Enantiomerically pure novel nucleosides having unusual branched sugars were synthesized in a stereospecific manner from a common chiral pool of (S, S)-1,4-bis(benzyloxy)-2,3-epoxybutane and evaluated for antiviral activity.

Animals↗

PubMedDate not supplied

Prediction of plasma levels of aminoglycoside antibiotic in patients with severe illness by means of an artificial neural network simulator.

PURPOSE: The purpose of this work was to predict plasma peak and trough levels of an aminoglycoside antibiotic in patients with severe illness in an intensive care unit by a novel approach. Plasma levels were predicted based on the values of 15 physiological measurements using an artificial neural network (ANN) simulator. METHOD: A data set of 15 physiological measurements for 30 patients was used to develop the model. The ANN structure consisted of three layers: an input layer comprised of 15 processing elements, a hidden layer comprised of 10 processing elements with a sigmoid function as an activation function, and an output layer of two processing elements (peak and trough levels). The weight between neurons was trained according to the delta rule back-propagation of errors algorithm. Predicted values were obtained by "leave-one-out" experiments by both ANN and multiple linear regression analysis (MLRA). RESULTS: The correlation coefficients between observed and predicted values obtained by ANN prediction using standardized data sets were r=0.825 and r=0.854 for peak and trough levels, respectively. The correlation coefficients obtained by MLRA were r=0. 037 and r=0.276 for peak and trough levels, respectively. These results indicate that ANN shows better performance in prediction of aminoglycoside plasma levels from patients' physiological measurements than MLRA. CONCLUSIONS: Prediction of plasma levels of antibiotic in patients with severe illness by ANN was superior to the standard statistical method. Standardization of input data was found to be important for better prediction. ANN has some advantages over standard statistical methods, as it can recognize complex relationships in the data.

Aminoglycosides↗

PubMedDate not supplied

Effect of polaprezinc on healing of acetic acid-induced stomatitis in hamsters.

PURPOSE: The purpose of this work was to investigate the potential effectiveness of polaprezinc in the treatment of stomatitis. Its effect on oral mucous membrane lesions was studied focusing on acetic acid-induced stomatitis in an animal model. METHOD: Stomatitis was induced in hamsters by local injection of 30 microL of 10% acetic acid solution into both cheek pouches. Change of the size of the acetic acid-induced white lesion caused by polaprezinc injection was compared with that of control (water injection). The process of healing of damaged membrane was also investigated histopathologically. Selective adhesion of polaprezinc on mucous membrane was studied using color development by complexation between zinc and dithizone. RESULTS: On day 4 after acetic acid injection, round white lesions were observed in the central area of both pouches. Observation on days 7, 10, and 14 showed that the size of the lesions decreased with time. Comparison with the control group of animals, in which healing took place naturally, showed that daily administration of polaprezinc (10 mg/kg) applied to the cheek pouches significantly promoted healing of the lesion from day 7 onward. Histopathological investigation of the mucous membrane in the cheek pouches 7 days after the induction of stomatitis by acetic acid injection showed thickening, and cell damage was evident. In the group of animals treated with polaprezinc, the thickening of the mucous membrane was less than that in animals of the group receiving no treatment and regeneration of damaged tissue was observed after 6 days of polaprezinc treatment. CONCLUSION: Polaprezinc is an effective treatment in this animal model of acetic acid-induced stomatitis. This suggests that the drug may be useful in promoting healing of stomatitis in the clinical setting. Extrapolating these to humans suggests that the drug has healing effect to severe stomatitis induced by anticancer drug therapy.

Acetic Acid↗

PubMedDate not supplied

Hemodynamics and the development of anastomotic intimal hyperplasia of the polytetrafluoroethylene graft in dogs.

To clarify whether or not changes in wall shear stress play a determinant role in the induction of anastomotic intimal hyperplasia of polytetrafluoroethylene (PTFE) grafts, two experimental models were devised. Based on our previous study (J Vasc Surg, 1985), wall shear stress was defined by variation of wall shear stress (tau-variation) in one cardiac cycle. In experiment I, PTFE grafts were implanted into dogs under conditions of 85.2 +/- 36.2 ml/min of low flow rate with 66.7 +/- 31.1 dyne/cm2 of low tau-variation. In experiment II PTFE grafts were implanted under conditions of 10.1 +/- 4.6 ml/min of low flow rate with 120.4 +/- 37.2 dyne/cm2 of moderate tau-variation. The intimal thickness of 581 +/- 127 microns at one month and 1230 +/- 260 microns at three months implantation at the distal anastomosis under an abnormal flow condition in experiment I was statistically significant compared with findings in the case of 124 +/- 36 microns at 1 month and 171 +/- 74 microns at 3 months at the proximal anastomosis under an abnormal flow condition in experiment I, and with those of 164 +/- 68 microns at 1 month and 195 +/- 57 microns at three months at the distal anastomosis in experiment II (p less than 0.01). Under a normal flow condition, there was no evident intimal hyperplasia at proximal and distal anastomotic sites in experiment I. These observations are pertinent evidence that change in wall shear stress and not the rate of blood flow is the determinant factor related to development of intimal hyperplasia of PTFE grafts at the distal anastomosis.

Animals↗

PubMedDate not supplied

Evaluation of proposed standards for runoff in femoropopliteal arterial reconstructions: correlation between runoff score and flow waveform pattern. A preliminary report.

The Ad Hoc Committee on Reporting Standards of the Society for Vascular Surgery and the International Society for Cardiovascular Surgery (SVS/ISCVS) proposed a new angiographic scoring system that grades the quality of vessels distal to the expected bypass site and calculates an overall runoff score. To assess the predictability of the bypass grafts by this runoff scoring system, we compared this runoff score with postoperative increase in the ankle/brachial index (delta ABI) and intraoperatively measured flow waveform patterns in 60 patients undergoing femoropopliteal bypass grafts. No correlation was found between delta ABI and the runoff score. Graft-patent survival time correlated with the runoff score (r = 0.44, p = 0.02). Grafts with type 0 or I flow waveform pattern with a satisfactory long-term patency had a significantly lower runoff score than grafts with type II, III or IV flow waveform pattern (p less than 0.05). When all the grafts were arbitrarily divided into two groups (grafts with a runoff score over 4.5 and those with a score of less than 4.0), a superior long-term patency was obtained in the low runoff score group with polytetrafluoroethylene (p less than 0.01) and saphenous vein grafts (p = 0.04), but not in the group with composite grafts (p = 0.25). Thus, the SVS/ISCVS runoff scoring system can be used to predict the fate of bypass grafts in femoropopliteal arterial reconstructions.

Adult↗