Biochemistry

Intramolecular Interactions in Derivatives of Uracil Tautomers

The influence of solvents on intramolecular interactions in 5- or 6-substituted nitro and amino derivatives of six tautomeric forms of uracil was investigated. For this purpose, the density functional theory (B97-D3/aug-cc-pVDZ) calculations were performed in ten environments (1 > ε > 109) us...
More

The influence of solvents on intramolecular interactions in 5- or 6-substituted nitro and amino derivatives of six tautomeric forms of uracil was investigated. For this purpose, the density functional theory (B97-D3/aug-cc-pVDZ) calculations were performed in ten environments (1 > ε > 109) using the polarizable continuum model (PCM) of solvation. The substituents were characterized by electronic (charge of the substituent active region, cSAR) and geometric parameters. Intramolecular interactions between non-covalently bonded atoms were investigated using the theory of atoms in molecules (AIM) and the non-covalent interaction index (NCI) method, which allowed discussion of possible interactions between the substituents and N/NH endocyclic as well as =O/−OH exocyclic groups. The nitro group was more electron-withdrawing in the 5 than in the 6 position, while the opposite effect was observed in the case of electron donation of the amino group. These properties of both groups were enhanced in polar solvents; the enhancement depended on the ortho interactions. Substitution or solvation did not change tautomeric preferences of uracil significantly. However, the formation of a strong NO∙∙∙HO intramolecular hydrogen bond in the 5-NO2 derivative stabilized the dienol tautomer from +17.9 (unsubstituted) to +5.4 kcal/mol (substituted, energy relative to the most stable diketo tautomer).
Less

Epidermal Differentiation Genes of the Common Wall Lizard Encode Proteins with Extremely Biased Amino Acid Contents

The epidermal differentiation complex (EDC) is a cluster of genes that code for protein components of cornified cells on the skin surface of amniotes. Squamates are the most species-rich clade of reptiles with skin adaptations to many different environments. As the genetic regulation of the skin epi...
More

The epidermal differentiation complex (EDC) is a cluster of genes that code for protein components of cornified cells on the skin surface of amniotes. Squamates are the most species-rich clade of reptiles with skin adaptations to many different environments. As the genetic regulation of the skin epidermis and its evolution has been characterized for only a few species so far, we aimed to determine the organization of the EDC in a model species of squamates, the common wall lizard (Podarcis muralis). By comparative genomics, we identified EDC genes of the wall lizard and compared them with homologs in other amniotes. We found that the EDC of the wall lizard has undergone a major rearrangement leading to a unique order of three ancestral EDC segments. Several subfamilies of EDC genes, such as those encoding epidermal differentiation proteins containing PCCC motifs (EDPCCC) and loricrins, have expanded by gene duplications. Most of the EDPCCC proteins have cysteine contents higher than 50%, whereas glycine constitutes more than 50% of the amino acid residues of loricrin 1. The extremely biased amino acid compositions indicate unique structural properties of these EDC proteins. This study demonstrates that cornification proteins of the common wall lizard differ from homologous proteins of other reptiles, illustrating the evolutionary dynamics of diversifying evolution in squamates.
Less

Unexpected abnormal coagulation test results in a 2-year-old child

Rejection of the sample with repeated blood withdrawal is always an unwanted consequence of sample nonconformity and preanalytical errors, especially in the most vulnerable population – children. Here is presented a case with unexpected abnormal coagulation test results in a 2-yearold child with...
More

Rejection of the sample with repeated blood withdrawal is always an unwanted consequence of sample nonconformity and preanalytical errors, especially in the most vulnerable population – children. Here is presented a case with unexpected abnormal coagulation test results in a 2-yearold child with no previously documented coagulation disorder. Child is planned for tympanostomy tubes removal under the anaesthesia driven procedure, and preoperative coagulation tests revealed prolonged prothrombin time, activated partial thromboplastin time and thrombin time, with fibrinogen and antithrombin within reference intervals. From the anamnestic and clinical data, congenital coagulation disorder was excluded, and with further investigation, sample mismatch, clot presence and accidental ingestion of oral anticoagulant, heparin contamination or vitamin K deficiency were excluded too. Due to suspected EDTA carryover during blood sampling another sample was taken the same day and all tests were performed again. The results for all tests were within reference intervals confirming EDTA effect on falsely prolongation of the coagulation times in the first sample. This case can serve as alert to avoid unnecessary loss in terms of blood withdrawal repetitions and discomfort of the patients and their relatives, tests repeating, prolonging medical procedures, and probably delaying diagnosis or proper medical treatment. It is the responsibility of the laboratory specialists to continuously educate laboratory staff and other phlebotomists on the correct blood collection as well as on its importance for the patient’s safety.
Less

Affordable Biologics for All

Diagnostic role of urine human epididymis protein 4 in ovarian cancer

Clinical importance of laboratory biomarkers in liver fibrosis

Hepatic cirrhosis is a major health problem across the world, causing high morbidity and mortality. This disease has many etiologies, yet the result of chronic hepatic injury is hepatic fibrosis causing cirrhosis and hepatocellular carcinoma, as the liver’s architecture is progressively destroyed....
More

Hepatic cirrhosis is a major health problem across the world, causing high morbidity and mortality. This disease has many etiologies, yet the result of chronic hepatic injury is hepatic fibrosis causing cirrhosis and hepatocellular carcinoma, as the liver’s architecture is progressively destroyed. While liver biopsy is currently the gold standard for fibrosis staging, it has significant disadvantages, leading to a growing interest in non-invasive markers. Direct biomarkers – hyaluronic acid, laminin, collagen type III N-peptide, type IV collagen and cholylglycine – are new and rarely applied in routine clinical practice. This is the case primarily because there is no general consensus regarding the clinical application and effectiveness of the individual biomarkers. The usage of these markers in routine clinical practice could be advantageous for patients with liver fibrosis, requiring a simple blood test instead of a biopsy. The former option would be especially attractive for patients who are contraindicated for the latter. This review summarizes recent findings on direct biomarkers of liver fibrosis and highlights their possible applications and potential benefit for liver fibrosis diagnostics and/or staging.
Less

A sudden creatinine increase: A case report

Creatinine and estimated glomerular filtration rate (eGFR) are first-line laboratory parameters in the diagnosis of various renal diseases. In recent decades, cystatin C (cysC) has furthered the laboratory repertoire regarding renal status assessment and has been implemented in many clinical guideli...
More

Creatinine and estimated glomerular filtration rate (eGFR) are first-line laboratory parameters in the diagnosis of various renal diseases. In recent decades, cystatin C (cysC) has furthered the laboratory repertoire regarding renal status assessment and has been implemented in many clinical guidelines. Accordingly, with the establishment of cysC as a renal routine biomarker, further opportunities for assessing eGFR have been attained. Nevertheless, various limitations are still associated with cysC and creatinine analysis. Preanalytical errors could cause false results in both biomarkers. In our case, we were confronted with implausibly elevated creatinine levels due to preanalytical errors.
Less

Underfilled blood tube containing EDTA

Introduction Blood samples having inappropriate volume are a substantial part of preanalytical errors. Inadequate sample volume for glycated haemoglobin (HbA1c) test may be a common problem of patients with diabetes mellitus having vascular changes. In this study, we compared HbA1c concentrations o...
More

Introduction Blood samples having inappropriate volume are a substantial part of preanalytical errors. Inadequate sample volume for glycated haemoglobin (HbA1c) test may be a common problem of patients with diabetes mellitus having vascular changes. In this study, we compared HbA1c concentrations of underfilled and appropriately filled blood collection tubes. Materials and methods To compare HbA1c concentrations, blood samples were collected into 2 mL tubes containing K3-EDTA from 109 subjects. Two blood samples (underfilled and appropriately filled) were drawn from a patient by the same personnel and materials. HbA1c measurements were assayed on a Cobas 6000 analyser module c 501 (Roche Diagnostics, Mannheim, Germany). The HbA1c% results were compared by t-test and Wilcoxon’s signed-rank statistical methods (SPSS Inc., Chicago, USA). Bias analysis was performed using Microsoft Excel 4.0. Results Underfilled samples were classified three groups (group 1, N = 44; group 2, N = 36; and group 3, N = 29) according to the filling ratio of the samples; 0.5 mL and below (< 25%), 0.5-1.0 mL (25-50%), and 1.0-2.0 mL (> 50%), respectively. When we compared underfilled tubes with pairing filled tubes, there was a statistically significant difference only with tubes filled less than 25% (P = 0.030). Furthermore, we have done bias analysis between paired tubes according to the diagnostic cut-off value of 6.5%. The bias was more prominent in up to 50% underfilled blood tubes (1.1%), when HbA1c concentrations were below the diagnostic cut-off of 6.5%. Conclusions We suggest that the blood tubes with EDTA for HbA1c measurement should be filled with at least 50% to avoid clinical variations.
Less

Defining laboratory medicine, or squaring the circle?

In the August 2020 issue of Clinical Chemistry and Laboratory Medicine, Giuseppe Lippi and Mario Plebani proposed a definition of laboratory medicine, which ends with this sentence: “The results of these measurements are translated into actionable information for improving the care and/or maintain...
More

In the August 2020 issue of Clinical Chemistry and Laboratory Medicine, Giuseppe Lippi and Mario Plebani proposed a definition of laboratory medicine, which ends with this sentence: “The results of these measurements are translated into actionable information for improving the care and/or maintaining the wellness of both a single individual and an entire population”. Nevertheless, the selfishness of individuals may, sometimes, jeopardize the interest of whole populations. The virtue of justice being within the reach of the entire human community more than of single individuals, the final sentence in the definition proposed by Giuseppe Lippi and Mario Plebani, should therefore, in our view, be rewritten, less selfishly, for example like this: “For a given investment, these measurements are preferably made when they bring as much beneficence, and non-maleficence, as possible to the whole population”.
Less

Complete blood count alterations in COVID-19 patients

Coronavirus disease 2019 (COVID-19) pandemic represents a scientific and social crisis. One of the main unmet needs for coronavirus disease 2019 is its unpredictable clinical course, which can rapidly change in an irreversible outcome. COVID-19 patients can be classified into mild, moderate, and sev...
More

Coronavirus disease 2019 (COVID-19) pandemic represents a scientific and social crisis. One of the main unmet needs for coronavirus disease 2019 is its unpredictable clinical course, which can rapidly change in an irreversible outcome. COVID-19 patients can be classified into mild, moderate, and severe. Several haematological parameters, such as platelets, white blood cell total count, lymphocytes, neutrophils, (together with neutrophil-lymphocyte and platelet-lymphocyte ratio), and haemoglobin were described to be associated with COVID-19 infection and severity. The purpose of these review is to describe the current state of the art about complete blood count alterations during COVID-19 infection, and to summarize the crucial role of some haematological parameters during the course of the disease. Decreased platelet, lymphocyte, haemoglobin, eosinophil, and basophil count, increased neutrophil count and neutrophil-lymphocyte and platelet-lymphocyte ratio have been associated with COVID-19 infection and a worse clinical outcome. Our study adds some novelty about the identification of effective biomarkers of progressive disease, and might be helpful for diagnosis, prevention of complications, and effective therapy.
Less