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1.
Klin Lab Diagn ; 66(4): 205-209, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33878240

RESUMO

The number of obese pregnant women increases annually and reaches 20-30%. The metabolism of hormones and minerals changes in the presence of a large amount of adipose tissue in the body of a pregnant woman, which leads to a number of obstetric and perinatal problems. The aim of the work is to study and compare the influence of the gestational process on the indicators of iron and copper metabolism in the blood serum of women with normal body weight and women with obesity. In the blood serum of 125 women of reproductive age, the content of hemoglobin, iron, transferrin, ferritin, copper and ceruloplasmin was determined. The influence of pregnancy on the indicators of iron and copper metabolism in the blood serum of women was revealed. Pregnancy in women with normal body weight increases the content of transferrin and ceruloplasmin. Correlation of ceruloplasmin and ferritin content with body mass index of obese pregnant women was revealed. In pregnancy with concomitant obesity, hyperferritinemia is formed with a reduced content of hemoglobin and serum iron. Knowledge of the indicators of iron and copper metabolism is necessary to optimize the observation of pregnant women, effective prevention and prediction of obstetric and perinatal complications.


Assuntos
Cobre , Ferro , Cobre/metabolismo , Feminino , Ferritinas , Humanos , Peso Corporal Ideal , Ferro/metabolismo , Obesidade , Gravidez
2.
Zhonghua Gan Zang Bing Za Zhi ; 29(3): 265-270, 2021 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-33902195

RESUMO

Objective: To investigate the correlation between serum ferritin (SF) level and liver damage in the acute stage of dengue fever. Methods: A retrospective study was conducted to analyze 171 cases diagnosed with dengue fever as dengue fever group and 130 healthy patients as control group in Hangzhou 3A grade hospital from July to December 2017. Clinical data, SF and liver function related indicators were collected from both groups: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) to analyze the correlation between liver damage and SF in patients with dengue fever. Results: ALT, AST, and SF levels were significantly higher in the dengue fever group than those in the healthy control group (Z = 11.553, 15.054 and 15.163, P < 0.001). SF levels were higher in the dengue fever combined with liver damage group than those without the liver damage group (z = 6.930, P < 0.001). However, there was no statistically significant differences in age, gender, peak body temperature, and history of liver disease (P > 0.05). In addition, Spearman's correlation analysis showed that SF was positively correlated with ALT, AST, and TBIL (r = 0.464, 0.531 and 0.315, P < 0.001). Among dengue patients with different SF levels, there were significant difference in ALT, AST levels and incidence of liver damage (H = 14.240 and 17.584, χ(2) = 49.547, P < 0.001). Patients with higher SF levels had higher ALT, AST levels and incidence of liver damage. Binary logistic regression analysis showed that hyperferritinemia (SF≥500 ng/ml) was the risk factor for dengue fever combined with liver damage (OR = 8.120, P < 0.001). Furthermore, ROC curve analysis showed that the AUC for SF to judge dengue fever combined liver damage was 0.846 (95% CI: 0.785-0.908), and the sensitivity and specificity when the SF cut-off value was 1 506 ng/ml were 74.8% and 83.3%. Conclusion: There is a certain correlation between the SF level and the degree of liver damage in acute stage of dengue fever patients, and hyperferritinemia is a risk factor for dengue fever combined with liver damage.


Assuntos
Dengue , Hepatopatias , Alanina Transaminase , Aspartato Aminotransferases , Dengue/complicações , Dengue/epidemiologia , Ferritinas , Humanos , Fígado , Estudos Retrospectivos
3.
Sheng Li Xue Bao ; 73(2): 244-252, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33903886

RESUMO

The aim of this study was to investigate the effects of polarization program on the ability of macrophages to regulate iron metabolism. M1 and M2 macrophages were propagated in vitro from porcine alveolar macrophages 3D4/2 and polarized by cytokines. The 3D4/2 macrophages were treated with 20 ng/mL interferon gamma (IFN-γ) and 10 ng/mL interleukin-4 (IL-4) combined with 10 ng/mL macrophage colony-stimulating factor (M-CSF) to induce polarization to M1 and M2, respectively. After incubation for 24 h, the expression levels of inflammatory factors and iron-metabolism genes were determined using real-time qPCR, Western bot and immunofluorescence. The M1/M2 macrophages culture media supernatant was collected and used to treat porcine intestinal epithelial cells IPEC-J2. The proliferation ability of IPEC-J2 was detected using CCK-8 assay kit. Following exogenous addition of ammonium ferric citrate (FAC) to M1/M2 macrophages, the phagocytic function of macrophages was detected using fluorescein isothiocyanate-dextran (FITC-dextran) and flow cytometry. The results showed that, compared with control, M1 macrophages had higher mRNA levels of iron storage proteins (ferritin heavy and light polypeptide, i.e. FtH and FtL), hepcidin and lipocalin-2, as well as iron content. Moreover, iron enhanced the ability of M1 macrophages to phagocytize FITC-dextran. There was no significant change in these mRNA expression levels in M2 macrophages, but the mRNA expression levels of ferroportin and transferrin receptor were up-regulated. In addition, the conditioned media supernatant from M2 macrophages promoted cell proliferation of IPEC-J2. These findings indicate that M1 macrophages tend to lock iron in the cell and reduce extracellular iron content, thereby inhibiting the proliferation of extracellular bacteria. While M2 macrophages tend to excrete iron, which contributes to the proliferation of surrounding cells and thus promotes tissue repair.


Assuntos
Citocinas , Macrófagos , Animais , Ferritinas , Ferro/metabolismo , Macrófagos/metabolismo , Macrófagos Alveolares/metabolismo , Suínos
4.
Arq Gastroenterol ; 58(1): 48-54, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909796

RESUMO

BACKGROUND: The treatment of patients with inflammatory bowel disease (IBD) consists of the induction and maintenance remission of the disease. Iron status indicators would be useful for the diagnosis of iron deficiency anemia, whereas the inflammation indicators would be for the diagnosis of chronic disease anemia. OBJECTIVE: To assess body iron status indicators and inflammation indicators during the treatment of IBD, consisted of conventional or infliximab therapy in children and adolescents. METHODS: A case-control study of a sample of 116 individuals, of which 81 patients with IBD, 18 of them receiving conventional therapy, 20 infliximab therapy, and 43 who were in remission of the disease, and 35 healthy (control group) children and adolescents. Iron status and inflammation indicators were investigated at baseline, and 2 and 6 months of both therapies - conventional and infliximab. RESULTS: The mean age was 12.1±4.3 years. At baseline, both groups - conventional therapy and infliximab - presented significant differences in most markers studied compared to the control group. After 2 months of conventional therapy, hemoglobin and serum iron levels were lower than those of the control group; and red cells distribution width (RDW), total iron-binding capacity, transferrin receptor/ferritin ratio, and interleukin-6 were higher than the control group. After 2 months of infliximab treatment, hemoglobin and serum iron levels were lower than those of the control group; and RDW, soluble transferrin receptor, soluble transferrin receptor/ferritin ratio, and interleukin-6 were higher than the control group. After 6 months of conventional therapy, hemoglobin and serum iron levels were lower than those of the control group, and RDW and interleukin-6 were higher than those of the control group. After 6 months of infliximab treatment, the hemoglobin and serum iron levels were lower than the control group, and RDW, soluble transferrin receptor, soluble transferrin receptor/ferritin ratio, erythrocyte sedimentation rate, and platelets were higher than the control group. Regarding patients under treatment for at least one year (remission group), all markers studied, except transferrin, were similar to the control group. CONCLUSION: In conclusion, there were some contradictions among the different body iron status indicators and inflammation indicators at two and 6 months of treatment with conventional and infliximab therapy, however after one year of treatment, as shown by the remission group, all indicators studied, except transferrin, were similar to healthy children and adolescents.


Assuntos
Anemia Ferropriva , Doenças Inflamatórias Intestinais , Adolescente , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/tratamento farmacológico , Estudos de Casos e Controles , Criança , Ferritinas , Humanos , Inflamação , Doenças Inflamatórias Intestinais/tratamento farmacológico , Ferro
5.
Viruses ; 13(3)2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807920

RESUMO

Cytokine storm syndrome in patients with COVID-19 is mediated by pro-inflammatory cytokines resulting in acute lung injury and multiorgan failure. Elevation in serum ferritin and D-dimer is observed in COVID-19 patients. To determine prognostic values of optimal serum cutoff with trajectory plots for both serum ferritin and D-dimer in COVID-19 patients with invasive ventilator dependence and in-hospital mortality. We used retrospective longitudinal data from the Cerner COVID-19 de-identified cohort. COVID-19 infected patients with valid repeated values of serum ferritin and D-dimer during hospitalization were used in mixed-effects logistic-regression models. Among 52,411 patients, 28.5% (14,958) had valid serum ferritin and 28.6% (15,005) D-dimer laboratory results. Optimal cutoffs of ferritin (714 ng/mL) and D-dimer (2.1 mg/L) revealed AUCs ≥ 0.99 for in-hospital mortality. Optimal cutoffs for ferritin (502 ng/mL) and D-dimer (2.0 mg/L) revealed AUCs ≥ 0.99 for invasive ventilator dependence. Optimal cutoffs for in-house mortality, among females, were lower in serum ferritin (433 ng/mL) and D-dimer (1.9 mg/L) compared to males (740 ng/mL and 2.5 mg/L, respectively). Optimal cutoffs for invasive ventilator dependence, among females, were lower in ferritin (270 ng/mL) and D-dimer (1.3 mg/L) compared to males (860 ng/mL and 2.3 mg/L, respectively). Optimal prognostic cutoffs for serum ferritin and D-dimer require considering the entire trajectory of laboratory values during the disease course. Females have an overall lower optimal cutoff for both serum ferritin and D-dimer. The presented research allows health professionals to predict clinical outcomes and appropriate allocation of resources during the COVID-19 pandemic, especially early recognition of COVID-19 patients needing higher levels of care.


Assuntos
/sangue , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Idoso , Biomarcadores/sangue , /mortalidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , /fisiologia
6.
BMC Infect Dis ; 21(1): 398, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926377

RESUMO

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.


Assuntos
/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Idoso , Aspartato Aminotransferases/sangue , /terapia , China/epidemiologia , Comorbidade , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/virologia , Feminino , Ferritinas/sangue , Humanos , Incidência , Contagem de Linfócitos , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Fatores de Risco
7.
Praxis (Bern 1994) ; 110(5): 249-250, 2021 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-33849295

RESUMO

CME Laboratory 63/Answers: Diagnostics of Iron Metabolism Abstract. Abstract: Iron deficiency is common and affects the course of many chronic diseases. The diagnosis of absolute and manifest iron deficiency anemia can be easily made by measuring hemoglobin and serum ferritin levels. In inflammatory diseases, the diagnosis can be facilitated by additional laboratory parameters such as soluble transferrin receptor. In several chronic diseases like cardiac or renal failure, different and higher thresholds for serum ferritin apply depending on the disease and stage, sometimes with additional consideration of transferrin saturation. Transferrin saturation is also important for the diagnosis of hemochromatosis. In patients with transferrin saturation >45 %, diagnosis usually requires evidence of homozygosity for the C282Y mutation in the HFE gene.


Assuntos
Ferritinas , Hemocromatose , Hemocromatose/diagnóstico , Hemocromatose/genética , Proteína da Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I , Humanos , Ferro , Laboratórios , Proteínas de Membrana , Transferrina
8.
Sci Rep ; 11(1): 7282, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790308

RESUMO

Favipiravir is considered a potential treatment for COVID-19 due its efficacy against different viral infections. We aimed to explore the safety and efficacy of favipiravir in treatment of COVID-19 mild and moderate cases. It was randomized-controlled open-label interventional phase 3 clinical trial [NCT04349241]. 100 patients were recruited from 18th April till 18th May. 50 patients received favipiravir 3200 mg at day 1 followed by 600 mg twice (day 2-day 10). 50 patients received hydroxychloroquine 800 mg at day 1 followed by 200 mg twice (day 2-10) and oral oseltamivir 75 mg/12 h/day for 10 days. Patients were enrolled from Ain Shams University Hospital and Assiut University Hospital. Both arms were comparable as regards demographic characteristics and comorbidities. The average onset of SARS-CoV-2 PCR negativity was 8.1 and 8.3 days in HCQ-arm and favipiravir-arm respectively. 55.1% of those on HCQ-arm turned PCR negative at/or before 7th day from diagnosis compared to 48% in favipiravir-arm (p = 0.7). 4 patients in FVP arm developed transient transaminitis on the other hand heartburn and nausea were reported in about 20 patients in HCQ-arm. Only one patient in HCQ-arm died after developing acute myocarditis resulted in acute heart failure. Favipiravir is a safe effective alternative for hydroxychloroquine in mild or moderate COVID-19 infected patients.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Hidroxicloroquina/uso terapêutico , Pirazinas/uso terapêutico , Adulto , Amidas/efeitos adversos , Antivirais/efeitos adversos , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oseltamivir/uso terapêutico , Pirazinas/efeitos adversos , Resultado do Tratamento
9.
Klin Lab Diagn ; 66(3): 147-153, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33793113

RESUMO

A study of interleukin-6 (IL-6), hepcidin-25 (GP-25) was conducted in 22 patients with breast cancer before neoadjuvant chemotherapy and in 27 healthy women in the control group. Significant expression of the GP-25 protein was revealed in breast cancer patients, compared to control. The rates were high both in patients with anemic sindrome (AS) and without it (p <0.01). Latent iron deficiency, AS, IDA and functional iron deficiency (FJ) were more often detected in patients with stage III disease. A significant difference in the parameters of GP-25 and IL-6 was noted, the indicators were higher in patients with stage III (p <0.01). No close correlation was found between IL-6, GP-25 and other acute-phase proteins (FR, CRP) at the initial stages of AS formation. On the contrary, a positive correlation was observed in patients with IDA and FJ between IL-6 and all acute-phase proteins (GP-25, FR, CRP). However, a small number of observations do not allow an unambiguous conclusion about the role of IL-6 and GP-25 expression in the development of AS in cancer patients with breast cancer and requires further study.


Assuntos
Anemia Ferropriva , Neoplasias da Mama , Anemia Ferropriva/complicações , Anemia Ferropriva/tratamento farmacológico , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Feminino , Ferritinas , Hepcidinas , Humanos , Interleucina-6/genética , Terapia Neoadjuvante
10.
Front Immunol ; 12: 627844, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679771

RESUMO

Background: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. Methods: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. Results: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. Conclusions: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.


Assuntos
/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , /metabolismo , Adulto , Idoso , China/epidemiologia , Intervalo Livre de Doença , Feminino , Ferritinas/sangue , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
11.
Nat Commun ; 12(1): 1645, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712594

RESUMO

Anemias of chronic disease and inflammation (ACDI) result from restricted iron delivery to erythroid progenitors. The current studies reveal an organellar response in erythroid iron restriction consisting of disassembly of the microtubule cytoskeleton and associated Golgi disruption. Isocitrate supplementation, known to abrogate the erythroid iron restriction response, induces reassembly of microtubules and Golgi in iron deprived progenitors. Ferritin, based on proteomic profiles, regulation by iron and isocitrate, and putative interaction with microtubules, is assessed as a candidate mediator. Knockdown of ferritin heavy chain (FTH1) in iron replete progenitors induces microtubule collapse and erythropoietic blockade; conversely, enforced ferritin expression rescues erythroid differentiation under conditions of iron restriction. Fumarate, a known ferritin inducer, synergizes with isocitrate in reversing molecular and cellular defects of iron restriction and in oral remediation of murine anemia. These findings identify a cytoskeletal component of erythroid iron restriction and demonstrate potential for its therapeutic targeting in ACDI.


Assuntos
Anemia/metabolismo , Anemia/terapia , Citoesqueleto/metabolismo , Ferro/metabolismo , Microtúbulos/metabolismo , Animais , Proliferação de Células , Modelos Animais de Doenças , Células Eritroides/metabolismo , Eritropoese/fisiologia , Feminino , Ferritinas/metabolismo , Isocitratos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredutases/metabolismo , Proteômica
12.
Biomolecules ; 11(2)2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671255

RESUMO

SARS-CoV-2, or COVID-19, has a devastating effect on our society, both in terms of quality of life and death rates; hence, there is an urgent need for developing safe and effective therapeutics against SARS-CoV-2. The most promising strategy to fight against this deadly virus is to develop an effective vaccine. Internalization of SARS-CoV-2 into the human host cell mainly occurs through the binding of the coronavirus spike protein (a trimeric surface glycoprotein) to the human angiotensin-converting enzyme 2 (ACE2) receptor. The spike-ACE2 protein-protein interaction is mediated through the receptor-binding domain (RBD) of the spike protein. Mutations in the spike RBD can significantly alter interactions with the ACE2 host receptor. Due to its important role in virus transmission, the spike RBD is considered to be one of the key molecular targets for vaccine development. In this study, a spike RBD-based subunit vaccine was designed by utilizing a ferritin protein nanocage as a scaffold. Several fusion protein constructs were designed in silico by connecting the spike RBD via a synthetic linker (different sizes) to different ferritin subunits (H-ferritin and L-ferritin). The stability and the dynamics of the engineered nanocage constructs were tested by extensive molecular dynamics simulation (MDS). Based on our MDS analysis, a five amino acid-based short linker (S-Linker) was the most effective for displaying the spike RBD over the surface of ferritin. The behavior of the spike RBD binding regions from the designed chimeric nanocages with the ACE2 receptor was highlighted. These data propose an effective multivalent synthetic nanocage, which might form the basis for new vaccine therapeutics designed against viruses such as SARS-CoV-2.


Assuntos
/química , Ferritinas/química , Nanoestruturas/química , Glicoproteína da Espícula de Coronavírus/química , /metabolismo , /metabolismo , Ferritinas/metabolismo , Humanos , Simulação de Dinâmica Molecular , Conformação Proteica , Domínios Proteicos , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas de Subunidades/química , Vacinas de Subunidades/metabolismo
13.
World J Emerg Surg ; 16(1): 9, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685484

RESUMO

BACKGROUND: SARS-CoV-2 infection has spread worldwide, and the pathogenic mechanism is still under investigation. The presence of a huge inflammatory response, defined as "cytokine storm," is being studied in order to understand what might be the prognostic factors implicated in the progression of the infection, with ferritin being one of such markers. The role of ferritin as a marker of inflammation is already known, and whether it changes differently between COVID and non-COVID patients still remains unclear. The aim of this retrospective analysis is to understand whether the inflammatory process in these two types is different. METHODS: In this retrospective analysis, we compared 17 patients affected by SARS-CoV-2, who had been admitted between February and April 2020 (group A) along with 30 patients admitted for acute surgical disease with SARS-CoV-2 negative swab (group B). A further subgroup of Covid negative patients with leukocytosis was compared to group A. RESULTS: In group A, the median (interquartile range) serum ferritin was 674 (1284) ng/mL, and it was double the cutoff (300 ng/mL) in 9 out of 17 (52%). The median (IQR) value of ferritin level in the total blood samples of group B was 231, and in the subgroup with leucocytosis, 149 (145). Group A showed a significantly higher ferritin median level compared to the entire group B (two-tailed Mann-Whitney test, p < 0.0001) as well as to the subgroup with leucocytosis (p < 0.0014). CONCLUSIONS: The role of iron metabolism appears to be directly involved in COVID infection. On the other hand, in the acute inflammation of patients admitted for surgery, and probably in other common phlogistic processes, iron modifications appear to be self-limited. However, our finding suggests the use of ferritin as a marker for COVID infection.


Assuntos
/métodos , /fisiopatologia , Ferritinas/sangue , Inflamação/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , /cirurgia , Estudos de Casos e Controles , Emergências , Feminino , Humanos , Inflamação/sangue , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios
14.
Sci Transl Med ; 13(583)2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658355

RESUMO

Seasonal influenza vaccines confer protection against specific viral strains but have restricted breadth that limits their protective efficacy. The H1 and H3 subtypes of influenza A virus cause most of the seasonal epidemics observed in humans and are the major drivers of influenza A virus-associated mortality. The consequences of pandemic spread of COVID-19 underscore the public health importance of prospective vaccine development. Here, we show that headless hemagglutinin (HA) stabilized-stem immunogens presented on ferritin nanoparticles elicit broadly neutralizing antibody (bnAb) responses to diverse H1 and H3 viruses in nonhuman primates (NHPs) when delivered with a squalene-based oil-in-water emulsion adjuvant, AF03. The neutralization potency and breadth of antibodies isolated from NHPs were comparable to human bnAbs and extended to mismatched heterosubtypic influenza viruses. Although NHPs lack the immunoglobulin germline VH1-69 residues associated with the most prevalent human stem-directed bnAbs, other gene families compensated to generate bnAbs. Isolation and structural analyses of vaccine-induced bnAbs revealed extensive interaction with the fusion peptide on the HA stem, which is essential for viral entry. Antibodies elicited by these headless HA stabilized-stem vaccines neutralized diverse H1 and H3 influenza viruses and shared a mode of recognition analogous to human bnAbs, suggesting that these vaccines have the potential to confer broadly protective immunity against diverse viruses responsible for seasonal and pandemic influenza infections in humans.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vacinas contra Influenza/imunologia , Primatas/imunologia , Animais , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/química , Complexo Antígeno-Anticorpo/química , Anticorpos Amplamente Neutralizantes/biossíntese , Anticorpos Amplamente Neutralizantes/química , Ferritinas/química , Ferritinas/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/química , Influenza Humana/imunologia , Influenza Humana/virologia , Macaca fascicularis , Modelos Moleculares , Nanopartículas/química , Pandemias , Primatas/virologia , Estrutura Quaternária de Proteína , Pesquisa Médica Translacional
15.
Sci Rep ; 11(1): 4863, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649408

RESUMO

The coronavirus 2019 disease (COVID-19) is characterised by a heterogeneous clinical presentation, a complex pathophysiology and a wide range of imaging findings, depending on disease severity and time course. We conducted a retrospective evaluation of hospitalized patients with proven SARS-CoV-2 infection, clinical signs of COVID-19 and computed tomography (CT) scan-proven pulmonary involvement, in order to identify relationships between clinical, serological, imaging data and disease outcomes in patients with COVID-19. Clinical and serological records of patients admitted to two COVID-19 Units of the Abruzzo region in Italy with proven SARS-CoV-2 pulmonary involvement investigated with CT scan, assessed at the time of admission to the hospital, were retrospectively evaluated. Sixty-one patients (22 females and 39 males) of median age 65 years were enrolled. Fifty-six patients were discharged while death occurred in 5 patients. None of the lung abnormalities detected by CT was different between discharged and deceased patients. No differences were observed in the features and extent of pulmonary involvement according to age and gender. Logistic regression analysis with age and gender as covariates demonstrated that ferritin levels over the 25th percentile were associated with the involvement of all 5 pulmonary lobes (OR = 14.5, 95% CI 2.3-90.9, p = 0.004), the presence of septal thickening (OR = 8.2, 95% CI 1.6-40.9, p = 0.011) and the presence of mediastinal lymph node enlargement (OR = 12.0, 95% CI 1.1-127.5, p = 0.039) independently of age and gender. We demonstrated that ferritin levels over the 25th percentile are associated with a more severe pulmonary involvement, independently of age and gender and not associated with disease outcomes. The identification of reliable biomarkers in patients with COVID-19 may help guiding clinical decision, tailoring therapeutic approaches and ultimately improving the care and prognosis of patients with this disease.


Assuntos
Ferritinas/sangue , Pulmão/diagnóstico por imagem , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , /diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Praxis (Bern 1994) ; 110(4): 181-186, 2021.
Artigo em Alemão | MEDLINE | ID: mdl-33726518

RESUMO

CME-Laboratory 63: Diagnostics of Iron Metabolism Abstract. Iron deficiency is common and affects the course of many chronic diseases. The diagnosis of absolute and manifest iron deficiency anemia can be easily made by measuring hemoglobin and serum ferritin levels. In inflammatory diseases, the diagnosis can be facilitated by additional laboratory parameters such as soluble transferrin receptor. In several chronic diseases like cardiac or renal failure, different and higher thresholds for serum ferritin apply depending on the disease and stage, sometimes with additional consideration of transferrin saturation. Transferrin saturation is also important for the diagnosis of hemochromatosis. In patients with transferrin saturation >45 %, diagnosis usually requires evidence of homozygosity for the C282Y mutation in the HFE gene.


Assuntos
Hemocromatose , Antígenos de Histocompatibilidade Classe I , Ferritinas , Hemocromatose/diagnóstico , Hemocromatose/genética , Proteína da Hemocromatose/genética , Humanos , Ferro , Laboratórios , Proteínas de Membrana , Transferrina
17.
Eur J Gastroenterol Hepatol ; 33(5): 695-700, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33787541

RESUMO

BACKGROUND: The data on clinical course and outcome of acute pancreatitis among patients with coronavirus disease 2019 (COVID-19) are sparse. In this study, we analyzed the clinical profiles of patients with COVID 19 and acute pancreatitis. METHODS: This retrospective study was conducted on Research Patient Data Registry data which was pooled from five Mass General Brigham Healthcare Network hospitals. We extracted data on demographics, symptoms, ICU transfer, mechanical ventilation, laboratories' profiles, imaging findings, and patient outcomes. RESULT: Of 985 screened adult patients, 17 were eligible for the study, 9 (52.9%) were admitted primarily for respiratory failure and developed acute pancreatitis after a median of 22.5 days (13-76 days) from the onset of COVID-19 symptoms. On contrary, eight patients presented with typical symptoms and were diagnosed with acute pancreatitis, the majority with mild severity (62.5%) on admission. Patients who were admitted primarily with severe COVID-19 illness were younger (median age 57 vs. 63 years), females (55.6 vs. 25%), of Hispanic ethnicity (55.6 vs. 25%), and obese (88.9 vs. 37.5%). The median peak lipase, C reactive protein, ferritin, lactate dehydrogenase, D-dimer were higher among patients who developed acute pancreatitis later during hospitalization. Patients who developed acute pancreatitis later also experienced higher episodes of necrotizing pancreatitis (11.1% vs. 0), thromboembolic complications (55.6 vs. 12.5%), and higher mortality (37.5 vs. 12.5%). CONCLUSION: Acute pancreatitis is not common among patients with COVID-19. Patients with COVID-19 who had acute pancreatitis on admission had more benign course and overall better outcome as compared to the patients who developed acute pancreatitis during hospitalization.


Assuntos
/fisiopatologia , Mortalidade Hospitalar , Pancreatite/fisiopatologia , /fisiopatologia , Adulto , Afro-Americanos , Distribuição por Idade , Idoso , Proteína C-Reativa/metabolismo , /metabolismo , Grupo com Ancestrais do Continente Europeu , Feminino , Ferritinas/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hispano-Americanos , Humanos , L-Lactato Desidrogenase/metabolismo , Tempo de Internação , Lipase/metabolismo , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Pancreatite/epidemiologia , Pancreatite/metabolismo , Pancreatite Necrosante Aguda/epidemiologia , /metabolismo , Estudos Retrospectivos , Índice de Gravidade de Doença , Distribuição por Sexo , Tromboembolia/epidemiologia
18.
Int J Mol Sci ; 22(4)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668605

RESUMO

Arsenoplatin-1 (AP-1), the prototype of a novel class of metallodrugs containing a PtAs(OH)2 core, was encapsulated within the apoferritin (AFt) nanocage. UV-Vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy measurements confirmed metallodrug encapsulation and allowed us to determine the average amount of AP-1 trapped inside the cage. The X-ray structure of AP-1-encapsulated AFt was solved at 1.50 Å. Diffraction data revealed that an AP-1 fragment coordinates the side chain of a His residue. The biological activity of AP-1-loaded AFt was comparatively tested on a few representative cancer and non-cancer cell lines. Even though the presence of the cage reduces the overall cytotoxicity of AP-1, it improves its selectivity towards cancer cells.


Assuntos
Antineoplásicos , Citotoxinas , Ferritinas , Neoplasias/tratamento farmacológico , Compostos de Platina , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Células 3T3 BALB , Citotoxinas/química , Citotoxinas/farmacologia , Ferritinas/química , Ferritinas/farmacologia , Humanos , Camundongos , Estrutura Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Compostos de Platina/química , Compostos de Platina/farmacologia , Relação Estrutura-Atividade
19.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669238

RESUMO

Protein assemblies provide unique structural features which make them useful as carrier molecules in biomedical and chemical science. Protein assemblies can accommodate a variety of organic, inorganic and biological molecules such as small proteins and peptides and have been used in development of subunit vaccines via display parts of viral pathogens or antigens. Such subunit vaccines are much safer than traditional vaccines based on inactivated pathogens which are more likely to produce side-effects. Therefore, to tackle a pandemic and rapidly produce safer and more effective subunit vaccines based on protein assemblies, it is necessary to understand the basic structural features which drive protein self-assembly and functionalization of portions of pathogens. This review highlights recent developments and future perspectives in production of non-viral protein assemblies with essential structural features of subunit vaccines.


Assuntos
Ferritinas/imunologia , Vacinas de Subunidades/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/imunologia , Animais , Antígenos Virais/imunologia , Bacteriófago T4/imunologia , Humanos , Nanopartículas/química , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta
20.
Innate Immun ; 27(3): 240-250, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33646058

RESUMO

Cell destruction results in plasma accumulation of cell-free DNA (cfDNA). Dynamic changes in circulating lymphocytes are features of COVID-19. We aimed to investigate if cfDNA level can serve in stratification of COVID-19 patients, and if cfDNA level is associated with alterations in lymphocyte subsets and neutrophil-to-lymphocyte ratio (NLR). This cross-sectional comparative study enrolled 64 SARS-CoV-2-positive patients. Patients were subdivided to severe and non-severe groups. Plasma cfDNA concentration was determined by real-time quantitative PCR. Lymphocyte subsets were assessed by flow cytometry. There was significant increase in cfDNA among severe cases when compared with non-severe cases. cfDNA showed positive correlation with NLR and inverse correlation with T cell percentage. cfDNA positively correlated with ferritin and C-reactive protein. The output data of performed ROC curves to differentiate severe from non-severe cases revealed that cfDNA at cut-off ≥17.31 ng/µl and AUC of 0.96 yielded (93%) sensitivity and (73%) specificity. In summary, excessive release of cfDNA can serve as sensitive COVID-19 severity predictor. There is an association between cfDNA up-regulation and NLR up-regulation and T cell percentage down-regulation. cfDNA level can be used in stratification and personalized monitoring strategies in COVID-19 patients.


Assuntos
/diagnóstico , DNA/sangue , Subpopulações de Linfócitos/patologia , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Proteína C-Reativa/análise , Estudos Transversais , Diagnóstico Diferencial , Feminino , Ferritinas/sangue , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Sensibilidade e Especificidade , Linfócitos T/patologia , Adulto Jovem
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