[Prospects and peculiarities of the procedure of ultrasound ablation of subcutaneous veins of the lower limbs]. / Perspektivy i osobennosti tekhnologii ul'trazvukovoi obliteratsii podkozhnykh ven nizhnikh konechnostei.

The last decade has seen active development of minimally invasive (endovenous) methods of surgical removal of lower limb varicose veins (LLVV); however, the problem of increasing efficacy of these methods and improving long-term results still remains of current importance. The authors of this work propose a method of ultrasound ablation of subcutaneous veins of lower extremities. Our experimental study was aimed at determining the pattern of venous wall damage after ultrasound exposure. Samples of segments of the trunk of the great saphenous vein (GSV) were divided into 5 groups: group 1 - the control group, group 2 - treatment with a sclerosant in the amount of 0.3 ml for 30 s, group 3 - treatment with ultrasound at a frequency of 26 kHz and amplitude 40 µm and 0.3-ml sclerosant for 30 s, group 4 - exposure to ultrasound at a frequency of 26 kHz and amplitude 40 µm and 0.3-ml sclerosant for 60 s, group 5 samples were exposed to ultrasound at 26 kHz and amplitude of 40 µm for 60 s. The results of analysing the histological sections of the samples of the 2nd and 3rd groups demonstrated that the degree of alteration in the GSV wall on combined exposure to ultrasound and a sclerosant was 4.5-fold higher as compared with treatment with a sclerosant solution alone. During ultrasound exposure, the maximum temperature of the venous wall of group 5 samples was by 20 °C higher than in samples of group 4. Analysing the histological sections demonstrated a similar pattern of structural alterations of the samples of group 4 and 5, thus suggesting a possibility of controlling the temperature of the venous wall during ultrasound ablation without changing quality of structural lesions. The obtained findings showed a possibility of initiating irreversible dystrophic alterations in the venous wall on exposure to ultrasound by means of combining the mechanisms of chemical, mechanical, and thermal ablation.

Assessment of enzymatic prodrug stability in human, dog and simulated intestinal fluids.

The aim of this study was to determine the stability of three ester prodrugs, chloramphenicol succinate, enalapril and candesartan cilexetil, in human proximal small intestinal fluid (HIF), dog proximal small intestinal fluids (DIF) and simulated intestinal fluid (FaSSIF), with the addition of pancreatin. The total protein content in the proximal jejunal fluids was determined in HIF and DIF, respectively. Candesartan cilexetil was significantly degraded in HIF (initial t(1/2(0-5 min))=5.4 ± 0.5 min) and in DIF (initial t(1/2(0-5 min))=5.7 ± 0.1 min), while chloramphenicol succinate and enalapril were stable in both media. The degradation of candesartan cilexetil was shown to be mediated by enzymes following Michaelis-Menten enzyme kinetics and was inhibited by addition of esterase inhibitors. The enzymatic capacity reflected by V(max) was 4-fold higher in DIF than in HIF and correlated to its 2-fold higher protein concentration. The degradation of candesartan cilexetil in the FaSSIF-pancreatin solution was slower (t(1/2)=207 ± 34 min) than the degradation in both HIF and DIF. Changing the pH to the enzyme optima or increasing the amount of pancreatin, increased the degradation rate of candesartan cilexetil, but not in the magnitude as in HIF. As a result, two in vitro models, based on in vivo intestinal fluids, were developed using candesartan cilexetil as a model drug. The DIF seems to be a reasonably good model for HIF, although the degradation capacity seems to be somewhat higher, possibly due to the higher enzyme concentration in DIF. Future investigations will develop novel enzymatic based in vitro models for rapid assessment and biopharmaceutical screening tools for prodrugs.