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Biomedical subjects

T Pantev

Publications and source records attributed to T Pantev.

At least 19 recordsLinked to original sources

Scintigraphic evaluation of functional hepatic mass in patients with advanced breast cancer.

Recent studies suggest a high specificity of 99mTc-galactosyl neoglycoalbumin (99mTc-NGA) receptor scanning in vivo by providing both morphological and functional diagnosis of liver disease. In 22 patients with advanced breast cancer 99mTc-NGA (150 MBq; 50 nmol) was exclusively trapped by the liver, the images showing 'cold spots' in areas of liver metastases formation. A two-tailed analysis was performed: the time activity curves recorded for the liver and precordial area were subjected to a kinetic receptor-calculating model allowing an estimation of the NGA-receptor concentration of the liver (i.e. hepatic binding protein, HBP) as well as calculation of the residual functional liver volume (RFLV) via the S.P.E.C.T.-study. In breast cancer patients with liver metastases a significantly (P < 0.01) lower HBP-concentration was estimated (0.65 +/- 0.16 vs 0.82 +/- 0.17 mumol l-1) as evidenced by a lower 99mTc-NGA-accumulation in the liver resulting also in a significantly (P < 0.001) lower RFLV (739 +/- 348 vs 1336 +/- 184 ml). In four amonafide-treated patients (800 mg m-2 intravenous infusion over 3 h) approximately one week after one chemotherapy cycle a significant (P < 0.05) increase in HBP-concentration (0.56 +/- 0.10 vs 0.72 +/- 0.06 mumol l-1) of the liver was found corresponding with an increase in RVLF (546 +/- 297 vs 670 +/- 265 ml). These regulatory mechanisms at the HBP level measured in vivo provide further evidence that 99mTc-NGA should have promise as a clinically useful receptor radiopharmaceutical for both quantification of liver function and assessment of liver morphology.

Aged↗

Evaluation of somatostatin receptors in human cancer.

The binding of 123I-Tyr-3-octreotide (SDZ-204-090; specific activity 1 mCi/nmol), a new somatostatin-receptor binding radiopharmaceutical, to human tumour membrane fractions was evaluated in presence of unlabeled Tyr-3-octreotide and octreotide (SMS-201-995; Sandostatin). Tumour tissue was obtained intraoperatively from 15 patients with different endocrine tumours (insulinoma, carcinoide, phaechromocytoma, hypophysal adenoma) and breast cancer. In equilibrium experiments, membrane fractions (200 micrograms protein/ml) were incubated with increasing concentrations of 123I-Tyr-3-octreotide (0.03-30 nM) in presence or absence of 5 microM of unlabeled agonist. Binding capacities ranged from 1-20 pmol/mg protein (Kd 4-100 nM). The IC50 values (2.5-112 nM versus 0.02-69 nM) were different for the octreotide and Tyr-3-octreotide indicating that octreotide was the better competitor as Tyr-3-octreotide for 123I-Tyr-3-octreotide binding sites. In ductal breast cancer high numbers of in vitro binding sites for the radiolabel were found. In initial clinical studies 123I-Tyr-3-octreotide was i.v.-injected (3 mCi) to 5 acromegaly patients with hypophyseal adenomas. Following rapid uptake by the liver, positive tumour imaging was obtained in 3 patients which correlated to computer tomographic findings. Positive images were obtained just some minutes after injection. Our results support recent data suggesting that the 123I-Tyr-3-octreotide would be a suitable receptor-radiopharmaceutical for the localization of endocrine tumours.

Adenoma↗

123I-tyrosine-(A14)-insulin: preparation and preliminary clinical studies.

Insulin was radioiodinated with 123I (123I-tyrosine-(A14)-insulin) to a specific activity of 1 micrograms/mCi, corresponding to 0.025 I.U. of insulin/mCi. This preparation was used for in vitro binding experiments with adipose tissue, showing active binding to the two subunits of the known insulin receptor. In a preliminary clinical investigation, 5 adipose patients with (n = 2) and without (n = 3) diabetes mellitus Type II, were subject to in vivo injection of the same radiolabeled product using 3 mCi/patient. During the first minutes of dynamic imaging, the liver was the major organ of tracer uptake in all patients. Furthermore, the pancreas, and in one patient the kidneys, were visualised. Further studies on insulin in vivo kinetics and quantification are under way.

Diabetes Mellitus↗

Antiradiation mixture and ionic-bond product of AET and adenyl nucleotides.

These experiments continued our line of inquiry into low-toxicity high-effectiveness radiomodifying agents obtained by binding radioprotective substances to biogenic and biologically active components or antidotes. Testes for toxicity and radioprotective effects were three preparations combining within one molecule AET and an adenyl nucleotide (AMP, ADP, or ATP). Ionic-bond formation was shown to have advantages over concomitant administration of AET and adenosine phosphoric acids as mixtures. The evidence obtained supports the rational foundation of the concept being developed by our laboratory.

Adenine Nucleotides↗

Antiradiation properties of alpha tocopherol, anthocyans, and pyracetam administered combined as a pretreatment course.

The effects of an pretreatment course (2 x 5 days) combining vitamin E 20 mg/kg, anthocyans 50 mg/kg, and pyracetam 200 mg/kg on animal survival after lethal irradiation (8 Gy) and blood formation after sublethal irradiation (6 Gy) were studied in mice. Assessments were based on records of an integral criterion, 30-day survival, of spleen weight and cellularity, and of bone-marrow cellularity. Pretreatment with the mixture distinctly raised survival rate (50%) in the protected population. The effect observed was shown to result from potentiating interactions between mixture components. Blood-forming organs experienced less radiation damage, and recovery processes in them were stimulated.

Animals↗

Cistiside-M, a new protective agent.

The toxicological and radiopharmacological properties of the agent Cistiside-M (2-mercaptoethylamine adenosine-5-phosphate) were investigated on male mice, lines C57Bl and H. The compound was administered intraperitoneally in doses from 1000 to 125 mg/kg, 15 min prior to lethal gamma-irradiation using a 137Cs source in the 6 to 15 Gy range. The radioprotective effect was assessed by the integral indices of 30-day survival, mean survival time, coefficient of protection alpha, S30 and the dose-reduction factor (DRF). The compound was characterized by low toxicity and good antiradiation effect in a wide dose range. Maximum degree of radioprotection (75% survival) was established when the agent was administered in a dose of 1000 mg/kg. DRF was 1.6. The dose of 250 mg/kg was interesting--with 50% survival rate and increase of the therapeutic index to 5.6. The low toxicity and the considerable radioprotective effect of the compound are due to its complex structure.

Adenosine Monophosphate↗

Effect of Eleutherococcus extract on the radioprotective action of adeturone.

The effect of successive prophylactic administration of the adaptogen Eleutherococcus and the chemical radioprotector Adeturone on the radiation injury in rats is investigated. The experiments were carried out on sexually mature male Wistar rats weighing 170 +/- 10 g. For 14 days the animals drank water containing Eleutherococcus extract (Medexport), 5 g/kg body weight. On the 7th and 14th days the daily dose of the extract was administered totally using a probe. One hour prior to the last intake, the rats were irradiated with 3 Gr using a 137Cs source, 15 min earlier part of them were injected intraperitoneally with 300 mg/kg Adeturone. The effect of the independent and successive administration of the two agents on the postradiation damage and recovery was tested on the 1st, 3rd, 10th, 20th and 30th days after the irradiation by the change in the leucocyte count and in the quantity of nucleic acids in the leucocytic mass of the blood. The independent application of the adaptogen and radioprotector have a favourable effect only on the course of the recovery processes. Successive administration of the two agents results in mutual potentiation of the effects and guarantees a high degree of protection. This is probably due to an increase in the natural radiation resistance and to the rats' capacity for adaptation during the acute phase of the radiation stress.

Adenosine Triphosphate↗

The effect of a normal tissue radioprotector Adeturone on the radiation sensitivity of Lewis lung carcinoma: an enhanced response.

The effect of the normal tissue radioprotector Adeturone (S-2-aminoethylisothiuronium adenosine-5'-triphosphate) on the response of primary and metastatic Lewis lung carcinoma to radiation was evaluated. It was found that this compound enhanced the antitumor effect of whole-body and local radiation. In experiments with whole-body radiation Adeturone eliminated the lethality due to radiation toxicity (for a daily treatment schedule--10 X 1 Gy/fraction) or reduced it from 50% to 25% (for an intermittent schedule--3 X 3.34 Gy/fraction). Following local radiation treatment combined with Adeturone, a higher TWI%, longer tumor doubling time and longer mean survival time were recorded than for either treatment alone. An enhanced activity against metastatic growth of Lewis lung carcinoma to the lungs was also found with combined therapy.

Adenosine Triphosphate↗

Protection of monkeys against prolonged gamma-irradiation.

The radioprotective effect of the Bulgarian drug Adeturone was tested on prolonged irradiated monkeys. The animals were gamma-irradiated (137Cs) in a dose of 8.3 Gy (exposure rate 3.95 X 10(-3) mA.kg-1; (0.92 R.min-1]. Adeturone, given by i.v. injection at a dose of 100 mg.kg-1 body weight according to a pre- and postradiation scheme will afford protection to monkeys by ensuring 50% survival and mitigating the severity of some symptoms of radiation disease. A similar effect was obtained with ATP-administration by two i.m. injections of 37 mg.kg-1 body weight. The survival in control group was only 5% (LD95/45).

Adenosine Triphosphate↗

[The prevention and treatment of experimental radiation injuries to the skin by using the Nucliderm-gel preparation].

Radiopreventive and radiotherapeutic efficacy of nuclyderm-gel was studied on tails of mice exposed to fractionated gamma-radiation of 90 Gy (15 + 30 + 45 Gy) and 75 Gy (45 + 30 Gy). Daily seven-day treatment with nuclyderm-gel prior to irradiation with increasing doses (15 + 30 + 45 Gy) and the subsequent continuous therapy were shown to delay and reduce skin reactions. Nuclyderm-gel was particularly effective when used therapeutically. The treatment of exposed areas, with the three-fold dose fractionation, was the optimum therapy scheme.

Administration, Cutaneous↗

[Effect of adeturon on postradiation macromolecular synthesis in the peripheral blood leukocytes of gamma ray-irradiated rats].

DNA, RNA and protein syntheses were studied in peripheral blood leucocytes of irradiated (1-7 Gy) rats. Adeturon was shown to produce a pronounced protective effect on DNA synthesis progressively inhibited by the doses applied. The protective effect of the agent was not manifest with the slightly increased synthesis of RNA. There was a trend toward normalization of the increased protein synthesis.

Adenosine Triphosphate↗