Cerebral ischemia has previously been shown to cause a systemic decrease in levels of the reduced forms of low-molecular-weight aminothiols [cysteine (Cys), homocysteine (Hcy), and glutathione (GSH)] in blood plasma. In this study, we examined the effect of beta-adrenergic receptor (β-AR) antagonists metoprolol (Met) and nebivolol (Neb) on the redox status of these aminothiols during acute cerebral ischemia in rats. We used a model of global cerebral ischemia (bilateral occlusion of common carotid arteries with hypotension lasting for 10 minutes). The antagonists were injected 1 hour before surgery. Total and reduced Cys, Hcy, and GSH levels were measured 40 minutes after the start of reperfusion. Neb (0.4 and 4 mg/kg) and Met (8 and 40 mg/kg) treatment increased the levels of reduced aminothiols and the global methylation index in the hippocampus. The treatments also prevented any decrease in reduced aminothiol levels in blood plasma during ischemia. Although both of these drugs eliminated delayed postischemic hypoperfusion, only Neb reduced neuronal damage in the hippocampus. The results indicate an essential role of β1-AR blockage in the maintenance of redox homeostasis of aminothiols in the plasma and brain during acute cerebral ischemia.

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These results suggest that plasma low-molecular-weight thiols are actively involved in oxidation reactions at early stages of cerebral ischaemia; therefore, their reduced forms or redox state may serve as a sensitive indicator of acute cerebrovascular insufficiency.

An approach that allows direct analysis of the ratio of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) by using CE is presented. The analytes were extracted on phenylboronic acid phase and eluted with 100 mmol/L HCl. CE separation of the analytes took place in the transient isotachophoresis mode with addition of NaCl and meglumine to the samples. The sensitivity (S/N = 3) and quantification limit (S/N = 10) of the method were 0.07 and 0.2 μmol/L, respectively, using a silica capillary with 50 μm internal diameter and 30.5 cm total length. The BGE was 0.02 mol/L Tris with 1 mol/L HCOOH (pH 2.2), and the separation voltage was 15-17 kV. Accuracy of SAM and SAH analysis in urine was 96 and 105%, respectively; interday precision for the SAM/SAH ratio was within 6%. The theoretical plate number exceeded a million. Total analysis time was 8.5 min.

Background: Myelodysplastic syndromes (MDS) can present a challenge for clinicians. Multicolor flow cytometry (MFC) can aid in establishing a diagnosis. The aim of this study was to determine the optimal MFC approach for MDS. Methods:The study included 102 MDS (39 low-grade MDS), 83 cytopenic patients without myeloid neoplastic disorders (control group), and 35 healthy donors. Bone marrow was analyzed using a six-color MFC. Analysis was conducted according to the "Ogata score," "Wells score," and the integrated flow cytometry (iFC) score. Results:The respective sensitivity and specificity values were 77.5% and 90.4% for the Ogata score, 79.4% and 81.9% for the Wells score, and 87.3% and 87.6% for the iFC score. Specificity was not 100% due to deviations of MFC parameters in the control group. Patients with paroxysmal nocturnal hemoglobinuria (PNH) had higher levels of CD34 + CD7 + myeloid cells than donors. Aplastic anemia and PNH were characterized by a high proportion of CD56 + cells among CD34 + precursors and neutrophils. The proportion of MDS-related features increased with the progression of MDS. The highest number of CD34 + blasts was found in MDS with excess blasts.MDS with isolated del(5q) was characterized by a high proportion of CD34 + CD7 + cells and low granularity of neutrophils. In 39 low-grade MDS, the sensitivities were 53.8%, 61.5%, and 71.8% for Ogata score, Wells score, and iFC, respectively. Conclusion:The results support iFC as a useful diagnostic tool in MDS.