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1.
Int J Mol Sci ; 25(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000056

RESUMO

The lack of specific biological materials and biomarkers limits our knowledge of the mechanisms underlying intrauterine regulation of iron supply to the fetus. Determining the meconium content of proteins commonly used in the laboratory to assess the transport, storage, and distribution of iron in the body may elucidate their roles in fetal development. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and calprotectin were determined by ELISA in meconium samples obtained from 122 neonates. There were strong correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL (p < 0.05). Meconium concentrations of ferritin were several-fold higher than the concentrations of the other proteins, with the exception of calprotectin whose concentration was approximately three-fold higher than that of ferritin. Meconium ceruloplasmin concentration significantly correlated with the concentrations of MPO, NGAL, lactoferrin, and calprotectin. Correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL may reflect their collaborative involvement in the storage and transport of iron in the intrauterine environment in line with their recognized biological properties. High meconium concentrations of ferritin may provide information about the demand for iron and its utilization by the fetus. The associations between ceruloplasmin and neutrophil proteins may indicate the involvement of ceruloplasmin in the regulation of neutrophil activity in the intrauterine environment.


Assuntos
Ceruloplasmina , Haptoglobinas , Ferro , Lipocalina-2 , Mecônio , Humanos , Ferro/metabolismo , Mecônio/metabolismo , Recém-Nascido , Ceruloplasmina/metabolismo , Feminino , Haptoglobinas/metabolismo , Lipocalina-2/metabolismo , Transferrina/metabolismo , Transferrina/análise , Ferritinas/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Lactoferrina/metabolismo , Lactoferrina/análise , Masculino , Peroxidase/metabolismo , Biomarcadores/metabolismo , Adulto
2.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39000114

RESUMO

Early diagnosis and treatment of chronic kidney disease (CKD) is a worldwide challenge. Subjects with albumin-to-creatinine ratio (ACR) ≥ 30 mg/g and preserved renal function are considered to be at no cardiorenal risk in clinical practice, but prospective clinical studies evidence increased risk, even at the high-normal (HN) ACR range (10-30 mg/g), supporting the need to identify other molecular indicators for early assessment of patients at higher risk. Following our previous studies, here we aim to stratify the normoalbuminuria range according to cardiorenal risk and identify the glycoproteins and N-glycosylation sites associated with kidney damage in subclinical CKD. Glycoproteins were analyzed in urine from hypertensive patients within the HN ACR range compared to control group (C; ACR < 10 mg/g) by mass spectrometry. A different cohort was analyzed for confirmation (ELISA) and sex perspective was evaluated. Patients' follow-up for 8 years since basal urine collection revealed higher renal function decline and ACR progression for HN patients. Differential N-glycopeptides and their N -glycosylation sites were also identified, together with their pathogenicity. N-glycosylation may condition pathological protein deregulation, and a panel of 62 glycoproteins evidenced alteration in normoalbuminuric subjects within the HN range. Haptoglobin-related protein, haptoglobin, afamin, transferrin, and immunoglobulin heavy constant gamma 1 (IGHG1) and 2 (IGHG2) showed increased levels in HN patients, pointing to disturbed iron metabolism and tubular reabsorption and supporting the tubule as a target of interest in the early progression of CKD. When analyzed separately, haptoglobin, afamin, transferrin, and IGHG2 remained significant in HN, in both women and men. At the peptide level, 172 N-glycopeptides showed differential abundance in HN patients, and 26 showed high pathogenicity, 10 of them belonging to glycoproteins that do not show variation between HN and C groups. This study highlights the value of glycosylation in subjects not meeting KDIGO criteria for CKD. The identified N-glycopeptides and glycosylation sites showed novel targets, for both the early assessment of individual cardiorenal risk and for intervention aimed at anticipating CKD progression.


Assuntos
Glicopeptídeos , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Glicopeptídeos/urina , Insuficiência Renal Crônica/urina , Pessoa de Meia-Idade , Glicosilação , Idoso , Biomarcadores/urina , Creatinina/urina , Glicoproteínas/urina , Progressão da Doença , Albuminúria/urina , Fatores de Risco , Haptoglobinas/metabolismo
3.
Nutr Diabetes ; 14(1): 48, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951151

RESUMO

BACKGROUND: This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk. METHODS: This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14-16 weeks' gestation for Hp genotyping. GDM was diagnosed between 24-28 weeks' gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk. RESULTS: Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2-2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk. CONCLUSION: Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2-2 genotype.


Assuntos
Diabetes Gestacional , Genótipo , Haptoglobinas , Hemoglobinas , Primeiro Trimestre da Gravidez , Humanos , Feminino , Gravidez , Diabetes Gestacional/genética , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Haptoglobinas/genética , Estudos Retrospectivos , Adulto , Hemoglobinas/análise , China/epidemiologia , Fatores de Risco , Povo Asiático/genética , Hemoglobinas Glicadas/análise , Glicemia/análise , Glicemia/metabolismo , Resistência à Insulina/genética , População do Leste Asiático
4.
Wiad Lek ; 77(4): 732-738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865630

RESUMO

OBJECTIVE: Aim: To investigate the effectiveness of rifaximin and probiotics for the correction of intestinal permeability in patients with metabolic-associated fatty liver disease (MAFLD) in combination with type 2 diabetes mellitus. PATIENTS AND METHODS: Materials and Methods: The prospective interventional randomized investigation included 68 patients with MAFLD in combination with type 2 diabetes, who were examined and divided into the 2 groups of treatment. RESULTS: Results: The serum levels of interleukin (IL) - 6, IL-10 and zonulin, indicators of liver functional activity, liver attenuation coefficient between treatment group vs. control group after 2 weeks, 1 month, 3 and 6 months of therapy were significant differed. The serum levels of IL-6 and zonulin significantly decreasing and increasing of IL-10 in the treatment group after 2 weeks, 1, 3 and 6 months of combined therapy. When comparing of stool short-chain fatty acids concentration between treatment group vs. control group after 2 weeks, 1 month, 3 and 6 months of therapy the levels of acetic, butyric and propionic acids significantly differences and increase in their levels were established. CONCLUSION: Conclusions: The results of the study in dynamics during 6 months show that the additional appointment of rifaximin, multispecies probiotic and prebiotic to metformin in patients with MAFLD and type 2 diabetes led to the elimination of subclinical inflammation, modulation of the permeability of the intestinal barrier and lowering increased intestinal permeability, as well as to the lower serum activity of liver aminotransferases and decrease the stage of steatosis.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Permeabilidade , Probióticos , Rifaximina , Humanos , Rifaximina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Permeabilidade/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Haptoglobinas/metabolismo , Rifamicinas/uso terapêutico , Rifamicinas/administração & dosagem , Resultado do Tratamento , Adulto , Interleucina-6/sangue , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Precursores de Proteínas/sangue , Função da Barreira Intestinal
5.
Calcif Tissue Int ; 115(2): 132-141, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38829421

RESUMO

Sarcopenia is related to disease severity in chronic kidney disease (CKD) patients; however, its pathophysiology remains poorly known. We investigated the associations of biomarkers of intestinal leak with sarcopenia in various stages of CKD. We recruited 61-76-year-old male controls and patients with various stages of CKD (n = 36-57/group) for measuring plasma lipopolysaccharide-binding protein (LBP) and zonulin (markers of intestinal leak), handgrip strength (HGS), skeletal mass index (SMI), and gait speed (markers of sarcopenia), and short physical performance battery (SPPB; marker of physical capacity). CKD stages 4 and 5 were associated with lower HGS, SMI, gait speed, and cumulative SPPB scores and a higher sarcopenia prevalence than controls and patients with CKD stages 1 and 2 (all p < 0.05). CKD patients (stages 1 and 2) had elevated plasma zonulin and LBP when compared with CKD stages 4 and 5. Plasma zonulin and LBP exhibited significant correlations with renal function, HGS, gait speed, SPPB scores, and oxidative stress markers in CKD stages 4 and 5 (all p < 0.05). However, similar relations were not found in early CKD. Collectively, intestinal leak may be contributing to sarcopenia and physical disability in the advanced stages of CKD.


Assuntos
Insuficiência Renal Crônica , Sarcopenia , Humanos , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/sangue , Sarcopenia/sangue , Sarcopenia/fisiopatologia , Sarcopenia/epidemiologia , Idoso , Pessoa de Meia-Idade , Biomarcadores/sangue , Força da Mão/fisiologia , Haptoglobinas , Precursores de Proteínas/sangue
6.
Clin Chim Acta ; 561: 119829, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38917868

RESUMO

BACKGROUND-AIM: Pregnancy induces physiological changes that can affect serologic and immunologic markers, potentially resulting in lower or undetectable haptoglobin values compared to non-pregnant counterparts. Such variations may lead to inaccurate diagnosis of hemolysis. METHODS: We report a case of a patient in second trimester of pregnancy receiving induction chemotherapy due to B-cell acute lymphocytic leukemia with undetectable haptoglobin levels in a routine laboratory sample collected less than 12 h posttransfusion of red cell unit. Despite undetectable haptoglobin, lactate dehydrogenase (LD) was within reference intervals (RI). The patient was evaluated for acute hemolytic transfusion reaction (AHTR) and followed up. Haptoglobin levels showed an upward trend during follow-up visits, reaching 15 mg/dL, and within RI in the third trimester. RESULTS: The patient did not meet the Center for Disease Control (CDC) criteria for AHTR. Alternative explanations for the observed laboratory findings were explored. Undetectable haptoglobin levels were attributed to various factors, including recent RBC transfusion, pregnancy-related physiological changes, and potential hyperhydration treatment plan due to chemotherapy. CONCLUSION: This case underscores the importance of cautious interpretation of laboratory results in pregnant patients, necessitating trimester-specific reference intervals for haptoglobin. A multidisciplinary approach to patient care is crucial for accurate diagnosis and management.


Assuntos
Haptoglobinas , Humanos , Haptoglobinas/análise , Haptoglobinas/metabolismo , Feminino , Gravidez , Adulto , Hemólise
7.
Clin Nutr ESPEN ; 62: 157-163, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38901937

RESUMO

AIMS: Patients with chronic obstructive pulmonary disease (COPD) frequently exhibit an inability to maintain postural balance. However, the contribution of increased intestinal permeability or leaky gut to the postural imbalance in COPD is not known. METHODS: We measured plasma zonulin, a marker of leaky gut, with relevance to postural balance in male controls (n = 70) and patients with mild (n = 67), moderate (n = 66), and severe (n = 58) COPD. We employed a short physical performance battery to evaluate postural balance in supine, tandem, and semi-tandem positions. We also measured handgrip strength (HGS), gait speed, plasma c-reactive proteins (CRP), and 8-isoprostanes as potential mechanistic connections between postural imbalance and leaky gut. RESULTS: COPD patients demonstrated higher plasma zonulin, CRP, and 8-isoprostanes levels and lower balance, HGS, and gait speed than controls (all p < 0.05). These findings were more robust in patients with moderate and severe than mild COPD. In addition, plasma zonulin exhibited significant potential in diagnosing poor balance, low HGS, and gait speed in COPD patients (all p < 0.05). We also found significant correlations of plasma zonulin with CRP and 8-isoprostanes, providing heightened inflammation and oxidative stress as mechanistic connections between leaky gut and postural imbalance. CONCLUSION: Plasma zonulin may be helpful in evaluating postural imbalance in COPD patients. Repairing intestinal leaks can be a therapeutic target to improve postural control in COPD.


Assuntos
Biomarcadores , Proteína C-Reativa , Haptoglobinas , Equilíbrio Postural , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Pessoa de Meia-Idade , Proteína C-Reativa/metabolismo , Biomarcadores/sangue , Força da Mão , Precursores de Proteínas/sangue , Toxina da Cólera/sangue , Estudos de Casos e Controles , Permeabilidade , Dinoprosta/análogos & derivados
8.
Biomed Khim ; 70(2): 114-124, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38711411

RESUMO

Existing knowledge on changes of the haptoglobin (Hp) molecule suggests that it may exist in multiple proteoforms, which obviously exhibit different functions. Using two-dimensional electrophoresis (2DE) in combination with mass spectrometry and immunodetection, we have analyzed blood plasma samples from both healthy donors and patients with primary grade IV glioblastoma (GBM), and obtained a detailed composite 2DE distribution map of ß-chain proteoforms, as well as the full-length form of Hp (zonulin). Although the total level of plasma Hp exceeded normal values in cancer patients (especially patients with GBM), the presence of particuar proteoforms, detected by their position on the 2DE map, was very individual. Variability was found in both zonulin and the Hp ß-chain. The presence of an alkaline form of zonulin in plasma can be considered a conditional, but insufficient, GBM biomarker. In other words, we found that at the level of minor proteoforms of Hp, even in normal conditions, there was a high individual variability. On the one hand, this raises questions about the reasons for such variability, if it is present not only in Hp, but also in other proteins. On the other hand, this may explain the discrepancy between the number of experimentally detected proteoforms and the theoretically possible ones not only in Hp, but also in other proteins.


Assuntos
Glioblastoma , Haptoglobinas , Precursores de Proteínas , Haptoglobinas/análise , Haptoglobinas/metabolismo , Haptoglobinas/química , Humanos , Feminino , Masculino , Glioblastoma/sangue , Glioblastoma/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Idoso , Eletroforese em Gel Bidimensional/métodos , Adulto
9.
Anim Sci J ; 95(1): e13960, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807417

RESUMO

During parturition, cows often experience intense pain and stress, which increases the risk of inflammatory diseases. This study aimed to compare the postpartum health status between healthy cows and those diagnoses with inflammatory diseases by examining behavioral and heart rate (HR) variability (HRV) changes, to provide information before the onset of disease. Eight Holstein cows were used in this study. HR, parameters of HRV (low-frequency power: LF; high-frequency power: HF; LF/HF ratio, and total power) and time budget of individual maintenance behaviors (standing, recumbency, feeding, rumination while standing and lying, and sleep) were continuously recorded from 0 to 168 h postpartum. Milk and blood samples were collected daily. Cows were categorized as diseases based on the positive result of California mastitis test and/or serum haptoglobin concentration that exceeded 50 µg/ml after all blood samples have been collected. Compared to healthy individuals (n = 3), diseased cows (n = 5) exhibited higher HR, LF/HF, and lower total power (p < 0.05), suggesting the dominance of the sympathetic nervous system in cows with inflammatory diseases. Additionally, diseased cows showed an increased standing time budget and reduced recumbency (p < 0.05), which may be a behavioral strategy in response to discomfort from inflammation.


Assuntos
Comportamento Animal , Doenças dos Bovinos , Frequência Cardíaca , Inflamação , Período Pós-Parto , Animais , Bovinos/fisiologia , Feminino , Período Pós-Parto/fisiologia , Frequência Cardíaca/fisiologia , Comportamento Animal/fisiologia , Inflamação/sangue , Doenças dos Bovinos/fisiopatologia , Doenças dos Bovinos/sangue , Haptoglobinas/metabolismo , Haptoglobinas/análise , Sistema Nervoso Simpático/fisiologia , Parto/fisiologia , Dor/veterinária , Nível de Saúde
10.
Food Res Int ; 186: 114338, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729719

RESUMO

Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.


Assuntos
Jejum , Peptídeo 2 Semelhante ao Glucagon , Obesidade , Permeabilidade , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/metabolismo , Feminino , Adulto , Jejum/sangue , Masculino , Peptídeo 2 Semelhante ao Glucagon/sangue , Mucosa Intestinal/metabolismo , Microbioma Gastrointestinal , Nutrientes , Adulto Jovem , Haptoglobinas/metabolismo , Endotoxemia , Receptores de Lipopolissacarídeos/sangue , Proteínas de Fase Aguda/metabolismo , Biomarcadores/sangue , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/metabolismo , Gorduras na Dieta , Glucose/metabolismo , Função da Barreira Intestinal , Proteínas de Transporte , Precursores de Proteínas
12.
Bioessays ; 46(7): e2400053, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38713161

RESUMO

Trypanosoma brucei is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long-term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, T. brucei acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin-hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent findings on the structure and cell biology of the receptors.


Assuntos
Trypanosoma brucei brucei , Tripanossomíase Africana , Trypanosoma brucei brucei/imunologia , Trypanosoma brucei brucei/metabolismo , Humanos , Animais , Tripanossomíase Africana/imunologia , Tripanossomíase Africana/parasitologia , Haptoglobinas/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/imunologia , Transferrina/metabolismo , Hemoglobinas/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/imunologia , Interações Hospedeiro-Parasita/imunologia , Ferro/metabolismo , Anticorpos Antiprotozoários/imunologia
13.
Braz J Cardiovasc Surg ; 39(3): e20230272, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748856

RESUMO

INTRODUCTION: Prevention of acute kidney injury during cardiopulmonary bypass (CPB) is still a challenge and has been the object of numerous studies. The incidence of acute kidney injury in the context of CPB is related to a multifactorial etiology. The role of hemadsorption in relation to cell-free hemoglobin and haptoglobin preservation is not well defined in the literature on CPB during cardiac surgery procedures. METHODS: This is a single-center pilot randomized report including 20 patients undergoing elective CPB procedures with an expected time > 120 minutes for each extracorporeal procedure. Patients were randomly allocated to either standard of care (n=10) or Jafron HA380 (n=10) during CPB. The primary outcome measured was the incidence of postoperative acute kidney injuries. RESULTS: The Jafron study group vs. control group reported postoperative values for cell-free hemoglobin at 10 minutes after CPB (mg/L) (11.6 ± 0.6 vs. 29.9 ± 0.3) (P-value 0.021), haptoglobin 10 minutes after CPB (mg/dl) (129.16 ± 1.22 vs. 59.17 ± 1.49) (P-value 0.017), creatinine peak after CPB (mg/dL) (0.92 ± 0.17 vs. 1.32 ± 0.9) (P-value 0.030), and acute kidney injury after 48 hours (number of patients) (one vs. four) (P-value 0.027). CONCLUSION: This pilot study suggested that the use of Hemoperfusion Cartridge HA380 Jafron for extended CPB time for complex cardiac surgery procedures was safe and effective and is associated with a better postoperative preservation of haptoglobin with a reduction of cell-free hemoglobin values and less incidence of acute kidney injury, though larger studies are warranted to confirm our result.


Assuntos
Injúria Renal Aguda , Ponte Cardiopulmonar , Haptoglobinas , Hemoglobinas , Humanos , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/etiologia , Haptoglobinas/análise , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Masculino , Projetos Piloto , Feminino , Pessoa de Meia-Idade , Hemoglobinas/análise , Idoso , Fatores de Tempo , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Resultado do Tratamento
14.
Nutrients ; 16(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732615

RESUMO

Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m2) were enrolled and randomly assigned to intervention (n = 30) or placebo (n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved (p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased (p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.


Assuntos
Carnosina , Suplementos Nutricionais , Lactoferrina , Magnésio , Músculo Esquelético , Permeabilidade , Sarcopenia , Humanos , Masculino , Idoso , Feminino , Sarcopenia/tratamento farmacológico , Sarcopenia/prevenção & controle , Carnosina/administração & dosagem , Lactoferrina/administração & dosagem , Lactoferrina/farmacologia , Magnésio/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Permeabilidade/efeitos dos fármacos , Idoso de 80 Anos ou mais , Valeratos/administração & dosagem , Valeratos/farmacologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Butiratos , Método Duplo-Cego , Haptoglobinas , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Precursores de Proteínas
15.
Rheumatol Int ; 44(8): 1487-1499, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38743252

RESUMO

BACKGROUND: A significant number of patients with axial spondyloarthritis (axSpA) do not respond to biological therapy. Therefore, we decided to investigate the specificity of this group of patients and, in particular, whether haptoglobin (Hp), its polymorphism and zonulin, in addition to other clinical features, are predictors of poor response to biological treatment. METHODS: 48 patients with axSpA who were unsuccessfully treated with standard drugs were converted to biological treatment, and from this time on, a 12-week follow-up was started to assess the failure of biological treatment (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decrease < 2 points). Predictors of treatment failure were identified using logistic regression analysis. RESULTS: 21% of subjects had biological treatment failure. Patients who had a higher zonulin level, a history of frequent infections, were older, had inflammatory bowel disease (IBD), had a lower Hp level at the time of inclusion in biological therapy showed an increased risk of treatment failure. CONCLUSIONS: The results of the study support the hypothesis that the effectiveness of biological treatment of axSpA is limited by changed microbiota and intestinal epithelial barrier dysfunction, as an increased risk of biological treatment failure was observed in patients who were older, had higher zonulin level, IBD and repeated courses of antibiotics due to frequent infections. Therefore, starting biological treatment should be followed by reducing intestinal permeability and regulating the disturbed gut microbiome.


Assuntos
Espondiloartrite Axial , Toxina da Cólera , Disbiose , Haptoglobinas , Permeabilidade , Falha de Tratamento , Humanos , Feminino , Masculino , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Espondiloartrite Axial/tratamento farmacológico , Precursores de Proteínas , Microbioma Gastrointestinal , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Polimorfismo Genético , Fatores de Risco , Função da Barreira Intestinal
16.
Acta Trop ; 254: 107215, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38604328

RESUMO

The livestock sector of Pakistan is increasing rapidly and it plays important role both for rural community and national economy. It is estimated that almost 8 million rural people are involved in livestock rearing and earning about 35-40 % of their income from the livestock sector. Mycoplasma bovis (M. bovis) infection causes significant economic losses in dairy animals especially young calf in the form of clinical illnesses such as pneumonia, poly-arthritis, respiratory distress and mortality. M. bovis is hard to diagnose and control because of uneven disease appearance and it is usually noticed in asymptomatic animals. For the identification of M. bovis in sub-clinical and clinical samples, determination of acute phase proteins i.e., haptoglobin (Hp) and serum amyloid A (SAA) are important tools for the timely diagnosis of disease. Therefore, early diagnosis of disease and hemato-biochemical changes are considered beneficial tools to control the infectious agent to uplift the economy of the dairy farmers. For this purpose, blood samples were collected from 200 calves of Bovidae family. Serum was separated from blood samples to determine the concentration of Hp and SAA, while blood samples were processed to determine hematological changes in blood from calves by using hematological analyzer. The blood plasma obtained from the blood samples was processed to measure oxidative stress factors. Lungs tissues from slaughterhouses/ morbid calves were collected to observe histopathological changes. The results of present study indicated that level of SAA and Hp remarkably increased (P < 0.05) in M. bovis infected calves in comparison to healthy calves. The oxidative stress markers indicated that nitric oxide and MDA levels in the infected calves increased significantly (P < 0.05), while infected claves had considerably lower levels of superoxide dismutase, catalase and glutathione. These findings indicate that oxidative stress play role to increase the level of APPs, while monitoring of APPs levels may serve as a valuable addition to the clinical evaluation of naturally infected calves with M. bovis. The hematological parameters were decreased significantly (P < 0.05). Altogether, this study suggests that Hp and SAA are proposed as promising biomarkers for detecting naturally occurring M. bovis infection in calves.


Assuntos
Biomarcadores , Doenças dos Bovinos , Haptoglobinas , Infecções por Mycoplasma , Mycoplasma bovis , Proteína Amiloide A Sérica , Animais , Haptoglobinas/análise , Haptoglobinas/metabolismo , Bovinos , Proteína Amiloide A Sérica/análise , Infecções por Mycoplasma/veterinária , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/sangue , Infecções por Mycoplasma/microbiologia , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/sangue , Biomarcadores/sangue , Paquistão , Pulmão/patologia , Pulmão/microbiologia , Estresse Oxidativo
17.
Shock ; 61(6): 828-835, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38661177

RESUMO

ABSTRACT: Background: Hemolysis is a frequent complication in patients with sepsis, ARDS, or extracorporeal membrane oxygenation (ECMO). Haptoglobin (Hp) can scavenge released cell-free hemoglobin (CFH). Hemolysis and low plasma concentrations of Hp may be independently associated with mortality in critically ill patients. Methods: This study used a retrospective analysis of 435 patients with ARDS and veno-venous ECMO therapy, admitted to a tertiary ARDS referral center (01/2007-12/2018). Hp depletion was defined as decrease in plasma Hp concentration <0.39 g/L within the first week after ECMO initiation. Patients with Hp depletion were compared to patients without Hp depletion. The primary endpoint was 28-day mortality. Secondary endpoints included organ dysfunction-free, renal replacement therapy-free, vasopressor-free, and ECMO-free composites. Results: Patients with Hp depletion (n = 269) had a significantly higher mortality 28 days after ECMO initiation compared to patients without Hp depletion (43.5% [95% CI 37.52-49.66] vs. 25.3% [19.03-32.74], P < 0.001). Furthermore, patients with Hp depletion had fewer organ dysfunction-free days (subdistribution hazard ratio [SHR] 0.35 [95% CI 0.25-0.50], P < 0.001), lower chances for successful weaning from renal replacement therapy (SHR 0.50 [0.32-0.79], P < 0.001), vasopressor therapy (SHR 0.39 [0.28-0.54], P < 0.001), and ECMO therapy (SHR 0.41 [0.30-0.57], P < 0.001) within 28 days after ECMO initiation. Patients with initial Hp <0.66 g/L had higher risks for Hp depletion than patients with initial Hp ≥0.66 g/L. Conclusion: Patients with Hp depletion within the first week of ECMO therapy might benefit from close monitoring of hemolysis with early detection and elimination of the underlying cause. They might be potential candidates for future Hp supplementation therapy to prevent overload of the CFH-scavenger system.


Assuntos
Oxigenação por Membrana Extracorpórea , Haptoglobinas , Síndrome do Desconforto Respiratório , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/mortalidade , Estudos Retrospectivos , Adulto , Idoso
18.
Nutrients ; 16(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674918

RESUMO

As gluten may trigger gastrointestinal disorders (GIDs), its presence or absence in the diet can change the diversity and proportion of gut microbiota. The effects of gluten after six weeks of a double-blind, placebo-controlled intervention with a gluten-free diet (GFD) were studied in participants with GIDs suffering from migraines and atopic dermatitis (n = 46). Clinical biomarkers, digestive symptoms, stool, the Migraine Disability Assessment questionnaire, and zonulin levels were analyzed. Next-generation sequencing was used to amplify the 16S rRNA gene of bacteria and the internal transcribed spacer (ITS) regions of fungi. The GFD increased Chao1 fungal diversity after the intervention, while the fungal composition showed no changes. Bacterial diversity and composition remained stable, but a positive association between bacterial and fungal Chao1 diversity and a negative association between Dothideomycetes and Akkermansia were observed. GIDs decreased in both groups and migraines improved in the placebo group. Our findings may aid the development of GID treatment strategies.


Assuntos
Dieta Livre de Glúten , Gastroenteropatias , Microbioma Gastrointestinal , Glutens , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/microbiologia , Feminino , Masculino , Gastroenteropatias/microbiologia , Adulto , Método Duplo-Cego , Glutens/efeitos adversos , Pessoa de Meia-Idade , Dermatite Atópica/microbiologia , Fezes/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Fungos , RNA Ribossômico 16S , Precursores de Proteínas , Haptoglobinas
19.
J Transl Med ; 22(1): 331, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575942

RESUMO

BACKGROUND: A better diagnostic marker is in need to distinguish breast cancer from suspicious breast lesions. The abnormal glycosylation of haptoglobin has been documented to assist cancer diagnosis. This study aims to evaluate disease-specific haptoglobin (DSHp)-ß N-glycosylation as a potential biomarker for breast cancer diagnosis. METHODS: DSHp-ß chains of 497 patients with suspicious breast lesions who underwent breast surgery were separated from serum immunoinflammatory-related protein complexes. DSHp-ß N-glycosylation was quantified by mass spectrometric analysis. After missing data imputation and propensity score matching, patients were randomly assigned to the training set (n = 269) and validation set (n = 113). Logistic regression analysis was employed in model and nomogram construction. The diagnostic performance was analyzed with receiver operating characteristic and calibration curves. RESULTS: 95 N-glycopeptides at glycosylation sites N207/N211, N241, and N184 were identified in 235 patients with benign breast diseases and 262 patients with breast cancer. DSHp-ß N-tetrafucosyl and hexafucosyl were significantly increased in breast cancer compared with benign diseases (p < 0.001 and p = 0.001, respectively). The new diagnostic model and nomogram included GN2F2, G6N3F6, GN2FS at N184, G-N&G2S2, G2&G3NFS, G2N3F, GN3 at N207/N211, CEA, CA153, and could reliably distinguish breast cancer from benign diseases. For the training set, validation set, and training and validation sets, the area under the curves (AUCs) were 0.80 (95% CI: 0.75-0.86, specificity: 87%, sensitivity: 62%), 0.77 (95% CI:0.69-0.86, specificity: 75%, sensitivity: 69%), and 0.80 (95% CI:0.76-0.84, specificity: 77%, sensitivity: 68%), respectively. CEA, CA153, and their combination yielded AUCs of 0.62 (95% CI: 0.56-0.67, specificity: 29%, sensitivity: 90%), 0.65 (95% CI: 0.60-0.71, specificity: 74%, sensitivity: 51%), and 0.67 (95% CI: 0.62-0.73, specificity: 60%, sensitivity: 68%), respectively. CONCLUSIONS: The combination of DSHp-ß N-glycopeptides, CEA, and CA153 might be a better serologic marker to differentiate between breast cancer and benign breast diseases. The dysregulated N-glycosylation of serum DSHp-ß could provide insights into breast tumorigenesis.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Nomogramas , Haptoglobinas/química , Glicosilação , Glicopeptídeos/análise
20.
Biomed Pharmacother ; 174: 116569, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38603886

RESUMO

Alpha-alpha diaspirin-crosslinked human hemoglobin (DCLHb or ααHb) was a promising early generation red blood cell (RBC) substitute. The DCLHb was developed through a collaborative effort between the United States Army and Baxter Healthcare. The core design feature underlying its development was chemical stabilization of the tetrameric structure of hemoglobin (Hb) to prevent Hb intravascular dimerization and extravasation. DCLHb was developed to resuscitate warfighters on the battlefield, who suffered from life-threatening blood loss. However, extensive research revealed toxic side effects associated with the use of DCLHb that contributed to high mortality rates in clinical trials. This study explores whether scavenging Hb and heme via the apohemoglobin-haptoglobin (apoHb-Hp) complex can reduce DCLHb associated toxicity. Awake Golden Syrian hamsters were equipped with a window chamber model to characterize the microcirculation. Each group was first infused with either Lactated Ringer's or apoHb-Hp followed by a hypovolemic infusion of 10% of the animal's blood volume of DCLHb. Our results indicated that animals pretreated with apoHb-Hb exhibited improved microhemodynamics vs the group pretreated with Lactated Ringer's. While systemic acute inflammation was observed regardless of the treatment group, apoHb-Hp pretreatment lessened those effects with a marked reduction in IL-6 levels in the heart and kidneys compared to the control group. Taken together, this study demonstrated that utilizing a Hb and heme scavenger protein complex significantly reduces the microvasculature effects of ααHb, paving the way for improved HBOC formulations. Future apoHb-Hp dose optimization studies may identify a dose that can completely neutralize DCLHb toxicity.


Assuntos
Haptoglobinas , Hemoglobinas , Animais , Hemoglobinas/farmacologia , Hemoglobinas/metabolismo , Humanos , Haptoglobinas/metabolismo , Masculino , Mesocricetus , Apoproteínas/química , Apoproteínas/farmacologia , Substitutos Sanguíneos/farmacologia , Substitutos Sanguíneos/química , Reagentes de Ligações Cruzadas/química , Cricetinae
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