Clinical Variability in Two Macedonian Families with Arterial Tortuosity Syndrome.

Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder caused by mutations in the solute carrier family 2 member 10 (SLC2A10) gene encoding a glucose/ascorbic acid transporter. The clinical features of ATS are mild-to-severe tortuosity of the large and medium arteries throughout the body, accompanied by dysmorphisms and joint laxity. Vascular changes in different parts of the body lead to stenosis and/or aneurysms requiring difficult surgical procedures. Here we present two new patients with ATS from two unrelated families. Patient 1 presented at 10 years of age with headache and typical physical appearance, delicate skeleton, large visible pulsation of the carotid arteries in the neck, and joint laxity. On computed tomography (CT) angiography she had severe tortuosity of the aortal branches and cerebral arteries, but no significant tortuosity of the pulmonary arteries. Two cousins of the girl carried the same homozygous c.254T>C, p.(Leu85Pro) mutation in SLC2A10, however, they additionally had a severe involvement of the pulmonary vessels. Patient 2 was a 9-year-old girl diagnosed with severe tortuosity and stenosis of the pulmonary arteries and progressive myocardiopathy. Her physical appearance was very similar to Patient 1, except that she also had growth retardation. After long-term follow-up by cardiologists, she underwent cardiac surgery abroad, with an unfavorable outcome. Homozygosity for the c.685C>T, p.(Arg229*) mutation in the SLC2A10 gene was detected. Consanguinity was disclosed within both families. Our findings confirm the intrafamilial phenotype variability of ATS. A novel finding is the severe tortuosity of cerebral arteries causing migraine that has not been described before in a child with ATS.

Synthesis and antitumour effect of N alpha-acyl derivatives of L-cystine-bis [N,N-di(2-chloroethyl)]dihydrazide.

A series of Na-acyl derivatives of L-cystine-bis [N,N-di(2-chloroethyl)]dihydrazide was synthesized. The effect of the acyl substituent on the antitumour activity of the synthesized compounds was studied. It was demonstrated that the introduction of short-chain Na-acyl substituents resulted in substances with higher antitumour effect and lower toxicity.

Chemo- and immunotherapy of an adenovirus-induced transplantable sarcoma in hamsters.

The subcutaneous transplantable adenovirus sarcoma (TAVS) in hamsters was created in 1972 at the Oncological Research Institute and maintained by serial subcutaneous transplantation. It showed the highest sensitivity against some alkylating drugs and antimetabolites--cyclophosphamide, sarcolysine, methotrexate and 6-mercaptopurine. In some degree, TAVS is able to differentiate antitumor drugs of one group by the intensity of their antitumor activity. Among the drugs, cyclophosphamide was the most active and 6-mercaptopurine and 5-fluorouracil the least active. Antitumor drugs of plant origin, antibiotics and methyl-CCNU had a weak activity on subcutaneous TAVS. Intramuscular TAVS showed a similar sensitivity, with some differences for olivomycin, bruneomycin and vinblastine. Intracerebral TAVS was sensitive against antitumor agents penetrating through the hemato-encephalic barrier and which were active against its subcutaneous and intramuscular form. BCG vaccine and levamisole applied separately did not show any activity on the growth of TAVS. Combined immunochemotherapy with cyclophosphamide plus BCG gave a better enhancement of the antitumor effect of the cytostatic than that of the combination of methotrexate plus BCG and cyclophosphamide plus levamisole. These results showed that TAVS in hamsters may be used as a suitable experimental model for pharmacological studies of antitumor agents and combined immunochemotherapy.

Influence of antitumor drugs of natural origin on the intramuscular and subcutaneous form of five transplantable tumor models.

The influence of six antitumor drugs of natural origin (rubomycin, bruneomycin, olivomycin, mitomycin C, vinblastine, and vincristine) on five transplantable tumor models (sarcoma 37, sarcoma 180, Ehrlich tumor, RL-67 and TAVS) was investigated. Each tumor was transplanted subcutaneously and intramuscularly, bilaterally, on one animal. Marked differences in the sensitivity between subcutaneous and intramuscular form of Ehrlich tumor and more slightly of TAVS were established. The used experimental regimen held out possibilities for saving labor, animals and substances as well as for the study of potential antitumor substances of natural origin at maximum equalized biological conditions.