RESUMO
Binding of dinitrosyl iron complex (DNIC) to albumin was studied using time-resolved fluorescence (TRF) and electron spin resonance (ESR) spectroscopy. It was found that the fluorescence lifetime of bovine serum albumin (BSA) and human serum albumin (HSA) decreases with binding and depends on DNIC concentration. The observed biexponential pattern of the BSA tryptophan (Trp) fluorescence decay is explained by the presence of two tryptophan residues in the protein molecule. We believe that DNIC forms stable complexes with the cysteine (Cys34) residue in the domain I of albumin. It was shown that the lifetime of albumin tryptophan fluorescence decreased during co-incubation of BSA with DNICs and glutathione. Effects of DNIC on the binding of specific spin-labeled fatty acids with albumin in human blood plasma were studied in vitro. The presence of DNIC in blood plasma does not change conformation of albumin domains II and III. We suggest that the most possible interaction between DNICs and albumin is the formation of a complex; and nitrosylation of the cysteine residue in the albumin domain I occurs without the changes in albumin conformation.
Assuntos
Ferro/farmacologia , Óxidos de Nitrogênio/farmacologia , Soroalbumina Bovina/efeitos dos fármacos , Albumina Sérica/efeitos dos fármacos , Albumina Sérica/metabolismo , Adulto , Idoso , Animais , Bovinos , Espectroscopia de Ressonância de Spin Eletrônica , Glutationa/química , Humanos , Ferro/química , Masculino , Pessoa de Meia-Idade , Óxidos de Nitrogênio/química , Conformação Proteica , Albumina Sérica/química , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Espectrometria de FluorescênciaRESUMO
Fluorine toxicity has negative effects on soft tissue besides skeletal and dental tissues. In the present study, we have investigated the protective effect of chitosan (CS) and chitosan oligosaccharide (COS) on liver tissue of fluorine-intoxicated rats taking the antioxidant characteristics of chitosan and its derivatives into consideration. In this study, 42 male Wistar albino rats were randomly selected to determine the control and experimental fluorosis groups. Our study lasted for 12 weeks. As a consequence of the study, MDA significantly increased in the liver tissue of NaF group while some antioxidant values significantly decreased. It was detected that serum AST and LDH levels increased significantly while ALB and TP values significantly decreased in NaF group. The degenerations were identified in the liver histopathology of all fluoride-treated groups. We have concluded according to the results that chitosan oligosaccharide can be more effective compared with chitosan.
Assuntos
Antioxidantes/farmacologia , Quitosana/farmacologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fluoreto de Sódio/toxicidade , Animais , Aspartato Aminotransferases/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Proteínas Sanguíneas/efeitos dos fármacos , Proteínas Sanguíneas/metabolismo , Quitosana/análogos & derivados , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , L-Lactato Desidrogenase/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Oligossacarídeos/farmacologia , Ratos , Ratos Wistar , Albumina Sérica/efeitos dos fármacos , Albumina Sérica/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
The gadolinium-based nanoagent named AGuIX® is a unique radiosensitizer and contrast agent which improves the performance of radiotherapy and medical imaging. Currently tested in clinical trials, AGuIX® is administrated to patients via intravenous injection. The presence of nanoparticles in the blood stream may induce harmful effects due to undesired interactions with blood components. Thus, there is an emerging need to understand the impact of these nanoagents when meeting blood proteins. In this work, the influence of nanoagents on the structure and stability of the most abundant blood protein, human serum albumin, is presented. Synchrotron radiation circular dichroism showed that AGuIX® does not bind to the protein, even at the high ratio of 45 nanoparticles per protein at 3 mg/L. However, it increases the stability of the albumin. Isothermal thermodynamic calorimetry and fluorescence emission spectroscopy demonstrated that the effect is due to preferential hydration processes. Thus, this study confirms that intravenous injection of AGuIX® presents limited risks of perturbing the blood stream. In a wider view, the methodology developed in this work may be applied to rapidly evaluate the impact and risk of other nano-products that could come into contact with the bloodstream.
Assuntos
Meios de Contraste/efeitos adversos , Gadolínio/efeitos adversos , Nanopartículas/efeitos adversos , Albumina Sérica/efeitos dos fármacos , Calorimetria , Dicroísmo Circular , Humanos , Espectrometria de Fluorescência , Testes de ToxicidadeRESUMO
Diabetic nephropathy (DN) is a multifactorial disease characterized by hyperglycemia and close interaction of hemodynamic, metabolic and inflammatory factors. Nuclear factor-κB (NF-κB) is a principal matchmaker linking hyperglycemia and inflammation. The present work investigates the cell-permeable peptide containing the inhibitor of kappa B kinase γ (IKKγ)/NF-κB essential modulator (NEMO)-binding domain (NBD) as therapeutic option to modulate inflammation in a preclinical model of type 2 diabetes (T2D) with DN. Black and tan, brachyuric obese/obese mice were randomized into 4 interventions groups: Active NBD peptide (10 and 6 µg/g body weight); Inactive mutant peptide (10 µg/g); and vehicle control. In vivo/ex vivo fluorescence imaging revealed efficient delivery of NBD peptide, systemic biodistribution and selective renal metabolization. In vivo administration of active NBD peptide improved albuminuria (>40% reduction on average) and kidney damage, decreased podocyte loss and basement membrane thickness, and modulated the expression of proinflammatory and oxidative stress markers. In vitro, NBD blocked IKK-mediated NF-κB induction and target gene expression in mesangial cells exposed to diabetic-like milieu. These results constitute the first nephroprotective effect of NBD peptide in a T2D mouse model that recapitulates the kidney lesions observed in DN patients. Targeting IKK-dependent NF-κB activation could be a therapeutic strategy to combat kidney inflammation in DN.
Assuntos
Peptídeos Penetradores de Células/administração & dosagem , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intracelular/química , Albumina Sérica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Sítios de Ligação , Linhagem Celular , Peptídeos Penetradores de Células/farmacologia , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/diagnóstico por imagem , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Células RAW 264.7 , Distribuição Aleatória , Distribuição Tecidual , Resultado do TratamentoRESUMO
Objective: To investigate the effect of 6% hydroxyethyl starch 130/0.4(HES) on protein in severe trauma orthopedic patients after acute hemodilution. Methods: Fourty-eight severe trauma patients who met the inclusion criteria were selected from June 2018 to December 2018 in Yantaishan Hospital, and were randomly divided into two groups (n=24): group A and group B. Group A was ringer's sodium lactate control group, and group B was HES treatment group. After the tracheal intubation, the patients of group A were infused with 10% blood volume of sodium lactate ringer at 0.5 ml·kg(-1)·min(-1), and the patients in group B were infused with 10% blood volume of HES at 0.5 ml·kg(-1)·min(-1). Total protein (TP), human serum albumin (HSA), numbers of circulating endothelium cells (CEC), C-reactive protein (CRP), and serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10 and IL-6 were measured immediately after acute hemodilution (T(0)), 24 hours (T(1)) and 48 hours (T(2)) after acute hemodilution. After infusion into human body, HES bond to HSA, and fluorescence spectroscopy was used to analyze the binding relationship between HES and HSA in order to further study the effects of HES on HSA. Results: The HSA, TP, CEC, TNF-α, IL-6, IL-10, CRP at T(0) of group A were (38±5) g/L, (66±5) g/L, (5.5±0.4)/0.9 µl, (24±5) µg/L, (8.9±0.8) µg/L, (44±6) µg/L, (13.6±1.4) mg/L; While at T(1) were (33±5) g/L, (60±6) g/L, (10.2±0.7)/0.9 µl, (87±9) µg/L, (38.8±2.3) µg/L, (57±7) µg/L, (23.4±2.4) mg/L. The HSA, TP, CEC, TNF-α, IL-6, IL-10, CRP at T(0) of group B were(38±4)g/L, (66±5) g/L, (5.4±0.6)/0.9 µl, (24±6) µg/L, (9.1±0.9) µg/L, (45±6) µg/L, (13.4±1.8) mg/L; While at T(1) were (35±5)g/L, (62±5)g/L, (7.4±0.6)/0.9 µl, (70±8) µg/L, (29.5±3.1) µg/L, (72±6) µg/L, (19.7±2.2) mg/L. HSA and TP decreased at T(1) in group A as compared with T(0) (P<0.05), contrarily CEC increased significantly at T(1), TNF-É, IL-6, IL-10 and CRP augmented at T(1) and T(2) in two groups (P<0.05). In comparison with the patients of group A, CEC decreased significantly at T(1) (P<0.05). TNF-É, IL-6, CRP reduced significantly at T(1) and T(2) (P<0.05), but IL-10 increased at T(1) and T(2) in group B (P<0.05). The secondary structure of HSA changed after HES was added in the HES solution. The fluorescence intensity of HSA decreased with the increase of HES concentration,which suggested that HES induced HSA fluorescence quenching. HES could bind to Trp-214 residue in HSA at a molecular ration of 1â¶1. Conclusions: 6% HES reduces the occurrence of low protein level in severe trauma patients after operation. HES could bind to Trp-214 amino acid residue in HSA and form the complex at a molecular ratio of 1â¶1. The formation of HES-HSA complex increases the volume of HES, avoids the vascular leakage, protects the vascular endothelial cells, and induces anti-inflammatory immunity in the patients with capillary syndrome.
Assuntos
Células Endoteliais , Derivados de Hidroxietil Amido/farmacologia , Albumina Sérica , Hemodiluição , Humanos , Lactato de Ringer , Albumina Sérica/efeitos dos fármacosRESUMO
A series of novel naphthalimide-benzimidazoles was designed and synthesized for the first time and studied for their effect on antiproliferative activity. Some of these compounds possessed good antitumor activity towards the tested cancer cell lines. Noticeably, (diethylamino)ethyl 15 and (dimethylamino)ethyl 23 derivatives displayed superior antiproliferative activity towards human cancer cell lines with MG_MID GI50 values of 1.43 and 1.83 µM, respectively. Preliminary investigation revealed that compounds 15 and 23 might bind with ct-DNA through the intercalation mode which is responsible for potent bioactivity. Moreover, transportation behaviour indicated that these molecules could efficiently bind to and be carried by bovine albumin, and the hydrogen bonding and hydrophobic interactions played important roles in interaction with serum albumin.
Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Naftalimidas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Benzimidazóis/química , Bovinos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA/química , DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Naftalimidas/química , Albumina Sérica/química , Albumina Sérica/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
L-Lysine (Lys) is a popular additive in foods, but the physiological effects of excess Lys supplementation are poorly understood and upper limits of safe intake have not been established. The objectives of this study were to examine the effects of dietary supplementation with increasing amounts of Lys on body weight (BW), food intake, and various blood hematological and biochemical parameters in rats. Male Sprague-Dawley rats at 10 weeks of age were assigned to ten diet groups (eight rats/group) and fed diets containing either 7% or 20% casein and supplemented with either 0% (Control), 1.5%, 3%, 6% Lys, or 6% Lys + 3% arginine for 1 week. Rats fed 7% casein with ≥ 1.5% Lys supplementation had lower serum albumin and leptin and higher LDL cholesterol (LDLC), ratios of total cholesterol (TC):HDL cholesterol (HDLC) and LDLC:HDLC than those fed 7% casein Control diet (P < 0.05). Rats fed 7% casein diet supplemented with 3% Lys diet had lower BW gain, food intake, serum alkaline phosphatase activity, and increased mean corpuscular hemoglobin concentration, blood urea nitrogen and serum pancreatic polypeptide compared to rats fed the Control diet (P < 0.05). Addition of 6% Lys in 7% casein caused significant BW loss (P < 0.001) and altered additional parameters. Addition of 6% Lys in a 20% casein diet reduced BW gain and food intake and altered numerous parameters. Arg supplementation normalized many of the endpoints changed by Lys. Collectively, these results show that Lys supplementation affects BW, food intake and a number of hematological and biochemical parameters. These effects of Lys supplementation were confined primarily in diets with lower levels of dietary protein. In the context of a low protein diet (7% casein), levels of Lys supplementation ≥ 1.5% may exert adverse health effects in rats.
Assuntos
Lisina/efeitos adversos , Lisina/farmacologia , Ração Animal , Animais , Composição Corporal/fisiologia , Peso Corporal/efeitos dos fármacos , Caseínas/análise , HDL-Colesterol/análise , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/análise , LDL-Colesterol/efeitos dos fármacos , Dieta , Suplementos Nutricionais , Ingestão de Alimentos , Leptina/análise , Leptina/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Albumina Sérica/análise , Albumina Sérica/efeitos dos fármacos , Aumento de PesoRESUMO
Edifenphos (EDF), an important organophosphate fungicide used in agriculture, is a great threat to human health and environment. To assess the toxicity of EDF at the level of protein molecule, the effect of EDF on human serum albumin (HSA) was investigated by biophysical and biochemical approaches. EDF-HSA complex is formed as a result of static quenching as revealed by the intrinsic fluorescence analysis. Thermodynamic analysis of the binding data suggests involvement of hydrophobic interactions in EDF-HSA complex formation, which is in line with molecular docking results. Moreover, thermodynamic parameters of binding between EDF and HSA suggest entropy-driven spontaneous interaction, presumably dominated by hydrophobic forces. Further, binding site of EDF seems to have been located within sub-domain IIA of HSA. EDF binding to HSA decreases its alpha helical content as analyzed by CD spectra. Marked micro-environmental changes around tryptophan/tyrosine residues in HSA upon EDF binding were recorded via three-dimensional fluorescence spectroscopy. Substantial release of protein carbonyl from HSA as a result of EDF treatment suggested involvement of ROS in EDF induced protein damage. This work is expected to provide some leads toward EDF induced toxicity in humans and would be helpful in reinforcing the check on food safety.
Assuntos
Fungicidas Industriais/metabolismo , Compostos Organotiofosforados/metabolismo , Albumina Sérica/metabolismo , Sítios de Ligação , Dicroísmo Circular , Fungicidas Industriais/toxicidade , Humanos , Interações Hidrofóbicas e Hidrofílicas , Compostos Organotiofosforados/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Albumina Sérica/efeitos dos fármacos , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , TermodinâmicaRESUMO
Mycophenolic acid (MPA) has been shown to be promising for the treatment of autoimmune diseases in dogs and cats. In humans, MPA is highly bound to plasma proteins (~97%). It has been recommended to monitor free drug plasma concentrations because the free MPA correlates with its immunosuppressive effect. However, it is unknown if MPA is highly bound to plasma proteins in dogs and cats. The objectives of this study were to determine the extent of plasma protein binding of MPA and evaluate the effect of prednisolone and dexamethasone on the extent of protein binding of MPA in dogs and cats. The extent of plasma protein binding of MPA was determined in plasma collected from clinically healthy adult cats (n = 13) and dogs (n = 14) by combining high-throughput dialysis and ultra-high-liquid chromatography. This study reveals that MPA is highly bound to plasma proteins (>90%) in dogs and cats, mean extent of binding of MPA at 15 µg/ml to plasma proteins being 96% (range, 95%-97%) and 92% (range, 90%-93%) for dogs and cats, respectively. In dog plasma, MPA is primarily bound to albumin. In vitro, prednisolone increased the unbound MPA in dogs (p < .01) but not in cats (p = .07) while dexamethasone had no effect on MPA plasma binding in either species (p > .05). Results of this study provide valuable information for designing future pharmacokinetic and pharmacodynamic studies and also therapeutic monitoring programs for dogs and cats.
Assuntos
Proteínas Sanguíneas/metabolismo , Dexametasona/farmacologia , Imunossupressores/metabolismo , Ácido Micofenólico/metabolismo , Prednisolona/farmacologia , Animais , Proteínas Sanguíneas/efeitos dos fármacos , Gatos , Cromatografia Líquida de Alta Pressão/veterinária , Dexametasona/administração & dosagem , Cães , Interações Medicamentosas , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/sangue , Prednisolona/administração & dosagem , Albumina Sérica/efeitos dos fármacos , Albumina Sérica/metabolismoRESUMO
BACKGROUND: In patients with locally advanced esophageal cancer treated by concurrent chemoradiotherapy (CCRT), baseline malnutrition and its progression have been shown to be associated with a poor outcome. We conducted this study to determine the variation in four blood test parameters including serum albumin level (ALB), creatinine (Cre), hemoglobin (Hb) and platelet (Plt) during CCRT for stage III esophageal cancer patients and its effect on patients' outcome. METHODS: One hundred eighty-three patients diagnosed with stage III esophageal cancer were retrospectively investigated. In addition to known prognostic factors, baseline level of the four blood test parameters and their variation at day 105 (ΔALB, ΔCre, ΔHb and ΔPlt, respectively) were analyzed. RESULTS: The median observation period for patients who survived was 57.2 months, and the 5-year overall survival rate was 35.6% (95% CI 34.2-36.9%). In multivariate analyses, baseline ALB (≥ 3.6 g/dL), higher ΔALB (≥ + 0.3 g/dL) were independent predictors for overall survival (p = 0.001 and < 0.001, respectively), in addition to other clinical factors including T stage and overall treatment time (OTT). For disease-free survival, ΔALB was only a predictor in hematological parameters (p = 0.001) in addition to T stage and OTT. No hematological and clinical parameters had significant correlation with local control in multivariate analysis. Furthermore, ΔALB showed significant correlation with OS and DFS in log-rank test (p = 0.002 and 0.002, respectively). CONCLUSIONS: Our results suggest improvement in ALB after treatment might be a favorable prognostic factor in esophageal cancer patients treated by CCRT.
Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/tratamento farmacológico , Albumina Sérica/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estado Nutricional , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Retrospectivos , Albumina Sérica/efeitos dos fármacos , Taxa de SobrevidaRESUMO
C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation-based prognostic score, was first developed as a prognostic score for septic patients. Recent reports show that CRP/Alb ratio is also a prognostic score for cancer patients, including esophageal cancer. However, the role of CRP/Alb ratio for those with neoadjuvant chemotherapy (NAC) and the changes of CRP/Alb ratio around NAC have never been discussed. The aim of this study is to evaluate the significance of CRP/Alb ratio around NAC for patients with cStage II/III esophageal squamous cell cancer (ESCC). A total of 149 patients who were diagnosed as cStage II/III ESCC were enrolled between February 2007 and December 2014. We retrospectively investigated the relation between pre-NAC and post-NAC CRP/Alb ratio and short and long outcomes. The optimal cutoff level for pre-NAC and post-NAC CRP/Alb ratio was 0.030 and 0.048, respectively. There was no relation between CRP/Alb ratio level and postoperative outcomes. Post-NAC CRP/Alb ratio < 0.048 had a significantly higher overall survival rate than CRP/Alb ratio ≥0.048 (P< 0.001). Univariate analysis showed that cT, cN, pre-NAC CRP/Alb ratio < 0.030 and post-NAC CRP/Alb ratio < 0.048 was prognostic factors (P= 0.003, P= 0.022, P= 0.033, and P< 0.001, respectively). Multivariate analysis showed that cT and post-NAC CRP/Alb ratio < 0.048 was independent prognostic factors (P= 0.030 and P< 0.001, respectively). Post-NAC CRP/Alb ratio is an independent prognostic factor in patients with cStage II/III ESCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína C-Reativa/metabolismo , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/terapia , Albumina Sérica/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proteína C-Reativa/efeitos dos fármacos , Carcinoma de Células Escamosas/secundário , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Neoplasias Esofágicas/patologia , Esofagectomia , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Albumina Sérica/efeitos dos fármacos , Taxa de SobrevidaRESUMO
Oxidative stress has the main role in protein conformational changes and consequent direct involvement in different kind of diseases. Potassium sorbate as a widespread industrial preservative and glucose are two important oxidants that can be involved in oxidative stress. In this study the effect of ellagic acid as a phenolic antioxidant on amyloid fibril formation of human serum albumin upon incubation of potassium sorbate and glucose was studied using thioflavin T assay, surface tension, atomic force microscopy, Amadori product, and carbonyl content assays. The thioflavin T assay and atomic force microscopy micrographs demonstrated the antiamyloidogenic effect of ellagic acid on the human serum albumin fibril formation. This antioxidant also had the repair effect on surface tension of the modified human serum albumin (amyloid intermediates), which was destructed, caused by potassium sorbate and glucose. This mechanism takes place because of potent carbonyl stress suppression effect of ellagic acid, which was strengthening by potassium sorbate in the presence and absence of glucose.
Assuntos
Ácido Elágico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Albumina Sérica/efeitos dos fármacos , Glucose/efeitos adversos , Glicosilação , Humanos , Conformação Proteica , Albumina Sérica/química , Albumina Sérica/ultraestrutura , Ácido Sórbico/efeitos adversos , Tensão Superficial/efeitos dos fármacosRESUMO
BACKGROUND: Massive postoperative ascites remains a major threat that can lead to liver failure and other fatal complications, especially in patients with poor liver function. Branched-chain amino acid (BCAA) administration increases biosynthesis and secretion of albumin by hepatocytes and increases oncotic pressure by elevating blood albumin concentration, thereby decreasing peripheral edema, ascites, and pleural effusion. METHOD: We randomly allocated consecutive patients undergoing major liver resection for hepatocellular carcinoma to either a group where oral BCAA administration was initiated 3 weeks before liver resection, or a non-BCAA group. The primary study endpoint was development of postoperative ascites. RESULTS: Overall, 39 patients were allocated to the BCAA group, while 38 were assigned to the non-BCAA group. No significant difference in the rate of refractory ascites, considered alone, was evident between the BCAA (5.1 %) and non-BCAA groups (13.2 %; p = 0.263). However, the occurrence of refractory ascites and/or pleural effusion was significantly less frequent in the BCAA group (5.1 %) than in the non-BCAA group (21.1 %; p = 0.047). Furthermore, the postoperative serum concentration of reduced-state albumin was greater immediately after liver resection in the BCAA group than in the non-BCAA group. CONCLUSION: Preoperative administration of BCAA did not significantly improve prevention of refractory ascites, but significant effectiveness in preventing ascites, pleural effusion, or both, as well as improving metabolism of albumin, was demonstrated [University Hospital Medical Information Network (UMIN) reference number 000004244].
Assuntos
Aminoácidos de Cadeia Ramificada/uso terapêutico , Ascite/prevenção & controle , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Feminino , Hepatectomia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Derrame Pleural/prevenção & controle , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios , Albumina Sérica/efeitos dos fármacos , Albumina Sérica/metabolismoRESUMO
Polycyclic Aromatic Hydrocarbons (PAHs) are discharged into aquatic environments through anthropogenic activities mainly industrial and municipal effluents. There is little information on the adverse effects of pyrene, a member of the PAH family which is classified as a priority pollutant by the USEPA, on fish biochemical and physiological endpoints, particularly thyroid hormones. The present study investigated the effects of subacute semi-static pyrene exposure on biochemical, enzymological and ionoregulatory responses as well as thyroid hormones in common carp (Cyprinus carpio). The fish (140±10g, 1(+) year) were exposed to 10, 50 and 100µg/l nominal concentrations of pyrene for 35 days. The results revealed that pyrene at these concentrations significantly altered plasma levels of glucose, cholesterol, triglyceride, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Moreover, plasma thyroid hormones (T3 and T4) were significantly decreased in fish exposed to pyrene. In contrast, plasma electrolytes (sodium, potassium and calcium) levels remained statistically unchanged after exposure to the various pyrene concentrations. In conclusion, the studied biomarkers may be used as monitoring tools to evaluate pyrene toxicity. Pyrene induced diverse effects on the physiological endpoints of common carp, thus this chemical should be considered in toxicity studies concerning PAHs. Furthermore, this study confirmed that there was an interaction between pyrene and the thyroid system in fish. Therefore, the thyroid system may be used to assess the impact of pyrene on fish.
Assuntos
Carpas/sangue , Pirenos/toxicidade , Tiroxina/sangue , Tri-Iodotironina/sangue , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Colesterol/sangue , Albumina Sérica/efeitos dos fármacos , Hormônios Tireóideos , Triglicerídeos/sangueRESUMO
BACKGROUND AND OBJECTIVES: The main objective of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with subclinical (SHypo) and overt hypothyroidism (OHypo), and to assess the effects of levothyroxine (LT4) therapy on the oxidative stress (OS) parameters. We also investigated the relationships among serum thyroid hormones, lipid parameters, and IMA and MDA in these patients. DESIGN AND METHODS: Thirty untreated patients with OHypo, 25 untreated patients with Shypo, and 30 age- and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters including IMA and MDA were evaluated in all patients just before and one month after the maintenance of euthyroidism. RESULTS: Compared with the control subjects, the levels of MDA and triglycerides (TG) significantly increased in patients with SHypo (p < 0.001 and p < 0.05, respectively), whereas high density lipoprotein cholesterol (HDL-C) levels significantly decreased (p = 0.01). Patients with OHypo showed significantly high MDA, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and TG levels (p = 0.001, p < 0.01, p = 0.01, and p < 0.01, respectively), and significantly low HDL-C levels compared with the controls (p < 0.05). MDA levels and lipid profile were not significantly different in the patients with OHypo when compared with the patients with SHypo. Serum IMA levels did not significantly change in patients with OHypo and SHypo compared with the controls. In the pre-treatment period, MDA levels were inversely correlated with HDL-C levels in patients with OHypo (r: -0.471, p = 0.009). Plasma MDA and LDL-C levels significantly decreased and HDL-C levels significantly increased in the groups of OHypo and SHypo after LT4 treatment. Serum IMA levels did not significantly change with the therapy in all patient groups. CONCLUSIONS: Increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis seen in these patients. Increased OS in patients with SHypo and OHypo could be improved by LT4 treatment. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.
Assuntos
Terapia de Reposição Hormonal/métodos , Hipotireoidismo , Malondialdeído/sangue , Albumina Sérica , Tiroxina/farmacologia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Albumina Sérica/efeitos dos fármacos , Albumina Sérica Humana , Tiroxina/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Marmoset wasting syndrome (MWS) is one of the leading causes of morbidity and mortality in captive marmosets, and thus far no reliable treatment has been found. Glucocorticoids are used widely to treat inflammatory conditions of the GI tract such as human and feline inflammatory bowel disease, which, such as MWS, are histologically characterized by chronic lymphoplasmacytic inflammation in the intestines. Budesonide is a glucocorticoid with few reported side effects due to the majority of it being metabolized into inactive compounds by the liver before entering the systemic circulation. METHOD: Eleven marmosets presented with antemortem signs consistent with MWS and were treated with oral prednisone or budesonide for 8 weeks. RESULTS: The marmosets in our study demonstrated a significant increase in both weight and albumin levels (relative to pre-treatment values) after glucocorticoid therapy. CONCLUSIONS: Glucocorticoids are an effective therapy to ameliorate the clinical signs associated with MWS with minimal side effects.
Assuntos
Budesonida/administração & dosagem , Callitrichinae , Glucocorticoides/administração & dosagem , Doenças dos Macacos/tratamento farmacológico , Prednisona/administração & dosagem , Síndrome de Emaciação/veterinária , Animais , Budesonida/farmacologia , Glucocorticoides/farmacologia , Prednisona/farmacologia , Albumina Sérica/efeitos dos fármacos , Síndrome de Emaciação/tratamento farmacológico , Redução de Peso/efeitos dos fármacosRESUMO
OBJECTIVE: Evaluate the performance of glycated albumin (GA) monitoring by comparing it to other measures of glycemic control during intensification of antidiabetic therapy. METHODS: This 12-week, prospective, multicenter study compared the diagnostic clinical performance of GA to glycated hemoglobin A1C (A1C), fructosamine corrected for albumin (FRA), fasting plasma glucose (FPG), and mean blood glucose (MBG) estimated from self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) in 30 patients with suboptimally controlled type 1 or 2 diabetes. RESULTS: Mean A1C decreased from 9.5% to 8.1%. Mean SMBG correlated closely with CGM (Pearson r = 0.783 for daily estimates and r = 0.746 for weekly estimates, P<.0001). Both GA and FRA levels significantly correlated with changes from baseline in A1C and mean weekly SMBG (P<.001). The lowest observed median GA occurred at 4 weeks, followed by a small increase and then a slight reduction, mirroring changes in overall mean SMBG values. The median A1C fell throughout the treatment period, failing to reflect short-term changes in SMBG. A ≥1% reduction in GA at 4 weeks was significantly associated with a ≥0.5% change in A1C at 12 weeks (odds ratio [OR] = 19.0, 95% confidence interval [CI]: 1.4, 944, P = .018). CONCLUSION: In patients receiving glucose-lowering therapy, changes in GA at 4 weeks were concordant with changes in A1C at 12 weeks, and both GA and FRA more accurately reflected short-term blood glucose fluctuations than A1C.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/metabolismo , Albumina Sérica/metabolismo , Adulto , Idoso , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia/instrumentação , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Frutosamina/sangue , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Produtos Finais de Glicação Avançada , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Albumina Sérica/análise , Albumina Sérica/efeitos dos fármacos , Fatores de Tempo , Albumina Sérica GlicadaRESUMO
The reactivity of parthenolide (PRT), a natural sesquiterpene lactone from Tanacetum parthenium (Asteraceae), with human serum albumin (HSA) was studied by UHPLC/+ESI-QqTOF MS analysis after tryptic digestion of albumin samples after incubation with this compound. It was found that the single free cysteine residue, C34, of HSA (0.6 mM) reacted readily with PRT when incubated at approximately 13-fold excess of PRT (8 mM). Time-course studies with PRT and its 11ß,13-dihydro derivative at equimolar ratios of the reactants revealed that PRT under the chosen conditions reacts preferably with C34 and does so exclusively via its α-methylene-γ-lactone moiety, while the epoxide structure is not involved in the reaction.
Assuntos
Extratos Vegetais/farmacologia , Albumina Sérica/efeitos dos fármacos , Sesquiterpenos/farmacologia , Cisteína/química , Humanos , Extratos Vegetais/química , Albumina Sérica/química , Sesquiterpenos/química , Tanacetum parthenium/químicaRESUMO
Advanced glycation end products (AGEs), which are the final products of glycation, have a major role in diabetic complication and neurodegenerative disorders. The 3-ß-hydroxybutyrate (3BHB), a ketone body which is produced by the liver, can be detected in increased concentrations in individuals post fasting and prolonged exercises and in diabetic (type I) patients. In this study, the inhibitory effect of 3BHB on AGEs formation by glucose from the human serum albumin (HSA) was studied at physiological conditions after 35 days of incubation, using physical techniques such as circular dichroism and fluorescence spectroscopy, as well as differential scanning calorimetry (DSC). The fluorescence intensity measurements of glycated HSA by glucose (GHSA) in the presence of 3BHB indicate a decrease in AGEs formation. The DSC deconvolution profile results also confirm the protective role of 3BHB on incubated with glucose by preventing the enthalpy reduction of the HSA tail segment, compared with the deconvolution profile seen for incubated with glucose alone. The concentration of 3BHB used in this study is in accordance with the concentration detected in the body of individuals post fasting and prolonged exercises.
Assuntos
Complicações do Diabetes/metabolismo , Glucose/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Albumina Sérica/efeitos dos fármacos , Ácido 3-Hidroxibutírico/administração & dosagem , Varredura Diferencial de Calorimetria , Dicroísmo Circular , Complicações do Diabetes/patologia , Exercício Físico/fisiologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/química , Glicosilação/efeitos dos fármacos , Humanos , Albumina Sérica/metabolismo , Espectrometria de Fluorescência , TermodinâmicaRESUMO
BACKGROUND: Most studies have demonstrated 4-NQO toxicity to oral epithelium during oral carcinogenesis induction, but systemic toxicity has been poorly addressed. The aim of this study was to describe the systemic effect of 4-NQO topical application during early phases of oral cancer induction. METHODS: A 4-NQO propylene glycol ointment was topically applied on the rat tongue three times a week for 16 weeks. Local and systemic 4-NQO toxicity was evaluated by body weight gain, hematology, and serum chemistry analyses, histopathology, and proliferating cell nuclear antigen (PCNA) immunohistochemistry. RESULTS: Significant reduction in body weight gain and in white blood cell count as well as significant increase in serum ALT and AST was observed after 16 weeks of 4-NQO topical application. Focal hepatic lobular necrosis, renal tubular degeneration, and decreased cellularity in the splenic white pulp were also detected. CONCLUSIONS: 4-NQO topical application on the tongue of rats for 16 weeks seems to have caused hepatic, renal, and splenic toxicity. Potential systemic toxicity should be considered to monitor for variables that could interfere in topical oral carcinogenesis experiments.