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1.
AIDS ; 38(8): 1163-1171, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38564437

ABSTRACT

The relationships between alterations in the intestinal barrier, and bacterial translocation with the development of metabolic complications in youth with perinatally acquired HIV (YPHIV) have not been investigated. The PHACS Adolescent Master Protocol enrolled YPHIV across 15 U.S. sites, including Puerto Rico, from 2007 to 2009. For this analysis, we included YPHIV with HIV viral load 1000 c/ml or less, with at least one measurement of homeostatic assessment of insulin resistance (HOMA-IR) or nonhigh density lipoprotein (non-HDLc) between baseline and year 3 and plasma levels of intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide-binding protein (LBP), and zonulin levels at baseline. We fit linear regression models using generalized estimating equations to assess the association of baseline log 10 gut markers with log 10 HOMA-IR and non-HDLc at all timepoints. HOMA-IR or non-HDLc was measured in 237, 189, and 170 PHIV at baseline, Yr2, and Yr3, respectively. At baseline, median age (Q1, Q3) was 12 years (10, 14), CD4 + cell count was 762 cells/µl (574, 984); 90% had HIV RNA less than 400 c/ml. For every 10-fold higher baseline I-FABP, HOMA-IR dropped 0.85-fold at baseline and Yr2. For a 10-fold higher baseline zonulin, there was a 1.35-fold increase in HOMA-IR at baseline, 1.23-fold increase in HOMA-IR at Yr2, and 1.20-fold increase in HOMA-IR at Yr3 in adjusted models. For a 10-fold higher baseline LBP, there was a 1.23-fold increase in HOMA-IR at baseline in the unadjusted model, but this was slightly attenuated in the adjusted model. Zonulin was associated with non-HDLc at baseline, but not for the other time points. Despite viral suppression, intestinal damage may influence downstream insulin sensitivity in YPHIV.


Subject(s)
Fatty Acid-Binding Proteins , HIV Infections , Haptoglobins , Insulin Resistance , Humans , Male , Adolescent , Female , Child , Fatty Acid-Binding Proteins/blood , Haptoglobins/analysis , Haptoglobins/metabolism , Puerto Rico , Protein Precursors/blood , United States , Carrier Proteins/blood , Cholera Toxin/blood , Membrane Glycoproteins/blood , Permeability , Acute-Phase Proteins/analysis , Viral Load
2.
Nutrients ; 13(12)2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34960024

ABSTRACT

A western diet and increased intestinal permeability may contribute to systemic inflammation and the development of cardio-metabolic alterations. The aim of this study was to assess the relationship between diet, biomarkers of intestinal permeability, and chronic low-grade inflammation on the cardiometabolic profile. A cross-sectional study was carried out in 238 young subjects aged 18-29 years, divided into two groups: with <3 cardiometabolic risk factors (CRF) and ≥3 risk factors. Anthropometric parameters, biochemical profile, and serum levels of zonulin, lipopolysaccharide (LPS), and high-sensitivity C-reactive protein (hs-CRP) were measured, and the macronutrient intake was evaluated. Interaction models showed elevated glucose levels in the presence of high biomarker levels: zonulin ≥51.6 ng/mL plus LPS ≥ 1.35 EU/mL (ß = 1.1, p = 0.006), and LPS ≥1.35 EU/mL plus hs-CRP ≥ 4.3 mg/L (ß = 1.2, p = 0.007). In addition, triglyceride levels increased in the presence of LPS ≥ 1.35 EU/mL and hs-CRP ≥ 4.3 mg/L (ß = 3.9, p = 0.01). Despite having increased biomarker levels, a higher consumption of water (≥2100 mL), polyunsaturated fatty acids (≥6.0 g), or fiber (≥30 g) decreased triglyceride (ß = -9.6, p = 0.03), total cholesterol (ß = -5.1, p = 0.01), and LDL-C levels (ß = -7.7, p = 0.01). These findings suggest that the increased consumption of water, PUFA and fiber may improve lipid profile in subjects with intestinal permeability dysfunction or low-grade systemic inflammation.


Subject(s)
C-Reactive Protein/metabolism , Cardiometabolic Risk Factors , Diet , Lipopolysaccharides/blood , Protein Precursors/blood , Adolescent , Adult , Female , Haptoglobins , Humans , Inflammation/blood , Inflammation/metabolism , Male , Young Adult
3.
PLoS One ; 16(6): e0253501, 2021.
Article in English | MEDLINE | ID: mdl-34170951

ABSTRACT

Zonulin is a protein associated with the tight junction complex opening at the intestinal epithelium, previously linked to obesity, cardiovascular diseases, type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, its role in CKD has not been totally elucidated. This study aimed to evaluate zonulin levels in subjects with diabetic kidney disease (DKD). This case-control study included two cases groups: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2; 2) Albuminuric T2DM cases: diabetic patients with urinary albumin excretion (UAE) >30mg/g creatinine, but with eGFR>60ml/min/1.73m2. Two control groups were also included: 1) T2DM controls: patients with T2DM without impaired kidney function; 2) Non-T2DM controls: subjects without T2DM and normal renal function. Serum levels of zonulin were measured by ELISA. Eighty-six individuals were included. Zonulin levels was different among study groups (P = 0.003). T2DM controls presented higher zonulin levels than non-T2DM controls [(131.35 (83.0-170.5) vs. 87.25 (54.7-111.8), P = 0.018] and advanced DKD cases [63.72 (45.03-106.0); P = 0.007]. Zonulin showed a positive correlation with eGFR (r = 0.222; P = 0.040), total cholesterol (r = 0.299; P = 0.034), LDL (r = 0.258; P = 0.021), and negative with albuminuria (r = -0.243; P = 0.024) and body fat (r = -0.271; P = 0.014). In the multivariate logistic regression analyses, zonulin levels were independently associated to renal outcomes [OR 0.99 (0.98-0.99, P = 0.012)] after 5-year inclusion. In conclusion, increased zonulin levels in patients with TD2M without renal disease suggest an impaired intestinal permeability. Moreover, its association with renal outcomes could indicate its use as a disease monitoring marker. However, the mechanisms behind this association should be better understood.


Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetic Nephropathies/blood , Intestinal Mucosa/metabolism , Protein Precursors/blood , Renal Insufficiency, Chronic/blood , Aged , Biomarkers/blood , Female , Glomerular Filtration Rate , Haptoglobins , Humans , Male , Middle Aged , Permeability , Retrospective Studies
4.
Front Immunol ; 12: 579140, 2021.
Article in English | MEDLINE | ID: mdl-33746942

ABSTRACT

Hashimoto thyroiditis (HT) is the most common autoimmune disease worldwide, characterized by chronic inflammation and circulating autoantibodies against thyroid peroxidase and thyroglobulin. Patients require hormone replacement with oral levothyroxine, and if untreated, they can develop serious adverse health effects and ultimately death. There is a lot of evidence that the intestinal dysbiosis, bacterial overgrowth, and increased intestinal permeability favor the HT development, and a thyroid-gut axis has been proposed, which seems to impact our entire metabolism. Here, we evaluated alterations in the gut microbiota in Brazilian patients with HT and correlated this data with dietary habits, clinical data, and systemic cytokines and zonulin concentrations. Stool samples from 40 patients with HT and 53 controls were analyzed using real-time PCR, the serum cytokine levels were evaluated by flow cytometry, zonulin concentrations by ELISA, and the dietary habits were recorded by a food frequency questionnaire. We observed a significant increase (p < 0.05) in the Bacteroides species and a decrease in Bifidobacterium in samples of patients with HT. In addition, Lactobacillus species were higher in patients without thyroid hormone replacement, compared with those who use oral levothyroxine. Regarding dietary habits, we demonstrated that there are significant differences in the consumption of vegetables, fruits, animal-derived proteins, dairy products, saturated fats, and carbohydrates between patients and control group, and an inverse correlation between animal-derived protein and Bacteroides genus was detected. The microbiota modulation by diet directly influences the inflammatory profile due to the generated microbiota metabolites and their direct or indirect action on immune cells in the gut mucosa. Although there are no differences in systemic cytokines in our patients with HT, we detected increased zonulin concentrations, suggesting a leaky gut in patients with HT. These findings could help understand the development and progression of HT, while further investigations to clarify the underlying mechanisms of the diet-microbiota-immune system axis are still needed.


Subject(s)
Dysbiosis/immunology , Gastrointestinal Microbiome/immunology , Hashimoto Disease/immunology , Intestines/immunology , Adult , Bacteria/classification , Bacteria/genetics , Cytokines/blood , Cytokines/immunology , Cytokines/metabolism , Dysbiosis/microbiology , Feces/microbiology , Feeding Behavior , Female , Haptoglobins/immunology , Haptoglobins/metabolism , Hashimoto Disease/blood , Hashimoto Disease/microbiology , Humans , Intestines/microbiology , Intestines/physiology , Male , Middle Aged , Permeability , Protein Precursors/blood , Protein Precursors/immunology , Protein Precursors/metabolism , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA
5.
Dig Dis Sci ; 66(10): 3359-3374, 2021 10.
Article in English | MEDLINE | ID: mdl-33104937

ABSTRACT

BACKGROUND/AIM: A link between an impaired intestinal barrier, endotoxemia, and the pathogenesis of metabolic diseases, such as type 2 diabetes mellitus (T2DM), has been proposed. In previous work, we have demonstrated that the tight junction (TJ)-mediated intestinal barrier in ileum/colon was marginally changed in prediabetic mice; therefore, it does not seem to mainly contribute to the T2DM onset. In this study, the TJ-mediated epithelial barrier in the duodenum and jejunum was evaluated in mice during the development of type 2 prediabetes. METHODS/RESULTS: HF diet induced prediabetes after 60 days associated with a significant rise in intestinal permeability to the small-sized marker Lucifer yellow in these mice, with no histological signs of mucosal inflammation or rupture of the proximal intestine epithelium. As revealed by immunofluorescence, TJ proteins, such as claudins-1, -2, -3, and ZO-1, showed a significant decrease in junctional content in duodenum and jejunum epithelia, already after 15 days of treatment, suggesting a rearrangement of the TJ structure. However, no significant change in total cell content of these proteins was observed in intestinal epithelium homogenates, as assessed by immunoblotting. Despite the changes in intestinal permeability and TJ structure, the prediabetic mice showed similar LPS, zonulin, and TNF-α levels in plasma or adipose tissue, and in intestinal segments as compared to the controls. CONCLUSION: Disruption of the TJ-mediated paracellular barrier in the duodenum and jejunum is an early event in prediabetes development, which occurs in the absence of detectable endotoxemia/inflammation and may contribute to the HF diet-induced increase in intestinal permeability.


Subject(s)
Diabetes Mellitus, Type 2/chemically induced , Diet, High-Fat/adverse effects , Endotoxemia/chemically induced , Intestine, Small/drug effects , Intestine, Small/pathology , Tight Junctions/drug effects , Animals , Haptoglobins/metabolism , Intestinal Mucosa/drug effects , Lipopolysaccharides/blood , Lipopolysaccharides/metabolism , Male , Mice , Protein Precursors/blood , Protein Precursors/metabolism , Random Allocation , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolism
6.
Ann Nutr Metab ; 76(1): 30-36, 2020.
Article in English | MEDLINE | ID: mdl-32172243

ABSTRACT

BACKGROUND: Vasopressin is elevated in response to heat and dehydration and has been postulated to have a role in the chronic kidney disease of unknown origin being observed in Central America. The aims of this study were to examine whether the vasopressin pathway, as measured by copeptin, is associated with the presence of kidney dysfunction, and to examine whether higher fluid intake is associated with lower circulating copeptin and thereby preserves kidney health among sugarcane workers exposed to hot conditions. METHODS: Utilizing a longitudinal study of 105 workers in Guatemala, we examined relationships between hydration indices, plasma copeptin concentrations, and kidney function markers at 3 times during the 6-month harvest. We also examined whether baseline copeptin concentrations increased the odds of developing an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS: Copeptin concentrations were positively associated with serum creatinine (ß 1.41, 95% CI 0.88-2.03) and negatively associated with eGFR (ß -1.07, 95% CI -1.43 to -0.70). In addition, as workers improved their hydration (measured by increases in fluid balance), copeptin concentrations were reduced, and this reduction was associated with an improvement in kidney function. CONCLUSIONS: Results suggest that copeptin should be studied as a potential prognostic biomarker.


Subject(s)
Agricultural Workers' Diseases/diagnosis , Dehydration/diagnosis , Glycopeptides/blood , Neurophysins/blood , Protein Precursors/blood , Renal Insufficiency, Chronic/diagnosis , Vasopressins/blood , Adult , Agricultural Workers' Diseases/epidemiology , Agricultural Workers' Diseases/etiology , Biomarkers/blood , Dehydration/blood , Dehydration/complications , Dehydration/epidemiology , Guatemala/epidemiology , Hot Temperature/adverse effects , Humans , Kidney/physiopathology , Kidney Function Tests , Longitudinal Studies , Male , Occupational Exposure/adverse effects , Prevalence , Prognosis , Prospective Studies , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , Saccharum
7.
Rev Soc Bras Med Trop ; 53: e20190418, 2020.
Article in English | MEDLINE | ID: mdl-32049203

ABSTRACT

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious pulmonary circulation disease caused by several etiologies, including schistosomiasis. The present study retrospectively evaluated the clinical and hemodynamic characteristics of patients with schistosomal PAH (PAH-Sch) compared to those of non-Sch PAH patients (non-Sch PAH). METHODS: Patients treated at the Pronto-Socorro Cardiológico de Pernambuco and diagnosed by right cardiac catheterization were divided into PAH-Sch and non-Sch PAH groups. Their socio-demographic and clinical characteristics, N-terminal-pro B-type natriuretic peptide (NT-proBNP), and echocardiography and hemodynamic parameters were retrospectively reviewed. RESULTS: Among the included 98 patients (mean age, 45 ± 14 years; 68 women [69.4%]), we found 56 PAH-Sch and 42 non-Sch PAH. The age distribution was heterogeneous in the PAH-Sch group, with patients predominantly ranging from 50-59 (p <0.004). Dyspnea was the most common symptom, reported by 92 patients (93.8%), and commonly present for over two years prior to diagnosis. Clinical symptoms were similar in both groups, with no differences in functional class, pulmonary artery systolic pressure (p = 0.102), 6-minute walk test score (p = 0.234), NT-proBNP serum levels (p = 0.081), or hemodynamic parameters. CONCLUSIONS: Patients with PAH-Sch present clinical, laboratory, and hemodynamic profiles similar to those with PAH resulting from other etiologies of poor prognosis. PAH is an important manifestation of schistosomiasis in endemic regions that is often diagnosed late.


Subject(s)
Atrial Natriuretic Factor/blood , Protein Precursors/blood , Pulmonary Arterial Hypertension/etiology , Schistosomiasis/complications , Adult , Aged , Biomarkers/blood , Echocardiography , Female , Humans , Male , Middle Aged , Pulmonary Arterial Hypertension/blood , Retrospective Studies , Socioeconomic Factors
8.
Clinics (Sao Paulo) ; 75: e1448, 2020.
Article in English | MEDLINE | ID: mdl-31994614

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate the relationship between the serum levels of calcitonin gene-related peptide (CGRP) and the prognosis of pediatric patients with severe pneumonia. METHODS: Children diagnosed with severe pneumonia (n=76) were stratified into the survival (n=58) and non-survival groups (n=18) according to their 28-day survival status and into the non-risk (n=51), risk (n=17) and high-risk (n=8) categories based on the pediatric critical illness score (PCIS). Demographic data and laboratory results were collected. Serum CGRP levels were determined by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic (ROC) curve was generated to determine the cutoff score for high CGRP levels. RESULTS: Serum CGRP levels were significantly higher in the survival group than in the non-survival group and were significantly higher in the non-risk group than in the risk and high-risk groups. The ROC curve for the prognostic potential of CGRP yielded a significant area under the curve (AUC) value with considerable sensitivity and specificity. CONCLUSION: Our findings show that CGRP downregulation might be a diagnostic marker that predicts the prognosis and survival of children with severe pneumonia.


Subject(s)
Calcitonin Gene-Related Peptide/genetics , Pneumonia/blood , Protein Precursors/blood , Vasodilator Agents/metabolism , Calcitonin , Calcitonin Gene-Related Peptide/blood , Calcitonin Gene-Related Peptide/metabolism , Child , Critical Illness , Female , Humans , Male , Pneumonia/mortality , Prognosis , ROC Curve , Survival Analysis
9.
Clinics ; Clinics;75: e1448, 2020. tab, graf
Article in English | LILACS | ID: biblio-1055884

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate the relationship between the serum levels of calcitonin gene-related peptide (CGRP) and the prognosis of pediatric patients with severe pneumonia. METHODS: Children diagnosed with severe pneumonia (n=76) were stratified into the survival (n=58) and non-survival groups (n=18) according to their 28-day survival status and into the non-risk (n=51), risk (n=17) and high-risk (n=8) categories based on the pediatric critical illness score (PCIS). Demographic data and laboratory results were collected. Serum CGRP levels were determined by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic (ROC) curve was generated to determine the cutoff score for high CGRP levels. RESULTS: Serum CGRP levels were significantly higher in the survival group than in the non-survival group and were significantly higher in the non-risk group than in the risk and high-risk groups. The ROC curve for the prognostic potential of CGRP yielded a significant area under the curve (AUC) value with considerable sensitivity and specificity. CONCLUSION: Our findings show that CGRP downregulation might be a diagnostic marker that predicts the prognosis and survival of children with severe pneumonia.


Subject(s)
Humans , Male , Female , Child , Pneumonia/blood , Protein Precursors/blood , Vasodilator Agents/metabolism , Calcitonin Gene-Related Peptide/genetics , Pneumonia/mortality , Prognosis , Calcitonin , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide/blood , Survival Analysis , ROC Curve , Critical Illness
10.
Rev. Soc. Bras. Med. Trop ; Rev. Soc. Bras. Med. Trop;53: e20190418, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057263

ABSTRACT

Abstract INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious pulmonary circulation disease caused by several etiologies, including schistosomiasis. The present study retrospectively evaluated the clinical and hemodynamic characteristics of patients with schistosomal PAH (PAH-Sch) compared to those of non-Sch PAH patients (non-Sch PAH). METHODS: Patients treated at the Pronto-Socorro Cardiológico de Pernambuco and diagnosed by right cardiac catheterization were divided into PAH-Sch and non-Sch PAH groups. Their socio-demographic and clinical characteristics, N-terminal-pro B-type natriuretic peptide (NT-proBNP), and echocardiography and hemodynamic parameters were retrospectively reviewed. RESULTS: Among the included 98 patients (mean age, 45 ± 14 years; 68 women [69.4%]), we found 56 PAH-Sch and 42 non-Sch PAH. The age distribution was heterogeneous in the PAH-Sch group, with patients predominantly ranging from 50-59 (p <0.004). Dyspnea was the most common symptom, reported by 92 patients (93.8%), and commonly present for over two years prior to diagnosis. Clinical symptoms were similar in both groups, with no differences in functional class, pulmonary artery systolic pressure (p = 0.102), 6-minute walk test score (p = 0.234), NT-proBNP serum levels (p = 0.081), or hemodynamic parameters. CONCLUSIONS: Patients with PAH-Sch present clinical, laboratory, and hemodynamic profiles similar to those with PAH resulting from other etiologies of poor prognosis. PAH is an important manifestation of schistosomiasis in endemic regions that is often diagnosed late.


Subject(s)
Humans , Male , Female , Adult , Aged , Protein Precursors/blood , Schistosomiasis/complications , Atrial Natriuretic Factor/blood , Pulmonary Arterial Hypertension/etiology , Socioeconomic Factors , Echocardiography , Biomarkers/blood , Retrospective Studies , Pulmonary Arterial Hypertension/blood , Middle Aged
11.
Ann Hepatol ; 18(6): 786-787, 2019.
Article in English | MEDLINE | ID: mdl-31494068

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Interestingly, the great majority of individuals affected by the tumor have underlying liver disease, therefore narrowing the population to be screened. Still, however, there is a clear lack of blood biomarkers, and surveillance in those at risk is performed by frequent imaging of the liver. A variety of multinational collaborations are currently invested in finding biomarkers for HCC based on liver-produced proteins. A new approach with assessment of peripheral proteins might be necessary for the successful early detection of this malignancy.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Biomarkers/blood , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/blood , Early Detection of Cancer , Glypicans/blood , Humans , Liver Cirrhosis , Liver Neoplasms/blood , Protein Precursors/blood , Prothrombin , Sensitivity and Specificity , Ultrasonography , alpha-Fetoproteins/metabolism , alpha-Glucosidases/blood
12.
Arch Endocrinol Metab ; 63(2): 121-127, 2019.
Article in English | MEDLINE | ID: mdl-31038593

ABSTRACT

OBJECTIVE: We investigated the utility of maternal fetuin-A, N-terminal proatrial natriuretic peptide (pro-ANP), high-sensitivity C-reactive protein (hs-CRP), and fasting glucose levels at 11-14 gestation weeks for predicting pregnancies complicated by gestational diabetes mellitus (GDM). SUBJECTS AND METHODS: This prospective cohort study included 327 low-risk pregnant women who completed antenatal follow-up at a tertiary research hospital between January and April 2014. Maternal blood samples were collected between 11-14 gestational weeks in the first trimester of pregnancy and then stored at -80 °C until further analyses. During follow-up, 29 (8.8%) women developed GDM. The study population was compared 1:2 with age- and body mass index-matched pregnant women who did not develop GDM (n = 59). Fasting plasma glucose (FPG) levels and serum fetuin-A, pro-ANP, and hs-CRP levels were measured using automated immunoassay systems. RESULTS: There was a significant negative correlation between fetuin-A and hs-CRP (CC = -0.21, p = 0.047) and a positive correlation between FPG and hs-CRP (CC = 0.251, p = 0.018). The areas under the receiver operating characteristic curve for diagnosing GDM were 0.337 (p = 0.013), 0.702 (p = 0.002), and 0.738 (p < 0.001) for fetuin-A, hs-CRP, and FPG, respectively. The optimal cut-off values were > 4.65, < 166, and > 88.5 mg/dL for maternal hs-CRP, fetuin-A, and FPG, respectively. CONCLUSION: Reduced fetuin-A, elevated hs-CRP, and FPG levels in women in the first trimester can be used for the early detection of GDM. Further research is needed before accepting these biomarkers as valid screening tests for GDM.


Subject(s)
Atrial Natriuretic Factor/blood , Blood Glucose/analysis , C-Reactive Protein/analysis , Diabetes, Gestational/blood , Protein Precursors/blood , alpha-2-HS-Glycoprotein/analysis , Adult , Atrial Natriuretic Factor/metabolism , Biomarkers/blood , Biomarkers/metabolism , Blood Glucose/metabolism , Body Mass Index , C-Reactive Protein/metabolism , Diabetes, Gestational/metabolism , Female , Gestational Age , Humans , Predictive Value of Tests , Pregnancy , Pregnancy Trimester, First/blood , Prospective Studies , Protein Precursors/metabolism , Sensitivity and Specificity , alpha-2-HS-Glycoprotein/metabolism
13.
Biosci Trends ; 13(6): 546-555, 2019.
Article in English | MEDLINE | ID: mdl-31956226

ABSTRACT

Prolonged or intense exposure to environmental noise (EN) has been associated with a number of changes in auditory organs as well as other brain structures. Notably, males and females have shown different susceptibilities to acoustic damage as well as different responses to environmental stressors. Rodent models have evidence of sex-specific changes in brain structures involved in noise and sound processing. As a common effect, experimental models have demonstrated that dendrite arborizations reconfigure in response to aversive conditions in several brain regions. Here, we examined the effect of chronic noise on dendritic reorganization and c-Fos expression patterns of both sexes. During 21 days male and female rats were exposed to a rats' audiogram-fitted adaptation of a noisy environment. Golgi-Cox and c-Fos staining were performed at auditory cortices (AC) and hippocampal regions. Sholl analysis and c-Fos counts were conducted for evidence of intersex differences. In addition, pro-BDNF serum levels were also measured. We found different patterns of c-Fos expression in hippocampus and AC. While in AC expression levels showed rapid and intense increases starting at 2 h, hippocampal areas showed slower rises that reached the highest levels at 21 days. Sholl analysis also evidenced regional differences in response to noise. Dendritic trees were reduced after 21 days in hippocampus but not in AC. Meanwhile, pro-BDNF levels augmented after EN exposure. In all analyzed variables, exposed males were the most affected. These findings suggest that noise may exert differential effects on male and female brains and that males could be more vulnerable to the chronic effects of noise.


Subject(s)
Auditory Cortex/metabolism , Brain-Derived Neurotrophic Factor/blood , Hippocampus/metabolism , Neuronal Plasticity , Noise/adverse effects , Protein Precursors/blood , Proto-Oncogene Proteins c-fos/metabolism , Animals , Auditory Cortex/pathology , Female , Hippocampus/pathology , Male , Rats, Wistar , Sex Characteristics , Stress, Physiological
14.
Acta Cir Bras ; 32(7): 568-575, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28793041

ABSTRACT

PURPOSE:: To evaluate the possibility of using peripheral-blood presurfactant protein B (Pro-SFTPB) for screening non-small cell lung cancer (NSCLC). METHODS:: A total of 873 healthy volunteers and 165 lung cancer patients hospitalized in the Fifth People's Hospital of Dalian were tested Pro-SFTPB once every half year from January 2014 to September 2015. The healthy volunteers were also conducted spiral computed tomography (CT) examination once every year. The data were then com-pared and statistically analyzed. RESULTS:: The positive expression rate of Pro-SFTPB in NSCLC was significantly higher than that in healthy volunteers, and significantly higher in lung adenocarcinoma than in squamous cell carcinoma; additionally, the expression rate was increased with the in-crease of smoking index, and the intergroup differences showed statistical signifi-cance (p≤0.05). The positive rate of newly diagnosed lung cancer was 29.55%, higher than healthy volunteers (22.34%), but there was no significant difference (p>0.05). CONCLUSION:: Pro-SFTPB is over expressed in non-small cell lung cancer, especially in lung adeno-carcinoma, but it can't be used as a clinical screening tool for lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/blood , Lung Neoplasms/diagnosis , Protein Precursors/blood , Pulmonary Surfactant-Associated Proteins/blood , Aged , Biomarkers, Tumor/blood , Case-Control Studies , Female , Humans , Male , Mass Screening , Sensitivity and Specificity
15.
Acta cir. bras ; Acta cir. bras;32(7): 568-575, July 2017. tab
Article in English | LILACS | ID: biblio-886221

ABSTRACT

Abstract Purpose: To evaluate the possibility of using peripheral-blood presurfactant protein B (Pro-SFTPB) for screening non-small cell lung cancer (NSCLC). Methods: A total of 873 healthy volunteers and 165 lung cancer patients hospitalized in the Fifth People's Hospital of Dalian were tested Pro-SFTPB once every half year from January 2014 to September 2015. The healthy volunteers were also conducted spiral computed tomography (CT) examination once every year. The data were then com-pared and statistically analyzed. Results: The positive expression rate of Pro-SFTPB in NSCLC was significantly higher than that in healthy volunteers, and significantly higher in lung adenocarcinoma than in squamous cell carcinoma; additionally, the expression rate was increased with the in-crease of smoking index, and the intergroup differences showed statistical signifi-cance (p≤0.05). The positive rate of newly diagnosed lung cancer was 29.55%, higher than healthy volunteers (22.34%), but there was no significant difference (p>0.05). Conclusion: Pro-SFTPB is over expressed in non-small cell lung cancer, especially in lung adeno-carcinoma, but it can't be used as a clinical screening tool for lung cancer.


Subject(s)
Humans , Male , Female , Aged , Protein Precursors/blood , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/blood , Pulmonary Surfactant-Associated Proteins/blood , Lung Neoplasms/diagnosis , Lung Neoplasms/blood , Biomarkers, Tumor/blood , Case-Control Studies , Mass Screening , Sensitivity and Specificity
16.
Int. braz. j. urol ; 43(1): 48-56, Jan.-Feb. 2017. tab
Article in English | LILACS | ID: biblio-840806

ABSTRACT

ABSTRACT Introduction To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. Materials and Methods This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated. Results PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7). Conclusions New markers, derivates of p2PSA (especially %p2PSA and PHI), represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL.


Subject(s)
Humans , Male , Aged , Prostatic Neoplasms/pathology , Prostatic Neoplasms/blood , Protein Precursors/blood , Prostate-Specific Antigen/blood , Prostate/pathology , Reference Values , Biopsy , Logistic Models , Cross-Sectional Studies , Predictive Value of Tests , Reproducibility of Results , ROC Curve , Statistics, Nonparametric , Neoplasm Grading , Middle Aged
17.
Int Braz J Urol ; 43(1): 48-56, 2017.
Article in English | MEDLINE | ID: mdl-28124526

ABSTRACT

INTRODUCTION: To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. MATERIALS AND METHODS: This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated. RESULTS: PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7). CONCLUSIONS: New markers, derivates of p2PSA (especially %p2PSA and PHI), represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL.


Subject(s)
Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Protein Precursors/blood , Aged , Biopsy , Cross-Sectional Studies , Humans , Logistic Models , Male , Middle Aged , Neoplasm Grading , Predictive Value of Tests , Prostate/pathology , ROC Curve , Reference Values , Reproducibility of Results , Statistics, Nonparametric
18.
Genet Mol Res ; 15(2)2016 Jul 14.
Article in English | MEDLINE | ID: mdl-27421011

ABSTRACT

The aim of this study was to investigate the diagnostic value of the serum markers HBsAg and HBeAg and PreS1 protein (PreS1-Ag) in quantifying the levels of hepatitis B virus (HBV) DNA in patients with chronic hepatitis B (CHB). One thousand CHB patients were recruited from Beijing You'an Hospital between June and December 2012. Serum HBsAg and HBeAg levels were detected by electrochemiluminescence immunoassay. Enzyme-linked immunosorbent assay and fluorescence quantitative PCR were used to determine the level of PreS1-Ag and HBV DNA, respectively. We observed a low correlation between HBsAg and HBV DNA (r = 0.172, P < 0.001) expression; however, the correlation coefficient increased gradually with the increase in HBV DNA levels, and was more significant when HBV DNA log10 > 7 (r = 0.597, P < 0.001). Additionally, HBsAg and HBV DNA showed a significant positive correlation in the HBeAg+ group (r = 0.321, P < 0.001), whereas no correlation was observed in the HBeAg- group (r = -0.016, P = 0.825). HBV DNA expression was correlated with HBeAg (χ2 = 83.07, P < 0.001) and PreS1-Ag (χ2 = 36.01, P < 0.001). HBV DNA-positive rate was higher in HBeAg/PreS1-Ag++ patients (72.26%) than that in the single-positive groups (P < 0.001). Therefore, serum HBsAg is not a good marker for the prediction of HBV replication, and co-detection of HBeAg and PreS1-Ag, which can better predict HBV DNA replication, can be used as a reliable method for the clinical diagnosis and treatment of CHB.


Subject(s)
DNA, Viral/analysis , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B, Chronic/diagnosis , Protein Precursors/blood , Adolescent , Adult , Aged , Biomarkers/blood , Child , Child, Preschool , DNA Replication , DNA, Viral/blood , Female , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/genetics , Hepatitis B, Chronic/virology , Humans , Male , Middle Aged
19.
Microbiology (Reading) ; 162(8): 1407-1421, 2016 08.
Article in English | MEDLINE | ID: mdl-27260249

ABSTRACT

Pathogenic bacteria of the genus Leptospira are the causative agent of leptospirosis, an emergent infectious disease that affects humans and animals worldwide. Severe forms of the disease in humans include jaundice, multiple organ failure and intense haemorrhage. Up to now, mechanisms associated with the haemorrhage foci are poorly understood. We report in this work that, despite the low levels of antithrombin III in convalescent human serum samples, virulent, culture-attenuated and saprophyte strains of Leptospira are unable to bind and/or degrade this thrombin inhibitor, suggesting an indirect mechanism of pathogenesis. Lower levels of prothrombin were found in serum samples at the onset and convalescent phase of the disease when compared to normal human sera. The concomitant decreased levels of antithrombin III and prothrombin suggest a process of stimulated coagulation, which is corroborated by the increase of prothrombin fragment F1+2 in the serum samples. Data obtained with hamsters experimentally infected with virulent Leptospira interrogans serovars Kennewicki and Canicola strongly point out that haemorrhage is correlated with decreased levels of thrombin inhibitors and prothrombin. Activated coagulation might lead to an overconsumption of coagulation factors ultimately leading to bleeding and organ failure.


Subject(s)
Antithrombin III/metabolism , Blood Coagulation Disorders/microbiology , Hemorrhage/microbiology , Leptospirosis/microbiology , Leptospirosis/pathology , Peptide Fragments/blood , Protein Precursors/blood , Animals , Bacterial Adhesion/physiology , Blood Coagulation/physiology , Cricetinae , Humans , Leptospira/metabolism , Male , Prothrombin
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