Kappa-opioid-receptor agonists modulate the renal excretion of water and electrolytes in anaesthetized rats.

1. Subcutaneous injection of the kappa-opioid agonists U50,488 (10 mg kg-1) and tifluadom (3.5 mg kg-1) into Inactin-anaesthetized, saline-infused rats was associated with a diuresis, antinatriuresis and antikaliuresis which lasted for up to 2 h. A high (5 mg kg-1), but not low (0.1 mg kg-1), dose of naloxone blocked the renal effects of U50,488. 2. U50,488 administration in anaesthetized, vasopressin-deficient Brattleboro DI rats was associated with an attenuated diuresis, though the antinatriuretic response remained intact. 3. The diuretic action of U50,488 was associated with an increase in glomerular filtration rate while fractional fluid reabsorption remained steady. In contrast, fractional sodium and potassium reabsorption were increased. 4. These data suggest that kappa-opioid agonists alter renal handling of both water and electrolytes. This appears to be mediated by two separate mechanisms: increased fluid loss largely reflects altered glomerular events while the fall in electrolyte excretion results from altered tubular handling.     

In vitro effects of detergent sclerosants on coagulation, platelets and microparticles.

OBJECTIVES: To investigate the in vitro effects of Sodium Tetradecyl Sulphate (STS) and Polidocanol (POL) on clotting tests, clotting factors, platelets and microparticles. MATERIALS AND METHODS: Platelet rich (PRP) and platelet poor (PPP) plasmas were incubated with varying concentrations of STS and POL. Clotting tests, platelet/plasma turbidity, and microparticle studies were performed. Specimens were mixed with individual factor deficient plasmas and clotting factor activities were studied. RESULTS: STS at high concentrations (>0.3%) destroyed platelets, microparticles and the clotting factors V, VII and X. It prolonged all clotting tests including prothrombin time (PT), activated partial thromboplastin time (APTT), non-activated partial thromboplastin time (NAPTT), thrombin time (TT), factor Xa clotting time (XACT) and surface activated clotting time (SACT). Higher concentrations of POL were required to achieve some anticoagulant activity. Low sclerosant concentrations shortened XACT and SACT, and induced release of procoagulant platelet derived microparticles. Increased exposure time resulted in increased procoagulant activity. STS at concentrations higher than 0.5% precipitated a complex containing apolipoprotein b and fibrinogen. CONCLUSIONS: Detergent sclerosants affect the clotting mechanism by interfering with clotting factor activities, procoagulant phospholipids and platelet derived microparticles. STS has more anticoagulant activity than POL in high concentrations. Low concentration sclerosants demonstrate procoagulant activity.     

EFFECT OF CROSS-FOSTERING ON NEONATAL SODIUM BALANCE AND ADULT BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. The aim of the present study was to compare electrolyte handling in naturally reared neonatal spontaneously hypertensive rats (SHR) with those reared by a Wistar-Kyoto (WKY) rat foster mother (denoted SHRX), as cross-fostering SHR pups to a WKY rat dam lowers adult blood pressure in the SHR. 2. The electrolyte content of WKY rat and SHR dams’ milk was determined and electrolyte intake and urinary excretion rates were calculated in both naturally reared and cross-fostered WKY rat and SHR pups. 3. The milk sodium concentration fell in both strains (WKY rat: 31.8 ± 2.0 to 15.2 ± 1.2 mmol/L; SHR 31.9 ± 2.5 to 18.2 ± 1.6 mmol/L; P < 0.001), as did potassium (P < 0.001), over lactation, but there were no differences between strains. Calcium and magnesium concentrations increased (P< 0.001), although SHR dam's milk contained less calcium (P < 0.001) than that of WKY rat dams during the third week of lactation. 4. Spontaneously hypertensive rat pups ingested less milk (P<0.05) than WKY rat pups; therefore, their cumulative sodium intake over postnatal days 4–15 was significantly lower than that of WKY rat pups (WKY rat vs SHR: 84.4 ± 3.6 vs 59.7 ± 2.6 μmol/g bodyweight, respectively; P < 0.05) and fostered SHRX pups (77.7 ± 7.0 μmol/g bodyweight; P < 0.05). Potassium and magnesium intakes were comparable between SHR, WKY rat and SHRX pups, but SHR pups ingested significantly less calcium than either WKY rat pups (136.1 ± 6.4 vs 200.1 ± 9.5p, mol/g bodyweight, respectively; P<0.05) or SHRX pups (200.0 ± 18.0 μmol/g bodyweight; P<0.05). 5. These data show that the neonatal SHR experiences a period of sodium deficiency during the developmental stage when cross-fostering is effective in lowering blood pressure. This is consistent with the reported up-regulation of the renin-angiotensin system observed in SHR at this time and may have a long-term influence on blood pressure.     

Impact of automatic orders to discontinue vancomycin therapy on vancomycin use in an antimicrobial stewardship program.

We examined the possible unintended consequences of a 72-hour automatic order to discontinue vancomycin therapy in an antimicrobial stewardship program (ASP). Of 120 patients, 11 had vancomycin therapy discontinued at 72 hours without a call to the ASP, and 7 experienced a treatment interruption of 6-36 hours. All discontinuation of therapy was considered appropriate, and the 7 treatment interruptions did not have clear clinical consequences. Only one-third of patients had ASP stickers that warned of impending discontinuation of vancomycin therapy placed appropriately in the medical record.