The detection of oligonucleotide N3'-->P5' phosphoramidate/RNA duplexes with capillary gel electrophoresis

Oligonucleotide N3'-->P5' phosphoramidates (3'-phosphoramidates) are DNA analogs that are presently under investigation as potential therapeutic agents. These compounds may also hold promise as a diagnostic tool. Here, we describe a rapid method for the analysis of single-stranded RNA fragments utilizing 3'-phosphoramidate oligonucleotides as probes in conjunction with capillary gel electrophoresis (CGE). 3'-Phosphoramidate 9-mers were mixed with complimentary RNA, and CGE was used to monitor duplex formation. Complimentary strands of RNA and 3'-phosphoramidate formed duplexes that gave unique relative mobilities based on an internal standard. The ability of CGE to discriminate between perfect duplexes and duplexes that contain a base mismatch was also investigated. However, the primary focus of this work was to determine CGE's ability to detect the presence of the 3'-phosphoramidates/RNA duplex under routine electrophoretic running conditions. Polyacrylamide gel electrophoresis analysis was utilized to verify duplex formation.     

Effects of surgery on the pharmacokinetic parameters of drugs

As with other forms of stress, surgery is a time of fluctuating haemodynamics, physiological shifts, intense metabolic changes, and protein catabolism and anabolism. At times, these changes can occur within hours. There is a reasonable body of literature concerning the adverse effects of surgery on gastric emptying, but not on the effects of surgery on the distribution, metabolism and excretion of drugs. Gastric emptying is diminished or absent following major procedures, which prevent the delivery of orally administered drugs to their major site of absorption, the small bowel. Changes in the paracellular absorption of drugs may occur postoperatively, although transcellular absorption appears to be unimpaired. Distribution is affected by changes in blood volume, alterations in circulation, increases in the extracellular fluid and changes in the circulating plasma protein levels, such as albumin and alpha 1-acid glycoprotein. Little is known about alterations in drug metabolism following surgery. However, it has been shown that systemic hypoxia alters the function of some of the cytochrome P450 (CYP) system and increased levels of cytokines have an effect on the metabolism of at least 1 drug. In addition, the renal elimination of drugs is affected in patients postoperatively, although the effects of biliary clearance in this period are difficult to determine. Despite the lack of research into pharmacokinetics during the postoperative period, and given the immense and often sudden changes observed in patients post-surgery, it is reasonable to recommend vigilance with respect to drug therapy during this period.     

Symptomatic subclavian steal syndrome four decades after operation for dysphagia lusoria

Congenital abnormalities of the aortic arch may lead to signs and symptoms of tracheal and esophageal obstruction secondary to a restrictive vascular ring. There are many case reports and monographs concerning the surgical management of dysphagia lusoria. This case provides the first example of long-term follow-up of surgical intervention for relief of dysphagia lusoria. A 45-year-old laborer presented with a several year history of episodic bilateral blindness and a more recent onset of "drop attacks." Notably this patient had presented at the age of 18 months with difficulty breathing and eating since birth. The patient also had frequent upper respiratory infections and episodes of pneumonia. Workup revealed a right-sided aortic arch with a left ligamentum arteriosum. When he was first seen in our clinic, history and physical examination revealed claudication and diminished pulses in the left upper extremity. Arteriography and duplex studies confirmed reversal of flow in the patient's left vertebral artery. The arteriogram demonstrated the presence of a right-sided aortic arch and descending aorta along with the proximal stump of the previously ligated left subclavian artery. He underwent left carotid to left axillary artery bypass for the treatment of symptomatic subclavian steal syndrome. His symptoms have resolved with return of antegrade vertebral flow and the presence of normal pulses in the left arm. Congenital aortic abnormalities that lead to tracheal and esophageal compromise are numerous and varied. Surgical management requires a thorough understanding of the person's anatomy and preoperative planning. The life expectancy of patients with dysphagia lusoria necessitates consideration of the long-term consequences of surgical intervention.     

Tocopherols in camel''s plasma and tissues

"Holistic therapy" can be just a slogan, a catchword. Two examples--the combination of behaviour therapy and pharmacotherapy on one side, the use of biofeedback in psychiatry on the other--shall present the possible integration of different therapeutic strategies into a holistic concept. The quality of different therapeutic concepts may be influenced by their possible combination. No more any therapeutic method (except some eclectic ones) can see itself as the one and only cure for everything. Of course this view has a consequence on psychopathology and diagnosis, which have to be more exact under these premisses. A holistic treatment requires more knowledge about details in psychopathology and diagnosis as well as about therapeutic methods.     

Restrained and nonrestrained eaters'' orienting responses to food and nonfood odors

This study attempted to induce a major shift in the utilization of endogenous substrates during exercise in men by the use of a potent inhibitor of adipose tissue lipolysis, Acipimox, and to see to what extent this affects the 13C/12C ratio in expired air CO2. Six healthy volunteers exercised for 3 h on a treadmill at approximately 45% of their maximum O2 uptake, 75 min after having ingested either a placebo or 250 mg Acipimox. The rise in plasma free fatty acids and glycerol was almost totally prevented by Acipimox, and no significant rise in the utilization of lipids, evaluated by indirect calorimetry, was observed. Total carbohydrate oxidation averaged 128 +/- 17 (placebo) and 182 +/- 21 g/3 h (Acipimox). Conversely, total lipid oxidation was 84 +/- 5 (placebo) and 57 +/- 6 g/3 h (Acipimox; P < 0.01). Under placebo, changes in expired air CO2 delta 13C were minimal, with only a 0.49/1000 significant rise at 30 min. In contrast, under Acipimox, the rise in expired air CO2 delta 13C averaged 1/1000 and was significant throughout the 3-h exercise bout; in these conditions calculation of a "pseudooxidation" of an exogenous sugar naturally or artificially enriched in 13C, but not ingested, would have given an erroneous value of 19.8 +/- 2.6 g/3 h. Thus under conditions of extreme changes in endogenous substrate utilization, an appropriate control experiment is mandatory when studying exogenous substrate oxidation by 13C-labeled substrates and isotope-ratio mass spectrometry measurements on expired air CO2.     

Computer modelling and analysis of the photodegradation effect in a-Si:H p-i-n solar cell

Using a previous model, which was developed to describe the light-induced creation of the defect density in the a-Si:H gap states, we present in this work a numerical modelling of the photodegradation effect in the a-Si:H p-i-n solar cell under continuous illumination. We first considered the simple case of a monochromatic light beam with a wavelength λ between 530-540 nm non uniformly absorbed, then the global standard solar spectrum (AM 1.5) illumination is taken into account. The photodegradation is analysed on the basis of the resulting changes in the free carrier's densities, recombination rate, band structure, electrical potential and field, space charge, and current densities. Changes in the cell's external parameters: the open circuit voltage V_oc, the short circuit current density J_sc, the fill factor FF and the maximum power density P_max are also presented.     

Synthesis and turnover of the regularly arranged surface protein of Acinetobacter sp. relative to the other components of the cell envelope

The formation of the components of the cell envelope of Acinetobacter sp. 199A was investigated by measuring the incorporation of [3H]leucine into protein, [14C]galactose into lipopolysaccharide, 32P into phospholipid, and [3H]diaminopimelic acid into peptidoglycan. Whereas the lipopolysaccharide and intrinsic protein of the outer membrane were stable, some of the regularly arranged surface protein, the alpha-protein, was lost into the growth medium. Only newly synthesized alpha-protein was lost. The peptidoglycan of the murein layer was also labile. Selective inhibition of the formation of individual components of the cell envelope with penicillin, chloramphenicol, and bacitracin showed that incorporation of protein into the outer membrane required the simultaneous formation of complete lipopolysaccharide. The converse was not true: protein synthesis was not required for lipopolysaccharide incorporation. Formation of the outer membrane and the murein layer proceeded independently.     

Mutagenic effect of small doses of diethylsulfate in laboratory mice studied by specific locus method]

Diethylsulphate solution was injected intraperitoneally twice a week to male mice B10.C3H having the wild-type colour at a 5 mg/kg dose. The treatment lasted 10 weeks, so that the total dose administered was 5-20 = 100 mg/kg. In fifth week after the end of the treatment these males were crossed to YT females homozygous for seven recessive mutant genes. In the control group all the F1 descendants were of wild-type colour, while in the experimental group among 5042 F1 mice derived from DES-treated spermatogonia there was one mutant d and 4 mosaics (3 with respect to the locus c and 1 with respect to the locusa). These results are interpreted as the evidence of the mutagenic effect of DES.