Cutaneous Manifestation of Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a hematological neoplasm characterized by the proliferation of immature lymphoblasts. Although it is more common in children, it can also occur in adults, presenting significant clinical challenges. This case describes a 46-year-old male patient with a history of hypertension and dyslipidemia, whose first clinical manifestation of ALL was cutaneous.

Reversible Pulmonary Hypertension Related to Hyperthyroidism: A Case Report.

A systematic assessment is crucial to confirm the diagnosis of pulmonary hypertension (PH) and classify it based on its etiological mechanism. This case report describes a young woman with a recent diagnosis of Graves' disease who presented with exertional dyspnea and fatigue. The initial ultrasound heart examination indicated moderate tricuspid regurgitation, an increased estimated systolic pulmonary artery pressure (sPAP), and suggestive alterations of atrial septal communication.

Saccharomyces cerevisiae DNA polymerase IV overcomes Rad51 inhibition of DNA polymerase δ in Rad52-mediated direct-repeat recombination.

Saccharomyces cerevisiae DNA polymerase IV (Pol4) like its homolog, human DNA polymerase lambda (Polλ), is involved in Non-Homologous End-Joining and Microhomology-Mediated Repair. Using genetic analysis, we identified an additional role of Pol4 also in homology-directed DNA repair, specifically in Rad52-dependent/Rad51-independent direct-repeat recombination. Our results reveal that the requirement for Pol4 in repeat recombination was suppressed by the absence of Rad51, suggesting that Pol4 counteracts the Rad51 inhibition of Rad52-mediated repeat recombination events.

A Case of Acute Generalized Exanthematous Pustulosis Induced by Ceftriaxone.

Acute generalized exanthematous pustulosis (AGEP) is a rare and severe skin disorder induced in more than 90% of cases by an adverse drug reaction. This condition is defined by an acute growth of numerous, pin-head-sized, non-follicular pustules on a background of edematous erythema that starts on the face or in the armpits and groin. It is accompanied by fever and increased inflammatory markers.

Cooperation between non-essential DNA polymerases contributes to genome stability in Saccharomyces cerevisiae.

DNA polymerases influence genome stability through their involvement in DNA replication, response to DNA damage, and DNA repair processes. Saccharomyces cerevisiae possess four non-essential DNA polymerases, Pol λ, Pol η, Pol ζ, and Rev1, which have varying roles in genome stability. In order to assess the contribution of the non-essential DNA polymerases in genome stability, we analyzed the pol4Δ rev1Δ rev3Δ rad30Δ quadruple mutant in microhomology mediated repair, due to recent studies linking some of these DNA polymerases to this repair pathway.

Effect of ionizing radiation exposure on Trypanosoma cruzi ubiquitin-proteasome system.

In recent years, proteasome involvement in the damage response induced by ionizing radiation (IR) became evident. However, whether proteasome plays a direct or indirect role in IR-induced damage response still unclear. Trypanosoma cruzi is a human parasite capable of remarkable high tolerance to IR, suggesting a highly efficient damage response system.

Eukaryotic DNA Polymerases in Homologous Recombination.

Homologous recombination (HR) is a central process to ensure genomic stability in somatic cells and during meiosis. HR-associated DNA synthesis determines in large part the fidelity of the process. A number of recent studies have demonstrated that DNA synthesis during HR is conservative, less processive, and more mutagenic than replicative DNA synthesis.

DNA polymerase beta from Trypanosoma cruzi is involved in kinetoplast DNA replication and repair of oxidative lesions.

Specific DNA repair pathways from Trypanosoma cruzi are believed to protect genomic DNA and kinetoplast DNA (kDNA) from mutations. Particular pathways are supposed to operate in order to repair nucleotides oxidized by reactive oxygen species (ROS) during parasite infection, being 7,8-dihydro-8-oxoguanine (8oxoG) a frequent and highly mutagenic base alteration. If unrepaired, 8oxoG can lead to cytotoxic base transversions during DNA replication.

Influence of chronic renal failure on stereoselective metoprolol metabolism in hypertensive patients.

The influence of chronic renal failure on the stereoselective metabolism of rac-metoprolol was investigated in 15 hypertensive patients, 7 of them with chronic renal failure and 8 with normal renal function. They were treated with rac-metoprolol (200 mg) for 7 days. The patients of both groups presented stereoselectivity in metoprolol metabolism, favoring the formation of 1'R-alpha-hydroxymetoprolol (AUC(1(')R/1(')S)(0-24) approximately 2.

Stereoselective analysis of metoprolol and its metabolites in rat plasma with application to oxidative metabolism.

We investigated the stereoselective kinetic disposition and metabolism of metoprolol (MET) in rats. The racemic MET (15 mg/kg) was given by oral gavage and blood samples were collected from 0 to 10h (n=6 at each time point). The enantiomeric concentrations of MET and its metabolites alpha-hydroxymetoprolol (alpha-OHM) and O-demethylmetoprolol (ODM) were determined by HPLC using a Chiralpak AD chiral column and fluorescence detection.

Stereoselective metabolism of metoprolol: enantioselectivity of alpha-hydroxymetoprolol in plasma and urine.

Direct stereoselective separation on chiral stationary phase was developed for HPLC analysis of the four stereoisomers of alpha-hydroxymetoprolol in human plasma and urine. Plasma samples were prepared using solid-phase extraction columns and urine samples were prepared by liquid-liquid extraction. The stereoisomers were separated on a Chiralpak AD column at 24 degrees C with fluorescence detection and a mobile phase consisting of a mixture of hexane:ethanol:isopropanol:diethylamine (88:10.

Enantioselective determination of metoprolol acidic metabolite in plasma and urine using liquid chromatography chiral columns: applications to pharmacokinetics.

Enantioselective separations on chiral stationary phases with or without derivatization were developed and compared for the HPLC analysis of (+)-(R)- and (-)-(S)-metoprolol acidic metabolite in human plasma and urine. The enantiomers were analysed in plasma and urine without derivatization on a Chiralcel OD-R column, and in urine after derivatization using methanol in acidic medium on a Chiralcel OD-H column. The quantitation limits were 17 ng of each enantiomer/ml plasma and 0.