Decreased Incorporation of [3H]Inositol and [3H]Glycerol into Glycerolipids of Sciatic Nerve from the Streptozotocin Diabetic Rat

The incorporation of [3H]myo-inositol into individual phosphoinositides and of [3H]glycerol into glycerolipids was determined in sciatic nerve obtained from normal and streptozotocin diabetic rats and incubated in vitro. The uptake of inositol into lipid was approximately linear with time. More than 80% of the label was present in phosphatidylinositol with the remainder divided about equally between phosphatidylinositol phosphate and phosphatidylinositol-4,5-bisphosphate. Labeling was unchanged 2 weeks after induction of diabetes, but was reduced by 32% after 20 weeks of the disease. Glycerol incorporation occurred primarily into phosphatidylcholine and triacylglycerol and was depressed up to 45% into major phosphoglycerides in nerves from both 2- and 20-week diabetic animals. Triacylglycerol labeling was also substantially decreased, and the reduction was comparable in intact and epineurium free nerve, suggesting that a metabolically active pool of this compound, which is sensitive to hyperglycemia and/or insulin deficiency, is located in or immediately adjacent to the nerve fibers. The considerable decline in incorporation of these lipid precursors in diabetic nerve may be related to impaired inositol transport and to decrease overall energy utilization by the tissue.     

Changes in the electrophoretic pattern of the venom of the bushmaster (Lachesis muta stenophrys) stored under various conditions

Liquid and lyophilized samples of Lachesis muta venom were stored at different temperatures and for different periods of time, and analyzed by polyacrylamide gel electrophoresis (PAGE) and immunoelectrophoresis. Only slight variations were evident when three pools of freeze-dried venom, that had been kept at -30 degrees C for several months were compared with fresh venom. These results suggest that L. muta venom is not altered drastically when stored under these conditions.     

Repopulation kinetics in irradiated mouse lip mucosa: the relative importance of treatment protraction and time distribution of irradiations

The repopulation kinetics of the irradiated lip mucosa of mice has been investigated. Split-dose experiments showed that, in this tissue, repopulation starts within 3 days after the first irradiation and increases exponentially within 10 days. To assess the relative importance of protraction and distribution of irradiations as a function of time, 10 fractions were given in (1) 3 days (three irradiations per day with a 4-hr interval), (2) 11 days (daily fractions), or (3) two short courses, each consisting of five fractions given in 1.5 days separated by a rest period of 8 days, with an overall time of 11 days. The results show that by protracting the treatment from 3 to 11 days (with daily irradiations) repopulation accounts for recovery of approximately 13 Gy. Delivering the radiation in two short courses separated by a rest period leads to an additional recovery of approximately 5 Gy. The most plausible explanation for this observation is that repopulation is much more efficient during the rest period between the two courses than during continuous daily irradiation. Although the regimen of two short courses with a rest period spares the acute reaction, it will not enhance the late tolerance. Before thorough knowledge about the repopulation kinetics of the tumors can be gained, caution should be observed for indiscriminate use of split-course multiple-fraction-per-day (MFD) regimens for treating various tumors.     

Respiratory effects of naloxone

The respiratory effects of naloxone (200 micrograms X kg-1) on dogs, was studied measuring the parameters breath rate, inspiratory volume, breath minute volume, inspiratory time, total time of cycle, inspiratory volume/inspiratory time ratio, and inspiratory time/total time of cycle ratio. The statistical study was made by using the analysis of variance. Naloxone increases all the parameters studied as well as the response to CO2 while it decreases inspiratory time. The results suggest that there are opioid neurons in the respiratory centre. The blockade of the opioid receptors by naloxone almost explains the respiratory effects observed.     

Effect of naloxone on coughing

Naloxone at doses of 200 micrograms X kg-1 increases cough, in experiments carried out on dogs. With stimuli of the same intensity, after naloxone, a significant increase in the number of coughs in each fit, is observed. Changes in the first cough burst, compared with spontaneous respiration at rest, are statistically significant and they contribute to define the characteristics of the cough burst. The increase of cough by naloxone blockade of endorphinic neurons of the respiratory center shows that usually the activity of these inhibitory neurons, tonically depresses the tussive response. The antitussive opiates would seem to operate by activating these inhibitory synapses.     

Stimulation of intestinal adenylate cyclase by cholera toxin in malnourished rats

The stimulation of intestinal adenylate cyclase by cholera toxin (CT) was studied in normal and malnourished rats 4 to 24 hr after a 30-min incubation of intestinal loops with the toxin. Whereas in control rats the enzyme activity returned to basal levels after 12 hr of incubation, in malnourished rats the activity of the enzyme remained significantly elevated even after 24 hr of the initial incubation. Malnourished animals had a reduced turnover rate of intestinal cells as determined by thymidine kinase activity. The delayed turnover of intoxicated cells may account for continuous activation of mucosal adenylate cyclase and possibly for prolongation of diarrhea in malnutrition.     

Synthesis and molecular structure of prolame, N-(3-hydroxy-1,3,5(10)-estratrien-17 beta-yl)-3-hydroxypropylamine; an amino-estrogen with prolonged anticoagulant and brief estrogenic effects

The synthesis and molecular structure of prolame, N-(3-hydroxy-1,3,5(10)-estratrien-17 beta-yl)-3-hydroxypropylamine, is described. It was characterized by ir, nmr, mass spectrometry and chemical analysis. The crystal structure of this compound was determined by single-crystal x-ray diffraction. Prolame belongs to space group P212121. Cell dimensions are: a = 8.356(2), b = 13.343(4) and c = 16.119(4) A. Z = 4; R = 4.1%.     

A three-dimensional computational simulation of some sources of measurement artifact in microvascular pulsed ultrasound Doppler velocimetry

Recent applications of 20 MHz pulsed ultrasound Doppler velocimetry (PUDVM) in microsurgical research have necessarily employed piezoelectric crystals whose diameter is not negligible compared to the lumen size (1-2 mm) of many vessels of interest. A three-dimensional numerical model was developed to explore relationships between actual and detected flow field parameters, for (steady) Poiseuille flow, when appreciable velocity gradients exist within the PUDVM sample volume. Validation studies showed that highly accurate velocity profiles could be obtained in the limiting case of a very small sample volume (0.1 mm radius), but that for currently employed crystals (approximately equal to 0.5 mm radius) there was appreciable underestimation of the centersteam velocity, and appreciable overestimation of the flow stream diameter. Errors in perceived velocity and flow rate were found to be relatively insensitive to perturbations in the sample volume thickness, in the size of the sampling range increment, or in the angle of insonation beam divergence. By contrast, these apparent flow parameters were found to be very sensitive to perturbations of sample volume diameter or of the Doppler angle. Small variations in the degree of partial sample volume overlap of the flowstream periphery were shown to be capable of causing large fluctuations in apparent flow stream diameter.     

Isoproterenol induces a ribosomal modification in the heart and the skeletal muscle of hamsters

The protein synthesis activity of heart, skeletal muscle and liver polysomes from isoprotenerol-treated and control hamsters has been compared in an in vitro non-inititating translation system. Heart and skeletal muscle polysomes from treated hamsters were less active than controls and required a higher magnesium concentration for optimal protein synthesis. These results suggest that there is a conformational modification in heart and skeletal muscle ribosomes from isoprotenerol-treated hamsters. No such change was observed with ribosomes from the liver of isoproterenol-treated hamsters.     

The steady-state rate equation for cytochrome c oxidase based on a minimal kinetic scheme

A minimal catalytic cycle for cytochrome c oxidase has been suggested, and the steady-state kinetic equation for this mechanism has been derived. This equation has been used to simulate experimental data for the pH dependence of the steady-state kinetic parameters, kcat and Km. In the simulations the rate constants for binding and dissociation of cytochrome c and for two internal electron-transfer steps have been allowed to vary, whereas fixed experimental values (for pH 7.4) have been used for the other rate constants. The results show that the dissociation of the product, ferricytochrome c, cannot be rate-limiting under all conditions, but that intramolecular electron-transfer steps also limit the rate. They also demonstrate that Km can differ considerably from the dissociation constant for the cytochrome c-oxidase complex. Published values for the rate constant for the dissociation of ferricytochrome c are too small to account for the steady-state rates. It is suggested that, at high concentrations, ferryocytochrome c transfers an electron to a cytochrome c molecule which remains bound to the oxidase. This can also explain the nonhyperbolic kinetics, which is observed at low substrate concentrations.