Marvin Sodicoff

Radioprotection by WR-2721 against long-term chronic damage to the rat parotid gland.

WR-2721 protected against the acute phase of radiation damage which is manifest during the first week after irradiation, though recovery occurred both in the presence and absence of such protection. The drug also protected against the chronic phase damage which appeared later (60 to 90 days postirradiation), with dose modification factors of 2.3 for gland weight, 3.2 for amylase, and 2.0 for total gland amylase, and roentgen increases ranging from 1.7 to 4.9 kR.

Short-Term Radioprotective Effects of WR-2721 on the Rat Parotid Glands

The radioprotective capacity of the chemoprotector WR-2721 was assessed in the rat parotid gland using gland weight and amylase content as the indicators of effect over the 9-day period following x irradiation with 1.6, 3.2, and 6.4 kR of acute x rays. The decline and recovery of weights and amylase content were measured and compared in animals which had and had not received WR-2721 just prior to irradiation. Analysis of the dose-response curves for the WR-2721 protected vs nonprotected animals yielded dose modification factors of 2.5 for gland weight, 1.7 for amylase concentration, and 1.8 for total gland amylase. Thus, WR-2721 was found to be effective in yet another tissue and to a degree consistent with that of other organs and systems.

Ultrastructural Radiation Injury of Rat Parotid Gland: A Histopathologic Dose-Response Study

Radiation damage to rat parotid acinar cells was evaluated by electron microscopy using exposures of 400, 800, 1600, and 6400 R. Evidence of intracellular damage was observed at all exposures by the presence of focal cytoplasmic lesions involving all of the organelles. The extent of the damage varied with dose, 400 R resulted in very mild injury while 6400 R caused extensive necrosis (1-4 days after irradiation) with signs of recovery in evidence by Day 6. In addition, at the lower doses, 400 and 800 R, the Golgi complex was found to be hypertrophied although at the higher doses, 1600 and 6400 R, this did not occur. Therefore, it was determined that x-irradiation results in histopathologic changes to the parotid gland at a relatively low dose and the extent of the damage varies directly with dose.

Effects of X-irradiation and the resultant inanition on amylase content of the rat parotid gland

Abstract X-irradiation exposures of 400, 800, 1600 and 6400 R resulted in dose-related alterations in amylase concentrations and parotid gland weights during the 8 days following irradiation. These effects were not due to irradiation alone but were caused by a combination of direct and indirect effects of the irradiation (food and water intake reduction). Reduction of gland weights and amylase content were minimal and alike at 400 and 800 R, but 1600 and 6400 R produced progressively more severe decreases, although recovery was in progress by 8 days in all groups. To evaluate the potential of irradiated tissue for amylase synthesis, 400 and 1600 R irradiated rats were injected with the secretogogue isoproterenol at 1 h, 1 day and 1 week after X-ray and amylase resynthesis studied. All animals were capable of amylase release and resynthesis at rates similar to controls, except that 1 week after exposure to 1600 R, rats showed a slower than normal resynthesis. Fractionated 6400 R exposure regimens were less destructive than single acute exposures.

Computer‐based neuroanatomy laboratory for medical students

To present the laboratory portion of our first‐semester Human Neuroanatomy course at Temple University Medical School more effectively and efficiently and to replace the glass slide/microscope‐based laboratory component of the course, we developed a computer‐based substitute.

Terbutaline-induced enlargement of the rat parotid gland

Abstract The β-sympathomimetic drug terbutaline was shown to be a powerful secretogogue for the rat parotid gland. It was also found to be capable of causing a transient enlargement of the parotid which was similar to that produced by isoproterenol.

LEUKOCYTOSIS-INDUCING FACTOR IN THE BLOOD OF X-IRRADIATED RATS.

Rats whose peripheral WBC counts had been lowered by 400 R of total-body X-irradiation served as donors of plasma which was injected intraperitoneally into recipient rats in 5-ml quantities under sterile and pyrogen-free conditions. Peripheral WBC and bone marrow data were obtained, and comparison was made with data obtained after injection of plasma from sham-irradiated donors. The effect of injection of plasma from irradiated donors was production of a leukocytosis, due to numerical increases of both neutrophils and lymphocytes. This leukocytosis was of greater magnitude than that resulting from injection of plasma from sham-irradiated donors. The more severe the leukopenia of the irradiated plasma donor, the greater was the capacity of the plasma to increase the peripheral white cell count of recipients; of the intervals tested, the effect was greatest at 4 days after irradiation. Quantitative analysis of the peripheral blood of recipients of plasma indicated that the resultant leukocytoses were due pr...

Transdermal absorption of radioprotectors using permeation-enhancing vehicles

Radioprotectors are not currently used clinically due to concerns regarding toxicity and uncertainties regarding tumor protection. Topical radioprotection of skin might find clinical applications with protectors such as WR-2721, but laboratory studies in which protectors have been applied in water have not been promising. We have studied the absorption of 14C-WR-2721 and [14C]cysteine dissolved in skin permeation-enhancing vehicles through the skin of hairless mice and compared the absorption to that in water. Skin concentration of WR-2721 was increased most by dimethylformamide (DMF), but only propylene glycol increased absorption as far as the dermis, as measured by plasma concentration. Skin concentration of cysteine was improved by DMF, 2-pyrrolidone (2-P), and methyl-2-pyrrolidone (M-2-P); only dimethylsulfoxide (DMSO) resulted in increased plasma levels of the protector. Pretreating skin with DMSO before application of WR-2721, irrespective of the vehicle, improved its concentration within the skin. Plasma levels were improved (10 and 12 times) only with 2-P and DMF. Therefore, by choosing the appropriate vehicle, it is possible to breach the barrier of the stratum corneum and enhance the presence of the protector in all layers of the skin.

Chemoradioprotection of the Rat Parotid Gland by Combined Use of WR-2721 and Ro-07-0582

The radioprotection of the rat parotid gland by WR-2721 alone (DMF, 2.4) was compared to the protection afforded when WR-2721 was given in combination with the hypoxic cell radiosensitizer Ro-07-0582 (DMF, 2.6). It was concluded that the radiosensitizer of malignant tumor cells Ro-07-0582 was compatible with and did not reduce the protection of normal tissue afforded by WR-2721.

Transdermal Absorption of Radioprotectors in the Rat Using Permeation-Enhancing Vehicles

Topical radioprotection of rat skin with WR-2721 has not been effective presumably because the drug does not cross the stratum corneum to reach the epidermis and dermis. Earlier, we showed in the mouse that WR-2721 and cysteine dissolved in permeation-enhancing vehicles passed through the skin more readily than when in water. However, the most effective vehicles in the mouse were not necessarily as effective in the rat. Here we report that the most effective transport vehicles in the rat were (1) water with WR-2721, (2) water and dimethylformamide (DMF) with cysteine, and (3) water and DMF with prostaglandin E2 (PGE2). Pretreatment of the skin with dimethylsulfoxide (DMSO) further improved the transfer of the radioprotectors across the skin in most cases. After pretreatment with DMSO, the most effective vehicles were (1) water for WR-2721, (2) water and methyl-2-pyrrolidone (M-2-P) for cysteine, and (3) DMF for PGE2.