SERUM NEUTROPHIL GELATINASE - ASSOCIATED LIPOCALIN (NGAL) AS A MARKER OF TUBULOINTERSTITIAL DAMAGE IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS

Determining of serum creatinine level, glomerular filtration rate and albuminuria gives us no information about tubulointerstitial kidney damage. So it is especially important to search for non - invasive diagnostic methods that allow to diagnose early stages of tubulointerstitial kidney damage and start adequate treatment. This circumstance attempts to use neutrophil gelatinase - associated lipocalin (NGAL) to assess tubulointerstitial kidney damage in patients with chronic glomerulonephritis (CGN). The aim: to analyze the morphological picture of the kidneys in patients with CGN with arterial hypertension (AH) and without, to investigate the relationship between serum NGAL and histological indexes of tubulointerstitial kidney damage in CGN patients with saved renal function. Materials and methods. We examined 81 patients with CGN. Patients were divided into two clinical groups: CGN patients with AH, CGN without AH. We analyzed indicators of tubulointerstitial kidney damage according to vivo morphological study, level of serum NGAL. Conclusion: there is a correlation of varying strength between serum NGAL and indexes of tubulointerstitial kidney damage in CGN patients, strong direct relationship is found between serum NGAL and IF. Diagnostics of IF by determing ofserum NGAL is a highly sensitive and specific method with the efficiency of95.3%. Increase ofserum NGAL above 5ng/ ml indicates a high probability of the IF in CGN patients.Results. Patients with AH have more pronounced histological damage of tubulointerstitial tissue than CGNpatients without AH. Serum NGAL levels are higher in CGN patients with AH and without than in the control group. We find a correlation between serum NGAL and indicators of tubulointer - stitial kidney damage. Analysis of the diagnostic operating characteristics of interstitial fibrosis (IF) by determining of serum NGAL shows that this method is highly sensitive and specific, with an efficiency of95,3%. Constructing ofa non - linear model revealed that increase of serum NGAL level above 5 ng/ml indicates a high probability of the IF in CGN patients

DAILY BLOOD PRESSURE RHYTM IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS AND NORMAL RENAL FUNCTION

To investigate indexes ofdaily blood pressure (BP) in patients with chronic glomerulonephri­tis (CGN) and normal renal function

BIOMARKERS OF KIDNEY DAMAGE IN PATIENTS WITH ARTERIAL HYPERTENSION

Involving of renal tubulointerstitial tissue (TIT) with fibrosis development plays an important role in the persistent renal dysfunction. This circumstance gave rise to the attempts of neutrophil gelatinase–associated lipocalin (NGAL), interleukin–18 (IL–18) use to estimate kidney TIT lesion in chronic glomerulonephritis (CGN) and essential hypertension (EH). Aim. To study the relationship between the biomarkers and clinical, morphological parameters reflecting renal TIT damage in CGN and EH patients. Materials and methods. We examined 44 hypertensive patients and 49 patients with CGN and hypertension. We used data of the kidney morphological study for the analysis of renal TIT lesion in CGN patients. Levels of blood and urine NGAL and IL–18 were determined using immunoassay kits. Results. All patients had preserved renal function. In hypertensive patients microalbuminuria (MAU) was detected in 32%. Patients with CGN had average daily proteinuria 0,5 (0,1:1,2) g/day. Morphologically tubular epithelium dystrophy was observed in 98% ofpatients with CGN. Interstitial fibrosis (IF) was seen in all patients with CGN, and 45% had focal character, while 55% – diffuse. Necrotic changes in the tubular epithelium were observed in 69% of cases, thickening of tubular basement membrane – 61% of patients. Correlation analysis found an association between the level of serum NGAL and IF(r=0,35, p=0,05), tubular basement membrane thickening (r=0,42, p=0,05); urinary NGAL levels and tubular epithelium dystrophy (r=0,29, p=0,05). Serum IL–18 was correlated with tubular epithelium dystrophy (r=0,69, p=0,05); tubular epithelium necrosis (r=0,37, p=0,05), IF (r=0,31, p=0,05). Despite normal renal function and absence of MAU (in 64% of cases), the indicators of renal TIT damage in hypertensive patients are increased. Conclusions. Serum, urine NGAL and serum IL–18 can be used as markers of renal TIT lesion in CGN and EH patients. Serum NGAL reflects most accurately IF and tubular basement membrane changes; urine NGAL – tubular epithelium dystrophy. Serum IL–18 is an indicator of tubular epithelium necrosis, IF

Circular dichroism and conformational polymorphism of DNA

Here we review studies that provided important information about conformational properties of DNA using circular dichroic (CD) spectroscopy. The conformational properties include the B-family of structures, A-form, Z-form, guanine quadruplexes, cytosine quadruplexes, triplexes and other less characterized structures. CD spectroscopy is extremely sensitive and relatively inexpensive. This fast and simple method can be used at low- as well as high-DNA concentrations and with short- as well as long-DNA molecules. The samples can easily be titrated with various agents to cause conformational isomerizations of DNA. The course of detected CD spectral changes makes possible to distinguish between gradual changes within a single DNA conformation and cooperative isomerizations between discrete structural states. It enables measuring kinetics of the appearance of particular conformers and determination of their thermodynamic parameters. In careful hands, CD spectroscopy is a valuable tool for mapping conformational properties of particular DNA molecules. Due to its numerous advantages, CD spectroscopy significantly participated in all basic conformational findings on DNA

Radioactive Phosphorylation of Alcohols to Monitor Biocatalytic Diels-Alder Reactions

Nature has efficiently adopted phosphorylation for numerous biological key processes, spanning from cell signaling to energy storage and transmission. For the bioorganic chemist the number of possible ways to attach a single phosphate for radioactive labeling is surprisingly small. Here we describe a very simple and fast one-pot synthesis to phosphorylate an alcohol with phosphoric acid using trichloroacetonitrile as activating agent. Using this procedure, we efficiently attached the radioactive phosphorus isotope 32P to an anthracene diene, which is a substrate for the Diels-Alderase ribozyme—an RNA sequence that catalyzes the eponymous reaction. We used the 32P-substrate for the measurement of RNA-catalyzed reaction kinetics of several dye-labeled ribozyme variants for which precise optical activity determination (UV/vis, fluorescence) failed due to interference of the attached dyes. The reaction kinetics were analyzed by thin-layer chromatographic separation of the 32P-labeled reaction components and densitometric analysis of the substrate and product radioactivities, thereby allowing iterative optimization of the dye positions for future single-molecule studies. The phosphorylation strategy with trichloroacetonitrile may be applicable for labeling numerous other compounds that contain alcoholic hydroxyl groups

Key Labeling Technologies to Tackle Sizeable Problems in RNA Structural Biology

The ability to adopt complex three-dimensional (3D) structures that can rapidly interconvert between multiple functional states (folding and dynamics) is vital for the proper functioning of RNAs. Consequently, RNA structure and dynamics necessarily determine their biological function. In the post-genomic era, it is clear that RNAs comprise a larger proportion (>50%) of the transcribed genome compared to proteins (≤2%). Yet the determination of the 3D structures of RNAs lags considerably behind those of proteins and to date there are even fewer investigations of dynamics in RNAs compared to proteins. Site specific incorporation of various structural and dynamic probes into nucleic acids would likely transform RNA structural biology. Therefore, various methods for introducing probes for structural, functional, and biotechnological applications are critically assessed here. These probes include stable isotopes such as 2H, 13C, 15N, and 19F. Incorporation of these probes using improved RNA ligation strategies promises to change the landscape of structural biology of supramacromolecules probed by biophysical tools such as nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and Raman spectroscopy. Finally, some of the structural and dynamic problems that can be addressed using these technological advances are outlined

The Dreamworld of Gajto Gazdanov in the Context of European Modernism

269 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2002.The motive of the vagabond in Gazdanov's prose, originated in vagrancy of exile, assumes deeper meaning as wandering through life to its final destination. For Gazdanov, presentiment of death penetrates every aspect of human existence. The theme of death, ethical judgement of good and evil, and the philosophy of Beauty and deformity are developed in Gazdanov's universe through a fairly complete philosophical system. The writer's worldview, which takes ultimate shape in his late novels and short stories, resembles, to a great extent, the philosophical ideas of French existentialists, Albert Camus and Jean-Paul Sartre.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD