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The secretion of thyroid stimulating hormone (thyrotropin, TSH), is characterized by a marked circadian rhythm. Plasma or serum TSH values are significantly lower in the afternoon and in the evening as compared to the early morning. As in clinical practice, blood sampling time shows an important variation, a reliable assessment of thyroid status is often not an easy task for the clinician. The biological variation of TSH plays a major role in the intra-individual variability of TSH results in serum or plasma. The observed intra-day variation largely exceeds the reported inter-vendor variation and the coefficient of variation of clinical TSH assays. Therefore, a mathematical solution was sought for correcting interpretation of TSH results for sampling time.We have developed a cosinor model which allows to compensate TSH decision values for the fluctuating serum or plasma TSH concentrations throughout the day.The following mathematical function could be derived: corrected TSH cutoff_value (mIU/L)=0.40 + 0.24*cos(((π/12) *T) + 6) in which T represents the time (hours). This mathematical function can be easily implemented into a laboratory’s informatics system and furthermore allows a better tailored diagnosis of (subclinical) hyperthyroidism, regardless the blood sampling time.Implementing the corrected cut-off values result in a marked reduction of apparent (false positive) hyperthyroidism diagnosis, in particular in the afternoon. [ABSTRACT FROM AUTHOR]

Haptoglobin (Hp) is a polymorphic protein that was initially described as a hemoglobin (Hb)-binding protein. The major functions of Hp are to scavenge Hb, prevent iron loss, and prevent heme-based oxidation. Hp regulates angiogenesis, nitric oxide homeostasis, immune responses, and prostaglandin synthesis. Genetic polymorphisms in the Hp gene give rise to different phenotypes, including Hp 1-1, Hp 2-1, and Hp 2-2. Extensive research has been conducted to investigate the association between Hp polymorphisms and several medical conditions including cardiovascular disease, inflammatory bowel disease, cancer, transplantation, and hemoglobinopathies. Generally, the Hp 2-2 phenotype is associated with increased disease risk and poor outcomes. Over the years, the Hp 2 allele has spread under genetic pressures. Individuals with the Hp 2-2 phenotype generally exhibit lower levels of CD163 expression in macrophages. The decreased expression of CD163 may be associated with the poor antioxidant capacity in the serum of subjects carrying the Hp 2-2 phenotype. However, the Hp 1-1 phenotype may confer protection in some cases. The Hp1 allele has strong antioxidant, anti-inflammatory, and immunomodulatory properties. It is important to note that the benefits of the Hp1 allele may vary depending on genetic and environmental factors as well as the specific disease or condition under consideration. Therefore, the Hp1 allele may not necessarily confer advantages in all situations, and its effects may be context-dependent. This review highlights the current understanding of the role of Hp polymorphisms in cardiovascular disease, inflammatory bowel disease, cancer, transplantation, hemoglobinopathies, and polyuria. [ABSTRACT FROM AUTHOR]

The early detection of gynecological cancers, which is critical for improving patient survival rates, is challenging because of the vague early symptoms and the diagnostic limitations of current approaches. This comprehensive review delves into the game-changing potential of infrared (IR) spectroscopy, a noninvasive technology used to transform the landscape of cancer diagnosis in gynecology. By collecting the distinctive vibrational frequencies of chemical bonds inside tissue samples, Fourier-transform infrared (FTIR) spectroscopy provides a 'molecular fingerprint' that outperforms existing diagnostic approaches. We highlight significant advances in this field, particularly the identification of discrete biomarker bands in the mid- and near-IR spectra. Proteins, lipids, carbohydrates, and nucleic acids exhibited different absorption patterns. These spectral signatures not only serve to distinguish between malignant and benign diseases, but also provide additional information regarding the cellular changes associated with cancer. To underscore the practical consequences of these findings, we examined studies in which IR spectroscopy demonstrated exceptional diagnostic accuracy. This review supports the use of IR spectroscopy in normal clinical practice, emphasizing its capacity to detect and comprehend the intricate molecular underpinnings of gynecological cancers. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch's membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage. [ABSTRACT FROM AUTHOR]

Background Augmented renal clearance (ARC), an increase in kidney function with enhanced elimination of circulating solute, has been increasingly recognized in critically ill adults. In a pediatric intensive care setting, data are scarce. The primary objective of this study was to investigate the prevalence of ARC in critically ill children. Secondary objectives included a risk factor analysis for the development of ARC and a comparison of two methods for assessment of renal function. Methods In 105 critically ill children between 1 month and 15 years of age, glomerular filtration rate (GFR) was measured by means of a daily 24-h creatinine clearance (24 h Cl.sub.Cr) and compared to an estimated GFR using the revised Schwartz formula. Logistic regression analysis was used to identify risk factors for ARC. Results Overall, 67% of patients expressed ARC and the proportion of ARC patients decreased during consecutive days. ARC patients had a median Cl.sub.Cr of 142.2 ml/min/1.73m.sup.2 (IQR 47.1). Male gender and antibiotic treatment were independently associated with the occurrence of ARC. The revised Schwartz formula seems less appropriate for ARC detection. Conclusions A large proportion of critically ill children develop ARC during their stay at the intensive care unit. Clinicians should be cautious when using Schwartz formula to detect ARC. Our findings require confirmation from large study cohorts and investigation of the relationship with clinical outcome., Author(s): Tatjana Van Der Heggen [sup.1] [sup.2] , Evelyn Dhont [sup.1] [sup.2] [sup.3] , Harlinde Peperstraete [sup.4] , Joris R. Delanghe [sup.5] , Johan Vande Walle [sup.1] , Peter De [...]