Correlation between 1.25 dihydroxyvitamin D serum levels and fractional rate of intestinal calcium absorption in hypercalciuric nephrolithiasis. role of phosphate

Summary Different mechanisms could explain the elevated calcium elimination, the main cause of calcium oxalate renal stones. Our results suggest that phosphate levels are decreased in patients with absorptive hypercalciuric nephrolithiasis and elevated serum dihydroxyvitamin D. This could be the reason why in this group of patients oral phosphate treatment prevented hypercalciuria and renal lithiasis.This work was supported by FlSss 89/0799     

CROMAKALIM SUPPRESSES HYPERTONIC SALINE-INDUCED RENAL VASOCONSTRICTION IN ANAESTHETIZED DOGS

1. Intrarenal arterial infusion of hypertonic saline (HS) transiently increased and then gradually reduced renal blood flow (RBF) in anaesthetized dogs. Glomerular filtration rate (GFR) but not filtration fraction decreased at the end of the infusion. 2. In the presence of a potassium channel opener cromakalim (0.3 μg/kg per min), HS infusion failed to reduce RBF; the initial increase in RBF was maintained throughout the infusion. Since cromakalim also prevented the decrease in GFR, HS infusion lowered filtration fraction. 3. The results suggest that cromakalim inhibits both pre-and postglomerular vasoconstriction induced by HS infusion.     

ACUTE EFFECT OF ETHANOL ON RENAL ELECTROLYTE TRANSPORT IN THE RAT

1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso-pressin (AVP) release. 2. Ethanol at a plasma concentration of 1.69 ±0.28 mmol/L produced an immediate increase in urine flow (174 ± 11 μL/min pre-ethanol and 189 ± 13 and then 206 ± 12 μL/min during the ethanol infusion; P<0.001) as well as an increase in fractional sodium excretion (0.17 ± 0.04 to 0.28 ± 0.05 and 0.27 ± 0.05%; P<0.001). There was also a brief phosphaturia. These increases in electrolyte excretion had returned to control values by 20 min despite a further increase in the plasma ethanol concentration. 3. The urinary excretion of potassium, calcium and magnesium was not altered nor was glomerular filtration rate or renal plasma flow. 4. Ethanol at a mean concentration of 1.60 mmol/L did not alter the action of a maximal concentration of AVP (75 ng/kg) on water or electrolyte transport. However, the antidiuretic effect of a submaximal concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of 1.63 and 0.98 mmol/L. 5. These studies suggest that the ethanol induced diuresis commonly ascribed to inhibition of AVP secretion may also be due to other intrarenal effects of ethanol, possibly acting within the proximal tubule. These results also confirm recent in vitro findings that while ethanol does not inhibit the action of a maximal concentration of AVP, it does modulate the effects of lower AVP concentrations.     

Cross-neutralisation of Australian brown and tiger snake venoms with commercial antivenoms: Cross-reactivity or antivenom mixtures?

Recently it has been suggested that the Australian snake antivenoms made by CSL Ltd. are in fact not truly monovalent and may contain antibodies to other snake venoms because the horses are injected with multiple snake venoms. It is unclear to what extent various monovalent antivenoms can neutralise the effect of other venoms, whether this is due to a mixture of antibodies or true cross-reactivity, and whether this has any clinical significance. We aimed to study the immunological and functional properties of brown snake (Pseudonaja spp.) antivenom (BSAV) and tiger snake (Notechis spp.) antivenom (TSAV) against their respective venoms using enzyme immunoassays (EIA) and in vitro clotting studies. There was significant overlap between the two antivenoms with both TSAV and BSAV being detected by EIA on brown snake venom (BSV)-coated and tiger snake venom (TSV)-coated wells, respectively. In a competition EIA, increasing amounts of immunoaffinity-purified hen anti-brown antibodies (IgYp) mixed with TSAV reduced TSAV measured on TSV-coated wells. Both BSAV and TSAV prevented the clotting activity of both venoms. IgYp also prevented the clotting activity of TSV, suggesting true cross-reactivity. The cross-reactivity of TSAV and BSAV with BSV and TSV, respectively, was likely due to each being a mixture of anti-brown and anti-tiger antibodies, but there was partial cross-reactivity demonstrated by the effect of IgYp. Single-polyvalent antivenom for brown snake and tiger snake may be feasible in the future.     

Distal radial fractures Injectable calcium phosphate bone cement versus conventional treatment

AMEDLINEsearchwasconductedtoidentifystudiespublishedfromJanuary1999toMarch2004thatcom-paredinjectablecalciumphosphatebone(NorianSRS)cementwithconventionaltreatmentindistalradialfrac-tures.Fromalistof13articlesidentifiedfromthesearchstrategy,fourarticleswe…     

Inhibition of the amorphous calcium phosphate phase transformation reaction by polyphosphates and metal ions

Summary The induction time for amorphous calcium phosphate (ACP) phase transformation was monitored at pH 7.4 and T=25°C with [Ca²⁺]₀=[PO₄]₀=4.0×10⁻³ M, as a function of added crystal growth inhibitors Mg²⁺, Sr²⁺, Zn²⁺, pyrophosphate (PP), and tripolyphosphate (TPP). Metal ions increase the induction time for the initiation of the phase change reaction in the order Zn²⁺<Sr²⁺<Mg²⁺. For polyphosphates it was observed that both PP and TPP are potent inhibitors with TPP more effective than PP as expected. The combination of Mg²⁺ or Sr²⁺ and PP or TPP leads to a synergistic delay in the onset of the phase conversion. The greatest inhibition was observed for Mg²⁺ and TPP. Reaction solutions containing 2.0×10⁻⁴ M Mg²⁺ and 4.0×10⁻⁵ M TPP resulted in a 90% increase in the induction time over what would be anticipated from an additive effect from these species.     

Characteristics of antibody responses induced in mice by protein allergens

Whereas many foreign proteins are immunogenic, only a proportion is also allergenic, having the capacity to induce the quality of immune response necessary to support the production of IgE antibody. We have demonstrated previously that intraperitoneal administration to mice of proteins such as ovalbumin (OVA) or the industrial enzyme A. oryzae lipase, which possess significant allergenic potential, stimulates the production of both IgG and IgE antibody. Identical exposure to bovine serum albumin (BSA), a protein with limited potential to cause immediate respiratory or gastrointestinal hypersensitivity reactions, induced IgG responses only. In the current investigations, the quality of immune responses induced following exposure to these proteins via mucosal tissue (intranasal) has been compared with those provoked following administration via a non-mucosal (intraperitoneal) route of exposure. Intranasal or intraperitoneal administration of BSA, OVA or A. oryzae lipase elicited in each case vigorous IgG and IgG1 antibody responses. For all three proteins, at every concentration tested, and via both routes of exposure, IgG1 antibody titres paralleled closely IgG titres. However, the three materials displayed a differential potential to provoke IgE responses and this correlated with their known allergenic potential in humans. Thus, OVA and A. oryzae lipase stimulated strong IgE antibody responses, whereas BSA provoked low titre IgE only at the highest concentration tested (5% administered intraperitoneally). The quality of induced responses was not affected by the route of exposure. It would appear, therefore, that the stimulation of IgG and IgG1 antibody responses is a reflection of protein immunogenicity whereas protein allergenicity is associated with the induction of strong IgE responses.     

Evaluation of filling materials in membrane‐protected bone defects. A comparative histomorphometric study in the mandible of miniature pigs.

In recent years, bone grafts and bone substitutes have been increasingly utilized underneath barrier membranes to optimize the treatment outcome of bone reconstructive therapy for defects in the alveolar process. In the present study, 4 different filling materials were evaluated in bone defects of similar dimensions in the mandible of miniature pigs. Blood clots and autografts were used as controls. The defects were covered with barrier membranes and allowed to heal for 4, 12 or 24 weeks. Histologic examination demonstrated that bone repair progressed through a programmed sequence of maturation steps closely resembling the pattern of bone development and growth regardless of whether bone grafts or substitutes were present or not. Histomorphometric analysis showed that autologous bone grafts (autografts) had the best osteoconductive properties during the initial healing period, with 39% of newly formed bone inside the membrane-covered defects at 4 weeks of healing. In addition, 87% of the graft surfaces were already covered by bone at this time. Both values were significantly higher for autografts than for the 4 alternative bone fillers (P < or = 0.05). At 12 weeks, these differences were no longer apparent, with all 5 filling materials showing similar values. Among the tested bone substitutes, tricalcium phosphate (TCP) showed a significantly higher percentage of bone fill at 24 weeks of healing. It can be concluded that sites filled with autografts clearly demonstrated the best results underneath barrier membranes in the early phase of healing. As far as degradation and substitution are concerned, TCP showed the most promising results. This filler, however, needs to be tested further in a more demanding animal model. Less favorable results were obtained for coral-derived hydroxyapatite granules and for demineralized freeze-dried bone allografts.     

Reversible Adsorption of Soluble Hexameric Insulin onto the Surface of Insulin Crystals Cocrystallized with Protamine: An Electrostatic Interaction

Mixing pharmaceutical preparations of soluble neutral regular insulin solution (NRI) and neutral protamine Hagedorn (NPH) crystalline insulin suspension leads to a reduction in the measurable amount of soluble insulin in the formulation supernatant. However in spite of the loss in soluble insulin, the time-actions of these components have been shown, in clinical trials, to be unaffected. The interaction between these different physical forms of insulin has been studied using reversed-phase HPLC, isothermal titrating calorimetry, and Doppler electrophoretic light scattering analysis. Sorbent surface and solution perturbation studies revealed that the NRI adsorbs to the surface of the NPH crystal with an equilibrium constant ranging from 10⁴ M^–1 to 10⁷ M^–!, depending on the protamine concentration, pH, ionic strength, and temperature. This adsorption behavior suggests that the binding is mediated by electrostatic interactions arising between the positively-charged NPH crystal and the negatively-charged NRI hexamer. Doppler electrophoretic light scattering results, used to probe the pH-dependent surface charge of NPH and soluble insulin hexamer, support the conclusion that electrostatic interactions mediate the adsorption process. Adsorption studies under physiological conditions indicate that the elevated temperature and ionic strength, in a subcutaneous depot, are sufficient to lead to the dissociation of the NRI/NPH complex that exists in these NPH mixture formulations.     

Phosphate end dialysis value : a misleading parameter of hemodialysis efficiency

Despite low end dialysis serum phosphate levels (P_e) the control of phosphate retention remains often unsatisfactory in dialyzed patients. In order to assess the value of P_e in dialyzed children as an indicator of dialytic phosphate removal, we studied serum phosphate kinetics over the period of dialysis and post dialysis and compared these with urea kinetics. A multicenter study was conducted in the 21 French pediatric hemodialysis units and included 144 children under 15 years of age. Blood urea and phosphate concentrations were measured at the beginning, at 45 min later, at the end of dialysis, and 30 min post dialysis. At 60 min and at 360 min post dialysis measurements were made only for a subgroup of 12 children. From the serum levels, reduction ratios for urea (URR) and phosphate (PRR) and post dialysis rebound for urea (PDUR) and phosphate (PDPR) were calculated. URR (over the dialysis session, 72%±9%) was higher than PRR (47%±12%). Moreover, urea removal continued throughout the dialysis period, while most of the reduction in phosphate occurred in the initial dialysis period. Post dialysis urea rebound was limited to the 60th min post dialysis, whereas post dialysis phosphate rebound occurred until the 360th min post dialysis; by this time the serum phosphate levels had almost reached the predialysis levels. In summary, serum phosphate kinetics over dialysis and post dialysis periods in children appear to be misleading for the quantification of phosphate removal, i. e., phosphate clearance is a poor indicator of dialytic phosphate removal. Received September 21, 1995; received in revised form and accepted June 11, 1996