Halothane and Isoflurane Differentially Affect the Regulation of Dopamine and Gamma-aminobutyric Acid Release Mediated by Presynaptic Acetylcholine Receptors in the Rat Striatum

Background: General anesthetics are thought to produce their hypnotic effects mainly by acting at ligand-gated ionic channels in the central nervous system (CNS). Although it is well established that volatile anesthetics significantly modify the activity of the acetylcholine nicotinic receptors of the neuromuscular junction, little is known about their actions on the acetylcholine receptors in the CNS. In this study, the effects of halothane and isoflurane on the regulation of dopamine (DA) (gamma-aminobutyric acid [GABA]) depolarization-evoked release mediated by nicotinic (muscarinic) presynaptic receptors were studied in the rat striatum.

Methods: Assay for GABA (dopamine) release consisted of3 H-GABA (sup 3 H-DA)-preloaded synaptosomes with artificial cerebrospinal fluid (0.5 ml/min, 37 degrees Celsius) and measuring the radioactivity obtained from 1-min fractions for 18 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of depolarizing agents combined with vaporized halothane and isoflurane (0.5-5%, 5 min), and finally with no pharmacologic stimulation (5 min). The depolarizing agents were potassium chloride (KCl; 9 mM) alone or with acetylcholine (10 sup -6 - 10 sup -4 M) and/or atropine (10 sup -5 M) for experiments with3 H-GABA, and KCl (15 mM) and nicotine (10 sup -7 - 5 x 10 sup -4 M) alone or with mecamylamine (10 sup -5 M) for experiments with3 H-DA.

Results: Potassium chloride induced a significant, Ca2+ -dependent release of both3 H-GABA and3 H-DA. Nicotine produced a concentration-related, mecamylamine-sensitive3 H-DA release that was significantly attenuated by nicotine (10 sup -7 M) preincubation. Acetylcholine elicited a dose-dependent, atropine-sensitive reduction of the KCl-evoked3 H-GABA release. Halothane and isoflurane significantly decreased the nicotine-evoked3 H-DA release but had only limited depressant effects on the KCl-stimulated3 H-DA and no action on the KCl-induced3 H-GABA release. The effects of acetylcholine on3 H-GABA release were reversed by halothane but not by isoflurane.     

Does an Arthroscopic Suture Bridge Technique Maintain Repair Integrity?: A Serial Evaluation by Ultrasonography

Biomechanical studies suggest a suture bridge technique enhances rotator cuff tendon footprint contact area, holding strength, and mean contact pressure. Based on these studies, we asked whether (1) the suture bridge technique would provide a high rate of cuff integrity after surgery, (2) the status of the repaired cuff would change with time, (3) preoperative factors could predict postoperative cuff integrity, and (4) patients with retears had less favorable pain, functional scores, range of motion (ROM), and muscle strength compared with those with intact repairs. We prospectively followed 78 patients with arthroscopic repairs in whom we used the suture bridge technique. The integrity of the rotator cuff repair was determined using ultrasonographic evaluation at 4.5 and 12 months after surgery. Ultrasonography revealed intact cuffs in 91% at 4.5 months postoperatively, all of which were maintained at the 12-month followup. Failure rates were 17.6% (three of 17) for massive tears, 11.1% (two of 18) for large tears, 6.3% (two of 32) for medium tears, and no failures for small tears. Preoperative fatty degeneration of the supraspinatus muscle was a strong predictor of cuff integrity. We found no correlation between the integrity and clinical outcomes except for a temporary decrease of abduction strength at 6 months. Arthroscopic repair using suture bridge technique can achieve a low retear rate in shoulders treated for rotator cuff tears, but the occurrence of retear did not influence the outcome.     

Immunoassay for soluble RANKL (receptor activator of NF-kappaB ligand) in serum

This paper describes a method for the direct measurement of human sRANKL (receptor activator of NF-kappaB ligand), a cytokine of the tumor necrosis factor superfamily, which is a key player in bone metabolism. Its role in the regulation of osteogenic disorders such as osteoporosis, Paget's disease and rheumatoid arthritis is being extensively discussed in the literature at present. We developed a highly specific, simple and reliable ELISA which allows the direct measurement of uncomplexed sRANKL in human serum. Assay characteristics such as analytical precision, sensitivity, interfering factors, sample stability and dilution linearity are shown. Reference values from healthy volunteers (n=57) were found to be between 0 and 2.7 pmol/l (10th-90th percentile) with a mean serum value of 1.3 pmol/l (median 0.9 pmol/l).     

Altered monocyte cyclooxygenase response to lipopolysaccharide in type 1 diabetes

Type 1 diabetes is caused by adaptive immune responses, but innate immunity is important because monocytes infiltrate islets. Activated monocytes express cyclooxygenase (COX)-2, promoting prostaglandin-E(2) (PGE(2)) secretion, whereas COX-1 expression is constitutive. We aimed to define monocyte COX expression in type 1 diabetes basally and after lipopolysaccharide (LPS) stimulation. Isolated CD14(+) monocytes were analyzed for COX mRNA and protein expression from identical twins (discordant for type 1 diabetes) and control subjects. Basal monocyte COX mRNA, protein expression, and PGE(2) secretion were normal in type 1 diabetic subjects. After LPS, twins and control subjects showed a COX mRNA isoform switch with decreased COX-1 mRNA (P < 0.01), increased COX-2 mRNA (P < 0.01), and increased COX-2 protein expression (P < 0.01). Compared with control subjects, both diabetic and nondiabetic twins showed greater LPS-induced downregulation of monocyte COX-1 mRNA (P = 0.02), reduced upregulation of COX-2 mRNA and protein (P < 0.03), and greater inhibition by the COX-2 inhibitor di-isopropylfluorophosphate (DFP) of monocyte PGE(2) (P < 0.007). We demonstrate an alteration in monocyte COX mRNA expression as well as monocyte COX-2 and PGE(2) production after LPS in type 1 diabetic patients and their nondiabetic twins. Because COX-2 response to LPS is proinflammatory, an inherited reduced response would predispose to chronic inflammatory diseases such as type 1 diabetes.     

Treatment of periodic limb movements in sleep with selegiline HCl.

Thirty-one patients undergoing treatment with selegiline HCl for periodic limb movements in sleep (PLMS) were examined with respect to specific sleep composition in a retrospective study. Pre- and post-treatment overnight polysomnographs revealed a highly significant decrease in the number of PLMS per hour of total sleep time (P < 0.0005). The alerting effect associated with selegiline was not found to have significant effect on patients' sleep efficiency or sleep-onset latency (P > 0.10). As controversy continues regarding the medicated treatment of PLMS, our findings with selegiline point to an alternative for clinicians to consider.