Cardiovascular effects of conventional sulfonylureas and glimepiride

Sulfonylureas have, in the past, been reported to have adverse cardiovascular effects. Glimepiride is a new sulfonylurea. In spite of stimulating less insulin secretion, it has, depending on the species, equal or higher blood glucose decreasing activity and according to preliminary studies less cardiovascular activity than glibenclamide. Further studies were performed to confirm the lower cardiovascular activity of glimepiride. The IC50 for inhibition of rilmakalim-activated KATP channel currents in isolated ventricular myocytes was 31.6 nM for glimepiride and 6.8 nM for glibenclamide. In endotoxin shock-rats at a dose of 1 x 2 mg/kg i.v., glibenclamide induced a significantly higher blood pressure increase than glimepiride. At two i.v. doses of 20 mg/kg 4 min apart, in normal rats, glibenclamide produced signs of ischemia in the ECG in nearly all animals, glimepiride almost none, in diabetic rats, glibenclamide produced in all animals a lethal cardiogenic shock preceeded by serious ECG changes, glimepiride only in one fifth of the animals. In open-chest dogs, on intracoronary infusion of equieffective blood glucose-lowering doses, glibenclamide, gliclazide and glimepiride all reduced coronary blood flow, increased coronary resistance, depressed the mechanical activity of the heart, enhanced myocardial O2-extraction, reduced the serum potassium level and induced a moderate endocardial ST-segment elevation, but glimepiride to a significantly less extent than glibenclamide and gliclazide. The presented data confirm that glimepiride at equivalent blood glucose decreasing doses has less cardiovascular activity than conventional sulfonylureas.     

Alumina scale growth at zirconia-MCrAlY interface: a microstructural study

High-temperature oxide scale growth at the ceramic-metal interface is a major contributor to the thermomechanical resistance of thermal barrier coatings for hot stages of gas turbines. In order to better understand this phenomenon, microstructural observations of the alumina scales formed at 1100 and 1200 °C under air, between low-pressure plasma-sprayed NiCrAlY and air plasma-sprayed ZrO₂-8.5 wt % Y₂O₃, have been performed by classical and analytical transmission electron microscopy on transverse thin foil specimens. The evolution of the oxide grain morphology from the metal-oxide to the oxide-oxide interface suggests that the scale growth principally takes place at the metal-oxide interface. Segregation of yttrium at oxide grain boundaries has been detected as well as significant quantities of zirconium inside the alumina grains. The oxide growth seems to be dominated by a classical grain-boundary oxygen diffusion mechanism. The presence of zirconium inside the alumina grains also suggests that Al₂O₃ partially forms by chemical reduction of ZrO₂ by AI. The comparison between the microstructures observed and that of alumina scales grown under similar conditions on bare MCrAlY alloys gives some insight into how the ceramic top-coat modifies NiCrAlY high-temperature oxidation mechanisms.     

Genetic diversity among clinical and environmental isolates of Aspergillus fumigatus

To determine if cases of invasive aspergillosis (IA) were caused by strains of Aspergillus fumigatus with unique characteristics, strains from immunosuppressed patients with IA were compared to strains obtained from sputa of patients with cystic fibrosis and to strains from the environment. An extremely high genomic diversity was observed among the 879 strains typed by Southern blotting with a retrotransposon-like element from A. fumigatus (C. Neuvéglise, J. Sarfati, J. P. Latgé, and S. Paris, Nucleic Acids Res. 24:1428-1434, 1996). Analysis of Southern blot hybridization patterns showed the absence of clustering between environmental isolates and clinical isolates from patients with IA or cystic fibrosis. In addition, strains could not be clustered depending on their geographical location. This study implies that practically any strain of A. fumigatus is potentially pathogenic and can provoke a case of IA when it encounters a favorable environment in an immunosuppressed host.     

Laparoscopic distal resection of the pancreas with the preservation of the spleen

Management of the pancreatic diseases is still a challenge to the laparoscopic technique. Some experience has been gained in the laparoscopic exploration of the pancreas and staging in cancer. Anatomically the accessibility of the distal pancreas provides the laparoscopic approach technically feasible. Patient and method: A case of insuloma in the tail of the pancreas is presented, where distal pancreatic resection was performed laparoscopically with the preservation of the spleen. In a 55 years old female patient with typical clinical symptoms of hyperinsulinism CT identified a 3 cm large solid tumor in the tail of the pancreas. Complete mobilization of the distal pancreas was enhanced by the use of an ultrasonic dissector (UltraCision). The pancreas is detached from the splenic hilum after dividing the spleen vessels. The pancreas is transected proximally by laparoscopic linear stapler. Preservation of the short gastric vessels provides the necessary blood supply of the spleen following division of the splenic artery and vein. Thus removal of the spleen is not a necessary step in this procedure. The operation was carried out within 4.5 hours. Postoperative course was uneventful, the patient left the hospital on the 5th postoperative day. Advantages of the procedure were the earlier mobilization and shorter recovery time, less postoperative pain. The procedure can be safely performed with a good experience in both pancreatic and laparoscopic surgery.     

A method for dynamic measurement of the resistance to dry heat exchange by footwear

Five different types of cold protective footwear have been tested with regard to their resistance to dry heat loss (i.e. the insulation) with a new electrically heated foot model. The model is able to simulate 'walking' movements in order to provide a more realistic simulation of wear conditions. Thermal insulation of shoes with and without a steel toe cap was the same. The insulating properties during simulated walking movements were 10-25% lower compared with static conditions. For two of the shoe models a significantly lower insulation value for the sole area was obtained when adding a weight of 30 kg. A significant difference could also be found between the insulation values of two different sizes of one of the models. Measurements with the standard method (EN 344) correlated well with the local insulation value of the sole part of the thermal foot. Correlation with the insulation value for the whole shoe was much less, variation was bigger and ranking in terms of cold protection differed between methods. The electrically heated foot model appears to provide a reproducible, accurate and more realistic method for measuring the insulation properties of shoes than EN 344.     

Inhibiting effects of serotonin and serotonin antagonists on the migration of mononuclear leucocytes

The effect of serotonin and the serotonin antagonists ketanserin, methiotepine and ICS-205-930 on the migration of leucocytes was studied by using the sealed capillary migration technique. The migration of mononuclear leucocytes was inhibited by serotonin at 10(-4) and 10(-6)-10(-10)mol/l. An inhibition of the mononuclear leucocyte migration was also caused by ICS-205-930 at 10(-4)mol/l, ketanserin at 10(-4) and 10(-8)-10(-10)mol/l and methiotepine at 10(-4) and 10(-6)-10(-8)mol/l. No inhibiting effects of serotonin or the serotonin antagonists were found on the migration of polymorphonuclear leucocytes. Thus, both serotonin and serotonin antagonists may inhibit mononuclear leucocyte migration.     

Surgical management of congenital high vaginal atresia

In the past 15 years five neonates and children have been treated for high vaginal atresia at the Surgical Unit of Department of Pediatrics, University Medical School, Pécs, Hungary. In three of the six patients distal atresia of the vagina was found (Type III). Two of the three were neonates and had a large hydrometrocolpos and the third, a 13-year-old girl, hematometrocolpos. In the fourth patient the vaginal atresia was associated with cloacal and anorectal malformation (Type V). In the fifth there was a duplication of uterus and vagina; however, only one of the two vaginas was atretic. In three patients a pull-through of the vagina was carried out, in one of them according to Pena, in another a transvesical approach, as suggested by Monfort, was used. Following repeated surgeries in the patient with cloacal malformation the vagina was replaced with large intestine. In the case of duplication of vagina and uterus one half of the duplication was removed.     

A one-site, two-state model for the binding of anions in photosystem II

Photosystem II membranes, dialyzed against a Cl(-)-free buffer to remove bound Cl-, lost about 65% of the control activity. A light-intensity study of the Cl(-)-free membranes showed that all PS II centers were able to evolve oxygen at about 35% of the control rate when measured in Cl(-)-free medium. The Cl(-)-depleted membranes were immediately (< 15 s) reactivated to 85-90% of the original activity by the addition of fairly high concentrations of Cl- (Kd = 0.5 mM), but both Cl- and the activity were promptly lost when the membranes immediately after reactivation were diluted in a Cl(-)-free medium. However, stabilization of Cl(-)-binding could be accomplished by prolonged incubation in the presence of Cl-. The transition to stable binding, followed using 36Cl-, occurred over several minutes. The stable binding was further characterized by a Kd of 20 microM and a t1/2 for dissociation of about 1h [Lindberg et al. (1993) Photosynth. Res. 38, 401-408]. The effects on S2 signals of removal of Cl- were studied using EPR. The depletion of Cl- was accompanied by a shift in intensity toward the g = 4.1 signal at the expense of the multiline signal. When Cl- or Br- but not F- was added to the depleted PS II membranes, the original distribution of the signals was immediately (< 30 s) restored. We propose that Cl(-)-binding responsible for high oxygen-evolution activity and normal EPR properties of the S2 state may occur either as high affinity (Kd = 20 microM) and slowly exchanging (t1/2 = 1 h), or as low affinity (Kd = 0.5 mM) and rapidly exchanging (t1/2 < 15 s). Our results suggest that Br- but not F- has a mode of binding similar to that of Cl-. The high-affinity state is the normal state of binding, but once Cl- has been removed, it will first rebind as low-affinity, rapidly exchanging followed by conversion into a high-affinity, slowly exchanging mode of binding.