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.     

Management of E. coli dependent factorial diseases in weaning piglets

The most important postweaning factorial diseases are at least partly caused by E. coli. The term postweaning coli complex can be subcategorized into the following manifestations: postweaning diarrhoea, edema disease, postweaning wasting and hemorrhagic gastroenteritis. In the presented study the effect of prophylactic zootechnique alone and zoo- and biotechnique in combination was evaluated during the first weeks postweaning. The results showed that combined zoo- and biotechnique is superior to simple zootechnique regarding food conversion (1.41 kg versus 1.73 kg), average daily weight gain (390 g versus 325 g) and postweaning piglet mortality (3.1% versus 4.9%). It is the opinion of the authors that combined postweaning zoo- and biotechnique should be performed in such pig production units where ETEC and/or SLTEC are present.     

The relationship of IL-6 to hormonal mediators, fuel utilization, and systemic hypermetabolism after surgical trauma

OBJECTIVES: To define the relationship between inflammatory cytokines, hormonal mediators, alteration of energy substrate and hypermetabolism during the early phase after surgical trauma. DESIGN: A prospective case-control study of 13 patients underwent elective surgery for carcinoma between November 1993 and January 1995. MATERIALS AND METHODS: They received parenteral supply of adequate glucose and amino acids through central venous catheter after surgery equally. Inflammatory cytokines such as TNF- alpha, IL-1 and IL-6, stress hormones such as norepinephrine, glucagon and insulin, and fuel utilization and hypermetabolism variables such as resting energy expenditure (REE), CRP, free fatty acid, respiratory quotient, the calculated rates of glucose and fat oxidation using indirect calorimetry were measured serially (the day before operation, the end of surgery, and postoperative day (POD) 1, 2 and 5). MEASUREMENTS AND MAIN RESULTS: TNF- alpha and IL-1 were not detected during the study period. Initial elevation and steady decline of IL-6 concentrations were seen after surgical injury, and this response related significantly to post-operative norepinephrine and glucagon levels throughout the study period, and to insulin levels only at the end of surgery. %REE (REE/BEEHB; basal energy expenditure according to the Harris-Benedict equation) on POD 2 and 5, and all CRP levels after surgery were significantly related to IL-6 levels more than hormone levels. Fuel utilization variables on POD 2 were related to both IL-6 and hormone levels. CONCLUSIONS: Initial elevation of IL-6 concentration might induce stress hormones such as norepinephrine and glucagon, but not insulin after surgical trauma. Moreover not only hormonal mediators but also cytokine such as IL-6 are responsible for the development of the stress response of the alteration of energy substrate and hypermetabolism.     

Functional palatoraphy and modified genioplasty in obstructive sleep apnea

10 patients with obstructive sleep apnea syndrome (OSAS) have been treated with the new surgical procedure functional palatoraphy and modified genioplasty. 5 months after surgery 7 patients with an apnea hypopnea index under 10 were cured. Three therapy refractory patients were all overweight with a body mass index of more than 29 kg/m2. Excessively overweight patients should therefore not be operated. Following the selection criteria we introduced an effective new treatment method for OSAS.     

Tyrosine phosphorylation in peripheral lymphocytes from patients with systemic lupus erythematosus

A comparative study of tyrosine phosphorylation was performed on peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients and from healthy donors. Freshly isolated SLE lymphocytes presented an elevated tyrosine phosphorylation level when compared to healthy donors lymphocytes (p = 0.005). Among all phosphorylated proteins, those called p120, p110, p80 and p55-p60 were more phosphorylated. The level of tyrosine phosphorylation of p120 and p110 proteins discriminated significantly (p = 0.0048, respectively, p = 0.02) between SLE patients and healthy donors. Lymphocytes form SLE patients and healthy donors were then stimulated by cross-linking T cell antigens (CD3, CD4, CD8) to further distinguish the signal transduction between normal and pathologic lymphocytes. No statistical differences in the tyrosine phosphorylation pattern, following CD4 or CD8 cross-linking, were observed between SLE patients and healthy donors lymphocytes. CD3 cross-linking induced an effect on tyrosine phosphorylation different in SLE patients versus healthy donors lymphocytes. Thus, the lymphocytes of SLE patients were refractile in anti-CD3 stimulation in comparison with the healthy donors lymphocytes. Chi-square analysis demonstrated that a significantly larger number of healthy donors responded to anti-CD3 stimulation compared to SLE patients (p = 0.03). The high frequency of tyrosine phosphorylation of p110 and p80 proteins, following CD3 stimulation, in normal versus SLE lymphocytes, suggested that these proteins could be involved in abnormal signal transduction in SLE cells.     

Mechanical behavior of double-aged AA8090

The short-transverse fracture toughness of AA8090 is dramatically improved by double aging treatments, which produce a transition from coarse planar slip to homogeneous deformation. Although the fracture mode remains intergranular, stress concentrations across the weak, highangle boundaries are reduced by homogeneous deformation, ultimately increasing fracture toughness. This behavior is attributed to dissolution of the shearable phase(δ’) and growth of the strong precipitate (S’). Predictions of slip distribution agree fairly well with observed deformation behavior. A number of tempers with improved strength-toughness relationships were developed, and fatigue crack growth behavior in laboratory air was not affected by double aging.     

Instron texture profile of buffalo milk cheddar cheese as influenced by composition and ripening changes

Buffalo milk Cheddar cheese samples of different ages were analysed for compositional attributes (CA), ripening indices (RI) and Instron Textural Profile (ITP). All samples were compositionally alike, except for pH and salt-in-moisture (SM) contents. RI showed significant variations. CA and RI showed highly significant correlations within themselves and with each other, except for moisture with pH, SM with moisture, MNFS, Fat and FDM and Fat with MNFS. The ITPs of cheeses showed significant variations and had highly significant intercorrelations indicating their interdependence. CA (except moisture and MNFS) and RI showed a highly significant correlationship with ITPs. Moisture content showed a highly significant correlationship with all ITPs, except cohesiveness and springiness, where it was significant. MNFS content showed significant correlations only with hardness and brittleness. Stepwise regression analysis revealed that MI was the most predominant factor influencing cheese texture, followed by pH, SM, FDM and TVFA. Knowing Ca and RI, the textural properties of cheeses can be forecast through mathematical equations. Similarly the age of cheese can also be predicted if RI and/or textural properties are known.     

Data management and analysis for high-throughput DNA sequencingprojects

The rapid advances in molecular biology have begun to shift many of the bottlenecks in genome research from the laboratory to the data analysis facility. The pace at which this has occurred creates a situation in which software development always has to catch up with the flow of data. Since such large-scale processes were not anticipated, the analysis infrastructure has not been fully established. Furthermore, most systems that have been built were designed by the biologists who collected the data. More recently, computer scientists, mathematicians, and engineers have taken an interest in this problem. This has had a positive effect, since it has created a tight synergy between the informatics and the biology. Several principles affected the design of the system developed at TIGR. Each of the sample preparation, sequencing, and analysis steps had to be managed, scheduled, and tracked. This information had to be made readily available to those who needed it for carrying out their tasks. Different skill levels of the users had to be taken into account. The degree of human intervention at each step had to be evaluated and built into the design. A mixed processing environment of Macintosh and Unix platforms had to be integrated. Most importantly, the system had to save time, reduce error, and ensure uniformity of the analysis and quality of the results. In the authors' experience, the tools they have built work well because of their early decisions as to which systems to use for development. The authors settled on a robust relational database management system (Sybase) and a portable development environment (C, C++)     

Effects of observer metamerism in the determination of human color-matching functions

This article addresses the results of the recent North and Fairchild article on observer metamerism. It reports on the results of a different experiment that produced similar results to those of North and Fairchild. The history of observer metamerism is outlined briefly and some possible sources of the large variations in inter-observer matches are suggested. Finally, a plea for a commercially viable special index of metamerism for change in observer is formulated. © 1995 John Wiley & Sons, Inc.