Maintenance of Toscana virus in Phlebotomus perniciosus by vertical transmission

Toscana virus was maintained in a laboratory colony of Phlebotomus perniciosus by vertical (transovarial) transmission for 13 consecutive generations over a 23-month period. No significant biological changes were noted in the virus after prolonged vertical passage in the sand flies, and transovarially infected females were able to transmit the agent by bite to susceptible animals. Chronic infection of Ph. perniciosus with Toscana virus had no apparent effect on the insects' rate of eclosion. In the absence of selection and with random matings, the virus infection rates in each subsequent generation of the colony decreased, suggesting that Toscana virus cannot be maintained in Ph. perniciosus by transovarial transmission alone. Alternative mechanisms for virus maintenance are discussed.     

Unsteady Fluid Dynamics of Several Mechanical Prosthetic Heart Valves Using a Two Component Laser Doppler Anemometer System

Abstract: Five typical mechanical heart valves (Starr-Edwards, Björk-Shiley convexo-concave (c-c), Björk-Shiley monostrut, Bicer-Val, and St. Jude Medical) were tested in the mitral position under the pulsatile flow condition. The test program included measurements of velocity and turbulent stresses at 5 downstream locations. The study was carried out using a sophisticated cardiac simulator in conjunction with a highly sensitive 2 component laser Doppler anemometer (LDA) system. The continuous monitoring of parametric time histories revealed useful details about the complex flow and helped to establish the locations and times of the peak parameter values. Based upon the nondimensional presentation of data, the following general conclusions can be made. First, all the 5 valve designs created elevated turbulent stresses during the accelerating and peak flow phases, presenting the possibility of thromboembolism and perhaps hemolysis. Second, the difference in valve configuration seemed to affect the flow characteristics; third, the bileaflet design of the St. Jude valve appeared to create a lower turbulence stress level.     

Effects of probucol on renal function in rats with bilateral ureteral obstruction

To ascertain the potential role of reactive oxygen metabolites in the pathophysiology of obstructive uropathy, we examined the effect of probucol, an antioxidant agent, on renal function in normal rats and rats with unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Rats were fed either a standard diet or a standard diet containing one percent probucol for two weeks prior to study. Probucol lowered serum cholesterol in both normal and BUO rats. Probucol did not significantly affect renal function in normal rats. BUO rats given probucol had greater inulin and PAH clearances at three to five hours and three days following release of BUO than rats with BUO not given probucol. Kidneys from obstructed rats had higher levels of malondialdehyde, an index of lipid peroxidation, a greater number of leukocytes in the cortex, decreased levels of reduced glutathione and increased levels of oxidized glutathione. Renal cortex from obstructed rats treated with probucol had significantly higher levels of reduced glutathione than kidneys of obstructed rats not given probucol. A decrease in cholesterol, using another lipid-lowering agent, lovastatin, did not modify renal function in rats with BUO. The data can be interpreted to indicate a role for reactive oxygen species in the pathophysiology of obstructive nephropathy. The improved renal function seen in probucol-treated rats with BUO may be due to an effect of this agent in affecting accumulation of reactive oxygen metabolites and/or decreasing the number of leukocytes infiltrating the renal cortex.     

N-methylcarbamate derivatives of ellipticine and olivacine with cytotoxic activity against four human lung cancer cell lines.

A series of analogues of the antitumor alkaloids ellipticine and olivacine were tested for cytotoxicity against four human lung cancer cell lines: H69, N417, H460, and H358. Adriamycin (doxorubicin), ellipticine, olivacine, and celiptinium were used as standards. Adriamycin was cytotoxic at 2 microM and celiptinium was inactive at the highest concentrations tested (IC50 > 48 microM). N-methylcarbamates of 9-methoxy-6H-pyrido[4,3-b]carbazole 1-,5-, and 11-methanols gave IC50 values ranging from 0.02 to 0.11 microM against N417, H460, and H358 and were only slightly less effective against H69.     

Influence of posture on hepatic perfusion and the presystemic biotransformation of propranolol: simulation of the food effect

Several research groups have reported that the oral administration of propranolol with protein-rich food leads to a marked increase (mean + 60%) in the area under the drug plasma concentration-time curve (AUC oral) of this highly metabolized and well-absorbed drug. It has been postulated that this "food effect" is caused at least in part by a transient increase in hepatic blood flow (QH) with its associated decrease in first-pass metabolism (hepatic extraction is a monotonic decreasing function of QH). A randomized crossover study using postural manipulations to produce changes in QH of the magnitude observed after food consumption (20% to 50%) was performed in an attempt to isolate the contribution of transient changes in QH to the food effect phenomenon. A solution of 80 mg propranolol HCl was taken orally and subjects were randomly assigned to postural manipulation protocols that should change QH such that AUC oral would be minimized (phase 1) or maximized (phase 2). Estimated QH (indocyanine green total body clearance from blood) was determined before and at three time points during each phase. It was observed that indocyanine green total body clearance during periods of standing was 15% to 40% below that observed during periods of seating (significant at p less than 0.05 for many of the appropriate comparisons). However, AUC oral for propranolol was not affected (mean +/- 1 SD; AUC phase 2/AUC phase 1+= 0.98 +/- 0.28) by these changes in QH, which are comparable to those encountered after food consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency dependence of spike timing reliability in cortical pyramidal cells and interneurons

Pyramidal cells and interneurons in rat prefrontal cortical slices exhibit subthreshold oscillations when depolarized by constant current injection. For both types of neurons, the frequencies of these oscillations for current injection just below spike threshold were 2--10 Hz. Above spike threshold, however, the subthreshold oscillations in pyramidal cells remained low, but the frequency of oscillations in interneurons increased up to 50 Hz. To explore the interaction between these intrinsic oscillations and external inputs, the reliability of spiking in these cortical neurons was studied with sinusoidal current injection over a range of frequencies above and below the intrinsic frequency. Cortical neurons produced 1:1 phase locking for a limited range of driving frequencies for fixed amplitude. For low-input amplitude, 1:1 phase locking was obtained in the 5- to 10-Hz range. For higher-input amplitudes, pyramidal cells phase-locked in the 5- to 20-Hz range, whereas interneurons phase-locked in the 5- to 50-Hz range. For the amplitudes studied here, spike time reliability was always highest during 1:1 phase-locking, between 5 and 20 Hz for pyramidal cells and between 5 and 50 Hz for interneurons. The observed differences in the intrinsic frequency preference between pyramidal cells and interneurons have implications for rhythmogenesis and information transmission between populations of cortical neurons.