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1.
Infect Dis Model ; 8(2): 445-457, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37131453

RESUMO

Objectives: To determine whether air pollution or changes in SARS-CoV-2 lineages lead to an increase in mortality. Methods: Descriptive statistics were used to calculate rates of infection (2020-2021). RT-PCR was used to compare viral loads from October 2020 to February 2021. Next-generation sequencing (NGS) (n = 92) was used to examine and phylogenetically map SARS-CoV-2 lineages. A correlative "air pollution/temperature" index (I) was developed using regression analysis. PM2.5, PM10, O3, NO2, SO2, and CO concentrations were analyzed and compared to the mortality. Results: The mortality rate during the last year was ∼32%. Relative SARS-CoV-2 viral loads increased in December 2020 and January 2021. NGS revealed that approximately 80% of SARS-CoV-2 linages were B.1.243 (33.7%), B1.1.222 (11.2%), B.1.1 (9%), B.1 (7%), B.1.1.159 (7%), and B.1.2 (7%). Two periods were analyzed, the prehigh- and high-mortality periods and no significant lineage differences or new lineages were found. Positive correlations of air pollution/temperature index values with mortality were found for IPM2.5 and IPM10. INO2. ISO2, and ICO but not for O3. Using ICO, we developed a model to predict mortality with an estimated variation of ∼±5 deaths per day. Conclusion: The mortality rate in the MZG was highly correlated with air pollution indices and not with SARS-CoV-2 lineage.

2.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674427

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (p = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, p = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, p = 0.0018, cut-off < 3.0875 Kb, sensitivity = 75%, specificity = 62%), whereas the prediction is improved with a logistic regression model including LTL plus age (AUC = 0.762, p = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla/genética , DNA Mitocondrial/genética , Variações do Número de Cópias de DNA , Leucócitos , Telômero/genética
3.
Transplant Proc ; 52(4): 1202-1205, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32164959

RESUMO

BACKGROUND: Severe ischemia-reperfusion injury (SIRI) seems to be the key factor that can significantly affect the function of both native kidneys and renal allografts. Therefore, the development of a successful strategy is of a paramount importance in both basic and clinical research. METHODS: To determine the effects of SIRI on the native kidney function, a murine model was planned as follows: group 1 (n = 6) mice underwent to nephrectomy plus ischemia-reperfusion injury for 30 minutes; group 2 (n = 6) mice underwent to nephrectomy without ischemia-reperfusion injury and thus served as sham controls for SIRI. The results of serum creatinine (SCr) were analyzed using Mann-Whitney U tests to calculate the significance between mean values. Survival between groups was measured by Kaplan-Meier test. RESULTS: To reliably achieve an elevation of SCr levels animals were exposed to a SIRI. The values of SCr increased from 0.35 (SD, 0.09) mg/dL to about 2-fold within 2 days and 3-fold within the following 5 days. Under these given conditions the mice displayed signs and histologic findings of severe kidney damage. The survival rate was about 83% of the animals within a week, and they showed no capacity of complete spontaneous self-regeneration. CONCLUSIONS: In this study, we aim to establish a murine model with extensive structural kidney damage and significant elevation of SCr levels, which could be used in basic and translational research of transplantation and regenerative therapies.


Assuntos
Modelos Animais de Doenças , Transplante de Rim , Insuficiência Renal/etiologia , Traumatismo por Reperfusão/complicações , Animais , Creatinina/sangue , Rim/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Insuficiência Renal/patologia , Insuficiência Renal/fisiopatologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia
4.
Colloids Surf B Biointerfaces ; 178: 199-207, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30856589

RESUMO

The conventional treatment (cytoreduction combined with cisplatin/carboplatin and taxane drugs) of ovarian cancer has a high rate of failure and recurrence despite a favorable initial response. This lack of success is usually attributed to the development of multidrug resistance mechanisms by cancer cells and avoidance of the anti-growth effects of monoclonal targeted therapeutic antibodies. The disease, like other cancers, is characterized by the overexpression of molecular markers, including HER2 receptors. Preclinical and clinical studies with trastuzumab, a HER2-targeted therapeutic antibody, reveal a low improvement of the outcomes of HER2 positive ovarian cancer patients. Therefore, here, we propose a cisplatin-loaded, HER2 targeted poly(lactic-co-glycolic) nanoplatform, a system capable to escape the drug-efflux effect and to take advantage of the overexpressed HER2 receptors, using them as docks for targeted chemotherapy. The NP/trastuzumab ratio was determined after fluorescein labeling of antibodies and quantification of fluorescence in NPs. The system was also characterized in terms of size, zeta potential, drug release kinetics, cytotoxicity and cellular internalization in the epithelial ovarian cancer cell line SKOV-3, and compared with the HER2 negative breast cancer cell line HCC70. Our results show an increased cytotoxicity of NPs as compared to free cisplatin, and moreover, an enhanced internalization and cytotoxicity due to the bionfunctionalization of NPs with the monoclonal antibody.


Assuntos
Cisplatino/química , Cisplatino/farmacologia , Nanopartículas/química , Neoplasias Ovarianas/metabolismo , Receptor ErbB-2/metabolismo , Anticorpos Monoclonais/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Trastuzumab/química , Trastuzumab/farmacologia
5.
Gac. méd. Méx ; 141(2): 157-160, mar.-abr. 2005. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-632057

RESUMO

En 1938 Laidiaw acuñó el término de nesidioblastosis refiriéndose a una neodiferenciación de los islotes de Langerhans, originada del epitelio de los conductos pancreáticos. Se presenta un caso clínico de un niño de 19 meses de edad, con convulsiones secundarias a hipoglucemia intratable. Se diagnosticó hiperinsulinismo con base en criterios clínicos y bioquímicos. Los hallazgos histopatológicos del páncreas mostraron la presencia de racimos de islotes de células P por todo el tejido acinar localizados en cabeza y un tercio proximal del cuerpo. Se realizó el diagnóstico de nesidioblastosis y para su tratamiento se practicó pancreatectomía proximal (60%), con una pancreático yeyunostomía distal (Y en Roux). Después del tratamiento, el paciente tuvo normalización de los niveles séricos de glucosa y de insulina. Se concluye que este procedimiento resultó efectivo al revertir la hipoglucemia, por lo que constituye el primer tratamiento alternativo al método convencional.


A 19 month old child who presented seizures secondary to intractable hypoglycemia, fulfilling the clinical and biochemical criteria for hyperinsulinism was studied. Histopathological findings of the pancreas showed the presence of small clusters of b cell islets throughout acinar tissue near ducts, in both the head and the proximal third of the body. Proximal pancreatectomy (60%) and distal pancreatic jejunostomy (Roux in Y) were performed. This procedure was effective in reverting hypoglycemia and constitutes the first successful alternative treatment.


Assuntos
Humanos , Lactente , Masculino , Hiperinsulinismo/etiologia , Hipoglicemia/etiologia , Nesidioblastose/complicações , Técnicas de Diagnóstico Endócrino , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/cirurgia , Hipoglicemia/diagnóstico , Hipoglicemia/cirurgia , Nesidioblastose/patologia , Nesidioblastose/cirurgia , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatectomia/métodos , Resultado do Tratamento
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