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1.
Mov Disord ; 37(9): 1841-1849, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35852957

RESUMO

BACKGROUND: Previous studies suggest a link between CAG repeat number in the HTT gene and non-Huntington neurodegenerative diseases. OBJECTIVE: The aim is to analyze whether expanded HTT CAG alleles and/or their size are associated with the risk for developing α-synucleinopathies or their behavior as modulators of the phenotype. METHODS: We genotyped the HTT gene CAG repeat number and APOE-Ɛ isoforms in a case-control series including patients with either clinical or neuropathological diagnosis of α-synucleinopathy. RESULTS: We identified three Parkinson's disease (PD) patients (0.30%) and two healthy controls (0.19%) carrying low-penetrance HTT repeat expansions whereas none of the dementia with Lewy bodies (DLB) or multisystem atrophy (MSA) patients carried pathogenic HTT expansions. In addition, a clear increase in the number of HTT CAG repeats was found among DLB and PD groups influenced by the male gender and also by the APOE4 allele among DLB patients. HTT intermediate alleles' (IAs) distribution frequency increased in the MSA group compared with controls (8.8% vs. 3.9%, respectively). These differences were indeed statistically significant in the MSA group with neuropathological confirmation. Two MSA HTT CAG IAs carriers with 32 HTT CAG repeats showed isolated polyQ inclusions in pons and basal nuclei, which are two critical structures in the neurodegeneration of MSA. CONCLUSIONS: Our results point to a link between HTT CAG number, HTT IAs, and expanded HTT CAG repeats with other non-HD brain pathology and support the hypothesis that they can share common neurodegenerative pathways. © 2022 International Parkinson and Movement Disorder Society.


Assuntos
Proteína Huntingtina , Doença de Huntington , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Sinucleinopatias , Alelos , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Masculino , Atrofia de Múltiplos Sistemas/genética , Doença de Parkinson/genética , Expansão das Repetições de Trinucleotídeos/genética
2.
Neurodegener Dis ; 21(1-2): 36-41, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34673649

RESUMO

BACKGROUND: Many evidences suggest a pathological link between neurodegenerative diseases and cancer. In fact, several epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson's disease (PD) patients and some PD genes are involved in cancer networks. OBJECTIVE: The aim of this study is to assess the influence of several factors in the risk of cancer in a cohort of 753 PD patients and to study how these variables interact with each other. METHODS: We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic or idiopathic PD), and two genetic variants, previously associated with cancer, rs5848-GRN and rs1042522-TP53. RESULTS: A higher age at PD onset was observed in patients who develop cancer before PD (p < 0.001). Alcohol consumption was a risk factor to develop cancer in PD patients (p = 0.011), while smoking was not a cancer risk factor in our cohort (p = 0.098). Among the genetic factors, the genotype TT GRN-rs5848 was statistically more frequent in PD patients without cancer (p = 0.05). CONCLUSIONS: Our study identified several factors, genetic and nongenetic, which contribute to the risk for cancer in PD.


Assuntos
Neoplasias , Doença de Parkinson , Estudos de Coortes , Predisposição Genética para Doença , Genótipo , Humanos , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Fatores de Risco
3.
Drug Dev Ind Pharm ; 41(10): 1632-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25391332

RESUMO

Traditional vaginal preparations reside in the vaginal cavity for relatively a short period of time, requiring multiple doses in order to attain the desired therapeutic effect. Therefore, mucoadhesive systems appear to be appropriate to prolong the residence time in the vaginal cavity. In the current study, mucoadhesive nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) intended for vaginal delivery of glycyrrhizic acid (GA) (a drug with well-known antiviral properties) were prepared and characterized. Nanoparticles were generated by a solvent displacement method. Incorporation of GA was performed during nanoprecipitation, followed by adsorption of drug once nanoparticles were formed. The prepared nanoparticles were characterized in terms of size, Z-potential, morphology, drug loading, interaction of GA with PVM/MA (by differential scanning calorimetry) and the in vitro interaction of nanoparticles with pig mucin (at two pH values, 3.6 and 5; with and without GA adsorbed). The preparation method led to nanoparticles of a mean diameter of 198.5 ± 24.3 nm, zeta potential of -44.8 ± 2.8 mV and drug loading of 15.07 ± 0.86 µg/mg polymer. The highest mucin interaction resulted at pH 3.6 for nanoparticles without GA adsorbed. The data obtained suggest the promise of using mucoadhesive nanoparticles of PVM/MA for intravaginal delivery of GA.


Assuntos
Antivirais/administração & dosagem , Portadores de Fármacos/química , Ácido Glicirrízico/administração & dosagem , Maleatos/química , Nanopartículas/química , Polietilenos/química , Adesividade , Administração Intravaginal , Animais , Varredura Diferencial de Calorimetria , Cromatografia em Camada Fina , Concentração de Íons de Hidrogênio , Mucinas/metabolismo , Tamanho da Partícula , Propriedades de Superfície , Suínos , Tecnologia Farmacêutica
4.
Parkinsonism Relat Disord ; 97: 79-83, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35364453

RESUMO

BACKGROUND: Previous studies linked disease-progression variables such as age at onset or survival to both genetic, and non-genetic factors in Parkinson's disease (PD) patients. OBJECTIVE: The aim of this study was to assess how genetic and non genetic factors act as modifiers of age at onset and survival and in a cohort of 753 PD patients, and to determine how these variables interact to define the overall risk. METHODS: We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic, gPD or idiopathic, iPD) and three genetic variants rs5848- GRN, rs1042522- TP53 and APOE. We studied two cohorts (PPMI and IPDGC) to replicate positive results. RESULTS: Regarding age at onset, male smokers PD had a significantly lower mean age compared to non-smoker (p = 0.001). APOE-Ɛ4 carriers had a younger onset-age compared to non-carriers (p = 0.03) in the Spanish cohort, but these results were not replicated in the other cohorts. Concerning survival, PD patients with an early onset (below 50 years) had an increased survival rate (p < 0.001). CONCLUSIONS: Our study showed how several genetic and non-genetic risk factors influenced the age at onset and survival in PD.


Assuntos
Doença de Parkinson , Idade de Início , Apolipoproteínas E/genética , Estudos de Coortes , Heterozigoto , Humanos , Masculino , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Fumar/efeitos adversos , Fumar/epidemiologia
5.
Neurobiol Aging ; 99: 99.e15-99.e22, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32972771

RESUMO

Frontotemporal dementia (FTD) is a clinical, genetic, and pathologic heterogeneous group of neurodegenerative diseases. In this study, we investigated the role of APOƐ4, rs5848 in GRN, and rs1042522 in TP53 gene as disease risk factors and/or phenotype modifiers in 440 FTD patients, including 175 C9orf72 expansion carriers. We found that the C9orf72 expansion carriers showing an earlier age at onset (p < 0.001). Among the clinical groups, the FTD-MND (motoneuron disease) showed the lowest survival (hazard ratio [HR] = 4.12), and the progressive nonfluent aphasia group showed the highest onset age (p = 0.03). In our cohort, the rs1042522 in TP53 was associated with disease onset (p = 0.02) and survival (HR = 1.73) and rs5848 GRN with a significantly shorter survival in CC homozygous patients (HR = 1.98). The frequency of APOƐ4 carriers was significantly increased in the C9orf72 noncarriers (p = 0.022). Although validation of our findings is necessary, our results suggest that TP53, GRN, and APOE genes may act as phenotype modifiers in FTD and should be considered in future clinical trials.


Assuntos
Apolipoproteínas E/genética , Demência Frontotemporal/genética , Estudos de Associação Genética , Variação Genética/genética , Progranulinas/genética , Proteína Supressora de Tumor p53/genética , Proteína C9orf72 , Feminino , Heterozigoto , Humanos , Masculino , Fenótipo
6.
Neurobiol Aging ; 87: 139.e1-139.e7, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31810584

RESUMO

We analyzed the frequency of intermediate alleles (IAs) in the ATXN1, ATXN2, and HTT genes in several neurodegenerative diseases. The study included 1126 patients with Alzheimer's disease (AD), 440 patients with frontotemporal dementia (FTD), and 610 patients with Parkinson's disease. In all cohorts, we genotyped ATXN1 and ATXN2 CAG repeats. In addition, in the FTD cohort, we determined the number of HTT CAG repeats. The frequency of HTT IAs was higher in patients with FTD (6.9%) versus controls (2.9%) and in the C9orf72 expansion noncarriers (7.2%) versus controls (2.9%), although the difference was nonsignificant after correction for multiple testing. Compared with controls, progressive nonfluent aphasia (PNFA) groups showed a significantly higher frequency of HTT IAs (13.6% vs. 2.9% controls). For the ATXN2 gene, we observed an increase in IA frequency in AD cases (AD 4.1% vs. controls 1.8%) and in the behavioral FTD group (4.8% vs. 1.8%). For the ATXN1 gene, we found a significant increase of IAs in patients with PNFA (18.6%) versus controls (6.7%). In conclusion, our work suggests that the HTT and ATXN1 IAS may contribute to PNFA pathogenesis and point to a link between ATXN2 IAS and AD.


Assuntos
Doença de Alzheimer/genética , Ataxina-1/genética , Ataxina-2/genética , Demência Frontotemporal/genética , Proteína Huntingtina/genética , Doença de Parkinson/genética , Repetições de Trinucleotídeos , Proteína C9orf72/genética , Estudos de Coortes , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Expansão das Repetições de Trinucleotídeos
7.
Nutr Hosp ; 35(4): 841-846, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30070872

RESUMO

BACKGROUND: iodine contributes to maintain the balance of the reduced and oxidized species and is also required for thyroid hormones synthesis as triiodothyronine (T3), which regulates energy metabolism in adults. Increased body mass index (BMI) is associated with inflammatory markers, oxidative stress, and abnormalities in adipocytokines secretions that are associated with obesity and chronic disease. OBJECTIVE: the aim of the study is to investigate the association between ioduria, oxidative stress, total antioxidant status, adiponectin and interleukin-1 (IL-1) with BMI in healthy adults. METHODS: a cross-sectional study was performed in 114 healthy adult volunteers, aged 25-44 years, divided according to their BMI in three groups: normal weight (BMI < 25), overweight (BMI ≤ 25 to < 30), obesity (BMI ≥ 30). Adiponectin and IL-1 were measured by immune-enzymatic assays; oxidative stress, by determination of malondialdehyde (MDA); and total antioxidant status (TAS) and ioduria were measured by colorimetric assays. Statistical association was done by Spearman's test. RESULTS: overweight and obese subjects have higher serum levels of MDA, TAS and IL-1 vs normal weight subjects. Moreover, overweight and obese subjects have lower levels of iodine and adiponectin vs normal weight subjects. MDA was positively related only with obese subjects (r = 0.787, p = 0.008) and TAS with overweight (r = 0.398, p = 0.049) and obese subjects (r = 0.448, p = 0.030). In contrast, a reverse correlation with ioduria was found in obese subjects (r = 0.463, p = 0.001). Adiponectin was negatively related only in obese subjects (r = -0.477, p = 0.001), while, IL-1 was positively related with the increase of BMI (overweight r = 0.287, p = 0.050; and obesity r = 0.515, p = 0.006). CONCLUSION: alteration in IL-1, adiponectin and oxidative stress levels were found to be related to overweight and obesity; also, iodine levels decreased when BMI increased, contributing to loss of redox equilibrium. All this data may play an important role in etiopathogenesis of chronic disease related to the increase of BMI.


Assuntos
Adiponectina/sangue , Índice de Massa Corporal , Interleucina-1/sangue , Iodo/urina , Estresse Oxidativo , Adipocinas/sangue , Adulto , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Obesidade/sangue , Sobrepeso/sangue , Fatores Socioeconômicos
8.
Clin Biochem ; 50(9): 481-484, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28109748

RESUMO

BACKGROUND: Chronic use of proton pump inhibitors (PPIs) leads to increases in gastrin and pepsinogen-I serum concentrations. AIM: To asses if chronic treatment with PPIs has an effect on serum gastrin and pepsinogen-I concentrations for the diagnosis of pernicious anaemia (PA). MATERIALS AND METHODS: Serum gastrin and pepsinogen-I were measured in 38 patients with PA and 74 without PA (controls); 17/38 PA patients and 36/74 controls were treated with PPIs. Receiver Operating Curves (ROC) were used to compare diagnostic accuracy of gastrin and pepsinogen-I for PA in patients under chronic treatment with PPIs and in untreated patients. RESULTS: PPI treatment increased pepsinogen-I in patients and in controls, while gastrin increased only in controls. In untreated patients, a pepsinogen-I <8.3ng/mL had 95.2% sensitivity and 100% specificity, whereas a gastrin >115pg/mL had 100% sensitivity and 92.11% specificity for PA diagnosis. In PPI-treated patients, a pepsinogen I<24.1ng/mL had a lower sensitivity (82.4%) but retained 100% specificity, however the best cut-off point for gastrin, 610pg/mL, had a very low sensitivity (58%). CONCLUSIONS: PPI chronic treatment decreased the diagnostic accuracy for the studied biomarkers, particularly of gastrin. In PPI-treated patients, serum pepsinogen-I concentrations >24.1ng/mL allowed rejecting a PA diagnosis with 100% specificity.


Assuntos
Anemia Perniciosa/sangue , Gastrinas/sangue , Pepsinogênio A/sangue , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/farmacocinética , Estudos Retrospectivos
9.
Nutr Hosp ; 34(3): 661-666, 2017 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-28627204

RESUMO

BACKGROUND: The antioxidant function of iodine and iodine deficiency as a risk factor of preeclampsia have been previously reported. AIM: To analyze the association between iodine deficiency, oxidative stress and antioxidant status with hypertensive disease of pregnancy (HPD). METHOD: Fifty-seven pregnant women were recruited in the last trimester of pregnancy; 20 were diagnosed with hypertensive disease (HPD) of pregnancy and 37 were normotensive pregnant women. Urinary iodine concentration (UIC), TSH, free T4 (fT4), total antioxidant status (FRP), superoxide dismutase (SOD), catalase (CAT), and oxidative stress (TBARS) were evaluated by colorimetric methods. RESULTS: UIC median for all pregnant women was 151.9 µg/l. The UIC for pregnant women with HPD was 50-149 µg/l, compared to 150-249 µg/l in normotensive women. No significant differences in levels of TSH and fT4 in normotensive pregnant compared with HPD women were found. Pregnant women with HPD had significant high levels of TBARS, and significant low levels of FRP, SOD, CAT and UIC compared to normotensive pregnant. In addition, pregnant women with optimal levels of UIC had a higher SOD activity (r = 0.354, p = 0.011), while iodine deficiency was associated with HPD (r = -0,281, p = 0.039). Similarly, pregnant women with HPD had a significant negative association with SOD activity (r = -0.702, p = 0.005), CAT (r = -0.409, p = 0.002), and FRP (r = -0.624, p = 0.003), and a positive association with TBARS (r = 0.744, p = 0.001). CONCLUSION: Iodine contributes to redox balance during pregnancy; its deficiency is associated with HPD. This study shows the importance of iodine during pregnancy.


Assuntos
Antioxidantes/metabolismo , Hipertensão Induzida pela Gravidez/metabolismo , Iodo/urina , Estresse Oxidativo/fisiologia , Adolescente , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , México/epidemiologia , Estado Nutricional , Gravidez , Adulto Jovem
10.
Clin Biochem ; 49(3): 295-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26562029

RESUMO

OBJECTIVES: Primary hyperaldosteronism (PHA) is one of the most common endocrine forms of secondary hypertension. Among the most used confirmatory tests for PHA is urinary aldosterone determination after oral sodium loading test. The primary aim of our study was to investigate if sodium concentrations interfere with urinary aldosterone in an automated competitive immunoassay (Liaison®) as well as to verify the manufacturer's specifications. DESIGN AND METHODS: 24-hr urine samples were collected and stored frozen until assayed. Two pools at low and high aldosterone concentrations were prepared. Verification of performance for precision was tested according to Clinical and Laboratory Standards Institute (CLSI) document EP15-A2 and interference with increasing concentrations of NaCl according to CLSI EP7-A2. RESULTS: The assay met the quality specifications according to optimal biological variation. Our results show that sodium concentrations up to 200mmol/L do not interfere on urinary aldosterone quantification, but sodium concentrations above 486mmol/L negatively interfere with the test. CONCLUSIONS: The Liaison® automated method is useful for aldosterone determination in the PHA confirmatory test, but interferences with NaCl may occur. It is therefore recommended to determine urinary NaCl before measuring urinary aldosterone to avoid falsely low results.


Assuntos
Aldosterona/urina , Imunoensaio/métodos , Sódio/urina , Aldosterona/química , Humanos , Hiperaldosteronismo/urina , Hipertensão , Reprodutibilidade dos Testes , Sódio/química , Cloreto de Sódio/metabolismo
11.
J Hazard Mater ; 267: 9-16, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24413046

RESUMO

Starvation and changing feeding conditions are frequently characteristics of wastewater treatment plants. They are typical causes of unsteady-state operation of biological systems and provoke cellular stress. The response of a membrane bioreactor functioning under feed-induced stress conditions is studied here. In order to simplify and considerably amplify the response to stress and to obtain a reference model, a pure culture of Pseudomonas putida was selected instead of an activated sludge and a sole substrate (salicylic acid) was employed. The system degraded salicylic acid at 100-1100mg/L with a high level of efficiency, showed rapid acclimation without substrate or product inhibition phenomena and good stability in response to unsteady states caused by feed variations. Under starvation conditions, specific degradation rates of around 15mg/gh were achieved during the adaptation of the biomass to the new conditions and no biofilm formation was observed during the first days of experimentation using an initial substrate to microorganisms ratio lower than 0.1. When substrate was added to the reactor as pulses resulting in rapidly changing concentrations, P. putida growth was observed only for substrate to microorganism ratios higher than 0.6, with a maximum YX/S of 0.5g/g. Biofilm development under changing feeding conditions was fast, biomass detachment only being significant for biomass concentrations on the membrane surface that were higher than 16g/m(2).


Assuntos
Reatores Biológicos/microbiologia , Pseudomonas putida/metabolismo , Ácido Salicílico/toxicidade , Poluentes Químicos da Água/toxicidade , Algoritmos , Biofilmes , Biomassa , Filtração , Concentração de Íons de Hidrogênio , Membranas Artificiais , Pseudomonas putida/efeitos dos fármacos , Esgotos/química , Espectrofotometria Ultravioleta
12.
Nutr. hosp ; 35(4): 841-846, jul.-ago. 2018. tab
Artigo em Inglês | IBECS (Espanha) | ID: ibc-179876

RESUMO

Background: iodine contributes to maintain the balance of the reduced and oxidized species and is also required for thyroid hormones synthesis as triiodothyronine (T3), which regulates energy metabolism in adults. Increased body mass index (BMI) is associated with inflammatory markers, oxidative stress, and abnormalities in adipocytokines secretions that are associated with obesity and chronic disease. Objective: the aim of the study is to investigate the association between ioduria, oxidative stress, total antioxidant status, adiponectin and interleukin-1 (IL-1) with BMI in healthy adults. Methods: a cross-sectional study was performed in 114 healthy adult volunteers, aged 25-44 years, divided according to their BMI in three groups: normal weight (BMI < 25), overweight (BMI ≤ 25 to < 30), obesity (BMI ≥ 30). Adiponectin and IL-1 were measured by immune-enzymatic assays; oxidative stress, by determination of malondialdehyde (MDA); and total antioxidant status (TAS) and ioduria were measured by colorimetric assays. Statistical association was done by Spearman’s test. Results: overweight and obese subjects have higher serum levels of MDA, TAS and IL-1 vs normal weight subjects. Moreover, overweight and obese subjects have lower levels of iodine and adiponectin vs normal weight subjects. MDA was positively related only with obese subjects (r = 0.787, p = 0.008) and TAS with overweight (r = 0.398, p = 0.049) and obese subjects (r = 0.448, p = 0.030). In contrast, a reverse correlation with ioduria was found in obese subjects (r = 0.463, p = 0.001). Adiponectin was negatively related only in obese subjects (r = -0.477, p = 0.001), while, IL-1 was positively related with the increase of BMI (overweight r = 0.287, p = 0.050; and obesity r = 0.515, p = 0.006).Conclusion: alteration in IL-1, adiponectin and oxidative stress levels were found to be related to overweight and obesity; also, iodine levels decreased when BMI increased, contributing to loss of redox equilibrium. All this data may play an important role in etiopathogenesis of chronic disease related to the increase of BMI


Antecedentes: el yodo contribuye a mantener el balance de especies reducidas y oxidadas y también es requerido para la síntesis de hormonas tiroideas como la triyodotironina (T3), que regula el metabolismo energético en el adulto. El incremento en el índice de masa corporal esta asociado con marcadores inflamatorios, estrés oxidativo y anormalidades en la secreción de adipocitocinas que están asociadas con la obesidad y enfermedades crónicas degenerativas. Objetivo: el objetivo del estudio es investigar la asociación entre yodaría, estrés oxidativo, estado antioxidante total, adiponectina, e interleucina 1, con el IMC en adultos saludables. Métodos: se realizo un estudio transversal con 114 adultos, 33 hombres y 81 mujeres, de entre 25 y 44 años, a los cuales se les midieron sus características clínicas, antropométricas y parámetros sociodemográficos. Los niveles de adiponectina e interleucina 1 se midieron por inmunoensayo; el estrés oxidativo, el estado antioxidante total y la yodaría, por métodos colorimétricos. Resultados: los sujetos con sobrepeso y obesidad tienen altos niveles de MDA, FRAP e IL-1 vs. los sujetos con peso normal. Sin embargo, los sujetos con sobrepeso y obesidad tienen bajos niveles de yodo y adiponectina vs. los sujetos con normopeso. El estrés oxidativo (MDA) se relacionó positivamente solo en sujetos obesos (r = 0,787, p = 0,008) y el estado antioxidante (FRAP) con sobrepeso (r = 0,398, p = 0,049) y obesidad (r = 0,448, p = 0,030). En contraste, se encontró una asociación entre yoduria y sujetos obesos (r = 0,463, r = 0,001). Los niveles de adiponectina se relacionaron negativamente solo en sujetos obesos (r = -0,477, p = 0,001), mientras que la IL-1 fue positivamente relacionada con el incremento de BMI (sobrepeso r = 0,287, p = 0,050; y obesidad r = 0,515, p = 0,006). Conclusión: La alteración en los niveles de interleucina-1, adiponectina y estrés oxidativo se relacionaron en sujetos con sobrepeso y obesidad; además, los niveles de yodo disminuyeron con el incremento del IMC, contribuyendo a la pérdida del equilibrio redox. Estos datos juegan un papel importante en la etiopatogenesis relacionada con enfermedades crónicas relacionadas con el incremento del IMC


Assuntos
Humanos , Masculino , Feminino , Adulto , Adiponectina/sangue , Índice de Massa Corporal , Interleucina-1/sangue , Iodo/urina , Estresse Oxidativo , Adipocinas/sangue , Estudos Transversais , Voluntários Saudáveis , Obesidade/sangue , Sobrepeso/sangue , Fatores Socioeconômicos
13.
Int J Nanomedicine ; 8: 2141-51, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23788833

RESUMO

A biodegradable polymeric system is proposed for formulating peptides and proteins. The systems were assembled through the adsorption of biodegradable polymeric nanoparticles onto porous, biodegradable microspheres by an adsorption/infiltration process with the use of an immersion method. The peptide drug is not involved in the manufacturing of the nanoparticles or in obtaining the microspheres; thus, contact with the organic solvent, interfaces, and shear forces required for the process are prevented during drug loading. Leuprolide acetate was used as the model peptide, and poly(d,l-lactide-co-glycolide) (PLGA) was used as the biodegradable polymer. Leuprolide was adsorbed onto different amounts of PLGA nanoparticles (25 mg/mL, 50 mg/mL, 75 mg/mL, and 100 mg/mL) in a first stage; then, these were infiltrated into porous PLGA microspheres (100 mg) by dipping the structures into a microsphere suspension. In this way, the leuprolide was adsorbed onto both surfaces (ie, nanoparticles and microspheres). Scanning electron microscopy studies revealed the formation of a nanoparticle film on the porous microsphere surface that becomes more continuous as the amount of infiltrated nanoparticles increases. The adsorption efficiency and release rate are dependent on the amount of adsorbed nanoparticles. As expected, a greater adsorption efficiency (~95%) and a slower release rate were seen (~20% of released leuprolide in 12 hours) when a larger amount of nanoparticles was adsorbed (100 mg/mL of nanoparticles). Leuprolide acetate begins to be released immediately when there are no infiltrated nanoparticles, and 90% of the peptide is released in the first 12 hours. In contrast, the systems assembled in this study released less than 44% of the loaded drug during the same period of time. The observed release profiles denoted a Fickian diffusion that fit Higuchi's model (t(1/2)). The manufacturing process presented here may be useful as a potential alternative for formulating injectable depots for sensitive hydrophilic drugs such as peptides and proteins, among others.


Assuntos
Química Farmacêutica/métodos , Preparações de Ação Retardada , Ácido Láctico/química , Microesferas , Nanopartículas/química , Ácido Poliglicólico/química , Adsorção , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Leuprolida/química , Leuprolida/farmacocinética , Modelos Químicos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade
14.
Nutr. hosp ; 34(3): 661-666, mayo-jun. 2017. tab
Artigo em Inglês | IBECS (Espanha) | ID: ibc-164124

RESUMO

Background: The antioxidant function of iodine and iodine deficiency as a risk factor of preeclampsia have been previously reported. Aim: To analyze the association between iodine deficiency, oxidative stress and antioxidant status with hypertensive disease of pregnancy (HPD). Method: Fifty-seven pregnant women were recruited in the last trimester of pregnancy; 20 were diagnosed with hypertensive disease (HPD) of pregnancy and 37 were normotensive pregnant women. Urinary iodine concentration (UIC), TSH, free T4 (fT4), total antioxidant status (FRP), superoxide dismutase (SOD), catalase (CAT), and oxidative stress (TBARS) were evaluated by colorimetric methods. Results: UIC median for all pregnant women was 151.9 μg/l. The UIC for pregnant women with HPD was 50-149 μg/l, compared to 150-249 μg/l in normotensive women. No significant differences in levels of TSH and fT4 in normotensive pregnant compared with HPD women were found. Pregnant women with HPD had significant high levels of TBARS, and significant low levels of FRP, SOD, CAT and UIC compared to normotensive pregnant. In addition, pregnant women with optimal levels of UIC had a higher SOD activity (r = 0.354, p = 0.011), while iodine deficiency was associated with HPD (r = -0,281, p = 0.039). Similarly, pregnant women with HPD had a significant negative association with SOD activity (r = -0.702, p = 0.005), CAT (r = -0.409, p = 0.002), and FRP (r = -0.624, p = 0.003), and a positive association with TBARS (r = 0.744, p = 0.001). Conclusion: Iodine contributes to redox balance during pregnancy; its deficiency is associated with HPD. This study shows the importance of iodine during pregnancy (AU)


Antecedentes: previamente se han reportado la función antioxidante del yodo y su deficiencia como un factor de riesgo de preeclampsia. Objetivo: analizar la asociación entre la deficiencia de yodo, el estrés oxidativo y el estado antioxidante con la enfermedad hipertensiva del embarazo (HPD). Métodos: cincuenta y siete mujeres embarazadas se reclutaron en el último trimestre del embarazo, 20 diagnosticadas de enfermedad hipertensiva del embarazo y 37 gestantes normotensas. La concentración urinaria de yodo (UIC), TSH, T4 libre (hT4), estado antioxidante total (FRP), superóxido dismutasa (SOD), catalasa (CAT), y estrés oxidativo (TBARS) se evaluaron por métodos colorimétricos. Resultados: la mediana de UIC para todas las mujeres embarazadas fue de 151,9 μg/l. La UIC para las mujeres embarazadas con HPD fue de entre 50 y 149 μg/l, comparada con 150-249 μg/l de las gestantes normotensas. No se encontraron diferencias significativas entre los niveles de TSH y fT4 en embarazadas normotensas y en mujeres con HPD. Las mujeres embarazadas con HPD tuvieron niveles altos de TBARS y niveles bajos de FRP, SOD, CAT y UIC comparadas con las gestantes normotensas. Además, las mujeres gestantes con niveles óptimos de UIC tuvieron la actividad SOD más alta (r = 0,354, p = 0,011), mientras que la deficiencia de yodo se asoció con HPD (r = -0,281, p = 0,039). De manera similar, las gestantes con HPD tuvieron una asociación negativa con la actividad de SOD (r = -0,702, p = 0,005), CAT (r = -0,409, p = 0,002) y FRP (r = -0,624, p = 0,003), y una asociación positiva con TBARS (r = 0,744, p = 0,001). Conclusión: el yodo coadyuva en el balance redox durante la gestación; su deficiencia está asociada con HPD. Este estudio muestra la importancia del yodo durante la gestación (AU)


Assuntos
Humanos , Feminino , Gravidez , Estresse Oxidativo , Antioxidantes/fisiologia , Hipertensão/tratamento farmacológico , Deficiência de Iodo/tratamento farmacológico , Fatores de Risco , Pré-Eclâmpsia/epidemiologia , Estudos de Casos e Controles , Deficiência de Iodo/prevenção & controle , Colorimetria/métodos , Tireotropina/análise , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia
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