[Treatment of hypertension with a fixed combination of bopindolol and chlorthalidone (Sandoretic)]. / Lécba hypertenze fixní kombinací bopindololu a chlorthalidonu (Sandoretic).

A multicentric, prospective, 16-week open study evaluated the effectivity and tolerance of the fixed combination of the beta-blocking agent bopindolol with the diuretic chlorthalidone--Sandoretic in 81 patients with mild to moderate hypertension. The combination of these two drugs is appropriate, since both drugs have long-term effects. Sandoretic induced a decrease of the mean sitting initial systolic blood pressure of 162.5 +/- 16.5 mmHg to 134.2 +/- 12.8 mmHg at the end of the study, a decrease of 28.3 mmHg. Diastolic blood pressure decreased after 16 weeks of treatment from the initial value of 103.9 +/- 4.9 mmHg to 85.3 +/- 6.0, a decrease of 18.6 mmHg. Changes of the standing systolic and diastolic blood pressures were of similar magnitude. Sandoretic treatment led to a normalization of the diastolic blood pressure (90 mmHg and lower) in 80.3% of patients. In 49.4% of patients treatment with Sandoretic led even to a diastolic blood pressure of 85 mmHg and lower and 29.6% patients had at the end of treatment diastolic blood pressure 80 mmHg and lower. Tolerance of the drug was excellent in 75.3% patients. Sandoretic induced a mild, however, significant decrease of potassium plasma levels. The increase of the uric acid plasma level was also significant. Monitoring of potassium plasma levels is therefore necessary during the treatment with Sandoretic. In patients showing a decrease of the potassium plasma level, potassium sparing diuretic-amiloride should be added or the dosage of the drug should be halved.

Distribution, kinetics and immunoscintigraphy of 131-I labelled intact antifibrinogen-fibrin antibody (AbFbg) and its F(ab')2 fragment.

131-I-labelled anti fibrin-fibrinogen antibody (AbFbg) was compared with its F(ab')2 fragment in distribution studies and by immunoscintigraphy with a view to tumour visualization in tumour bearing rats. The distribution studies indicated that the intact antibody is more concentrated in tumour tissue than the F(ab')2 fragment. By 168h after injection, when tumour-to-tissue ratios were highest in the majority of tissues, the tumour concentration of intact antibody was 3 to 4 times that of the F(ab')2 fragment. The intact antibody is more suitable than the F(ab')2 fragment for tumour imaging especially in the abdominal region where the highest tumour-to tissue ratios were obtained with intact antibody in liver, spleen, intestines and kidneys.

An experimental immunoscintigraphic study with anti-CEA monoclonal antibody (DG2).

Monoclonal antibody D11-DG2 (DG2) against carcinoembryonic antigen (CEA) was examined for suitability for radioimmunodetection of human tumors grown in nude mice. Antibodies DG2 and a control antibody of the same IgG1 subclass were labeled with 131I and injected into mice bearing one of three types of CEA-containing tumors (cell lines LS 174T, HT-29 and Rec S) and/or a CEA-negative tumor (Rec R). Gamma-camera imaging and distribution studies revealed that CEA-containing tumors selectively accumulate DG2 but Rec R does not. As the tumors differ in CEA-content, the highest accumulation of 131I-DG2 (corresponding to the best scintigraphic imaging) was found in LS 174T tumors, intermediate in Rec S and lowest in HT-29 tumors. The mean tumor-to-blood ratios on the sixth day after antibody administration were 4.6, 3.2, and 2.1, respectively, in the control experiments the value of this parameter was always lower than 1. The results showed the applicability of DG2 for immunoscintigraphic studies in patients. Furthermore, a positive correlation was found between the uptake of anti-CEA antibody and CEA-content in the tumors.

[Immunoscintigraphy in experiments and clinical practice: its possibilities, advantages and limitations]. / Imunoscintigrafie v experimentu, klinice, její moznosti, výhody a omezení.

The authors present their experience gained in preparing, isolating and labeling antibodies with radionuclides for the purpose of using them in immunoscintigraphy. The experimental part includes results obtained with different labeled antibodies and their F/ab/2 fragments in distribution studies, involving also immunoscintigraphic imaging of tumors. The clinical part presents results of immunoscintigraphy obtained with the commercial antibody kits Iodomab and Imacis in patients with tumors of the digestive tract.

Antiferritin antibodies in immunoscintigraphic detection of human tumor xenografts.

Affinity-purified antibodies against human placental ferritin and their F(ab)2 fragments labeled with 131I were examined for suitability for radioimmunodetection of ferritin-containing tumors. The nude mouse model (BALB/c, nu/nu) with xenografts of HeLa cell tumors and human adenocarcinoma of the rectum (with proven ferritin content) was used. Gamma-camera imaging and tissue distribution studies revealed that both kinds of tumor selectively accumulate antiferritin antibodies and their fragments. In large necrotic tumors nonspecific uptake of radiolabeled normal IgG occurred, but otherwise there was no tumor localisation. This study, in accordance with the literature, confirms the utility of antiferritin antibodies for the detection of human tumors in an animal model.

The use of protein as a carrier of methotrexate for experimental cancer chemotherapy. I. Preparation of pea seed lectin-methotrexate derivative and the preliminary experiments.

A method of preparation of pea seed lectin-methotrexate derivative by means of hydroxy-succinimide ester of methotrexate was elaborated. Five moles of methotrexate was bound to one lectin mole on the average as verified by analysis. For the distribution study lectin was labeled with 131I. Labeled lectin was administered intravenously to Yoshida sarcoma bearing rats and its distribution in the organism was monitored. After 24 hours the labeled lectin was entrapped predominantly in the reticuloendothelial system but after 48 and 72 hours the accumulation was seen also in thyroid, urinary bladder and tumor (1/4 cases only). The discrepancy in distribution of lectin in the tumor has been discussed.

Immunoscintigraphy and distribution study of experimental tumours using 131I-labelled anti-fibrinogen antibodies.

131I-labelled antibodies to the fragment E of human fibrin, anti-rat fibrinogen, non-immune rabbit IgG and 67Ga-citrate were used for scintigraphy and distribution studies in experimental tumours in rats. The best visualisation was achieved with 131I-labelled anti-rat fibrinogen antibodies at intervals longer than 48 h after administration. Tumour to tissue ratios found in distribution studies performed formed more than 48 h after administration were higher in most examined tissues when using 131I-labelled antibodies than those obtained with 67Ga-citrate.

Functional imaging of uptake of radiopharmaceuticals as a method for tumor visualisation in rats.

Dynamic studies of kinetics of 99mTcO4, 57Co-Bleomycin, 67Ga, A2 fraction of 57Co-Bleomycin in Yoshida sarcoma bearing rats were undertaken. Then the regional variations of rate of the initial uptake of a radiopharmaceutical were examined using functional representation of the rate constants as a function of position. It was concluded that--for radiopharmaceuticals with a high initial uptake rate--the method resulted in visualization of tumor and in suppression of the blood background, within five to eight minutes after administration. This approach based on an evaluation of the parameters of the radiopharmaceutical kinetics in organs and tumor makes possible the use of short-lived radionuclides for tumor visualization and could offer some possibilities of distinguishing the tumor from other accumulating organs.

Chemical and biological properties of bleomycin labelled with 57Co.

The chemical composition of bleomycin labelled with 57Co and its distribution and kinetics in the organs of tumour bearing rats were studied. For separating bleomycin, the chromatography on a CM-Sephadex C-25 column with a gradient of ammonium formate was found to be most suitable. It is also possible to use paper chromatography in 10% NH4Cl and thin layer chromatography in 10% ammonium acetate with methyl alcohol 1:1. The fractions obtained by the chromatographic separation were identified as A2, B2 and A1. Labelling with 57Co given rise to a more complicated mixture of labelled compounds, all of them differing chromatographically from the original non-labelled components. Using carrier-free 57Co two main radioactive compounds are formed apparently corresponding to the fractions A2 and B2 containing one atom of Co per molecule. The amount of another two labelled components grows progressively with increasing amount of carrier CoCl2. Since their chromatographic properties are even more different from those of the original compounds, it was concluded that they probably contain two atoms of Co in their molecules. During distribution studies, rapid excretion of labelled bleomycin into the urine and stool was observed. Increased activities were retained in the liver, kidney, intestine and tumour.