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1.
Artículo en Inglés | MEDLINE | ID: mdl-37647163

RESUMEN

Low vitamin D levels and adverse effects have been reported in SARS-COV-2 positive patients. This study examined the effect of the vitamin D receptor gene BsmI polymorphism on SARS-COV-2 positive patients. A total of 80 SARS-COV-2 positive inpatients were included in the study, and 110 healthy individuals were included as a control group. The 25-(OH) vitamin D3, lymphocyte, and activated partial thromboplastin time levels of SARS-COV-2 positive patients were lower than those of the control group. The prothrombin time (PT), international normalized ratio (INR), D-dimer, C-reactive protein (CRP), procalcitonin, and ferritin levels of SARS-COV-2 positive patients were higher than those of the control group. A negative correlation was found between 25-(OH) vitamin D3 levels and white blood cell count, PT, INR, D-dimer, CRP, procalcitonin, and ferritin levels in SARS-COV-2 positive patients. The 25-(OH) vitamin D3 level in individuals with the BB genotype was higher than the 25-(OH) vitamin D3 level in individuals with the Bb and bb genotype. A statistically significant difference was found between the groups in terms of the genotype and allele distributions of BsmI polymorphism. When the genotypes were analyzed in terms of bb versus Bb + BB, a statistically significant difference was found between the groups. However, this finding was not found between the intensive care inpatient subgroup and the other inpatient subgroup. In conclusion, BsmI b allele and bb genotype were associated with hospitalization for SARS-COV-2 infection. This may be because individuals with b allele have low levels of vitamin D.


Asunto(s)
COVID-19 , Receptores de Calcitriol , Humanos , Receptores de Calcitriol/genética , SARS-CoV-2/genética , Polipéptido alfa Relacionado con Calcitonina/genética , COVID-19/genética , Vitamina D , Genotipo , Colecalciferol , Hospitalización , Ferritinas/genética , Predisposición Genética a la Enfermedad
2.
Can J Physiol Pharmacol ; 100(1): 19-25, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34822305

RESUMEN

To explore the correlation between the activating transcription factor 4 (ATF4) and procalcitonin (PCT) expressions combined with RET mutation and the pathological staging and clinical prognosis of sporadic medullary thyroid carcinoma (SMTC). Fifty cases (tumor tissue) of SMTC diagnosed by clinicopathology were collected and the patients with nodular goiter were selected as normal control. The RET mutation site was analyzed by detection kit and expressions of PCT and ATF4 in SMTC were analyzed by Western blot and immunohistochemistry. Multiple linear regression was used to analyze the correlation of risk factors (PCT or ATF4 expression, RET mutation, tumor differentiation, SMTC stage, lymphatic metastasis) for 5-year recurrence and survival of SMTC. The ATF4 and PCT expressions were significantly decreased and increased, respectively, with the increase of the SMTC stage. The most frequent mutation of RET gene in cancer tissue was M 22458A in exon 16. The ATF4 and PCT expressions, as well as RET mutation, were significantly associated with a 5-year recurrence, while the ATF4 expression was significantly related to better 5-year survival. ATF4 and PCT expressions combined with RET mutation are related to the clinical prognosis of SMTC and can predict SMTC staging.


Asunto(s)
Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Expresión Génica/genética , Estudios de Asociación Genética , Mutación , Polipéptido alfa Relacionado con Calcitonina/genética , Polipéptido alfa Relacionado con Calcitonina/metabolismo , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Adulto , Carcinoma Neuroendocrino/mortalidad , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Neoplasias de la Tiroides/mortalidad
3.
PLoS One ; 16(12): e0261385, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34905580

RESUMEN

OBJECTIVES: Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). METHODS: In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene expression mRNA panel were measured in 286 subjects with ARI from four emergency departments. Multinomial logistic regression and leave-one-out cross validation were used to evaluate the protein and mRNA tests. RESULTS: The mRNA panel performed better than alternative strategies to identify bacterial infection: AUC 0.93 vs. 0.83 for the protein panel and 0.84 for procalcitonin (P<0.02 for each comparison). This corresponded to a sensitivity and specificity of 92% and 83% for the mRNA panel, 81% and 73% for the protein panel, and 68% and 87% for procalcitonin, respectively. A model utilizing all three strategies was the same as mRNA alone. For the diagnosis of viral infection, the AUC was 0.93 for mRNA and 0.84 for the protein panel (p<0.05). This corresponded to a sensitivity and specificity of 89% and 82% for the mRNA panel, and 85% and 62% for the protein panel, respectively. CONCLUSIONS: A gene expression signature was the most accurate host response strategy for classifying subjects with bacterial, viral, or non-infectious ARI.


Asunto(s)
Bacterias/aislamiento & purificación , Infecciones Bacterianas/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Virosis/diagnóstico , Virus/aislamiento & purificación , Adulto , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/metabolismo , Infecciones Bacterianas/microbiología , Biomarcadores/metabolismo , Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Diagnóstico Diferencial , Servicio de Urgencia en Hospital , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Polipéptido alfa Relacionado con Calcitonina/genética , Polipéptido alfa Relacionado con Calcitonina/metabolismo , Pronóstico , Curva ROC , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Infecciones del Sistema Respiratorio/etiología , Infecciones del Sistema Respiratorio/metabolismo , Infecciones del Sistema Respiratorio/patología , Estudios Retrospectivos , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Estados Unidos/epidemiología , Virosis/complicaciones , Virosis/virología
4.
Mediators Inflamm ; 2021: 5593806, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34326704

RESUMEN

AIM: To investigate the clinical significance of procalcitonin (PCT) elevation on hospital admission for coronavirus disease-19 (COVID-19) and its association with mortality in oldest old patients (age > 75 years). METHODS: The clinical records of 1074 patients with chest high-resolution computed-tomography (HRCT) positive for interstitial pneumonia and symptoms compatible for COVID-19, hospitalized in medical wards during the first pandemic wave in a single academic center in Northern Italy, were retrospectively analyzed. All patients had serum PCT testing performed within six hours from admission. Information on COVID-19-related symptoms, comorbidities, drugs, autonomy in daily activities, respiratory exchanges, other routine lab tests, and outcomes were collected. Clinical characteristics were compared across different admission PCT levels and ages. The association of admission PCT with mortality was tested separately in participants aged > 75 and ≤75 years old by stepwise multivariate Cox regression model with forward selection. RESULTS: With increasing classes of PCT levels (<0.05, 0.05-0.49, 0.5-1.99, and ≥2 ng/ml), there was a significant trend (P < 0.0001) towards older age, male gender, wider extension of lung involvement on HRCT, worse respiratory exchanges, and several other laboratory abnormalities. Each incremental PCT class was associated with increased risk of hospital death at multivariate models in subjects older than 75 (hazard ratio for PCT ≥ 2 vs. <0.05 ng/ml: 30.629, 95% confidence interval 4.176-224.645, P = 0.001), but not in subjects aged 75 or younger. CONCLUSIONS: In patients admitted for COVID-19, PCT elevation was associated with several clinical, radiological, and laboratory characteristics of disease severity. However, PCT elevation was strongly associated with hospital mortality only in oldest old subjects (age > 75).


Asunto(s)
COVID-19/sangre , COVID-19/mortalidad , Polipéptido alfa Relacionado con Calcitonina/sangre , Polipéptido alfa Relacionado con Calcitonina/genética , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Prueba de COVID-19 , Comorbilidad , Electrocardiografía , Femenino , Mortalidad Hospitalaria , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Admisión del Paciente , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , Tomografía Computarizada por Rayos X
6.
Biomed Res Int ; 2020: 4357910, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33145348

RESUMEN

BACKGROUND: Human adenoviruses (HAdVs) are commonly causing respiratory disease. We molecularly genotyped HAdV circulating in Chinese hospitalized children with respiratory infections and summarized the clinical profiles and common inflammatory biomarkers, so as to better determine their associations with disease severity. METHOD: Children with respiratory single HAdV infection cases that occurred from December 2017 to March 2019 were enrolled for a cross-sectional study. Clinical/laboratory features based on the genotypes of respiratory HAdV infection were reviewed for comparative analysis. RESULTS: A total of 84 patients were enrolled, and HAdV types were identified from 82 patients. Species B (HAdV-7, 44%; HAdV-3, 43%, and HAdV-14, 5%) was the most common, followed by C (HAdV-2, 4% and HAdV-1, 1%) and E (HAdV-4, 1%). Severe HAdV infection and HAdV-7 infection groups were associated with significantly longer duration of fever and hospitalized days, higher morbidity of tachypnea/dyspnea, more pleural effusion, more respiratory rales, more frequently required mechanical ventilation, and significantly higher fatality rate. The elevated procalcitonin (PCT) and C-reactive protein (CRP) levels were significantly associated with severe HAdV infection. CONCLUSIONS: HAdV-7 and HAdV-3 were the most common types among children with respiratory adenovirus infection; vaccines against these two genotypes are in urgent need. PCT and CRP are significantly associated with the severity of HAdV infection.


Asunto(s)
Infecciones por Adenoviridae/diagnóstico , Adenovirus Humanos/genética , Proteína C-Reactiva/genética , Disnea/diagnóstico , Derrame Pleural/diagnóstico , Polipéptido alfa Relacionado con Calcitonina/genética , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones por Adenoviridae/mortalidad , Infecciones por Adenoviridae/patología , Infecciones por Adenoviridae/virología , Adenovirus Humanos/clasificación , Adenovirus Humanos/aislamiento & purificación , Adenovirus Humanos/patogenicidad , Adolescente , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Niño , Preescolar , Estudios Transversales , Disnea/mortalidad , Disnea/patología , Disnea/virología , Femenino , Expresión Génica , Genotipo , Humanos , Lactante , Tiempo de Internación/estadística & datos numéricos , Masculino , Epidemiología Molecular , Filogenia , Derrame Pleural/mortalidad , Derrame Pleural/patología , Derrame Pleural/virología , Polipéptido alfa Relacionado con Calcitonina/sangre , Respiración Artificial/estadística & datos numéricos , Infecciones del Sistema Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/patología , Infecciones del Sistema Respiratorio/virología , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
7.
Artículo en Inglés | MEDLINE | ID: mdl-32026790

RESUMEN

BACKGROUND: There is a need for rapid and accurate diagnostic biomarker for diagnosis of Salmonella fever. AIMS: The aim of the present study was to assess the importance of procalcitonin (PCT), Soluble Triggering Receptors expressed on Myeloid Cells 1 (sTREM1) and C- reactive protein (CRP) in the diagnosis of enteric fever with positive blood culture for S.typhi. METHODS: Blood samples were withdrawn from 200 patients with suspected enteric fever and subjected for the determination of CRP, PCT and sTREM-1. RESULTS: The sensitivity and specificity for PCT cut off were 97.7% & 82.5%, for CRP the sensitivity and specificity were 95.3% and 77% and for s-TREM-1 the sensitivity and specificity were 95.3% & 77%. CONCLUSION: S-TREM-1 may be considered as a novel biomarker for the diagnosis of enteric fever with good sensitivity and specificity.


Asunto(s)
Receptor Activador Expresado en Células Mieloides 1/biosíntesis , Receptor Activador Expresado en Células Mieloides 1/sangre , Fiebre Tifoidea/sangre , Fiebre Tifoidea/diagnóstico , Adulto , Biomarcadores/sangre , Estudios Transversales , Femenino , Expresión Génica , Humanos , Masculino , Polipéptido alfa Relacionado con Calcitonina/biosíntesis , Polipéptido alfa Relacionado con Calcitonina/sangre , Polipéptido alfa Relacionado con Calcitonina/genética , Salmonella typhi/genética , Salmonella typhi/aislamiento & purificación , Receptor Activador Expresado en Células Mieloides 1/genética , Fiebre Tifoidea/genética
8.
Eur J Clin Pharmacol ; 76(4): 515-523, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31932875

RESUMEN

AIMS: Voriconazole (VCZ) displays highly variable pharmacokinetics affecting treatment efficacy and safety. We aimed to identify the factors affecting VCZ steady-state trough concentration (Cssmin) to provide evidence for optimizing VCZ treatment regimens. METHODS: A total of 510 Cssmin of 172 patients with hematopoietic stem cell transplantation and hematologic malignancies and their clinical characteristics and genotypes of FMO, POR, and PXR were included in this study. RESULTS: In univariate analysis, the standard loading dose of VCZ significantly increased the Cssmin of VCZ (P < 0.001). The Cssmin of VCZ was significantly correlated with patients' total bilirubin (TB) (P < 0.001) and procalcitonin (PCT) (P < 0.001). FMO3 rs2266780 (P = 0.025), POR rs10954732 (P = 0.015), PXR rs2461817 (P = 0.010), PXR rs7643645 (P = 0.003), PXR rs3732359 (P = 0.014), PXR rs3814057 (P = 0.005), and PXR rs6785049 (P = 0.013) have a significant effect on Cssmin of VCZ. Loading dose, TB, PCT level, and PXRrs3814057 polymorphism were independent influencing factors of VCZ Cssmin in the analysis of multivariate linear regression. And loading dose, PCT, and PXR rs3814057 had significant effects on the probability of the therapeutic window of VCZ. CONCLUSION: The high variability of VCZ Cssmin may be partially explained by loading dose, liver function, inflammation, and PXR polymorphisms. This study suggests the VCZ standard loading dose regimen significantly increased Cssmin and probability of the therapeutic window providing treatment benefits. Patients in the high PCT group may be more likely to exceed 5.5 µg/mL, thus suffering from VCZ toxicity.


Asunto(s)
Antifúngicos/administración & dosificación , Antifúngicos/sangre , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Polimorfismo de Nucleótido Simple , Receptor X de Pregnano/genética , Polipéptido alfa Relacionado con Calcitonina/genética , Voriconazol/administración & dosificación , Voriconazol/sangre , Antifúngicos/uso terapéutico , Monitoreo de Drogas , Femenino , Genotipo , Neoplasias Hematológicas/sangre , Humanos , Masculino , Micosis/prevención & control , Farmacogenética , Estudios Retrospectivos , Voriconazol/uso terapéutico
9.
Pak J Pharm Sci ; 32(5(Special)): 2437-2441, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31894031

RESUMEN

This study was aimed to investigate the changes of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase inhibitor-1 (TIMP-1) in cerebrospinal fluid (CSF) of neonates with purulent meningitis. 195 cases (n=195) were divided into PM group (neonatal purulent meningitis), VM group (neonatal virus meningitis) and control group (healthy neonates). The expression levels of MMP-2 and TIMP-1 were detected by ELISA while the level of PCT was determined by chemiluminescence analyzer. The levels of MMP-2 and TIMP-1 in CSF and PCT in serum were compared in three groups and the correlation was discussed. The level of MMP-2 in CSF in 3 groups were statistically significant (F=16.126, P<0.05) similarly the level of TIMP-1 in CSF of 3 groups were statistically significant (F=16.093, P<0.05). The serum level of PCT in PM group was 14.73±2.14ng/l, in VM group was 9.06±1.05ng/l and in control group it was 0.37±0.12ng/l. The levels of MMP-2 and TIMP-1 in CSF were positively correlated with the serum level of PCT in both PM and VM group. The expression of MMP-2, TIMP-1 and serum PCT in CSF of newborns with purulent meningitis was increased. The findings suggest that MMP-2, TIMP-1 and PCT are involved in the occurrence and development of neonatal purulent meningitis.


Asunto(s)
Metaloproteinasa 2 de la Matriz/líquido cefalorraquídeo , Meningitis Bacterianas/líquido cefalorraquídeo , Polipéptido alfa Relacionado con Calcitonina/líquido cefalorraquídeo , Inhibidor Tisular de Metaloproteinasa-1/líquido cefalorraquídeo , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Humanos , Recién Nacido , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Meningitis Viral/líquido cefalorraquídeo , Polipéptido alfa Relacionado con Calcitonina/genética , Polipéptido alfa Relacionado con Calcitonina/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismo
10.
Sci Rep ; 8(1): 8913, 2018 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-29891911

RESUMEN

For years, procalcitonin (PCT) has been employed as a diagnostic biomarker for the severity of sepsis and septic shock, as well as for guiding the application of antibiotics. However, the molecular/cellular basis for the regulation of PCT production is not fully understood. In this study, we identified the signalling pathway by which the expression of PCT was induced by lipopolysaccharide in human hepatocytes at the mRNA and protein levels. This expression was dependent on nuclear transcription factor κB (NF-κB), as indicated by a NF-κB binding site (nt -53 to -44) found in the PCT promoter region. We also showed that microRNA-513b (miR-513b) was also able to bind to the 3'-untranslated region (UTR) of the PCT promoter sequence. Meanwhile, the activation of NF-κB down-regulated the expression of miR-513b. In conclusion, we suggest that NF-κB is capable of enhancing the expression of PCT by either directly activating the transcription of the PCT gene or indirectly modulating the expression of its regulatory component, miR-513b. Our results indicate a molecular mechanism responsible for the regulation of PCT production.


Asunto(s)
Regulación de la Expresión Génica , Hepatocitos/efectos de los fármacos , Lipopolisacáridos/metabolismo , MicroARNs/metabolismo , FN-kappa B/metabolismo , Polipéptido alfa Relacionado con Calcitonina/metabolismo , Sitios de Unión , Línea Celular , Humanos , MicroARNs/genética , Hibridación de Ácido Nucleico , Polipéptido alfa Relacionado con Calcitonina/genética , Regiones Promotoras Genéticas , Unión Proteica , Transducción de Señal
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