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BACKGROUND: Ischemia-reperfusion (IR) injury is one of the leading causes of early graft dysfunction in liver transplantation. Techniques such as ischemic preconditioning protect the graft through the activation of the hypoxia-inducible factors (HIF), which are downregulated by the EGLN family of prolyl-4-hydroxylases, a potential biological target for the development of strategies based on pharmacological preconditioning. For that reason, this study aims to evaluate the effect of the EGLN inhibitor sodium (S)-2-hydroxyglutarate [(S)-2HG] on liver IR injury in Wistar rats. METHODS: Twenty-eight female Wistar rats were divided into the following groups: sham (SH, n = 7), non-toxicity (HGTox, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days), IR (n = 7, total liver ischemia: 20 minutes, reperfusion: 60 minutes), and (S)-2HG+IR (HGIR, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days, total liver ischemia as the IR group). Serum ALT, AST, LDH, ALP, glucose, and total bilirubin were assessed. The concentrations of IL-1ß, IL-6, TNF, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured in liver tissue, as well as the expression of Hmox1, Vegfa, and Pdk1, determined by RT-qPCR. Sections of liver tissue were evaluated histologically, assessing the severity of necrosis, sinusoidal congestion, and cytoplasmatic vacuolization. RESULTS: The administration of (S)-2HG did not cause any alteration in the assessed biochemical markers compared to SH. Preconditioning with (S)-2HG significantly ameliorated IR injury in the HGIR group, decreasing the serum activities of ALT, AST, and LDH, and the tissue concentrations of IL-1ß and IL-6 compared to the IR group. IR injury decreased serum glucose compared to SH. There were no differences in the other biomarkers assessed. The treatment with (S)-2HG tended to decrease the severity of hepatocyte necrosis and sinusoidal congestion compared to the IR group. The administration of (S)-2HG did not affect the expression of Hmox1 but decreased the expression of both Vegfa and Pdk1 compared to the SH group, suggesting that the HIF-1 pathway is not involved in its mechanism of hepatoprotection. In conclusion, (S)-2HG showed a hepatoprotective effect, decreasing the levels of liver injury and inflammation biomarkers, without evidence of the involvement of the HIF-1 pathway. No hepatotoxic effect was observed at the tested dose.
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The progression and distribution of the SARS-CoV-2 pandemic are continuously changing over time and can be traced by blood donors' serological survey. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in blood donors in Nuevo Leon, Mexico during 2020 as a strategy for the rapid evaluation of the spread of SARS-CoV-2 and asymptomatic case detection. We collected residual plasma samples from blood donors who attended two regional donation centers from January to December of 2020 to identify changes in anti-SARS-CoV-2 IgG prevalence. Plasma samples were analyzed on the Abbott Architect instrument using the commercial Abbott SARS-CoV-2 IgG chemiluminescent assay. We found a total of 99 reactive samples from 2068 analyzed plasma samples, resulting in a raw prevalence of 4.87%. Donors aged 18-49 years were more likely to be seropositive compared to those aged >50 years (p < 0.001). Weekly seroprevalence increased from 1.8% during the early pandemic stage to 27.59% by the end of the year. Prevalence was 1.46-fold higher in females compared to males. Case geographical mapping showed that Monterrey city recorded the majority of SARS-CoV-2 cases. These results show that there is a growing trend of seroprevalence over time associated with asymptomatic infection that is unnoticed under the current epidemiological surveillance protocols.
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Anticorpos Antivirais/sangue , Infecções Assintomáticas/epidemiologia , Doadores de Sangue , COVID-19/epidemiologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Doadores de Sangue/estatística & dados numéricos , COVID-19/transmissão , Estudos Transversais , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Soroepidemiológicos , Fatores Sexuais , Adulto JovemRESUMO
INTRODUCTION: Algorithms have been developed to predict the platelet yield after apheresis from the donor's data, as well as the effect on the blood cell count, to extract an acceptable platelet number without affecting the donor. However, the evaluation of these algorithms has not been widely reported. This study aimed to assess the accuracy of the predictive algorithms of the Trima Accel v. 6 blood collection system. METHODS: Platelet concentrates (PCs) obtained by apheresis were analyzed. Platelet count and hematocrit were compared pre- and post-apheresis. Calculated post-apheresis platelet count (CPAPC), hematocrit (CPAH), and platelet yield (CPY), and their actual values were correlated. The bias of the algorithms was assessed with Bland-Altman plots, and the prediction of the extraction of single or double platelet products was evaluated. RESULTS: Two hundred and seventy-nine PCs were analyzed. Post-apheresis platelet count (PAPC) and hematocrit were decreased. A moderate correlation was observed between CPY and the actual yield, with a negative bias, and a trend to increase alongside the magnitude of the measurements. CPAPC and CPAH were strongly correlated with their actual values without bias. Prediction of single or double platelet product extraction showed a significant agreement with the actual outcomes. CONCLUSIONS: The predictive algorithm for the platelet yield showed bias, and a trend to underestimate the actual platelet yields when they are higher. The algorithms for the prediction of the PAPC and hematocrit did not show bias, proving their accuracy. Prediction of a single or double platelet product extraction has a strong agreement with the APY.
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Plaquetoferese/métodos , Adulto , Algoritmos , Feminino , Humanos , Masculino , Contagem de Plaquetas , SoftwareRESUMO
BACKGROUND: Ischemia-reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. METHODS: (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. RESULTS: (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. CONCLUSION: None of the compounds were hepatotoxic at the tested doses. (S)-2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.
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INTRODUCTION: Kidney ischemia-reperfusion (I/R) injury is the main cause of delayed graft function in solid organ transplantation. Sonchus oleraceus is a plant with well-known antioxidant and anti-inflammatory activities; however, its effects on renal I/R are unknown. OBJECTIVE: To evaluate whether S. oleraceus extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats. MATERIALS AND METHODS: Animal groups (n = 6): sham, I/R (45 min/15 h), S.O.e (300 mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function, proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress, and histology were evaluated. RESULTS: None of the mediators evaluated differed significantly between the S.O.e and sham groups. Levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were higher, and superoxide dismutase (SOD) was lower in the I/R group than in the sham group. Histology showed tubular epithelial necrosis in the medulla and cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines induced, SOD was maintained, and histology showed discontinuous necrosis in the medulla but no necrosis in the cortex. CONCLUSIONS: S.O.e was neither hepatotoxic nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against I/R.