Jashovam Shani

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.

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.

Adverse reactions to radiopharmaceuticals

This review covers the side effects and adverse reactions to radiopharmaceuticals that were reported in the literature over the past 25 years. The information published prior to 1970 is sporadic, but due to the increased utilization of nuclear medicine procedures and the recognition that radiopharmaceuticals may have pharmacologic side effects, a registry has existed since 1971 to tabulate information on such effects. This survey is medical, rather than pharmaceutical in emphasis and so the adverse reactions are classified according to the target-organ systems involved rather than according to the specific radionuclides or to pharmaceuticals. If any of the radiopharmaceuticals of present or past use are not mentioned in this review, it is because no reports on their side effects were retrived by us. Hopefully, the organized registry system suggested by the Society of Nuclear Medicine (SNM) will enable a more complete recording of side effects from radiopharmaceuticals in the future.

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.

Labeling and comparative biodistribution of the monoclonal antibody KS14 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.

A New Approach to Organ Pharmacokinetics Using Noninvasive Radionuclide Measurement Methods

Proper chemotherapy requires that the right dose of the right drug be administered to a given patient at the correct rate. This can be achieved if there is proper monitoring of the drugs biodistribution and metabolism in an individual patient. We have documented that radionuclidic measurements, coupled to a systems-based multicompartmental model approach, are ideally suited in providing proper monitoring of the time course of a drug in a patient. The results achieved to date can best be illustrated through the studies we have conducted with cisplatin and with KS1 /4, a monoclonal antibody directed against a human lung tumor. Radiolabeled cisplatin has been used to monitor the relative rate of drug localization and retention in patients with brain astrocytomas, following either standard intravenous (IV) or intraarterial (IA) drug administration. The preliminary results obtained in such patient studies have shown that a much higher amount of radioactive platinum (Pt) was deposited in such tumors during IA infusion. The differential diffusion (washout) rates of radioactive platinum from these tumors are consistent with higher local uptake of the free (eg, active) drug following IA administration. It is of interest to note that no detectable differences could be observed in the blood levels of either the free drug, platinated proteins, or RBC bound Pt, following either IV or IA administration to the same patient. A six-compartment subsystem has been proposed to help analyze and rationalize these data. Similarly, a nine-compartmental model has been shown to represent the biodistribution of KS1 /4 labeled with iodine 131I. The studies reported here illustrate that the pharmacokinetics of drug biodistribution, targeting, and metabolism can be estimated using noninvasive measuring techniques coupled with compartmental model analysis. The availability of such new pharmacokinetic data should be of value in helping to monitor and optimize chemotherapeutic regimens in patients.