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Biomedical subjects

J Shani

Publications and source records attributed to J Shani.

At least 91 records · Page 5Linked to original sources

The ability of ethanol extract of propolis to stimulate plaque formation in immunized mouse spleen cells.

Ethanolic extract of propolis (EEP) is capable of increasing the number of plaque-forming cells in spleen cell population of immunized male BALB/c mice, demonstrating their ability to produce antibodies. The single EEP dose exerting the maximal plaque formation (a three-fold increase over control) is 500 micrograms/mouse. When this dose is repeated within 24 hours--the plaque-producing effect is even stronger, but further increases in the propolis dose or in the number of its administrations, have an inhibitory effect on the formation of the plaques. The time interval between administration of the EEP and the immunization process should not exceed 48 hours.

Animals↗

Effect of Dead-Sea brine and its main salts on cell growth in culture.

Diluted Dead-Sea brine and solutions of certain of its salts (chlorides and bromides of Na, K and Mg) were found to reversibly inhibit cell proliferation in culture. Bromides were more powerful as inhibitors than their chloride counterparts, and K salts were more effective than those of Na and Mg. KBr had the strongest inhibitory effect, which equalled that of diluted Dead-Sea brine at the same concentration. The favourable results of the Dead-Sea Spa treatment of psoriasis may thus be partly due to the penetration of minerals into the body, via the skin, with subsequent reinforcement of anti-proliferative mechanisms.

Animals↗

Free amino acids in cytosol of rat brain after intraventricular administration of 5,6-dihydroxytryptamine and 6-hydroxydopamine.

Levels of 24 free amino acids were estimated in the brain after administration of 5,6-dihydroxytryptamine and 6-hydroxydopamine into the lateral brain ventricles of male Wistar rats. These neurotransmitters caused serotoninectomy and sympathectomy in the diencephalon, striatum, brain stem and medulla, thalamus and hypothalamus, cerebral cortex and cerebellum. The most abundant amino acids in these brain structures were: glutamic acid, serine, aspartic acid, cystine, gamma-aminobutyric acid, glycine, tryptophan and alanine. We detected and quantified changes in the levels of these and other amino acids in the investigated regions of the rat central nervous system, under the influence of these two neurotransmitters.

5,6-Dihydroxytryptamine↗

Free amino acids in the cytosol of human atrium and ventricle of the heart, as analyzed by gas-liquid chromatography.

Size and composition of the amino acid pool in the cell cytosol of atrial and ventricular heart muscle of 6-8 week old human embryos was evaluated by gas-liquid chromatography. It was found that the free amino acid pool in the ventricular heart muscle is about 50% higher than in the atrium. Arginine constituted the most abundant amino acid in the ventricular and atrial heart muscle as well. Glutamic acid and alanine were the next most common amino acids and represented 10-18% and 7-10% of the amino acid pools, respectively. After appropriate biotransformation, these amino acids may not only be important substrates for the energy cycles of the heart, but may also play a critical role as stimulators of mitosis and regulators of the synthesis of nucleic acids and proteins.

Amino Acids↗

Etiology and clinical significance of new fascicular conduction defects following coronary bypass surgery.

Two hundred consecutive patients undergoing only coronary bypass surgery were studied. Forty-five patients (group A) developed new fascicular conduction blocks and 155 patients (group B) did not. The 45 patients in group A developed the following fascicular conduction blocks: right bundle branch block 47%, right bundle branch block and left anterior hemiblock 8%, right bundle branch block and first-degree atrioventricular block 2%, left anterior hemiblock 11%, left bundle branch block 18%, right bundle branch block-left anterior hemiblock and first-degree atrioventricular block 5%. There were no significant differences in sex, incidence of diabetes, number of grafts performed, ejection fraction (less than 55%), and perioperative infarction. Group A patients were older (p less than 0.01). Hypertension was found frequently in group A (27 vs 45 patients; p less than 0.01) and was present for a mean of 12.4 years in group A and 4.9 years in group B (p less than 0.01). Preoperative use of digitalis was found in 14 (31%) patients in group A and in 18 (12%) patients in group B (p less than 0.01). Twenty-one (47%) patients in group A had significant disease (greater than 70%) of the left main coronary artery as compared to 17 (10.9%) in group B (p less than 0.001). There was no difference in the recurrence of angina or the survival rate at 14 months. In conclusion, the incidence of new fascicular conduction block after bypass surgery is 22.5%. Long-standing hypertension, left main coronary disease, and the preoperative use of digitalis appear to be predisposing factors. New fascicular conduction block does not affect prognosis.

Age Factors↗

Free amino acids in bee hive product (propolis) as identified and quantified by gas-liquid chromatography.

Propolis is a natural resinous product collected by honey bees and containing, among other biochemical constituents, a variety of free amino acids. Acid extraction and quantification of these amino acids by gas-liquid chromatography reveals that their total concentration in this honey bee product is over 40% w/w, and that arginine and proline constitutes over 50% of the crude acid extract. As propolis was shown to stimulate mammalian tissue regeneration, we suggest that the physiological significance of arginine in the propolis product lies in its ability to stimulate mitosis and to enhance protein biosynthesis, and that the biochemical importance of proline in it, stems from its capability to promote build-up of collagen and elastin, two essential components in the matrix of connective tissues.

Amino Acids↗

Criteria for the selection of the most desirable radionuclide for radiolabeling monoclonal antibodies.

Efficient labeling of monoclonal antibodies depends on a number of key factors, mostly related to the characteristics of the radionuclide itself and to the manner of its incorporation into the protein. Such factors include the physical half-life, the photon or particle energy of the radionuclide and its selective deposition of energy in tissues, the method of labeling used (covalent binding or chelation), and the effect that the chemical changes inherent in the labeling process may have on the properties of the protein or of its fragments. The major biological factor in determining the radionuclide of choice for labeling is the projected use of the labeled antibody. When the intended use is diagnostic, then what is required is high-photon density for achieving the high resolution needed for imaging, whereas therapeutic use requires radionuclides with high energy deposition at the target sites, i.e. beta or alpha emitters. A further consideration is to be given to the mode of administration of the radiolabeled monoclonal antibody: determination of the radiopharmacokinetic parameters of compartmental models of biodistribution of the labeled monoclonal antibody and/or its fragments may also assist in selecting which radionuclide may be best to use for radiolabeling a given monoclonal antibody intended for either tumor diagnosis, prognosis and/or therapy.

Antibodies, Monoclonal↗

Labeling and comparative biodistribution of the monoclonal antibody KS1/4 in nude mice bearing human lung adenocarcinoma.

In order to evaluate some of the key factors that may allow the optimization of radiolabeled monoclonal antibodies for use as diagnostic and therapeutic tools to detect and treat human neoplasia, we compared the biodistribution of the anti-lung-tumor monoclonal antibody KS1/4, labeled with four different radionuclides, in athymic (nu/nu) mice bearing human lung adenocarcinoma. Several radiolabeling methods were used: the first involved coupling a suitable bifunctional chelating agent, such as DTPA, to the KS1/4 monoclonal antibody, followed by binding the radiometal, either 113mIn or 111In. Radioiodination was carried out by the chloramine-T method with 131I, and intrinsic labeling by generating the hybridoma in the presence of 75Se-methionine. An examination of tumors and major organs of mice injected with one of the above radiolabeled KS1/4 MoAbs, and biodistribution at various time intervals up to 96 h post injection revealed that iodination and intrinsic labeling yield the highest tumor uptake. Because of the relatively high deiodination that occurs in vivo, and the high 75Se content in the circulation, the preferential uptake (tumor-to-blood ratio) of these radiopharmaceuticals lags behind the equivalent ratios for the In-labeled MoAb. In the latter group of animals, a second consecutive injection of the labeled MoAb resulted in elevated blood level of radioindium, as well as a corresponding decrease in tumor-to-blood ratios.

Adenocarcinoma↗

Increased erythrocyte glutathione peroxidase activity in psoriatics consuming high-selenium drinking water at the Dead-Sea Psoriasis Treatment Center.

Erythrocyte selenium-dependent glutathione peroxidase activity was measured in psoriatic Danes, before and after their four-week balneological therapy at the Ein-Bokek International Psoriasis Treatment Center, on the Dead-Sea shore in Israel. The drinking water in Ein-Bokek was found to be rich in selenium, a trace element with anticarcinogenic properties and of great importance in human nutrition and health. The most reliable biological parameter for increase in selenium bioavailability is the erythrocytes' glutathione-peroxidase activity. As psoriasis is a proliferative skin disease, the activity of this enzyme was assayed in 35 psoriatic Danes and in 25 long-term local hotel workers, as well as in 34 volunteers drinking low-selenium water. The glutathione peroxidase activity in the psoriatic patients increased significantly during their four-week stay in Ein-Bokek. Erythrocyte glutathione peroxidase activity in the hotel workers was 50% higher than that in the healthy volunteers consuming low-selenium water. A possible role of selenium in psoriasis is suggested.

Adult↗

Skin penetration of minerals in psoriatics and guinea-pigs bathing in hypertonic salt solutions.

Penetration of electrolytes through the human skin was measured in healthy volunteers and in psoriatic patients after bathing in the Dead-Sea or in simulated bath-salt solutions. Significant increases in the levels of serum Br, Rb, Ca and Zn were noticed only in the psoriatic patients after daily bathing in the Dead-Sea for a 4-week regimen. Guinea-pigs "bathed" in simulated Dead-Sea bath-salt solutions containing radionuclides of Ca, Mg, K and Br. Traces of each radionuclide were detected in the blood and in some internal organs after 60 minutes of bathing. The radionuclides showed a physiological pattern in their organ distribution. Even though the whole investigation was carried out in hypertonic solutions, there is a definite penetration of salts through healthy (human and guinea-pigs) and damaged (psoriatic) epidermis. This finding suggests that improvement of the psoriatic condition after bathing in the Dead-Sea, may be partly attributed (in addition to ultraviolet irradiation) to the minerals' effect on the psoriatic skin.

Adolescent↗

Comparative radiopharmacokinetics of 18F-5-fluorouracil administered i.v. to rats bearing a mammary tumor.

In an attempt to compare the efficacy of various 5-fluorouracil (5-FU) regimens, we studied the kinetics of 18F-labeled and unlabeled 5-FU in rats. 18F-5-FU was synthesized in our laboratory and was administered in tracer doses to Fischer rats bearing either the 13762 or the R3230 mammary adenocarcinoma, and to Sprague-Dawley rats bearing the Walker-256 carcinosarcoma, with or without pre-treatment with a therapeutic dose of unlabeled 5-FU. In addition, the non-radioactive 5-FU was administered to control rats of both strains. All animals were followed for 70 min either by measuring their 18F blood levels continuously using an extracorporeal blood-loop, or by determining their 5-FU blood levels at discrete time intervals. The biphasic kinetic profile was characterized by determining alpha and beta rate constants and their corresponding half-lives. Differences in 18F elimination, as measured by the area under the curve during the elimination phase, were observed between the pre-treated 13762-bearing rats and the untreated group bearing the same tumor, as well as the pre-treated non-tumored controls and both W-256-bearing groups. Such differences could reveal changes in the ability of those rats to metabolize 5-FU, and hence correlate to the level of active metabolite(s) available to their tumor sites.

Adenocarcinoma↗

Sex-dependent organ distribution of radiopharmaceuticals: effect of hormones on localization of acetyl-103Ru-ruthenocene.

This paper demonstrates modification of organ distribution of a radiopharmaceutical, acetyl-103Ru-ruthenocene, by competing drugs. This radiopharmaceutical concentrates in kidneys of male Wistar rats 15-fold higher than in females of the same strain and age. This concentration in the male is age-dependent. Moreover, the retention of that radiopharmaceutical in male rats' kidneys is markedly reduced by pre-treatment of the rats with estradiol, and this effect is dose-dependent. Estradiol is competetively inhibiting the retention of acetyl-ruthenocene by the kidneys, the same effect also being obtained by tamoxifen, an anti-estrogen used clinically for regression of mammary carcinoma. Blocking the retention of acetyl-ruthenocene was also obtained by testosterone and cyproterone-acetate, as well as by ovariectomy, but the block after castration was partially compensated with time. Blood clearance of acetyl-ruthenocene is biphasic, with a first t 1/2 of about 12 h, and a second t 1/2 of about 48 h. The retention of the label is sex-specific also in mice, but only the female mice show a high adrenal affinity and significant changes in its organ distribution. These effects may be due to competition of acetyl-ruthenocene for steroid receptors, or due to its activation of enzymes that are responsible for its transformation into a bindable moiety.

Animals↗

Standardization of CDI-mediated DTPA-coupling to IgG and IgG2a antibodies for 113mIn labeling.

A systematic analysis of various factors involved in the CDI-mediated coupling of DTPA to IgG have been carried out, in order to optimize the labeling yield of a monoclonal antibody labeled to high specific activity. Various CDI-to-DTPA ratios were tested, followed by a range of DTPA (activated) to IgG ratios. Specific activities as high as 600 Ci/mmol could be obtained following labeling with 113mIn, when an IgG : DTPA : CDI ratio of 0.01 : 1:20 was used. Other aspects, such as the volume of each of the reactants, the pH and the reaction times, were also standardized to yield a labeled IgG2a (KS1/4) that could be consistently tested for biodistribution and tumor-binding.

Carbodiimides↗

Placental transfer of radioactive salts in the pregnant rabbit.

The risks of radionuclidic contamination due to the easy transfer of water-soluble ions from the circulation of the pregnant woman to her fetus, encouraged us to study whether the ease of penetration of such ions is size-dependent. Three radiochemicals--22NaCl, 99mTcO4Na and 201TlCl were injected i.v. into pregnant rabbits on the 16th day of their pregnancy, and the rabbits were killed 15, 30, 60 or 120 min later. From each rabbit the blood, heart, kidney, liver and muscle were sampled and counted as well as placenta, amniotic fluid and some fetuses. At 15 and 60 min hearts and livers were excised from selected fetuses and blood clearance, organ-to-muscle and fetus-to-placenta ratios were calculated. The results indicate that the transplacental transfer of the small radionuclide 22Na+ is faster than that of 99mTcO4- and 201Tl+, reaching equilibrium about 3 h after its injection to the pregnant rabbit. 201Tl+ demonstrated a high localization in the pregnant rabbits' and fetuses' heart and kidneys, with a similar myocardial retention in both groups. Due to the concentration of 201Tl+, in spite of its large diameter, into the fetuses' heart muscle, careful consideration should be taken when injecting 201TlCl into pregnant women for myocardial imaging.

Animals↗

Synthesis and receptor-binding affinity of fluorotamoxifen, a possible estrogen-receptor imaging agent.

Aminotamoxifen was totally synthesized from p-nitrobenzoyl chloride via a Friedel-Crafts acylation. Then, by means of a Balz-Schiemann reaction, aminotamoxifen was converted into fluorotamoxifen. The triazene variation of this conversion, with a 25% yield, enables a rapid, one-step diazotization, incorporating a fluorine atom into the phenyl ring of the tamoxifen. This reaction may be useful for the preparation of low specific activity 18F-labeled tamoxifen, for distribution, and for estrogen-receptor studies. For these in vivo and in vitro studies, fluorotamoxifen was also synthesized from p-fluorobenzoyl chloride, and its chemical intermediates were compared with estradiol and hexestrol, for their receptor binding and competition, as well as for their uterotropic activity. It is demonstrated that tamoxifen and fluorotamoxifen are strong estradiol agonists and partial hexestrol agonists, while aminotamoxifen is a weak estradiol and hexestrol agonist.

Animals↗

Assay and time course of 5-fluorouracil incorporation into RNA of L1210/0 ascites cells in vivo.

A method for determination of levels of incorporation of nonradiolabeled 5-fluorouracil (FUra) into RNA (F-RNA) in tissue samples is shown to be applicable to tissues in vivo. BDF1 mice bearing L1210 ascites cells were injected intraperitoneally with [14C]FUra, 100 mg/kg. The time course of F-RNA levels in L1210 cells was determined by following the radiolabeled drug, and by NaB3H4 labeling of isolated and derivatized nucleoside. RNA ribonucleotides were obtained by KOH hydrolysis of perchloric acid precipitates of cell sonicates. FUMP nucleotides were separated from remaining nucleotides by DEAE-cellulose chromatography. FUMP fractions were treated with alkaline phosphatase, and FUrd was separated from non-FUrd nucleoside contaminants by additional DEAE-cellulose chromatography. FUrd was quantitated by periodate oxidation of ribose and NaB3H4 reduction of the resulting nucleoside dialdehydes. Isolation of tritiated FUrd-trialcohol from remaining tissue contaminants and background radioactivity was done by silica gel thin layer chromatography. Comparison of results obtained by isolation of [14C]FUrd with results of NaB3H4 labeling of the same samples showed parallel results with comparable biological standard deviations, although the tritium method consistently gave slightly lower values. The peak level of F-RNA at 3 hr was 1 base substitution per 174 normal nucleotides. The level of F-RNA after 3 hr declined slowly, so that at 96 hr there still remained 1 FUra base per 597 normal nucleotides. Serial determinations of RNA content showed marked decreases, on the basis of either DNA or protein level, that continued up to 96 hr after FUra administration. These biochemical effects are among the most prolonged reported for FUra, suggesting the possibility that F-RNA represents a storage compartment for release of toxic metabolites and emphasize the need for additional study of RNA effects at long time points. Our method for assay of F-RNA appears to be suitable for study of biopsy specimens of tumors and normal tissues following nonradiolabeled-FUra administration.

Animals↗