Determinación simultánea de anticonvulsirantes y sus principales metabolitos por cromatografía de líquidos de alta resolución

Tesis (Maestría en Ciencias con Especialidad en Química Analítica Biomédica) UANLUANLhttp://www.uanl.mx

Quantification of nitric oxide by high‑performance liquid chromatography‑fluorometric method in subgenomic hepatitis C virus‑replicon expressing Huh7 cells upon treatment with acetylsalicylic acid

As nitric oxide (NO) expression levels are lower in hepatocytes compared with other cell types, it is difficult to quantify this compound via Griess assay. The aim of the present study was to quantify NO concentration in the cell culture medium from a subgenomic hepatitis C virus (HCV)‑replicon expressing Huh‑7 cell system using a high‑performance liquid chromatography (HPLC)‑fluorescence detector in the presence or absence of acetylsalicylic acid (ASA) treatment. HCV‑replicon cells were incubated with ASA (4 mM) for 24, 48 and 72 h. Thereafter, the medium was collected to measure nitrites (NO2-) as an indirect indicator of NO levels using diaminonaphtalene as a derivate agent. NO levels were significantly higher (1.7‑fold) in Huh‑7 replicon cells treated with ASA (72 h post‑treatment) than untreated cells (P<0.05); NO inhibitor reduced ~30% the level of NO in Huh‑7 replicon cells treated with ASA (48 h post‑treatment; P<0.05). The findings suggested that the HPLC‑fluorescence method provided an accurate and efficient measurement of NO production in Huh‑7‑HCV‑replicon cells culture medium

Neolignanos de Krameria ramosissima (A.Gray) S. Watson con actividad contra Porphyromonas gingivalis, evaluación citotóxica y mutagénica

Porphyromonas gingivalis, es una de las bacterias asociadas a la enfermedad periodontal, y ha sido relacionada con lesiones coronarias, neumonía y preeclamsia. El propósito de este estudio fue evaluar el extracto metanólico de raíces de Krameria ramosissima contra P. gingivalis (ATCC 53978), determinar su actividad citotóxica en broblastos humanos (ATCC CRL-7222 Hs 274.T) y su potencial mutagénico mediante la prueba de Ames. Las concentraciones a evaluar fueron 500, 400, 300, 200, 150, 100, 75 y 50 μg/mL, siendo la concentración mínima inhibitoria de 300 μg/mL. Mediante cromatografía en columna se obtuvieron 14 fracciones, de las cuales la 7 y la 9 presentaron mayor actividad (P<0.05). Se identicaron por espectrometría de masas dos neolignanos en las fracciones 7 y 9 con pesos moleculares de 314 y 296 respectivamente. El extracto y las fracciones activas evaluadas a la concentración de 300 μg/mL fueron negativas en las pruebas de citotoxicidad y mutagenecidad

Circulating Tumor Cells in Hepatocellular Carcinoma: A Comprehensive Review and Critical Appraisal

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and a major cause of cancer-related death worldwide. There is no ideal biomarker allowing early diagnosis of HCC and tumor surveillance in patients receiving therapy. Liquid biopsy, and particularly circulating tumor cells (CTCs), have emerged as a useful tool for diagnosis and monitoring therapeutic responses in different tumors. In the present manuscript, we evaluate the current evidence supporting the quantitative and qualitative assessment of CTCs as potential biomarkers of HCC, as well as technical aspects related to isolation, identification, and classification of CTCs. Although the dynamic assessment of CTCs in patients with HCC may aid the decision-making process, there are still many uncertainties and technical caveats to be solved before this methodology has a true impact on clinical practice guidelines. More studies are needed to identify the optimal combination of surface markers, to increase the efficiency of ex-vivo expansion of CTCs, or even to target CTCs as a potential therapeutic strategy to prevent HCC recurrence after surgery or to hamper tumor progression and extrahepatic spreading

Flourensia cernua: Hexane Extracts a Very Active Mycobactericidal Fraction from an Inactive Leaf Decoction against Pansensitive and Panresistant Mycobacterium tuberculosis

The efficacy of decoction in extracting mycobactericidal compounds from Flourensia cernua (Hojasé) leaves and fractionation with solvents having ascending polarity was compared with that of (i) ethanol extraction by still maceration, extraction with a Soxhlet device, shake-assisted maceration, or ultrasound-assisted maceration, followed by fractionation with n-hexane, ethyl acetate, and n-butanol; (ii) sequential extraction with n-hexane, ethyl acetate, and n-butanol, by still maceration, using a Soxhlet device, shake-assisted maceration, or ultrasound-assisted maceration. The in vitro mycobactericidal activity of each preparation was measured against drug-sensitive (SMtb) and drug-resistant (RMtb) Mycobacterium tuberculosis strains. The results of which were expressed as absolute mycobactericidal activity (AMA). These data were normalized to the ΣAMA of the decoction fraction set. Although decoction was inactive, the anti-RMtb normalized ΣAMA (NAMA) of its fractions was comparable with the anti-RMtb NAMA of the still maceration extracts and significantly higher than the anti-SMtb and anti-RMtb NAMAs of every other ethanol extract and serial extract and fraction. Hexane extracted, from decoction, material having 55.17% and 92.62% of antituberculosis activity against SMtb and RMtb, respectively. Although the mycobactericidal activity of decoction is undetectable; its efficacy in extracting F. cernua active metabolites against M. tuberculosis is substantially greater than almost all pharmacognostic methods

Asociación entre el síndrome metabólico y los niveles de transaminasas

Introducción: En la patología del síndrome metabólico, de acuerdo con distintas investigaciones y la práctica clínica se han visto manifestaciones de daño hepático. Objetivo: Estimar la prevalencia de transaminasas elevadas (alanina aminotransaminasa y aspartato aminotransaminasa) y determinar su asociación con síndrome metabólico. Métodos: Estudio transversal con procedimientos analíticos. Análisis secundario de los datos generados por el registro electrónico en salud de un policlínico ocupacional. La variable principal fue el diagnóstico del síndrome metabólico. Para definir aspartato aminotransaminasa elevada se consideraron valores > 30 U/L en mujeres y valores > 36 U/L en hombres. Para alanina aminotransaminasa, se consideraron valores > 30 U/L en mujeres y valores > 40 U/L en hombres. Resultados: La prevalencia de síndrome metabólico fue de 21,82 %, de aspartato aminotransaminasa elevada fue del 10,30 % y alanina aminotransaminasa elevada del 16,67 %. En la regresión múltiple, se ajustó por las covariables confusoras sexo, edad, ocupación, índice de masa corporal, fumar, alcohol y actividad física. Se observó que los pacientes con aspartato aminotransaminasa elevada tenían 128 % mayor frecuencia de síndrome metabólico, respecto a quienes no presentaban valores elevados (razón prevalencia= 2,28; IC95 %: 1,64 – 3,17; p< 0,001). Se encontró que los pacientes con alanina aminotransaminasa elevada tenían 148 % mayor frecuencia de presentar síndrome metabólico respecto a quienes no presentaban valores elevados (razón prevalencia= 2,48; IC95 %: 1,77 – 3,47; p< 0,001). Conclusiones: Existe asociación entre las transaminasas hepáticas elevadas y la presencia de síndrome metabólico.Campus Lima Nort

Tau Protein Phosphorylated at Threonine-231 Is Expressed Abundantly in the Cerebellum in Prion Encephalopathies

ACKNOWLEDGMENTS: The authors want to express their gratitude to the following: Dr. P. Davies † (Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder † (North Western, Chicago, IL, USA) for the generous gift of mAbs TG-3 and Alz-50, and Tau-1, Tau-5 and Tau-7, respectively; Tec. Amparo Viramontes Pintos for the handling of the brain tissue; support in the confocal microscopy unit of CIIDIR Durango, Instituto Politécnico Nacional; Union Medica University Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected with Alzheimer's disease and made our research possible. This work is dedicated to the memory of Professor Dr. José Raúl Mena López †. †Deceased. This work was supported by Fondo Nacional de Ciencia y Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015-3A2-127 to MP-H) and (2018-2019-2A3-208 to JL-M and MP-H).Peer reviewedPublisher PD

Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry

Background and Purpose In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. Methods Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score 85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score 3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). Results Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). Conclusions Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic : a matched analysis

The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannul

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study

Background: The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. Methods: We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero ([removed]2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. Findings: 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16–0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26–0·57; p[removed]11 página