Urine contains compounds that modulate the nucleation, growth and aggregation of crystals as well as their attachment to renal epithelial cells. These compounds may function to protect the kidneys against: 1, the possibility of crystallization in tubular fluid and urine, which are generally metastable with respect to calcium salts, 2, crystal retention within the kidneys thereby preventing stone formation and 3, possibly against plaque formation at the nephron basement membrane. Since oxalate is the most common stone type, the effect of various modulators on calcium oxalate (CaOx) crystallization has been examined in greater details. Most of the inhibitory activity resides in macromolecules such as glycoproteins and glycosaminoglycans while nucleation promotion activity is most likely sustained by membrane lipids. Nephrocalcin, Tamm-Horsfall protein, osteopontin, urinary prothrombin fragment 1, and bikunin are the most studied inhibitory proteins while chondroitin sulfate (CS), heparan sulfate (HS) and hyaluronic acid (HA) are the best studied glycosaminoglycans. Crystallization modulating macromolecules discussed here are also prominent in cell injury, inflammation and recovery. Renal epithelial cells on exposure to oxalate and CaOx crystals produce some of the inflammatory molecules such as monocyte chemoattractant protein-1 (MCP-1) with no apparent role in crystal formation. In addition, macrophages surround the CaOx crystals present in the renal interstitium. These observations indicate a close relationship between inflammation and nephrolithiasis.

The chances of stone formation occurring through a free particle mechanism were calculated using the approach of Finlayson and Reid [1]. For these calculations we used new data on nephron dimensions, supersaturation and crystal growth rates in urine, and also incorporated the size increasing effect of crystal agglomeration. The calculations were performed assuming different levels of oxalate excretion, simulating the diurnal variation and acute hyperoxaluria following a dietary load. In addition urinary flow conditions were varied according to changes in daily urinary volume. It is shown that during the normal transit time of urine through the nephron, particles can obtain a size big enough to be retained in the nephron. This is mainly due to the size-increasing effect of the agglomeration process. The precipitable amount of oxalate present is not limiting for the maximum attainable particle size. However, acute increases in oxalate excretion do pose a risk because supersaturation is reached earlier in the nephron and consequently the crystal particles are allowed more time to increase in size. In conclusion, the present calculations demonstrate that during the normal transit time through the kidney, crystalline particles can be formed which are large enough to be retained because of their size and thus form the nidus of a stone. The highest risk is encountered at the end of those collecting ducts where crystals formed in nephrons with a long loop of Henle meet and agglomerate.

Paroxysmal non-epileptic events can cause diagnostic confusion, particularly in children with developmental delay, epilepsy or an epileptiform EEG. Accurate diagnosis can be reached in the majority of cases using video EEG monitoring.

We have applied Raman spectroscopy to discriminate between nontumor and tumor bladder tissue and to determine the biochemical differences therein. Tissue samples from 15 patients were collected, and frozen sections were made for Raman spectroscopy and histology. Twenty-five pseudocolor Raman maps were created in which each color represents a cluster of spectra measured on tissue areas of similar biochemical composition. For each cluster, the cluster-averaged spectrum (CAS) was calculated and classified as tumor and nontumor in accordance to pathohistology. Unguided hierarchical clustering was applied to display heterogeneity between and within groups of nontumor and tumor CAS. A linear discriminant analysis model was developed to discriminate between CAS from tumor and nontumor. The model was tested by a leave-one-patient-out validation, 84 of the 90 CAS (93%) were correctly classified with 94% sensitivity and 92% specificity. Biochemical differences between tumor and nontumor CAS areas were analyzed by fitting spectra of pure compounds to the CAS. Nontumor CAS showed higher collagen content while tumor CAS were characterized by higher lipid, nucleic acid, protein, and glycogen content. Raman spectroscopy enabled effective discrimination between tumor and nontumor bladder tissue based on characterized biochemical differences, despite heterogeneity expressed in both tumor and nontumor CAS.

Coccoliths of the unicellular marine alga Emiliania Izuxleyi are formed intracellularly in a specialized vesicle. Closely associated with the CaC0, crystals of the coccoliths is an acid CaZ +-binding polysaccharide. The latter is considered to fulfil a regulatory function in CaC03 crystallization. In this study it is demonstrated that the coccolith polysaccharide is able to inhibit CaCO, precipitation in vitro. The degree of inhibition is dependent on the nature of the cations bound to the acid groups of the polysaccharide. After substitution of Na' by Ca2+ ions the polysaccharide is far less effective in inhibiting CaC0, precipitation.The coccolith polysaccharide contains two types of acid groups: uronic acids and sulphate esters. Only the uronic acids are responsible for the inhibition of CaCO, precipitation. Desulphated polysaccharide inhibits precipitation to the same extent as the native molecule whereas the carboxyl-reduced polysaccharide is unable to block CaCO, crystallization.Inhibition of CaC0, precipitation can be suppressed by the presence of ethanol. Presumably the conformation of the molecule is altered under these conditions. Alginic acid [poly(mannuronic-iduronic acid)] and poly(ga1acturonic acid) also inhibit CaC0, precipitation. Inhibition of precipitation is effected by the coccolith polysaccharide and alginic acid at comparable concentrations. The concentration of poly(ga1acturonic acid) needed to obtain the same result is about 20-times higher. Contrary to the coccolith polysaccharide, both poly(uronic acid)s inhibit CaC0, precipitation in the absence as well as in the presence of ethanol. These results suggest that conformational changes of the coccolith polysaccharide may play a role in CaCO, crystallization in vivo.