treated as distinct diagnostic entities but are integrated into one single LD category. In support of this new classification, it has been argued that the various types of LD overlap to a great extent in their cognitive functioning profiles and therefore do not exhibit a distinct set of cognitive causes. In contrast, ICD-11 still adheres to the idea of discrete categories and thus follows the specificity hypothesis of LD. Using latent profile analysis (LPA), we therefore tested the specificity of cognitive strengths and weaknesses in children with different types of LD. Secondly, we aimed at examining the extent to which observed LD characteristics (type and severity of LD as well as IQ-achievement discrepancy) were consistent with the membership of a given latent profile. Method: 302 German third-graders (134 girls; IQ ≥ 85; M age = 111.05 months; SD = 5.76) with single or comorbid types of LD in the domains of mathematics, reading, and spelling completed a wide range of domain-specific and domain-general cognitive functioning measures. Results: Five qualitative distinct profiles of cognitive strengths and weaknesses were identified. Profile 1 (23% of the sample) showed Comprehensive Cognitive Deficits, performing low in all measures except for naming speed, language, and inhibition. Profile 2 (21%) included children with a Double Deficit in Phonological Awareness and Phonological Short-term Memory. Profile 3 (20%) was characterized by a Double Deficit of Phonological Awareness and Naming Speed. Profile 4 (19%) included children with a Single Deficit in Attention, and profile 5 (17%) consisted of children without any cognitive deficits. Moreover, type and severity of LD as well as IQ-achievement discrepancy discriminated between the profiles, which is in line with the specificity hypothesis of LD. Discussion: Overall, the finding of specific associations between the LD types and the identified cognitive profiles supports the ICD-11 classification of LD. Yet, those inferences may not be valid for an individual child but need to be examined through comprehensive diagnostic.
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BACKGROUND: l-Tryptophan reduces energy intake in healthy men. The underlying mechanisms, including appetite, plasma cholecystokinin (CCK), tryptophan (Trp), and the ratio of Trp to large neutral amino acids (Trp:LNAAs ratio), and whether responses differ in lean and obese individuals, are uncertain. OBJECTIVES: We evaluated the effects of intragastric Trp on energy intake (primary outcome) and their potential mechanisms, pre- and postmeal, in lean men and those with obesity. METHODS: Twelve lean men [mean ± SD age: 30 ± 3 y; BMI (in kg/m2): 23 ± 1] and 13 men with obesity (mean ± SD age: 31 ± 3 y; BMI: 33 ± 1) received, on 3 separate occasions, in double-blind, randomized order, 3 g ("Trp-3") or 1.5 g ("Trp-1.5") Trp, or control ("C"), intragastrically, 30 min before a buffet-meal. Energy intake from the buffet-meal, hunger, fullness, and plasma CCK and amino acid concentrations were measured in response to Trp alone and for 2 h postmeal. Data were analyzed using maximum likelihood mixed-effects models, with treatment, group, and treatment-by-group interaction as fixed effects. RESULTS: Trp alone increased plasma CCK, Trp, and the Trp:LNAAs ratio (all P < 0.001), with no difference between groups. Trp suppressed energy intake (P < 0.001), with no difference between groups (lean, C: 1085 ± 102 kcal, Trp-1.5: 1009 ± 92 kcal, Trp-3: 868 ± 104 kcal; obese, C: 1249 ± 98 kcal, Trp-1.5: 1217 ± 90 kcal, Trp-3: 1012 ± 100 kcal). Postmeal, fullness was greater after Trp-3 than after C and Trp-1.5 (all P < 0.05), and in men with obesity than in lean men (P < 0.05). Plasma Trp and the Trp:LNAAs ratio were greater after Trp-3 and Trp-1.5 than after C (all P < 0.001), and tended to be less in men with obesity than in the lean (P = 0.07) (Trp:LNAAs ratio: lean, C: 1.5 ± 0.2, Trp-1.5: 6.9 ± 0.7, Trp-3: 10.7 ± 1.4; obese, C: 1.4 ± 0.1, Trp-1.5: 4.6 ± 0.7, Trp-3: 7.8 ± 1.3). There were inverse correlations of energy intake with plasma Trp and the Trp:LNAAs ratio in both groups (lean, both r = -0.50, P < 0.01; obese, both r = -0.40, P < 0.05). CONCLUSIONS: Intragastric Trp has potent energy intake-suppressant effects, in both lean men and those with obesity, apparently related to the Trp:LNAAs ratio.
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Apetite , Triptofano , Adulto , Colecistocinina , Método Duplo-Cego , Ingestão de Energia , Humanos , Masculino , ObesidadeRESUMO
(1) Background: Whey protein lowers postprandial blood glucose in health and type 2 diabetes, by stimulating insulin and incretin hormone secretion and slowing gastric emptying. The branched-chain amino acids, leucine, isoleucine and valine, abundant in whey, may mediate the glucoregulatory effects of whey. We investigated the comparative effects of intragastric administration of leucine, isoleucine and valine on the plasma glucose, C-peptide and glucagon responses to and gastric emptying of a mixed-nutrient drink in healthy men. (2) Methods: 15 healthy men (27 ± 3 y) received, on four separate occasions, in double-blind, randomised fashion, either 10 g of leucine, 10 g of isoleucine, 10 g of valine or control, intragastrically, 30 min before a mixed-nutrient drink. Plasma glucose, C-peptide and glucagon concentrations were measured before, and for 2 h following, the drink. Gastric emptying of the drink was quantified using 13C-acetate breath-testing. (3) Results: Amino acids alone did not affect plasma glucose or C-peptide, while isoleucine and valine, but not leucine, stimulated glucagon (p < 0.05), compared with control. After the drink, isoleucine and leucine reduced peak plasma glucose compared with both control and valine (all p < 0.05). Neither amino acid affected early (t = 0-30 min) postprandial C-peptide or glucagon. While there was no effect on overall gastric emptying, plasma glucose at t = 30 min correlated with early gastric emptying (p < 0.05). (4) Conclusion: In healthy individuals, leucine and isoleucine lower postprandial blood glucose, at least in part by slowing gastric emptying, while valine does not appear to have an effect, possibly due to glucagon stimulation.
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Aminoácidos de Cadeia Ramificada/farmacologia , Glicemia/metabolismo , Peptídeo C/sangue , Esvaziamento Gástrico/efeitos dos fármacos , Glucagon/sangue , Isoleucina/farmacologia , Leucina/farmacologia , Valina/farmacologia , Adulto , Diabetes Mellitus Tipo 2 , Método Duplo-Cego , Polipeptídeo Inibidor Gástrico/sangue , Humanos , Insulina , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial/efeitos dos fármacos , Proteínas do Soro do Leite/farmacologia , Adulto JovemRESUMO
BACKGROUND: Breast carcinoma with extensive peritumoral vascular invasion (ePVI-BC) is a cancer with massive vascular invasion (>10) detected in more than one slide. This neoplasm shows clinic-pathological affinity with inflammatory breast carcinoma (IBC). In this paper we evaluate their biological relationship through the study of surrogate markers (ß-catenin and NFAT5) of Canonical (cWnt) and non-canonical (nWnt) Wnt pathways activation. METHODS: By immunoistochemistry, we investigate ß-catenin and NFAT5 in 39 IBC, 74 ePVI-BC and 84 control cases (CG-BC). RESULTS: cWnt was activated in 100 % of ePVI-BC, in 64 % of IBC and 10 % of CG-BC. nWnt was activated in 20 % of ePVI-BC, 50 % of IBC and 1% of CG-BC. The prognosis of carcinomas with nWnt activated was poor similar to IBC. The statistical analysis evidences as both the pathways are synergistic in malignant progression and survival time. ß-catenin show an important association with prognostic factors and NFAT5 shows a relevant prognostic role on OS (p = 1.5*10-6) and DFS (P = 1,2*10-4). nWnt is associated with a worse prognosis independently of cWnt. cWnt is associated with adverse prognosis (DFS p = 0.0469; OS p = 0.004891) but its prognostic role is indifferent in carcinoma with nWnt activated. CONCLUSIONS: Canonical Wnt pathway is involved in malignant progression with dominant role for vascular invasion whereas non canonical Wnt pathway plays an important role on survival time including the capacity to identify carcinomas with IBC-like prognosis. Furthermore ePVI may represent a "prodromal form of IBC" as demonstrated by its clinicopathological and biological similarity with IBC.
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Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Inflamação/metabolismo , Neoplasias Inflamatórias Mamárias/metabolismo , Via de Sinalização Wnt/fisiologia , Idoso , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismoRESUMO
Enzymes are essential biocatalysts and very attractive as therapeutics. However, their functionality is strictly related to their stability, which is significantly affected by the environmental changes occurring during their usage or long-term storage. Therefore, maintaining the activity of enzymes is essential when they are exposed to high temperature during usage or when they are stored for extended periods of time. Here, we stabilize and protect enzymes by coencapsulating them with trehalose into polymersomes. The anhydrobiotic disaccharide preserved up to about 81% of the enzyme's original activity when laccase/trehalose-loaded nanoreactors were kept desiccated for 2 months at room temperature and 75% of its activity when heated at 50 °C for 3 weeks. Moreover, the applicability of laccase/trehalose-loaded nanoreactors as catalysts for bleaching of the textile dyes orange G, toluidine blue O, and indigo was proven. Our results demonstrate the advantages of coencapsulating trehalose within polymersomes to stabilize enzymes in dehydrated state for extended periods of time, preserving their activity even when heated to elevated temperature.
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Lacase , Trealose , Preservação BiológicaRESUMO
AIMS: In healthy individuals, intragastric administration of the branched-chain amino acids, leucine and isoleucine, diminishes the glycaemic response to a mixed-nutrient drink, apparently by stimulating insulin and slowing gastric emptying, respectively. This study aimed to evaluate the effects of leucine and isoleucine on postprandial glycaemia and gastric emptying in type-2 diabetes mellitus (T2D). METHODS: 14 males with T2D received, on 3 separate occasions, in double-blind, randomised fashion, either 10 g leucine, 10 g isoleucine or control, intragastrically 30 min before a mixed-nutrient drink (500 kcal; 74 g carbohydrates, 18 g protein, 15 g fat). Plasma glucose, insulin and glucagon were measured from 30 min pre- until 120 min post-drink. Gastric emptying of the drink was also measured. RESULTS: Leucine and isoleucine stimulated insulin, both before and after the drink (all P < 0.05; peak (mU/L): control: 70 ± 15; leucine: 88 ± 17; isoleucine: 74 ± 15). Isoleucine stimulated (P < 0.05), and leucine tended to stimulate (P = 0.078), glucagon before the drink, and isoleucine stimulated glucagon post-drink (P = 0.031; peak (pg/mL): control: 62 ± 5; leucine: 70 ± 9; isoleucine: 69 ± 6). Neither amino acid affected gastric emptying or plasma glucose (peak (mmol/L): control: 12.0 ± 0.5; leucine: 12.5 ± 0.7; isoleucine: 12.0 ± 0.6). CONCLUSIONS: In contrast to health, in T2D, leucine and isoleucine, administered intragastrically in a dose of 10 g, do not lower the glycaemic response to a mixed-nutrient drink. This finding argues against a role for 'preloads' of either leucine or isoleucine in the management of T2D.
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Aminoácidos de Cadeia Ramificada/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Esvaziamento Gástrico/efeitos dos fármacos , Isoleucina/uso terapêutico , Leucina/uso terapêutico , Período Pós-Prandial/efeitos dos fármacos , Adulto , Idoso , Aminoácidos de Cadeia Ramificada/farmacologia , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Bebidas Energéticas , Humanos , Isoleucina/farmacologia , Leucina/farmacologia , Masculino , Pessoa de Meia-IdadeRESUMO
Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces postprandial glucose levels in humans. However, the effect of chronic-isoleucine supplementation on body weight and glucose tolerance in obesity is unknown. This study aimed to investigate the impact of chronic isoleucine on body weight gain and glucose tolerance in lean and high-fat-diet (HFD) induced-obese mice. Male C57BL/6-mice, fed a standard-laboratory-diet (SLD) or HFD for 12 weeks, were randomly allocated to: (1) Control: Drinking water; (2) Acute: Drinking water with a gavage of isoleucine (300 mg/kg) prior to the oral-glucose-tolerance-test (OGTT) or gastric-emptying-breath-test (GEBT); (3) Chronic: Drinking water with 1.5% isoleucine, for a further six weeks. At 16 weeks, an OGTT and GEBT was performed and at 17 weeks metabolic monitoring. In SLD- and HFD-mice, there was no difference in body weight, fat mass, and plasma lipid profiles between isoleucine treatment groups. Acute-isoleucine did not improve glucose tolerance in SLD- or HFD-mice. Chronic-isoleucine impaired glucose tolerance in SLD-mice. There was no difference in gastric emptying between any groups. Chronic-isoleucine did not alter energy intake, energy expenditure, or respiratory quotient in SLD- or HFD-mice. In conclusion, chronic isoleucine supplementation may not be an effective treatment for obesity or glucose intolerance.
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Glicemia/metabolismo , Suplementos Nutricionais , Isoleucina/administração & dosagem , Resultados Negativos , Fenômenos Fisiológicos da Nutrição/fisiologia , Obesidade/metabolismo , Obesidade/prevenção & controle , Magreza/metabolismo , Aumento de Peso/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/dietoterapia , Intolerância à Glucose/prevenção & controle , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/prevenção & controle , Isoleucina/farmacologia , Masculino , Camundongos Endogâmicos C57BLRESUMO
Circulating tryptophan/large neutral amino acids (tryptophan/LNAA) ratio, an indicator of brain serotonin levels, may be important in appetite regulation, together with gastrointestinal (gastric emptying, plasma cholecystokinin) mechanisms. We have compared effects of intragastric tryptophan ('Trp') on the plasma tryptophan/LNAA ratio in lean and obese men, and the associations of the tryptophan/LNAA ratio, gastric emptying and CCK concentrations with energy intake. Lean and obese male participants (n = 16 each) received 3 g Trp or volume-matched control intragastrically, 15 min before a mixed-nutrient drink (300 mL, 400 kcal) (t = 0 min) in randomised, double-blind fashion. Plasma amino acid (for calculation of the plasma tryptophan/LNAA ratio) and CCK concentrations were measured from t = -20-60 min. Gastric emptying was assessed from t = 0-60 min, and ad-libitum energy intake from a standardised buffet-style meal from t = 60-90 min. The increase in the plasma tryptophan/LNAA ratio was less in obese, than lean, participants (P < 0.05), and greater in lean participants who reduced their energy intake (by >0 kcal) after Trp compared with those who did not (by ≤0 kcal) (P < 0.05). Moreover, in participants who reduced their energy intake, the ratio was lower in obese, than in lean (P < 0.05). There was a trend for an inverse correlation between energy intake with the plasma tryptophan/LNAA ratio in lean (r = -0.4, P = 0.08), but not in obese, participants. There was no significant difference in gastric emptying or CCK between participants who reduced their energy intake and those who did not. In conclusion, the plasma tryptophan/LNAA ratio appears to be a determinant of the suppression of energy intake in response to tryptophan in normal-weight people, but not in those with obesity. The role of the plasma tryptophan/LNAA ratio to regulate energy intake, and potential changes in obesity, warrant evaluation in prospective studies.
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Aminoácidos Neutros/sangue , Ingestão de Energia/efeitos dos fármacos , Obesidade/sangue , Triptofano/administração & dosagem , Triptofano/sangue , Adulto , Aminoácidos/sangue , Regulação do Apetite/efeitos dos fármacos , Índice de Massa Corporal , Colecistocinina/sangue , Método Duplo-Cego , Esvaziamento Gástrico/efeitos dos fármacos , Humanos , Peso Corporal Ideal , Infusões Parenterais , Masculino , Refeições/efeitos dos fármacos , Obesidade/tratamento farmacológicoRESUMO
Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor originating from perivascular epitheloid cells showing melanocytic and smooth muscle differentiation. The uterus represents the second most common site of origin. A 49 years woman presented to our Hospital for a vaginal spontaneous expulsion of a mass suggestive for malignant mesenchymal tumor. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy and the histopathological report was compliant with a PEComa with aggressive behavior. Medical Literature databases about PEComa were searched. The current literature identified near 90 cases of uterine PEComas and they are categorized as uncertain malignant potential or with aggressive behavior. Primary surgical excision represents the gold-standard treatment. Recently targeted therapy with mTOR inhibitors has been introduced with an important beneficial. In this paper we review the Literature about the uPEComa with aggressive behavior reporting the first case of spontaneous vaginal expulsion.
Assuntos
Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The fatty acid, lauric acid (C12), and the amino acid, leucine (Leu) stimulate gut hormones, including CCK, associated with suppression of energy intake. In our recent study, intraduodenal infusion of a combination of C12 and l-tryptophan, at loads that individually did not affect energy intake, reduced energy intake substantially, associated with much greater stimulation of CCK. We have now investigated whether combined administration of C12 and Leu would enhance the intake-suppressant effects of each nutrient, when given at loads that each suppress energy intake individually. Sixteen healthy, lean males (age: 23 ± 2 yr) received, in randomized, double-blind fashion, 90-min intraduodenal infusions of control (saline), C12 (0.4 kcal/min), Leu (0.45 kcal/min), or C12+Leu (0.85 kcal/min). Antropyloroduodenal pressures were measured continuously and plasma CCK at 15-min intervals, and energy intake from a standardized buffet-meal, consumed immediately postinfusion, was quantified. All nutrient infusions stimulated plasma CCK compared with control (P < 0.05). Moreover, C12 and C12+Leu stimulated CCK compared with Leu (P < 0.05) (mean concentration, pmol/L; control: 2.3 ± 0.3, C12: 3.8 ± 0.3, Leu: 2.7 ± 0.3, and C12+Leu: 4.0 ± 0.4). C12+Leu, but not C12 or Leu, stimulated pyloric pressures (P < 0.05). C12+Leu and C12 reduced energy intake (P < 0.05), and there was a trend for Leu to reduce (P = 0.06) energy intake compared with control, with no differences between the three nutrient treatments (kcal; control: 1398 ± 84, C12: 1226 ± 80, Leu: 1260 ± 92, and C12+Leu: 1208 ± 83). In conclusion, combination of C12 and Leu, at the loads given, did not reduce energy intake beyond their individual effects, possibly because maximal effects had been evoked.
Assuntos
Colecistocinina/sangue , Ingestão de Energia , Motilidade Gastrointestinal/efeitos dos fármacos , Ácidos Láuricos/farmacologia , Leucina/farmacologia , Adolescente , Adulto , Apetite/efeitos dos fármacos , Método Duplo-Cego , Ingestão de Alimentos/efeitos dos fármacos , Humanos , Ácidos Láuricos/administração & dosagem , Leucina/administração & dosagem , Masculino , Adulto JovemRESUMO
Due to their desirable elastic modulus and density that are similar to natural bone, non-toxic element containing magnesium alloys are regarded as promising bio-degradable materials. A biodegradable HA-particle-reinforced magnesium-matrix composite Mg-3Zn-0.2Ca-1HA (wt%) was fabricated for biomedical application by a combination of high shear solidification (HSS) and hot extrusion technology. The microstructure, mechanical properties, corrosion resistance and cell biocompatibility of the composite were subsequently investigated. In comparison with the matrix alloy, the as-cast Mg-3Zn-0.2Ca-1HA composite obtained by HSS technology exhibited a uniform and fine grained structure, further refined after a hot extrusion ratio of 36:1. The yield strength (0.2%YS), ultimate tensile strength and elongation of the extruded composite were 322â¯MPa, 341â¯MPa and 7.6%, respectively. The corrosion rate of the as-extruded Mg-3Zn-0.2Ca-1HA composite was measured to be 1.52â¯mm/y. Electrochemical and immersion tests showed that the corrosion resistance of the composite is slightly improved comparing to that of the matrix alloy.
Assuntos
Ligas/química , Materiais Biocompatíveis/química , Durapatita/química , Magnésio/química , Zinco/química , Animais , Linhagem Celular , Corrosão , Fibroblastos/citologia , Teste de Materiais , Camundongos , Resistência à TraçãoRESUMO
BACKGROUND: The fatty acid, lauric acid ('C12'), and the amino acid, L-tryptophan ('Trp'), modulate gastrointestinal functions including gut hormones and pyloric pressures, which are important for the regulation of energy intake, and both potently suppress energy intake. OBJECTIVE: We hypothesized that the intraduodenal administration of C12 and Trp, at loads that do not affect energy intake individually, when combined will reduce energy intake, which is associated with greater modulation of gut hormones and pyloric pressures. DESIGN: Sixteen healthy, lean males (age: 24 ± 1.5 y) received 90-min intraduodenal infusions of saline (control), C12 (0.3 kcal/min), Trp (0.1 kcal/min), or C12 + Trp (0.4 kcal/min), in a randomized, double-blind, cross-over study. Antropyloroduodenal pressures were measured continuously, and plasma cholecystokinin (CCK), ghrelin, and glucagon-like peptide-1 (GLP-1) concentrations, appetite perceptions, and gastrointestinal symptoms at 15-min intervals. Immediately after the infusions, energy intake from a standardized buffet meal was quantified. RESULTS: C12 + Trp markedly reduced energy intake (kcal; control: 1,232 ± 72, C12: 1,180 ± 82, Trp: 1,269 ± 73, C12 + Trp: 1,056 ± 106), stimulated plasma CCK (AUC(area under the curve)0-90 min, pmol/L*min; control: 21 ± 8; C12: 129 ± 15; Trp: 97 ± 16; C12 + Trp: 229 ± 22) and GLP-1 (AUC0-90 min, pmol/L*min; control: 102 ± 41; C12: 522 ± 102; Trp: 198 ± 63; C12 + Trp: 545 ± 138), and suppressed ghrelin (AUC0-90 min, pg/mL*min; control: -3,433 ± 2,647; C12: -11,825 ± 3,521; Trp: -8,417 ± 3,734; C12 + Trp: -18,188 ± 4,165) concentrations, but did not stimulate tonic, or phasic, pyloric pressures, compared with the control (all P < 0.05), or have adverse effects. C12 and Trp each stimulated CCK (P < 0.05), but to a lesser degree than C12 + Trp, and did not suppress energy intake or ghrelin. C12, but not Trp, stimulated GLP-1 (P < 0.05) and phasic pyloric pressures (P < 0.05), compared with the control. CONCLUSION: The combined intraduodenal administration of C12 and Trp, at loads that individually do not affect energy intake, substantially reduces energy intake, which is associated with a marked stimulation of CCK and suppression of ghrelin. The study was registered as a clinical trial at the Australian and New Zealand Clinical Trial Registry (www.anzctr.org.au,) as 12613000899741.