Formation of thrombin-antithrombin III complex using polyamide and hemophan dialyzers.

The recently developed ELISA for the thrombin-antithrombin III complex (TAT) is a sensitive, specific, and simplified means of detecting intravascular coagulation. For further evaluation of the thrombogenicity of a polyamide (P) and a Hemophan (H) hollow-fibre dialyzer a cross-over study was done in ten stable patients on maintenance hemodialysis. At the same doses of heparin (mean bolus of 30 U/kg bw and maintenance doses of 86 U/kg bw), thrombin time and partial thromboplastin time were significantly lower using H. At the end of dialysis TAT was significantly higher in H (mean +/- SEM before HD 3.57 +/- .56, at 240 min 14.9 +/- 6.5 ng/ml, p less than 0.05, Wilcoxon-test) than in P (before HD 4.36 +/- .98, at 240 min 8.95 +/- 3.0 ng/ml, p less than 0.05 H 240 vs. P 240, Wilcoxon-test). Visible clotting was more pronounced in the H filter. Among other favourable features of blood compatibility the polyamide/polyvinylpyrrolidone copolymer with a hydrophilic/hydrophobic microdomain structure has less thrombogenicity. The modified cellulosic membrane H has advantages in complement activation and leukocyte depression, but thrombogenicity seems less favourable since the incorporated diethyl-amino-ethyl groups with their positive charge bind and inactivate negatively charged heparin.     

The characterization and localization of the glutamate receptor subunit GluR1 in the rat brain.

The cloning of cDNAs that encode functional glutamate receptors makes it possible to produce antibodies that can be used as high-affinity probes for the localization and characterization of these receptors in the mammalian brain. We have made antibodies to different regions of the first cloned member of this family, GluR1, using bacterially overproduced antigen. On Western blots, these antisera detect glycoprotein(s) of 105 kDa present in crude membranes of the hippocampus and cerebellum. The 105-kDa band is associated with postsynaptic densities, and it is observed in cultured cells upon transfection with the GluR1 cDNA. Although glutamate receptors are thought to be the most prevalent excitatory ligand-gated ion channel in the mammalian brain, immunohistochemistry reveals that the receptors recognized by these antisera are localized predominantly in neurons of the cerebellum and some structures of the limbic system, including the hippocampus, the central nucleus of the amygdala, and portions of the septum. This pattern of expression is, in general, consistent with the distribution of GluR1 mRNA as determined by in situ hybridization histochemistry. Our results suggest that glutamate excitatory circuits recognized by these antisera are predominantly found in regions of the limbic system that are reciprocally interconnected.     

Über die „Vitamin-sparende Wirkung“ des Sorbits beim Menschen

Journal of Molecular Medicine -     

Relationship between swimming velocity and lactic concentration during continuous and intermittent training exercises

The present study examined the relationship between lactic acid concentration in capillary blood and swimming velocity during 11 typical endurance exercises (continuous swimming for 30 and 60 min, interval swimming with distances between 50 and 400 m, and with rest periods of 10 and 30 s) and during the "two-speed test" recently described by Mader. It was expected that a better understanding of these relationships could provide evidence how to adjust training intensities from results obtained during the two-speed test. Fifty-nine male swimmers of the German national level participated in this study. After a 30-min maximal swimming test, a mean lactic acid concentration of 4.01 +/- 0.75 mmol/l was found. The corresponding mean velocity was similar to the speed (V4) calculated for the 4 mmol/l level on the basis of the results obtained during the two-speed test (2 X 400). During 30 min continuous swimming at 95% to 105% of the velocity V4, there was a significant correlation (r = 0.82, P less than 0.001) between the swimming speed and the lactic acid concentration. In the 30-min maximal test, the velocity V4 correlated significantly with both the lactic acid concentration (r = -0.58, P less than 0.005) and the swimming speed (r = 0.97, P less than 0.001). During the interval exercises with rest periods of 10 s, the swimming velocities corresponding to the same lactic acid level as during continuous swimming, increased for the 50, 100, 200, and 400 m by 11.23%, 4.21%, 2.95%, and 2.02% of V4, respectively. With rest periods of 30 s, the swimming velocity for the 100, 200, and 400 m increased by 7.34%, 4.22%, and 3.01% of V4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Survivorship and Patient-Reported Outcomes of an Uncemented Vitamin E–Infused Monoblock Acetabular Cup: A Multicenter Prospective Cohort Study

BackgroundAddition of vitamin E to polyethylene is theorized to reduce the potential for oxidative wear in acetabular components. This paper presents a multicenter prospective cohort study that reports on outcomes from use of a Vitamin E–infused highly cross-linked polyethylene acetabular cup.MethodsPatients were recruited across nine medical institutions. Clinical outcome measures recorded were the Harris Hip Score, visual analogue score for pain and satisfaction. Evidence of implant loosening or osteolysis was collected radiologically. Cup survival and reasons for revision in relevant cases were also recorded. Data collection was undertaken preoperatively, at 6-12 weeks, 6 months, 1 year, 2 years, and 5 years. A total of 675 patients were recruited, with 450 cases available at final review. Data regarding cup survival was available to 8 years and 9 months postoperatively.ResultsImprovements in both the Harris Hip Score and visual analogue score for pain and satisfaction were recorded at all time points, with these being maintained through the length of follow-up. In total, 89% of cups were implanted within the Lewinnek safe zone. A lucent line was identified in one case, with no evidence of acetabular osteolysis observed throughout the follow-up period. Cup survival was 98.9% at 8 years and 9 months. No revisions for aseptic loosening were observed.ConclusionsThe use of a vitamin E–infused polyethylene acetabular cup demonstrates reassuring patient-reported outcomes, radiological measures, and cup survival at medium to long-term follow-up.     

Local anesthetic inhibition of m1 muscarinic acetylcholine signaling

BACKGROUND: Local anesthetics inhibit lipid mediator signaling (lysophosphatidate, thromboxane) by acting on intracellular domains of the receptor or on the G protein. On receptors for polar agonists, the ligand-binding pocket could form an additional site of interaction, possibly resulting in superadditive inhibition. The authors therefore investigated the effects of local anesthetics on m1 muscarinic receptor functioning. METHODS: The authors expressed receptors in isolation using Xenopus oocytes. Using a two-electrode voltage clamp, the authors measured the effects of lidocaine, QX314 (permanently charged), and benzocaine (permanently uncharged) on Ca2+-activated Cl- currents elicited by methylcholine. The authors also characterized the interaction of lidocaine with [3H] quinuclydinyl benzylate ([3H]QNB) binding to m1 receptors. RESULTS: Lidocaine inhibited muscarinic signaling with a half-maximal inhibitory concentration (IC50 18 nm) 140-fold less than that of extracellularly administered QX314 (IC50 2.4 microm). Intracellularly injected QX314 (IC50 0.96 mm) and extracellularly applied benzocaine (IC50 1.2 mm) inhibited at high concentrations only. Inhibition of muscarinic signaling by extracellularly applied QX314 and lidocaine was the result of noncompetitive antagonism. Intracellularly injected QX314 and benzocaine inhibited muscarinic and lysophosphatidate signaling at similar concentrations, suggesting an action on the common G-protein pathway. Combined administration of intracellularly injected (IC50 19 microm) and extracellularly applied QX314 (IC50 49 nm) exerted superadditive inhibition. Lidocaine did not displace specific [3H]QNB binding to m1 receptors. CONCLUSIONS: m1 Muscarinic signaling is inhibited by clinically relevant concentrations of lidocaine and by extracellularly administered QX314, suggesting that the major site of action is a extracellular domain of the muscarinic receptor. An additional less potent but superadditive inhibitory effect on the G-protein is suggested.     

The Redox Modulating Sonlicromanol Active Metabolite KH176m and the Antioxidant MPG Protect Against Short-Duration Cardiac Ischemia-Reperfusion Injury

Cardiovascular Drugs and Therapy - Sonlicromanol is a phase IIB clinical stage compound developed for treatment of mitochondrial diseases. Its active component, KH176m, functions as an antioxidant,...