Effects of a new pteridine derivative on urinary sodium, potassium and magnesium excretion in conscious saline-loaded rats.

1. Two recently synthesized pteridine derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.     

Effect of middle ear effusion on the vestibular labyrinth.

Although middle ear effusion was once described as the most common cause of vestibular disturbance in children, the association between glue ear and symptoms of dysequilibrium has never been quantified objectively. In this study the effect of middle ear effusion on the vestibular system of the inner ear was studied in a select group of children suffering from long lasting effusion in the middle ear with no evidence of infection at least one year prior to the study. The results were compared with results obtained from otitis free children, as well as from examinations of children after the insertion of ventilating tubes. The results of this study confirm the assumption that middle ear effusion has an adverse effect on the vestibular system, which can be resolved following the insertion of ventilation tubes. This effect may also contribute to the adverse effect that otitis media has on a child's development.     

Effect of colchicine on T cell subsets of healthy volunteers

We examined the effect of oral colchicine (1-2 mg/day) on four healthy volunteers' T cell subsets. Colchicine significantly (P less than 0.01) decreased the mean (+/- SD) percent of OKT3+ total T cells (from 70 +/- 16 to 47 +/- 13), OKT4+ helper/inducer T cells (from 44 +/- 9 to 24 +/- 6), and OKT8+ suppressor/cytotoxic T cells (from 27 +/- 7 to 17 +/- 7), but did not significantly affect the OKT4:OKT8 ratio (from 1.64 +/- 0.21 to 1.48 +/- 0.45) or concanavalin A-induced suppressor cell function (from 44 +/- 9% to 47 +/- 13%). Thus, colchicine non-selectively decreased the circulating helper/inducer and suppressor/cytotoxic T cells.     

Tonic inhibition of neuronal calcium channels by G proteins removed during whole-cell patch-clamp experiments

The barium current through voltage-dependent calcium channels was recorded from cultured rat cortical neurons with the whole-cell configuration of the patch-clamp technique. The maximal current evoked by depolarising pulses from –80 mV to 0 mV was divided into inactivating and non-inactivating fractions. During the first minutes of whole-cell recording, the amplitude of the inactivating fraction increased from less than 0.1 nA to an average value of 1 nA, whereas the amplitude of the non-inactivating component remained essentially the same. This increase in amplitude was prevented when the perforated-patch technique was used, suggesting that some intracellular factor that inhibited the barium current was lost or destroyed during conventional whole-cell experiments. When GTP[-S] or GTP was added to the pipette solution, no increase or only a weak rise of the inactivating current was seen, whereas GDP[-S] accelerated its increase. The results suggest that some of the calcium channels expressed in cultured cortical neurons are inhibited by a G protein even in the absence of added neurotransmitter. The current increase observed during whole-cell recordings may be due to a loss of intracellular GTP and the subsequent inactivation of an inhibitory G protein.     

Biodegradation of Titanium Implants After Long-Time Insertion Used for the Treatment of Fractured Upper and Lower Jaws Through Osteosynthesis: Element Analysis by Electron Microscopy and EDX or EELS

Twelve patients underwent an osteosynthesis with titanium to treat upper and lower jaw fractures. Six to 12 months later, the miniplates were removed. Tissue samples were analyzed by light and electron microscopy for detection of a metallosis. The analysis showed new bone formation like callus tissue around the miniplates. In some cases small, rounded deposits and accumulation of colloid-like particles located next to bigger titanium artifacts were detected in the cytoplasm of histiocytes and in the matrix of connective tissue. The titanium was identified by elemental analysis using EDX in SEM as well as by EELS and electron diffraction in TEM. Both kinds of particles contain titanium, but they seem to be different in composition and derivation. The bigger particles seem to consist of metallic titanium and sourced by working on the metallic implants during the implantation itself. On the other hand, the colloidal-like, small, rounded particles in tissue macrophages and outside the cells in the matrix of connective tissue are presumably of other origin; for example, they could be derived from biodegradation and chemical conversion of the metallic implants. The titanium miniplates were examined before and after implantation by using ESCA technique and revealed metallic titanium and different compositions with other elements. The amount of titanium load of the tissue was very low in most cases and presumably not of biomedical relevance.     

Clopidogrel tapering as a strategy to attenuate platelet rebound phenomenon in patients with bare-metal stents

Early clustering of adverse cardiovascular events after abrupt cessation of clopidogrel has been reported in patients with acute coronary syndromes. A platelet rebound phenomenon may contribute to this increased thrombotic risk and a gradual drug tapering may attenuate this proposed platelet effect. Accordingly, we aimed to assess the effect of clopidogrel tapering on platelet reactivity. Twenty patients who underwent elective percutaneous coronary interventions with bare metal stents receiving 3 months of clopidogrel therapy (75 mg daily) were randomized to either of two discontinuation strategies: (1) Off group–abrupt drug cessation or (2) Tapering group–receiving clopidogrel 75 mg every other day for 4 weeks duration. Light transmission aggregometry, induced by ADP (5 and 10 μM) and collagen, was measured at four time-points (at baseline and 2, 4 and 6 weeks after randomization). In the off group, there was an early rise in platelet reactivity at 2 weeks after abrupt drug cessation compared to baseline, as measured by ADP 5 μmol/l (39.6 ± 2.8 vs. 67.9 ± 6.0, P < 0.001). The tapering regimen suppressed this rebound platelet aggregation by ADP 5 μmol/l at 2 weeks (P = 0.001) and 4 weeks (P = 0.001). Similar results were found with ADP 10 μmol/l and collagen agonists. Abrupt cessation of clopidogrel results in an early rise in platelet aggregability in patients with BMS that is attenuated by a tapering regimen. Clopidogrel administration every other day may achieve similar levels of platelet inhibition as full dose therapy. Further investigations evaluating clopidogrel tapering strategies and their potential clinical impact are warranted.