This study indicates that both individual cell injury (loss of lipid asymmetry) and generalized cell monolayer injury (loss of cell polarity) result in the presentation of different cell surfaces and that both forms of injury result in an increased affinity for crystal attachment. Both mechanisms could be important independently or collectively in the retention of microcrystals to renal collecting duct cells in urolithiasis.

Background : Although nephrotoxic in high doses, ethylene glycol (EG) has been used with ammonium chloride (NH 4 Cl) or vitamin D 3 to study calcium oxalate stone formation in rat models. In the present study we used EG alone or with NH 4 Cl to study hyperoxaluria, crystaluria, and crystal attachment to renal epithelial cells in rats with minimal renal damage . Methods : Six-week-old male Sprague-Dawley (SD) rats were given food and special drinking water.In experiment 1 the drinking water contained 1.0% NH 4 Cl plus four different concentrations of EG (0.8%, 0.4%, 0.2%, 0.1%). In experiment 2 the drinking water contained EG alone (0.8%, 0.4%, 0.2%, 0.1%). Urine was collected for 24 h before the rats were sacrificed. In experiment 1 the rats were sacrificed 5-13 days after starting the special water. In experiment 2 the rats were sacrificed 7-21 days after starting the special water. Bladder urine was also obtained. Blood and urine were tested for calcium, phosphorus, and creatinine. In addition, urine was tested for pH, oxalate and Nacetyl-b -D glucosaminidase (NAG). Kidney sections were stained with hematoxylin-eosin, von Kossa and Pizzolato stain. Crystal morphology was determined using polarizing microscopy, and composition was determined using high-resolution X-ray powder diffraction . Results : Experiment 1: Aggravation of renal function, an increase in urinary oxalate and NAG excretion, and crystals observed in the kidneys all correlated with EG concentration and length of drinking time. In bladder urine, calcium oxalate monohydrate (COM) crystals exceeded calcium oxalate dihydrate (COD) crystals. Experiment 2: Renal function remained unchanged. Oxalate excretion increased and NAG increased slightly. Crystals occurred only in the papillary tip region. Crystals in bladder urine were mostly COD . Conclusion : In the current rat model, calcium oxalate crystaluria could be induced without severe renal damage in selected cases. Either and/or both COM and COD might form and interact with kidney epithelium. We propose different experimental conditions to study the various phases of calcium oxalate stone formation in young male SD rats.

One of the critical steps in the development of crystal-induced lung diseases is thought to be the interaction of crystal surfaces with cell membranes. The effect of chemical modifications of the surface of alpha-quartz on the development of lung disease has been investigated by treating quartz with various organosilanes. The functional groups attached to the quartz surfaces were (-CN), (-CH3), (-NH2), and -(N(CH3)3+). After intratracheal injection of each modified crystal at a constant surface area into mice, pulmonary inflammation and fibrosis were assessed 6 wk postexposure to the crystals by lung wet weight (lung index) and by the level of hydroxyproline in the lung. The crystals showing the highest degree of biologic activity were native quartz, which has a negative charge, -N(CH3)3+ modified quartz, which has a positive charge, and -CN modified quartz, which has no charge. One of the crystals with chemical groups capable of hydrogen bonding, the -NH2 modified quartz, was as unreactive as the crystal preparation modified with a hydrophobic group, -CH3. If the -CH3 and -NH2 modified quartz are compared as a less reactive group with the more reactive native quartz and -N(CH3)3+ modified quartz, these experiments suggest that electrostatic interactions may be more important in determining effective biologic activities than are hydrogen bonding interactions.

Thirty inpatients with evidence of tardive dyskinesia secondary to antipsychotic medications participated in this double-blind, controlled, randomized study comparing reserpine, alpha-methyldopa and placebo. Reserpine at doses of 0.75--1.5 mg daily, or alpha-methyldopa at doses of 750--1,500 mg daily, produced a statistically significant improvement in tardive dyskinesia symptomatology compared to the results obtained with placebo.

The effect of stone growth inhibitors (citrate, pyrophosphate, ethane diphosphonate, methane diphosphonate, chondroitin sulfate A, chondroitin sulfate C, heparin and ribonucleic acid) on crystal-membrane interactions of whewellite, weddellite, apatite, brushite, struvite, uric acid, monosodium urate and quartz (control) stones was quantitated. As a model for the initial retention of microcrystals by kidney epithelial membranes, crystal-induced membranolysis of red blood cells served as a measure of crystal-membrane interactions. The inhibitors induced changes in hemolytic potential from approximately 320 per cent enhancement to 80 per cent inhibition. No inhibitor behaved the same way for all crystals studied. However, some crystals showed consistent trends in altered hemolytic potential in the presence of inhibitors. These crystals included weddellite and sodium urate, which were inhibited consistently, and apatite and quartz, which were enhanced consistently. Whewellite, uric acid, brushite and struvite exhibited mixed patterns in the altered hemolytic potentials owing to the inhibitors.