Synthesis, cytostatic activity and ADME properties of C-5 substituted and N-acyclic pyrimidine derivatives.

The synthesis of the novel 5-alkyl pyrimidine derivatives, 5,6-dihydrofuro[2,3-d]pyrimidines and 5-alkyl N-methoxymethyl pyrimidine derivatives and evaluation of their cytostatic activities are described. The mechanism of antiproliferative effect of 5-(2-chloroethyl)-substituted pyrimidine 3 that exerted the pronounced cytostatic activity was studied in further details on colon carcinoma (HCT116) cells. The cell cycle perturbation analysis demonstrated severe DNA damage (G2/M arrest) pointing to a potential DNA alkylating ability of 3.

[Diagnostic significance of mild hyperhomocysteinemia in a population of children with parents or grandparents who have peripheral or coronary artery disease].

Background: A rise of the homocysteine plasma level--mild hyperhomocysteinaemia--is considered an independent risk factor for the development of vascular damage. It is due to hereditary deficiency of 5,10-methylene-tetrahydrofolate reductase with accentuation of vitamin deficiency (folic acid, vitamin B6 and B12). In previous studies the authors confirmed this fact in the population of patients with aortocoronary or peripheral arterial bypasses.

[The Williams syndrome in adulthood].

A case report of a 45-year-old woman with Williams syndrome who was indicated, because of increasing problems, for surgery of a supravalvular stenosis of the ascending aorta. In addition to lesions on the aorta, examination revealed multiple stenoses of branches of the pulmonary artery. The patient showed no facial changes or signs of mental retardation.

[Atypical aneurysms of the abdominal aorta].

The authors submit a report on two patients with pseudoaneurysmatic bulging in the subrenal portion of the abdominal aorta. They present detailed histological findings in the two operated patients and discuss the aetiology of these formations. They draw attention on the failure of aortographic examinations in the diagnosis of these formations and the necessity of sonographic or CT examination.

[Early changes in the structure of venous grafts, their prevention and significance].

The authors investigated, using optic and electron microscopy, the course of regressive changes in smooth muscle cells of the media in venous grafts, in relation to various physical and chemical factors. They recorded the influence of a temperature of 4 degrees C and 22 degrees C, the influence of various types of crystalloid and colloid solutions and some pharmaceutical preparations. In previous work they found that, as a result of ischaemia, regressive changes take place in the smooth muscle cells of the media, while plasmatic structures of these cells and fibrillar structures of the venous wall remain intact.

[Early changes in the structure of vein grafts and their significance in the development of complications after revascularization surgery].

By means of light and electron microscopy the development of regressive changes in the media of vascular graft were studied. The authors found out that as a result of warm and cold ischaemia to which the vascular graft is exposed before implantation changes in nuclei of smooth muscle cells arise. The development of these changes can be postponed by keeping the graft in a suitable medium before implantation.

[Long-term results after implantation of the femoro-popliteal vein graft in relation to preoperative values of the ankle pressure index and peroperative flow].

The authors investigated the importance of ankle pressure indices (aPi), peroperative blood flow and angiographic findings on peripheral arteries for the long-term patency of F-P venous bypasses. They found that neither the preoperative value of aPi nor the size of the peroperative flow through the bypass has an impact on the long-term patency of the reconstruction. As a result of general factors which lead to progression of the atherothrombosis in the arterial circulation in the implanted bypass, obstructions of the reconstruction occur even in patients with high preoperative aPi values and with a major preoperative flow, with patent peripheral arteries at the time of operation.

[Fine morphology of the lymphatics and tissue spaces in the liver parenchyma in man and its significance in hepatobiliary surgery].

The authors investigated the intrahepatic lymphatic vessels of the human liver under a light and electron microscope. The histological material was obtained from 10 patients operated on account of simple cholecystolithiasis. The beginnings of the lymphatic capillaries are in the periphery of the perilobular connective tissue of the portobiliary space in the vicinity of openings of Mall's space.

[The place of postoperative angiography after vascular reconstruction].

In 284 patients after angioplasty of the aortoiliac vessels postoperative angiography discovered complications in 63 cases (22%), most frequently in case of prostheses at the bifurcation. Late thrombosis was the prime complication. In 221 patients with reconstructions in the femoropopliteal region complications were found in 24.