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1.
Anal Chem ; 93(36): 12175-12180, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34469115

RESUMO

Malaria and typhoid fever are two febrile illnesses prevalent in the tropics that often present overlapping symptoms. In this work, we demonstrate an optical reader-based diagnostics platform for rapid codetection and quantification of two antigen targets: lipopolysaccharide (LPS) for typhoid fever and plasmodium lactate dehydrogenase (pLDH) for malaria infections. We report a limit of detection (LoD) of 5 ng/mL for LPS and 10 ng/mL for pLDH in a spiked serum test. We also validated the duplex test's performance of differentiating malaria infection, typhoid fever infection, and coinfection by testing clinical samples in human serum. Our platform provides the potential for further multiplexing by encoding different color codes to various detection targets. The rapid result (∼15 min), low cost (∼$2), and minimal volume requirement for human serum clinical samples (4 µL) of our diagnostic platform offer great potential for deployment in resource-limited settings to help distinguish common causes for acute febrile illnesses at the point-of-need.


Assuntos
Malária , Plasmodium , Febre Tifoide , Humanos , L-Lactato Desidrogenase , Malária/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Febre Tifoide/diagnóstico
2.
Medicine (Baltimore) ; 100(38): e27329, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559153

RESUMO

ABSTRACT: It is important to diagnose epilepsy in a timely and accurate manner, and also to distinguish it from non-epileptic conditions. The present study was aimed at determining postictal serum prolactin levels and lactate dehydrogenase (LDH) activities in patients with new-onset seizure admitted to the emergency department in order to assess whether they could be used in the differentiation of epileptic seizure (ES) from nonepileptic seizure (NES).Eighty-five patients were included prospectively in this study. Patients were divided into 2 groups with respect to epilepsy diagnosis, and the final groups were comprised of 36 patients with ES and 49 patients with NES. Blood samples were obtained within 1 hour of seizure.No significant differences between groups were observed in prolactin levels and in the percentage of patients with abnormal prolactin level (P = .569 and .239, respectively). The median LDH activity was significantly higher in those with ES compared with those with NES (P = .031). The percentage of patients with elevated LDH levels was similar between 2 groups (P = .286).This was the first study to examine LDH activities in terms of its role in differentiation of seizure origin in the postictal period in patients hospitalized with seizure. Our study demonstrated that serum LDH activities within 1 hour after the seizure appear to be increased in patients with ES compared with those with NES, suggesting the potential role of LDH activities as a diagnostic tool in distinction of seizure types. Our study supports the hypothesis that LDH-antagonists may have a role in the management of seizure and epilepsy.


Assuntos
Epilepsia/diagnóstico , L-Lactato Desidrogenase/sangue , Prolactina/sangue , Convulsões/sangue , Adulto , Idoso , Estudos Transversais , Diagnóstico Diferencial , Epilepsia/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Aging (Albany NY) ; 13(17): 20896-20905, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495869

RESUMO

BACKGROUND: This study aimed to explore the significance of neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), D-dimer, and CT score in evaluating the severity and prognosis of coronavirus disease 2019 (COVID-19). METHODS: Patients with laboratory-confirmed COVID-19 were retrospectively enrolled. The baseline data, laboratory findings, chest computed tomography (CT) results evaluated by CT score on admission, and clinical outcomes were collected and compared. Logistic regression was used to assess the independent relationship between the baseline level of the four indicators (NLR, LDH, D-dimer, and CT score) and the severity of COVID-19. RESULTS: Among the 432 patients, 125 (28.94%) and 307 (71.06%) were placed in the severe and non-severe groups, respectively. As per the multivariate logistic regression, high levels of NLR and LDH were independent predictors of severe COVID-19 (OR=2.163; 95% CI=1.162-4.026; p=0.015 for NLR>3.82; OR=2.298; 95% CI=1.327-3.979; p=0.003 for LDH>246 U/L). Combined NLR>3.82 and LDH>246 U/L increased the sensitivity of diagnosis in patients with severe disease (NLR>3.82 [50.40%] vs. combined diagnosis [72.80%]; p=0.0007; LDH>246 [59.2%] vs. combined diagnosis [72.80%]; p<0.0001). CONCLUSIONS: High levels of serum NLR and LDH have potential value in the early identification of patients with severe COVID-19. Moreover, the combination of LDH and NLR can improve the sensitivity of diagnosis.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico por imagem , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , L-Lactato Desidrogenase/sangue , Linfócitos/patologia , Neutrófilos/patologia , Tomografia Computadorizada por Raios X , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC
4.
Front Immunol ; 12: 715072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539644

RESUMO

Background: Prediction of the severity of COVID-19 at its onset is important for providing adequate and timely management to reduce mortality. Objective: To study the prognostic value of damage parameters and cytokines as predictors of severity of COVID-19 using an extensive immunologic profiling and unbiased artificial intelligence methods. Methods: Sixty hospitalized COVID-19 patients (30 moderate and 30 severe) and 17 healthy controls were included in the study. The damage indicators high mobility group box 1 (HMGB1), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), extensive biochemical analyses, a panel of 47 cytokines and chemokines were analyzed at weeks 1, 2 and 7 along with clinical complaints and CT scans of the lungs. Unbiased artificial intelligence (AI) methods (logistic regression and Support Vector Machine and Random Forest algorithms) were applied to investigate the contribution of each parameter to prediction of the severity of the disease. Results: On admission, the severely ill patients had significantly higher levels of LDH, IL-6, monokine induced by gamma interferon (MIG), D-dimer, fibrinogen, glucose than the patients with moderate disease. The levels of macrophage derived cytokine (MDC) were lower in severely ill patients. Based on artificial intelligence analysis, eight parameters (creatinine, glucose, monocyte number, fibrinogen, MDC, MIG, C-reactive protein (CRP) and IL-6 have been identified that could predict with an accuracy of 83-87% whether the patient will develop severe disease. Conclusion: This study identifies the prognostic factors and provides a methodology for making prediction for COVID-19 patients based on widely accepted biomarkers that can be measured in most conventional clinical laboratories worldwide.


Assuntos
COVID-19/patologia , Diagnóstico por Computador/métodos , Índice de Gravidade de Doença , Máquina de Vetores de Suporte , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/análise , Citocinas/sangue , Feminino , Proteína HMGB1/sangue , Humanos , L-Lactato Desidrogenase/sangue , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Prognóstico , Estudos Prospectivos , SARS-CoV-2
5.
Medicine (Baltimore) ; 100(30): e26719, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397705

RESUMO

ABSTRACT: Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ±â€Š0.9 vs 37.5 ±â€Š0.8 degC, P = .011), higher total white cell counts (6.95 ±â€Š2.29 vs 6.39 ±â€Š2.19 x109/L, P = .021), serum ferritin (240 ±â€Š274 vs 165 ±â€Š198 ng/ml, P = .002) and lactate dehydrogenase (632 ±â€Š912 vs 389 ±â€Š107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.


Assuntos
Aspartato Aminotransferases/sangue , COVID-19/complicações , L-Lactato Desidrogenase/sangue , Hepatopatias/etiologia , Adulto , COVID-19/sangue , Feminino , Ferritinas/sangue , Humanos , Contagem de Leucócitos , Hepatopatias/sangue , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Singapura
6.
FASEB J ; 35(9): e21825, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34383978

RESUMO

Ubiquitination is an essential post-translational modification that regulates protein stability or function. Its substrate specificity is dictated by various E3 ligases. The human C-terminal to LisH (CTLH) complex is a newly discovered multi-subunit really interesting new gene (RING) E3 ligase with only a few known ubiquitination targets. Here, we used mass spectrometry-based proteomic techniques to gain insight into CTLH complex function and ubiquitination substrates in HeLa cells. First, global proteomics determined proteins that were significantly increased, and thus may be substrates targeted for degradation, in cells depleted of CTLH complex member RanBPM. RanBPM-dependent ubiquitination determined using diGLY-enriched proteomics and the endogenous RanBPM interactome further revealed candidate ubiquitination targets. Three glycolysis enzymes alpha-enolase, L-lactate dehydrogenase A chain (LDHA), and pyruvate kinase M1/2 (PKM) had decreased ubiquitin sites in shRanBPM cells and were found associated with RanBPM in the interactome. Reduced polyubiquitination was validated for PKM2 and LDHA in cells depleted of RanBPM and CTLH complex RING domain subunit RMND5A. PKM2 and LDHA protein levels were unchanged, yet their activity was increased in extracts of cells with downregulated RanBPM. Finally, RanBPM deficient cells displayed enhanced glycolysis and deregulated central carbon metabolism. Overall, this study identifies potential CTLH complex ubiquitination substrates and uncovers that the CTLH complex inhibits glycolysis via non-degradative ubiquitination of PKM2 and LDHA.


Assuntos
Glicólise/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/fisiologia , Animais , Linhagem Celular Tumoral , Células HeLa , Humanos , L-Lactato Desidrogenase/metabolismo , Camundongos , Proteômica/métodos , Especificidade por Substrato , Ubiquitina/metabolismo
7.
PLoS One ; 16(8): e0256023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34375366

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common in coronavirus disease-2019 (COVID-19) and the severity of AKI is linked to adverse outcomes. In this study, we investigated the factors associated with in-hospital outcomes among hospitalized patients with COVID-19 and AKI. METHODS: In this multicenter retrospective observational study, we evaluated the characteristics and in-hospital renal and patient outcomes of 578 patients with confirmed COVID-19 and AKI. Data were collected from 34 hospitals in Turkey from March 11 to June 30, 2020. AKI definition and staging were based on the Kidney Disease Improving Global Outcomes criteria. Patients with end-stage kidney disease or with a kidney transplant were excluded. Renal outcomes were identified only in discharged patients. RESULTS: The median age of the patients was 69 years, and 60.9% were males. The most frequent comorbid conditions were hypertension (70.5%), diabetes mellitus (43.8%), and chronic kidney disease (CKD) (37.6%). The proportions of AKI stages 1, 2, and 3 were 54.0%, 24.7%, and 21.3%, respectively. 291 patients (50.3%) were admitted to the intensive care unit. Renal improvement was complete in 81.7% and partial in 17.2% of the patients who were discharged. Renal outcomes were worse in patients with AKI stage 3 or baseline CKD. The overall in-hospital mortality in patients with AKI was 38.9%. In-hospital mortality rate was not different in patients with preexisting non-dialysis CKD compared to patients without CKD (34.4 versus 34.0%, p = 0.924). By multivariate Cox regression analysis, age (hazard ratio [HR] [95% confidence interval (95%CI)]: 1.01 [1.0-1.03], p = 0.035], male gender (HR [95%CI]: 1.47 [1.04-2.09], p = 0.029), diabetes mellitus (HR [95%CI]: 1.51 [1.06-2.17], p = 0.022) and cerebrovascular disease (HR [95%CI]: 1.82 [1.08-3.07], p = 0.023), serum lactate dehydrogenase (greater than two-fold increase) (HR [95%CI]: 1.55 [1.05-2.30], p = 0.027) and AKI stage 2 (HR [95%CI]: 1.98 [1.25-3.14], p = 0.003) and stage 3 (HR [95%CI]: 2.25 [1.44-3.51], p = 0.0001) were independent predictors of in-hospital mortality. CONCLUSIONS: Advanced-stage AKI is associated with extremely high mortality among hospitalized COVID-19 patients. Age, male gender, comorbidities, which are risk factors for mortality in patients with COVID-19 in the general population, are also related to in-hospital mortality in patients with AKI. However, preexisting non-dialysis CKD did not increase in-hospital mortality rate among AKI patients. Renal problems continue in a significant portion of the patients who were discharged.


Assuntos
Injúria Renal Aguda/patologia , COVID-19/patologia , Injúria Renal Aguda/etiologia , Idoso , COVID-19/complicações , COVID-19/mortalidade , COVID-19/virologia , Comorbidade , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Unidades de Terapia Intensiva , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Fatores Sexuais , Turquia
8.
Molecules ; 26(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34443533

RESUMO

Quercetin is a polyphenolic compound, the effects of which raise scientists' doubts. The results of many experiments show that it has anticancer, antiinflammatory, and antioxidant properties, while other studies indicate its pro-oxidative and cytotoxic action. This compound can react with reactive oxygen species, and due to its chemical properties, it can be found in the hydrophobic-hydrophilic area of cells. These features of quercetin indicate that its action in cells will be associated with the modification of membranes and its participation in maintaining the redox balance. Therefore, this study distinguishes these two mechanisms and determines whether they are important for cell function. We check: (1) Whether the selected concentrations of quercetin are cytotoxic and destructive for SK-N-SH cell membranes (MTT, LDH, MDA tests) in situations with and without the applied oxidative stress; (2) what is the level of changes in the structural/mechanical properties of the lipid part of the membranes of these cells due to the presence of polyphenol molecules; and (3) whether the antioxidative action of quercetin protects the membrane against its modification. Our results show that changes in the stiffness/elasticity of the lipid part of the membrane constitute the decisive mechanism of action of quercetin, potentially influencing cellular processes whose initial stages are associated with membranes (e.g., reception of signals from the environment, transport).


Assuntos
Membrana Celular/efeitos dos fármacos , Neuroblastoma/patologia , Quercetina/farmacologia , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , L-Lactato Desidrogenase/metabolismo , Ozônio/farmacologia , Pressão , Temperatura
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1119-1122, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362490

RESUMO

OBJECTIVE: To investigate the auxiliary diagnostic value of serum adenosine deaminase (ADA) in acute leukemia (AL) at clinical test. METHODS: 123 AL patients hospitalized in Zhejiang hospital from November 2018 to March 2020 were enrolled as the observation group, and 98 healthy people in the same period were randomly enrolled as the control group. AL patients were divided into two groups: 77 acute myeloid leukemia (AML) patients for AML group and 46 acute lymphoblastic leukemia (ALL) patients for ALL group. The levels of adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) and homocysteine (Hcy) in serum of the patients were detected, and the correlation of ADA with these items was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the clinical diagnostic value of ADA, Yoden index was used to confirm the best cut-off point. RESULTS: The serum ADA level in AL patients was significant higher than that in control group (P < 0.05). The results of Pearson correlation analysis showed that there was a significant positive correlation of ADA with Hcy, ALT, AST, GGT, LDH in AML group (r = 0.47, r = 0.28, r = 0.37, r = 0.22, r = 0.55); and also there was a significant positive correlation of ADA with GGT in ALL group (r = 0.54). In AML group, the maximum area under ROC curve was 0.761 (P = 0.00), 95% confidence interval was 0.682-0.841, sensitivity was 54.50%, specificity was 98.90%, and the best cut-off point was 17.1 U/L. In ALL group, the maximum area under ROC curve was 0.785, 95% confidence interval was 0.694-0.877, sensitivity was 65.90%, specificity was 84.00%, and the best cut-off point was 13.45 U/L. CONCLUSION: The detection of ADA in serum can be used as an auxiliary examination in patients with AL, which can provide a certain value for the diagnosis of the disease.


Assuntos
Adenosina Desaminase , Leucemia Mieloide Aguda , Humanos , L-Lactato Desidrogenase , Leucemia Mieloide Aguda/diagnóstico , Curva ROC , Estudos Retrospectivos
10.
Environ Toxicol Pharmacol ; 87: 103725, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34416396

RESUMO

The objective of this study was to evaluate the toxic effects of Cr6+ on bioaccumulation, digestion, immunity, oxidative stress, apoptosis and inflammation-related genes in Channa asiatica. The fish was exposed to waterborne Cr6+ concentrations (0, 0.5, 1.0 and 2.0 mg/L) for 28 and 56 days. Our results demonstrated that the accumulation of Cr6+ in tissues increased in a concentration-dependent manner, and the content in tissue was liver > gill > gut > muscle. Meanwhile, Cr6+ exposure led to a remarkable suppression of digestion, immunity and antioxidant capacity in C. asiatica. Inversely, MDA and PC content were positively correlated with Cr6+ exposure concentration. Furthermore, the expression of genes went up with the increase of waterborne Cr6+ concentration. Among them, HSP90, NF-κB and TNF-α have a sharp increase. These results elucidate that waterborne Cr6+ exposure may induce bioaccumulation, inhibit digestion and immunity, promote oxidative stress and up-regulate the expression of apoptosis and inflammation-related genes in C. asiatica.


Assuntos
Cromo/toxicidade , Poluentes Químicos da Água/toxicidade , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Bioacumulação , Citocinas/sangue , Citocinas/genética , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Peixes/genética , Peixes/imunologia , Peixes/metabolismo , Expressão Gênica/efeitos dos fármacos , Brânquias/metabolismo , Imunoglobulina M/sangue , Mucosa Intestinal/metabolismo , L-Lactato Desidrogenase/sangue , Fígado/metabolismo , Muramidase/sangue , Músculos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estômago/efeitos dos fármacos , Estômago/enzimologia
11.
Parasitol Res ; 120(9): 3335-3339, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34405281

RESUMO

"Bug as drug" is a concept recognized over a century ago and has gained significant research attention recently for fighting diseases such as immune disorders and others. Bacteria and viruses are constantly studied for this purpose, but the use of parasitic organisms is still rare. Recently, we found that Toxoplasma gondii mutants lacking two lactate dehydrogenases (ME49 Δldh1-Δldh2) were avirulent in mice but able to stimulate high levels of Th1 immunity. This outcome prompted us to determine whether Δldh mutants also displayed antitumor activities. Using a mouse melanoma model, we showed that intratumoral administration of Δldh1-Δldh2 repressed the growth of established tumors and helped to inhibit lethal tumor development in the mice. The sera of parasite-treated mice had high levels of TNF-α and INF-γ, which likely contributed to the tumor-repressing activity. We also found that chronic Toxoplasma infection, which is common in animals and humans, also led to antitumor activity. In addition, pre-existing chronic infections did not affect the antitumor efficiency of the Δldh1-Δldh2 mutant. Together, these results suggest that the attenuated T. gondii mutant Δldh1-Δldh2 has the potential to be a good antitumor therapy and provide new insights into the development of novel tumor therapeutics.


Assuntos
Melanoma/terapia , Toxoplasma , Animais , L-Lactato Desidrogenase/genética , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/terapia , Toxoplasma/enzimologia , Toxoplasma/genética
12.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200394

RESUMO

Zinc is an effective anti-inflammatory and antioxidant trace element. The aim of this study was to analyse the protective effect of zinc and zinc-prolactin systems as additives of preservation solutions in the prevention of nephron damage caused during ischemia. The study used a model for storing isolated porcine kidneys in Biolasol®. The solution was modified with the addition of Zn at a dose of 1 µg/L and Zn: 1 µg/L with prolactin (PRL): 0.1 µg/L. After 2 h and 48 h of storage, the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, sodium, potassium, creatinine and total protein were determined. Zinc added to the Biolasol® composition at a dose of 1 µg/L showed minor effectiveness in the protection of nephrons. In turn, Zn2+ added to Biolasol + PRL (PRL: 0.1 µg/L) acted as a prolactin inhibitor. We do not recommend the addition of Zn(II) (1 µg/L) and Zn(II) (1 µg/L) + PRL (0.1 µg/L) to the Biolasol solution.


Assuntos
Isquemia/metabolismo , Rim/metabolismo , Prolactina/metabolismo , Zinco/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Creatinina/metabolismo , Criopreservação/métodos , L-Lactato Desidrogenase/metabolismo , Preservação de Órgãos/métodos , Perfusão/métodos , Potássio/metabolismo , Sódio/metabolismo , Suínos
13.
Int J Mol Sci ; 22(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299084

RESUMO

During pregnancy, freely floating placental villi are adapted to fluid shear stress due to placental perfusion with maternal plasma and blood. In vitro culture of placental villous explants is widely performed under static conditions, hoping the conditions may represent the in utero environment. However, static placental villous explant culture dramatically differs from the in vivo situation. Thus, we established a flow culture system for placental villous explants and compared commonly used static cultured tissue to flow cultured tissue using transmission and scanning electron microscopy, immunohistochemistry, and lactate dehydrogenase (LDH) and human chorionic gonadotropin (hCG) measurements. The data revealed a better structural and biochemical integrity of flow cultured tissue compared to static cultured tissue. Thus, this new flow system can be used to simulate the blood flow from the mother to the placenta and back in the most native-like in vitro system so far and thus can enable novel study designs.


Assuntos
Gonadotropina Coriônica/metabolismo , Vilosidades Coriônicas/crescimento & desenvolvimento , L-Lactato Desidrogenase/metabolismo , Trofoblastos/citologia , Técnicas de Cultura de Células , Vilosidades Coriônicas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Gravidez , Trofoblastos/metabolismo
14.
Anticancer Res ; 41(8): 3885-3889, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281850

RESUMO

BACKGROUND/AIM: Currently, there is no established prognostic serum parameter except PSA in clinically regional lymph node-positive prostate cancer. The aim of this study was to identify serum prognostic factors in clinically regional lymph node-positive prostate cancer. PATIENTS AND METHODS: Patients diagnosed with regional lymph node-positive prostate cancer between 2008 and 2017 were included. The prognostic value of serum parameters for progression-free survival (PFS) and overall survival (OS) was investigated. RESULTS: Univariate and multivariate analyses showed a statistically significant increased hazard risk for PFS and OS for men with lactate dehydrogenase (LDH) ≥230 IU/l at diagnosis. PFS at 5 years for patients with high and low LDH levels were 69.9% (95% CI=56.8-79.8%) and 18.9% (95% CI=1.23-53.2%), respectively (p=0.003). OS at 5 years for low and high LDH levels were 89.2% (95% CI=78.6-94.7%) and 46.3 (95% CI=11.2-76.2%), respectively (p=0.006). CONCLUSION: This study shows that LDH is an independent predictor of PFS and OS in patients with regional lymph node metastatic prostate cancer.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , L-Lactato Desidrogenase/sangue , Metástase Linfática , Neoplasias da Próstata/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Idoso , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Metástase Linfática/radioterapia , Masculino , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia
15.
Anticancer Res ; 41(8): 3925-3931, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281855

RESUMO

BACKGROUND/AIM: This study clarified the predictive impact of serum biomarkers on therapeutic sensitivity to nivolumab in patients with gastric cancer (GC). PATIENTS AND METHODS: The outcomes of 27 patients who received nivolumab to treat postoperative recurrent or unresectable advanced GC were reviewed. Blood testing was performed immediately before and after two courses of nivolumab. We also focused on the rate of change of each blood variable. RESULTS: The decrease in albumin (Alb) levels (p=0.035) and increase in lactate dehydrogenase (LDH) levels (p=0.012) after two courses of nivolumab were significantly larger in patients with disease progression. Furthermore, therapeutic resistance was significantly associated with an elevated LDH-to-Alb ratio (LAR) after two courses of nivolumab. CONCLUSION: Decreased Alb or increased LDH levels after two courses of nivolumab predicted nivolumab sensitivity in patients with GC. An increased LAR was a meaningful predictor of nivolumab resistance.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , L-Lactato Desidrogenase/sangue , Nivolumabe/uso terapêutico , Albumina Sérica/análise , Neoplasias Gástricas/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/farmacologia , Biomarcadores/sangue , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Nivolumabe/farmacologia , Prognóstico , Neoplasias Gástricas/sangue
16.
Anticancer Res ; 41(7): 3535-3542, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230149

RESUMO

BACKGROUND/AIM: No biomarkers that predict the benefit from anti-vascular endothelial growth factor (VEGF) antibodies have been identified. It is necessary to discover biomarkers that can identify patients who are more likely to benefit from bevacizumab-containing treatment, especially those who are more likely to benefit from treatment with bevacizumab beyond progression (BBP). Levels of serum lactate dehydrogenase (LDH), reported to be an indirect marker of hypoxia and angiogenesis, may be a useful marker for monitoring the efficacy of suppression of angiogenesis. PATIENTS AND METHODS: The clinical data of 91 patients with unresectable metastatic colorectal cancer who were treated with bevacizumab-containing chemotherapy as first-line treatment were collected and studied. RESULTS: In the second-line treatment, the bevacizumab plus chemotherapy group showed significantly better progression-free survival (PFS) in comparison to the chemotherapy-alone group in patients with low post-first-line-treatment serum LDH levels. On the other hand, no significant differences in the PFS rate were observed between the two groups in patients with high post-first-line-treatment serum LDH levels. CONCLUSION: The post-first-line-treatment serum LDH levels may, therefore, be useful marker for predicting the efficacy of treatment with BBP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , L-Lactato Desidrogenase/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
17.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198937

RESUMO

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic rats were either treated with distilled water (diabetic control (DC) group), MP (300 mg/kg b.w./day), metformin (300 mg/kg b.w./day) or MP + metformin for four weeks. We found significant increases in serum creatinine, urea and uric acid levels, decreases in serum sodium and chloride levels, and increase in kidney lactate dehydrogenase activity in DC group. Furthermore, malondialdehyde level increased significantly, while kidney antioxidant enzymes activities, glutathione level and total antioxidant capacity decreased significantly in DC group. Similarly, kidney immunoexpression of nuclear factor kappa B, tumor necrosis factor-α, interleukin (IL)-1ß and caspase-3 increased significantly, while IL-10 immunoexpression decreased significantly in DC group relative to normal control group. Histopathological observations for DC group corroborated the biochemical data. Intervention with MP, metformin or both significantly mitigated these effects and improved renal function, with the best outcome following the combined therapy. MP attenuates diabetic nephropathy and exhibits combined beneficial effect with metformin.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Metformina/administração & dosagem , Própole/administração & dosagem , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Creatinina/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Sinergismo Farmacológico , L-Lactato Desidrogenase/metabolismo , Masculino , Metformina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Própole/farmacologia , Ratos , Estreptozocina , Regulação para Cima , Ureia/sangue , Ácido Úrico/sangue
18.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202757

RESUMO

The aim of this study was to investigate the effect of the application of homocysteine as well as its effect under the condition of aerobic physical activity on the activities of matrix metalloproteinases (MMP), lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) in cardiac tissue and on hepato-renal biochemical parameters in sera of rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C: 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.); H: homocysteine 0.45 µmol/g b.w./day s.c.; CPA saline (0.9% NaCl 0.2 mL/day s.c.) and a program of physical activity on a treadmill; and HPA homocysteine (0.45 µmol/g b.w./day s.c.) and a program of physical activity on a treadmill. Subcutaneous injection of substances was applied 2 times a day at intervals of 8 h during the first two weeks of experimental protocol. Hcy level in serum was significantly higher in the HPA group compared to the CPA group (p < 0.05). Levels of glucose, proteins, albumin, and hepatorenal biomarkers were higher in active groups compared with the sedentary group. It was demonstrated that the increased activities of LDH (mainly caused by higher activity of isoform LDH2) and mMDH were found under the condition of homocysteine-treated rats plus aerobic physical activity. Independent application of homocysteine did not lead to these changes. Physical activity leads to activation of MMP-2 isoform and to increased activity of MMP-9 isoform in both homocysteine-treated and control rats.


Assuntos
Hiper-Homocisteinemia/metabolismo , Rim/metabolismo , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Malato Desidrogenase/metabolismo , Metaloproteinases da Matriz/metabolismo , Miocárdio/metabolismo , Condicionamento Físico Animal , Animais , Biomarcadores , Pesos e Medidas Corporais , Ativação Enzimática , Hiper-Homocisteinemia/etiologia , Miocárdio/enzimologia , Especificidade de Órgãos , Ratos , Fatores de Tempo
19.
PLoS One ; 16(7): e0255154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34324560

RESUMO

BACKGROUND: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. METHODS: This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. RESULTS: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). DISCUSSION: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making.


Assuntos
COVID-19/patologia , Proteína C-Reativa/metabolismo , COVID-19/metabolismo , Transtornos Cerebrovasculares/metabolismo , Transtornos Cerebrovasculares/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Troponina I/metabolismo
20.
J Infect Dev Ctries ; 15(6): 766-772, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34242184

RESUMO

INTRODUCTION: COVID-19 is the infection caused by the new coronavirus. Specific treatment for COVID-19 has not been established, yet. It is important to determine the disease severity of the patients at the first admission. Therefore, the exploration of biomarkers is deemed necessary. We aimed to assess the diagnostic and early prognostic value of CRP and LDH levels in possible COVID-19 patients presenting with a severe clinical picture. METHODOLOGY: We evaluated the correlations of relevant routine laboratory test results with disease severity in COVID-19 patients admitted to our infectious diseases clinic. Patients were divided into severe and non-severe disease groups based on clinical findings, oxygen saturation levels in the arterial blood, biochemical test results, and radiological findings. Differences in the findings between the two disease severity groups were examined to determine potential biomarkers. RESULTS: Median age and the CRP and LDH levels in the severe disease group were statistically significantly higher compared to the nonsevere group (p < 0.0001). No other parameters statistically significant differences have been observed between the two groups (P > 0.05). CONCLUSIONS: CRP and LDH levels were positively correlated with lung lesions in early-stage COVID-19, potentially reflecting disease severity. Because LDH and CRP levels can potentially reflect the pulmonary function, they can be potential predictors of COVID-19- related respiratory failure. For avoiding poor prognosis; LDH and CRP should be considered as potential predictors for identifying the need for thoracic CT scans, close monitoring of pulmonary function, and aggressive supportive therapy early in the course of COVID-19.


Assuntos
Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/diagnóstico , L-Lactato Desidrogenase/sangue , Índice de Gravidade de Doença , Adulto , Biomarcadores/sangue , COVID-19/classificação , Feminino , Hospitalização , Humanos , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Turquia
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