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Increase in magnesium plasma level after orally administered trimagnesium dicitrate.

Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.

Administration, Oral↗

Urolithiasis after kidney transplantation--clinical and mineralogical aspects.

Urolithiasis is a rare complication following kidney transplantation. Experience with this complication in 6 of 426 transplantations performed from 1968 to 1979 is reviewed. The clinical symptoms are different from the disease in non-transplant patients. Three major predisposing causes for the development of calculi after kidney transplantation were found in our patients--urodynamic disorders following complications of the ureterovesical anastomosis, persistent bacteriuria and renal tubular acidosis and, less importantly, the presence of hypercalcemia and hypercalciuria as a result of secondary hyperparathyroidism. Crystal-optical and x-ray-diffraction studies contributed to the interpretation of the constituents and texture of the calculi and of the aetiological factors concerned.

Adolescent↗

The bacteriology of the urine and renal calculi.

The bacteriological status of the pre-operative urine, removed calcium and the pelvic urine was studied in 63 consecutive patients undergoing removal of intrarenal calculi. The overall infection rates in the pre-operative urine, removed calculi and pelvic urine were 29%, 38% and 30% respectively. In patients with staghorn calculi, 58% of patients had an infected pre-operative M.S.S.U., and 82.5% of removed calculi demonstrated significant bacterial growth, with Proteus mirabilis being the predominant organism isolated. In patients with single or multiple oxalate calculi, 17% had an infected pre-operative M.S.S.U., and 22% of removed calculi demonstrated a significant bacterial growth. The findings would indicate that the presence of a positive M.S.S.U. in a patient with a renal calculus is an indication for surgical removal.

Adult↗

Experimental induction of crystalluria in rats using mini-osmotic pumps.

Crystalluria was induced in male Sprague-Dawley rats by implanting potassium-oxalate-containing mini-osmotic pumps. Urine of all experimental animals had abundant crystals of calcium oxalate, hydroxypatite, struvite, and calcium phosphate. These crystals were similar in morphology to the crystals found in human crystalluria. Histological examination of kidneys and tissue samples from other organs revealed no abnormality. One group of animals was injected with sodium oxalate in addition to implantation of potassium-oxalate-containing mini-osmotic pumps. Bladder urine from these animals contained calcium oxalate microstones and their kidneys had deposits of calcium oxalate crystals.

Animals↗

The effects of fractioned human urine on urease-induced crystallisation in vitro.

Previous studies have shown human urine to have an inhibitory action on urease-induced crystallisation. Centrifugation and 0.45 microns filtration of the urine did not reduce this activity. This eliminates larger urine particles as being the cause of the inhibitory activity. Both the retenate and the filtrate after ultrafiltration of urine with a 100.000 mol weight cut-off influenced the urease-induced crystallisation of magnesium ammonium phosphate and calcium phosphate. The results indicate that the inhibitory action is exerted by more than one urinary component.

Calcium Phosphates↗

Studies on the crystallization of magnesium ammonium phosphate in urine.

The crystallization of magnesium ammonium phosphate (MAP) was studied in salt solutions and dialysed urine at similar levels of MAP supersaturation. At pH levels of 7.1 or higher crystallization occurred to the same extent in solutions with and without urinary macromolecules. Whereas crystals in the size range 3.5-5 microns were observed in the salt solution at pH 7.0, this was not so in dialysed urine. When the crystal size distribution was determined after 30 min larger crystals were observed in dialysed urine, indicating a promoting effect by urinary macromolecules on the formation of MAP crystals. A modified AP(MAP) index was formulated based on calculations with the EQUIL 2 programme in order to improve the relationship between this simplified estimate and the ion-activity product of MAP (APMAP). This index had the following form: [formula: see text] for 24-h values of magnesium (Mg), ammonium (NH4), phosphate (P), pH and urine volume (V). The APMAP required for the formation of 2,000 crystals in the size range 3.5-5 microns varied between 226 x 10(-15) and 293 x 10(-15) (mmol/l)2 in dialysed urine. An experimental system was designed based on the measurement of pH during the addition of NH4OH. At the point assumed to correspond to the start of crystallization, AP(MAP) index values between 409 and 903 were recorded. Such a test might provide useful information on the crystallization properties in urine.

Crystallization↗

How variations in the composition of urine influence urease-induced crystallization.

To Study how the composition of urine influences urease-induced crystallization, human urine samples were incubated with urease and the subsequent precipitation measured. Beside the pH increase, the urinary content of magnesium and calcium had profound effects on the precipitation of magnesium ammonium phosphate and calcium phosphate, respectively. Urine phosphate, ammonium and osmolarity had no direct effects on the precipitation. Among the urine components with potential inhibitory properties, only albumin was found to be correlated with such an effect. This inhibitory activity was especially influential in urines with high calcium and magnesium levels. These findings suggest that the composition of urine could also influence the formation of stones consisting of magnesium ammonium phosphate and calcium phosphate.

Calcium Oxalate↗

Effect of extracorporeal shock wave lithotripsy on bacterial viability. Relationship to the treatment of struvite stones.

The aim of this study was to determine whether extracorporeal shock wave lithotripsy (ESWL) affected the viability of the infecting bacteria within a simulated struvite stone matrix. A strain, Proteus mirabilis 28cii, was prepared in three forms: (1) suspended in saline and urine, (2) artificially encapsulated by suspending in agar beads and (3) artificially encapsulated and mineralised by suspending in agar beads with calcium carbonate crystals. The preparations were placed in capped vials partially immersed in degassed water and held in the focal point of the Siemens Lithostar and given 1,000 shocks. Subsequent viability testing showed that bacteria suspended in urine were greatly affected by shock treatments (55% loss in viability), but incorporation into agar beads negated this effect (even if the cells were exposed to 2000 shocks). Mineralisation of the beads with calcium carbonate crystals caused a decrease in viability of 82% that was significantly different from controls. However, this still left 2.3 X 10(8) viable organisms (82% of 2.8 X 10(8], easily enough to form the focus for further infections. A series of control experiments carried out using an ultrasonic cell sonicator probe gave comparable results to those obtained with ESWL. These results demonstrate the ESWL treatment of infected stones must be accompanied by antimicrobial coverage.

Humans↗

Effects of dietary calcium, magnesium and phosphorus on the formation of struvite stones in the urinary tract of rats.

After feeding various diets we studied the effects of dietary calcium, magnesium and phosphorus on the formation of struvite stones in rats with urinary tract infections, and also studied the effects of the administration of vitamin D3 and aluminium gel on stone formation. A low-magnesium diet decreased urinary magnesium and prevented stone formation, but a medium-calcium diet did not significantly decrease stone weight. A high-calcium diet decreased urinary phosphorus and inhibited stone formation. A high-calcium and high-phosphorus diet decreased urinary excretion of magnesium and inhibited stone formation. Although the administration of vitamin D3 did not inhibit stone formation, aluminium gel decreased the urinary level of phosphorus and prevented stone formation. A marked decrease in urinary magnesium and/or phosphorus may prevent struvite stone formation in rats with urinary tract infections.

Aluminum↗

Proteus mirabilis biofilms and the encrustation of urethral catheters.

Bacterial biofilms were observed on 69 of 75 catheters taken from patients undergoing long-term bladder management. Ten catheters were colonized by pure cultures of Proteus mirabilis. In each of these cases the bacteria formed layers on the catheter surface, underlying encrustations of struvite and hydroxyapatite which partially or completely occluded the catheter lumen. Encrustation was also apparent on catheters colonized by P. mirabilis plus other species, but was rarely seen on catheters colonized by non-urease-producing species. These observations support the hypothesis that catheter encrustation is brought about by the activity of urease-producing biofilms and confirms that the main target in the control of catheter encrustation should be P. mirabilis.

Catheterization↗

Rare-earth elements in urinary calculi.

In vitro studies have demonstrated that trace elements have inhibitory as well as stimulatory effects on the crystallization of urinary stones. Little is known about the activities of rare-earth elements (REEs) in the human body. Although their physiological role is unclear, an effect on calcium transport mechanisms is discussed. In the present study, ten kidney stones (six oxalate and four phosphate stones) were analyzed by neutron-activation analysis for their REE patterns. Urinary stones are capable of concentrating these elements, and some fractionation into light and heavy REEs appears to take place during deposition. Significantly elevated concentrations of heavy REEs such as europium, terbium, and lutetium were detected in phosphate stones as compared with oxalate stones (P < 0.005).

Calcium Oxalate↗

Relationship between the incidence infection stones and the magnesium-calcium ratio of tap water.

In a previous study we showed that the magnesium-calcium ratio of tap water is negatively correlated with the incidence of calcium-containing urinary stones. In this study we examined the relationship between the incidence of struvite stones, water hardness and the regional geological features on the basis of our previous study and an epidemiological study of urolithiasis performed in Japan. The magnesium-calcium ratio of tap water was found to correlate positively with the incidence of struvite stones. The tap water magnesium-calcium ratio was high in regions of basalt and sedimentary rock and was low in granite and limestone areas. The incidence of struvite stones in the regions of basalt and sedimentary rock was higher than that in the granite and limestone areas. Thus, this study suggested that the incidence of struvite stones is related to the magnesium-calcium ratio of tap water and to the regional geology, as is the case for calcium-containing stones.

Calcium↗

Food intake and struvite crystalluria in ferrets.

Four adult, castrated, male ferrets were studied in two similar trials for effects of food intake on variables hypothesized to promote struvite (ammonium, magnesium, phosphate hexahydrate) crystal formation in urine. Struvite crystalluria occurred in three of the four ferrets. Urine pH (UpH) averaged 6.6 for these ferrets. UpH in the ferret without crystalluria was 6.0. By simple linear regression analysis, no relationship was found between the amount of food ingested and the urinary concentration and excretion of magnesium and phosphorous. However, urine osmolality and excretion of both protein and ammonium were correlated to food intake (P less than .05). Ways in which these effects could promote struvite crystal formation are discussed.

Animals↗

Infection of catheterised patients: bacterial colonisation of encrusted Foley catheters shown by scanning electron microscopy.

The surfaces of 32 encrusted urinary catheters were examined by scanning electron microscopy to investigate the association of bacteria with the encrusting deposits. Deposits consisted of struvite crystals surrounded by aggregates of very small crystallites of hydroxyapatite. Underneath these minerals there was a layer of closely packed bacteria. Impressions of bacteria were also observed in hydroxyapatite. Crystals were often engulfed by the bacterial layer, which thus appeared to bind the crystals to each other and to the catheter surface. This thick layer of bacteria associated with crystals may protect both the bacteria from antibiotics and the crystals from acidic bladder washout solutions intended to dissolve them. Furthermore, the existence of this sessile population explains why urease-producing bacteria are not invariably detected in the urine of patients with encrusted catheters. The observation of this bacterial layer (or "biofilm") by scanning electron microscopy provided direct evidence for infection being implicated in catheter encrustation.

Bacterial Adhesion↗

Resistance of catheters coated with a modified hydrogel to encrustation during an in vitro test.

Mid-shaft specimens were cut from latex catheters coated with a modified hydrogel, latex catheters coated with silicone elastomer, and 100% silicone catheters. These specimens were subjected to controlled in vitro encrustation conditions. During a test period of 11 weeks, there was no significant difference in the quantities of encrusting deposits formed on the three materials.

Catheters, Indwelling↗

Urease-induced crystallizations of calcium phosphate and magnesium ammonium phosphate in synthetic urine and human urine.

An aggregometer technique was used to study urease-induced crystallizations in synthetic urine and human urine from healthy subjects and patients with chronic spinal cord injuries. The two different phases of crystallization, calcium phosphate and magnesium ammonium phosphate, were easily evaluated with a single assay using this technique. The crystallization of calcium phosphate and magnesium ammonium phosphate varied markedly among the different urine specimens after incubation with urease. The turbidity curves from human urine were divided into four patterns. We assumed that the variations in the patterns of the turbidity curves appeared to be mainly due to differences in the composition of the urine and in the original pH, and that the calcium and magnesium concentrations were very important in the urinary constituents.

Calcium Phosphates↗

Actin-attached and detached crossbridges in myofibrils: segregation into two populations according to their sensitivity to proteolytic digestion of myosin heavy chain.

Tryptic digestion of myofibrils was used to assess the interaction of crossbridges with thin filaments in the presence of ATP analogues. The relative amounts of 200 kDa fragment produced by trypsin from myosin heavy chain when the crossbridge is attached to actin, and of 160 kDa fragment produced when the crossbridge is detached from actin, served as a measure of crossbridge-actin interaction. In rigor only the 200 kDa fragment was produced suggesting that a great majority of the crossbridges were strongly attached to actin; in the presence of MgPPi at 0 degrees C only the 160 kDa fragment was finally produced suggesting that eventually all crossbridges detached from actin. In the presence of MgPPi or MgAMPPNP at 25 degrees C both 200 and 160 kDa fragments were present for several minutes after myosin heavy chain had been completely digested, suggesting that two populations of crossbridges (attached and detached) co-existed at the same time within the myofibril. It is concluded that the addition of ATP analogues to muscle does not simply affect the chemical equilibrium of binding of myosin heads to actin but that it causes rapid dissociation of one crossbridge population without significant effect on binding to actin of the remaining crossbridge population.

Actins↗