Reticulocyte Antioxidant Enzymes mRNA Levels versus Reticulocyte Maturity Indices in Hereditary Spherocytosis, ß-Thalassemia and Sickle Cell Disease.

The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxiredoxin 2 (Prx2) are particularly important in erythroid cells. Reticulocytes and other erythroid precursors may adapt their biosynthetic mechanisms to cell defects or to changes in the bone marrow environment. Our aim was to perform a comparative study of the mRNA levels of CAT, GPX1, PRDX2 and SOD1 in reticulocytes from healthy individuals and from patients with hereditary spherocytosis (HS), sickle cell disease (SCD) and ß-thalassemia (ß-thal), and to study the association between their transcript levels and the reticulocyte maturity indices. In controls, the enzyme mRNA levels were significantly correlated with reticulocyte maturity indices for all genes except for SOD1. HS, SCD and ß-thal patients showed younger reticulocytes, with higher transcript levels of all enzymes, although with different patterns. ß-thal and HS showed similar reticulocyte maturity, with different enzyme mRNA levels; SCD and HS, with different reticulocyte maturity, presented similar enzyme mRNA levels. Our data suggest that the transcript profile for these antioxidant enzymes is not entirely related to reticulocyte maturity; it appears to also reflect adaptive mechanisms to abnormal erythropoiesis and/or to altered erythropoietic environments, leading to reticulocytes with distinct antioxidant potential according to each anemia.

Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.

Iron overload (IOL) is hypothesized to contribute to dysplastic erythropoiesis. Several conditions, including myelodysplastic syndrome, thalassemia and sickle cell anemia, are characterized by ineffective erythropoiesis and IOL. Iron is pro-oxidant and may participate in the pathophysiology of these conditions by increasing genomic instability and altering the microenvironment. There is, however, lack of in vivo evidence demonstrating a role of IOL and oxidative damage in dysplastic erythropoiesis. NRF2 transcription factor is the master regulator of antioxidant defenses, playing a crucial role in the cellular response to IOL in the liver. Here, we crossed Nrf2-/- with hemochromatosis (Hfe-/-) or hepcidin-null (Hamp1-/-) mice. Double-knockout mice developed features of ineffective erythropoiesis and myelodysplasia including macrocytic anemia, splenomegaly, and accumulation of immature dysplastic bone marrow (BM) cells. BM cells from Nrf2/Hamp1-/- mice showed increased in vitro clonogenic potential and, upon serial transplantation, recipients disclosed cytopenias, despite normal engraftment, suggesting defective differentiation. Unstimulated karyotype analysis showed increased chromosome instability and aneuploidy in Nrf2/Hamp1-/- BM cells. In HFE-related hemochromatosis patients, NRF2 promoter SNP rs35652124 genotype TT (predicted to decrease NRF2 expression) associated with increased MCV, consistent with erythroid dysplasia. Our results suggest that IOL induces ineffective erythropoiesis and dysplastic hematologic features through oxidative damage in Nrf2-deficient cells.

Serum amyloid A proteins reduce bone mass during mycobacterial infections.

Introduction: Osteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. Methods: Genetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussion: We found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFNγ- and TNFα-dependent manner. IFNγ produced during infection enhanced macrophage TNFα secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.

The effect of a natural polyphenol supplement on iron absorption in adults with hereditary hemochromatosis.

OBJECTIVES: We developed a natural polyphenol supplement that strongly chelates iron in vitro and assessed its effect on non-heme iron absorption in patients with hereditary hemochromatosis (HH). METHODS: We performed in vitro iron digestion experiments to determine iron precipitation by 12 polyphenol-rich dietary sources, and formulated a polyphenol supplement (PPS) containing black tea powder, cocoa powder and grape juice extract. In a multi-center, single-blind, placebo-controlled cross-over study, we assessed the effect of the PPS on iron absorption from an extrinsically labelled test meal and test drink in patients (n = 14) with HH homozygous for the p.C282Y variant in the HFE gene. We measured fractional iron absorption (FIA) as stable iron isotope incorporation into erythrocytes. RESULTS: Black tea powder, cocoa powder and grape juice extract most effectively precipitated iron in vitro. A PPS mixture of these three extracts precipitated ~ 80% of iron when 2 g was added to a 500 g iron solution containing 20 µg Fe/g. In the iron absorption study, the PPS reduced FIA by ~ 40%: FIA from the meal consumed with the PPS was lower (3.01% (1.60, 5.64)) than with placebo (5.21% (3.92, 6.92)) (p = 0.026)), and FIA from the test drink with the PPS was lower (10.3% (7.29 14.6)) than with placebo (16.9% (12.8 22.2)) (p = 0.002). CONCLUSION: Our results indicate that when taken with meals, this natural PPS can decrease dietary iron absorption, and might thereby reduce body iron accumulation and the frequency of phlebotomy in patients with HH. TRIAL REGISTRY: clinicaltrials.gov (registration date: 9.6.2019, NCT03990181).

Iron Related Biomarkers Predict Disease Severity in a Cohort of Portuguese Adult Patients during COVID-19 Acute Infection.

Large variability in COVID-19 clinical progression urges the need to find the most relevant biomarkers to predict patients' outcomes. We evaluated iron metabolism and immune response in 303 patients admitted to the main hospital of the northern region of Portugal with variable clinical pictures, from September to November 2020. One hundred and twenty-seven tested positive for SARS-CoV-2 and 176 tested negative. Iron-related laboratory parameters and cytokines were determined in blood samples collected soon after admission. Demographic data, comorbidities and clinical outcomes were recorded. Patients were assigned into five groups according to severity. Serum iron and transferrin levels at admission were lower in COVID-19-positive than in COVID-19-negative patients. The levels of interleukin (IL)-6 and monocyte chemoattractant protein 1 (MCP-1) were increased in COVID-19-positive patients. The lowest serum iron and transferrin levels at diagnosis were associated with the worst outcomes. Iron levels negatively correlated with IL-6 and higher levels of this cytokine were associated with a worse prognosis. Serum ferritin levels at diagnosis were higher in COVID-19-positive than in COVID-19-negative patients. Serum iron is the simplest laboratory test to be implemented as a predictor of disease progression in COVID-19-positive patients.

Chromosome 6p SNP microhaplotypes and IgG3 levels in hemochromatosis probands with HFE p.C282Y homozygosity.

Subnormal IgG1 or IgG3 levels occurred in 30% of hemochromatosis probands with HFE p.C282Y homozygosity and were concordant in HLA-identical siblings. We sought to identify factors associated with IgG subclasses in Alabama probands with p.C282Y homozygosity evaluated for 500 kb microhaplotypes AAT and GGG defined by SNPs in chromosome 6p genes PGBD1, ZNF193, and ZNF165. In regressions on IgG subclasses, we used: age; sex; GGG (dichotomous); iron removed to achieve depletion; CD8+ T-lymphocytes; and other IgG subclasses. Among 49 probands, AAT and GGG occurred in 95.9% and 16.3%, respectively. Thirteen probands (26.5%) had subnormal IgG1; 11 probands (22.4%) had subnormal IgG3. Mean IgG3 was higher in probands with than without GGG (75 mg/dL [95% confidence interval 63, 89] vs. 58 mg/dL [49, 71], respectively; p = 0.0321). Regression on IgG3 revealed: GGG positivity (p = 0.0106); and IgG1 (p = 0.0015). In a replication cohort of 22 Portugal probands with p.C282Y homozygosity, mean IgG3 was higher in probands with than without GGG (46 ±â€¯16 vs. 31 ±â€¯12 mg/dL, respectively; p = 0.0410). We conclude that mean IgG3 levels are higher in hemochromatosis probands with p.C282Y homozygosity with chromosome 6p microhaplotype GGG than in probands homozygous for microhaplotype AAT.

HFE Related Hemochromatosis: Uncovering the Inextricable Link between Iron Homeostasis and the Immunological System.

The HFE gene (OMIM 235200), most commonly associated with the genetic iron overload disorder Hemochromatosis, was identified by Feder et al. in 1996, as a major histocompatibilty complex (MHC) class I like gene, first designated human leukocyte antigen-H (HLA-H). This discovery was thus accomplished 20 years after the realization of the first link between the then "idiopathic" hemochromatosis and the human leukocyte antigens (HLA). The availability of a good genetic marker in subjects homozygous for the C282Y variant in HFE (hereditary Fe), the reliability in serum markers such as transferrin saturation and serum ferritin, plus the establishment of noninvasive methods for the estimation of hepatic iron overload, all transformed hemochromatosis into a unique age related disease where prevention became the major goal. We were challenged by the finding of iron overload in a 9-year-old boy homozygous for the C282Y HFE variant, with two brothers aged 11 and 5 also homozygous for the mutation. We report a 20 year follow-up during which the three boys were seen yearly with serial determinations of iron parameters and lymphocyte counts. This paper is divided in three sections: Learning, applying, and questioning. The result is the illustration of hemochromatosis as an age related disease in the transition from childhood to adult life and the confirmation of the inextricable link between iron overload and the cells of the immune system.

Is Low-Dose Radiation Exposure a Risk Factor for Atherosclerotic Disease?

Nontargeted late effects of radiation include an increased risk of cardiovascular disease, although this is still debatable in the context of low-dose radiation. Tinea capitis patients treated in childhood with X rays to induce scalp epilation received a low dose of radiation to their carotids. To better clarify this issue, we evaluated carotid atherosclerosis in a cohort of such patients treated in 1950-1963 in Portugal. A group of 454 individuals randomly chosen from previously observed Portuguese tinea capitis patients and a control group mainly composed of their spouses (n = 280) were enrolled. Cardiovascular risk factors such as waist circumference, body mass index, blood pressure and tobacco consumption, as well as biochemical measurements were obtained. Ultrasound imaging of carotid arteries for intima media thickness and stenosis evaluation were performed according to a standardized protocol. In comparison to the control group, the irradiated cohort members were significantly older, more frequently never smokers, hypertensive, and presented higher glycated hemoglobin and alkaline phosphatase levels. In addition, the irradiated cohort showed a higher frequency of carotid stenosis ≥30% than the nonirradiated group (13.9% vs. 10.7%), although this was not significant ( P = 0.20). Stenosis was ≥50% in 2.9% of the irradiated group and 0.4% of the nonirradiated group ( P = 0.02). Likewise, the frequency of intima media thickness ≥1 mm was significantly higher in the irradiated group (16.8% vs. 10.7%; P = 0.02). Multivariate analysis, including other cardiovascular risk factors, showed that exposure to low-dose radiation increased the risk of carotid stenosis by ≥50% [odds ratio (OR) = 8.85; P = 0.04] and intima media thickness by ≥1 mm (OR = 1.82; P = 0.02). These findings confirm that low-dose exposure is a risk factor of carotid atherosclerotic disease.

Hemoglobin Himeji and inconsistent hemoglobin A1c values: a case report.

BACKGROUND: Hemoglobin A1c is used to evaluate the glycemic control in patients with diabetes and is a risk marker for chronic complications of diabetes. Hemoglobin variants are reported to falsely lower or increase hemoglobin A1c test results. We present a case report of a patient with diabetes with discrepancy between fasting plasma glucose and hemoglobin A1c due to the presence of hemoglobin Himeji, a clinically silent and very rare hemoglobinopathy. CASE PRESENTATION: A 76-year-old white woman, born and living in Portugal, with type 2 diabetes presented to the family physician for a routine visit. She had no active complaints, including history or symptoms of hypoglycemia, and her physical examination was unremarkable. A review of her laboratory data showed fasting plasma glucose of 190 mg/dL and a hemoglobin A1c of 4.1%. The remaining blood test results were clinically insignificant; a further review of her laboratory data over the past 4 years revealed that her fasting plasma glucose had ranged from 130 to 250 mg/dL and hemoglobin A1c was consistently lower than 5%. A study of hemoglobins detected 32.8% of abnormal hemoglobin. Genetic sequencing identified a heterozygous mutation compatible with hemoglobin Himeji (c.422C>A; p.Ala141Asp). We tracked her family (three sons, six grandchildren, and two greatgrandchildren) for the presence of this hemoglobin variant, but none had this hemoglobinopathy. CONCLUSIONS: Despite the advantages of hemoglobin A1c in the follow-up and treatment of diabetes, the factors that interfere with its results must be known to ensure a correct estimation of the degree of glycemic control and a proper management of the disease. Therefore, health professionals should suspect the existence of hemoglobin variants when: the hemoglobin A1c value is above 15% or below the lower limit of its reference interval; there is a significant modification in its result coinciding with a change in assay methods; and there is a low correlation between plasma glucose and hemoglobin A1c. In patients with hemoglobin Himeji, alternate ways of monitoring glycemic control (fructosamine or glycated serum albumin) should be used.

IL6-174 G>C Polymorphism (rs1800795) Association with Late Effects of Low Dose Radiation Exposure in the Portuguese Tinea Capitis Cohort.

Head and neck cancers, and cardiovascular disease have been described as late effects of low dose radiation (LDR) exposure, namely in tinea capitis cohorts. In addition to radiation dose, gender and younger age at exposure, the genetic background might be involved in the susceptibility to LDR late effects. The -174 G>C (rs1800795) SNP in IL6 has been associated with cancer and cardiovascular disease, nevertheless this association is still controversial. We assessed the association of the IL6-174 G>C SNP with LDR effects such as thyroid carcinoma, basal cell carcinoma and carotid atherosclerosis in the Portuguese tinea capitis cohort. The IL6-174 G>C SNP was genotyped in 1269 individuals formerly irradiated for tinea capitis. This sampling group included thyroid cancer (n = 36), basal cell carcinoma (n = 113) and cases without thyroid or basal cell carcinoma (1120). A subgroup was assessed for atherosclerosis by ultrasonography (n = 379) and included matched controls (n = 222). Genotypes were discriminated by real-time PCR using a TaqMan SNP genotyping assay. In the irradiated group, we observed that the CC genotype was significantly associated with carotid plaque risk, both in the genotypic (OR = 3.57, CI = 1.60-7.95, p-value = 0.002) and in the recessive (OR = 3.02, CI = 1.42-6.42, p-value = 0.004) models. Irradiation alone was not a risk factor for carotid atherosclerosis. We did not find a significant association of the IL6-174 C allele with thyroid carcinoma or basal cell carcinoma risk. The IL6-174 CC genotype confers a three-fold risk for carotid atherosclerotic disease suggesting it may represent a genetic susceptibility factor in the LDR context.

Effects of acupuncture on leucopenia, neutropenia, NK, and B cells in cancer patients: a randomized pilot study.

Chemotherapy is one of most significant therapeutic approaches to cancer. Immune system functional state is considered a major prognostic and predictive impact on the success of chemotherapy and it has an important role on patients' psychoemotional state and quality of life. In Chinese medicine, chemotherapy is understood as "toxic cold" that may induce a progressive hypofunctional state of immune system, thus compromising the fast recovery of immunity during chemotherapy. In this study, we performed a standardized acupuncture and moxibustion protocol to enhance immunity in cancer patients undergoing chemotherapy and to assess if the improvement of immunity status correlates with a better psychoemotional state and quality of life.

Neutrophil gelatinase-associated lipocalin in the diagnosis of type 1 cardio-renal syndrome in the general ward.

BACKGROUND AND OBJECTIVES: The early identification of acute heart failure (HF) patients with type 1 cardio-renal syndrome should be the first step for developing prevention and treatment strategies for these patients. This study aimed to assess the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C in the early detection of type 1 cardio-renal syndrome in patients with acute HF. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One-hundred nineteen patients admitted with acute HF were studied. NGAL and creatinine were measured in the first hospitalization morning; creatinine was also measured at least after 48 to 72 hours. Physicians were blinded to NGAL and cystatin C levels. Type 1 cardio-renal syndrome was defined as an increase in the creatinine level of at least 0.3 mg/dl or 50% of basal creatinine. RESULTS: Type 1 cardio-renal syndrome developed within 48 to 72 hours in 14 patients (11.8%). Admission NGAL levels were higher in these patients: 212 versus 83 ng/dl. At a cutoff value of 170 ng/L, NGAL determined type 1 cardio-renal syndrome with a sensitivity of 100% and a specificity of 86.7%. The area under the receiver-operating characteristic curve of NGAL was 0.93 and that of cystatin C was 0.68. CONCLUSIONS: Above a cutoff value of 170 ng/L, NGAL predicts 48- to 72-hour development of type 1 cardio-renal syndrome with a negative predictive value of 100% and a positive predictive value of 50%. NGAL independently associates with type 1 cardio-renal syndrome and might be a useful biomarker in the early recognition of these patients.

Qualidade da assistência de enfermagem ao paciente enfartado: avaliação através do prontuário / Quality of the nursing attendance with heart attack patient: evaluation through the handbook

Trata-se de um estudo retrospectivo analítico que tem como objeto de avaliação a qualidade da assistência de enfermagem ao paciente com infarto agudo do miocárdio (IAM) na unidade coronariana de um hospital escola da cidade de Salvador, no período de janeiro a maio de 1997. Tem como objetivos: a) oferecer subsídios para a avaliação da qualidade da assistência de enfermagem segundo as anotações no prontuário e de acordo com o padrão estabelecido...

Tolerância a dor em pacientes de cirurgia cardiaca / Tolerance of pain in patients who have undergone cardiac surgery

Visando identificar os fatores que interferem na tolerância à dor, em paciente submetidos a cirurgia cardíaca, foram selecionadas as variáveis: expectativa e conhecimento de dor; características individuais e grau de ansiedade no pré-operatório. Sentimentos e emocöes antes e após a realizaçäo da cirurgia, säo também analizados, buscando-se aprender o significado do fenômeno dor para estes pacientes. Os dados foram coletados em três hospitais gerais de Salvador, através da aplicaçäo de um formulário. O estudo tomou como marco referencial, a Teoria Holística de Myra Lavine. Os resultados obtidos permitiram concluir que: o estado civil, a experiência cirúrgica anterior e o grau de ansiedade no pré-operatório, säo fatores que estäo relacionados com a tolerância à dor no pós-operatório de cirurgia cardíaca

Aplicaçäo da Teoria de Peplau na assistência ao idoso / The Peplaus's Theory in the care to the elderly

A teoria de H. Peplau encara as relaçöes interpessoais como processo terapêutico significativo na assistência de enfermagem ao cliente. A aplicaçäo desta teoria no atendimento ao idoso está baseada nas dificuldades que os indivíduos dessa faixa etária manifestam no relacionamento com outras pessoas. Tentará descobrir meios de facilitar tal relacionamento, com vistas a um diagnóstico e atençäo de enfermagem específicos das necessidades dos mesmos.

Assistência de enfermagem ao paciente no trans-operatório / Nursing care to the patient in the intraoperative period

O trabalho aborda alguns aspectos da assistência de enfermagem no período trans-operatório. Considera o uso de uma metodologia científica e a visita pré-operatória, como elementos importantes para a interaçäo enfermeiro-paciente, neste período. Por fim, utiliza uma formulário para identificar as atividades desenvolvidas pelos enfermeiros de centro cirúrgico em três hospitais da cidade de Salvador