Microwave-enhanced nucleophilic fluorination in the synthesis of fluoropyridyl derivatives of [3,2-c]pyrazolo-corticosteroids, potential glucocorticoid receptor-mediated imaging agents.

Fluoropyridyl derivatives of [3,2-c]pyrazolo-corticosteroids have high affinity for the glucocorticoid receptor (GR) and are highly active glucocorticoids. They are thus considered to be excellent candidates for PET imaging of GR containing tissues when labeled with fluorine-18 (t(1/2)=110 min). Previously reported syntheses of these fluorinated glucocorticoids were accomplished by conventional thermal nucleophilic halogen exchange reactions with chloropyridyl precursors. These reactions were found to proceed at rates too slow for feasible application to radiosynthesis using [(18)F]fluoride. We have applied microwave-heating methods to these reactions and found that significant rate enhancements can be realized. Kinetic experiments showed an average relative rate ratio of 3/1 for microwave versus conventional heating and preparative experiments showed an average relative conversion ratio of 4.5/1 during the initial 120 min, a period approximating one half-life of the isotope. The microwave method described was used to prepare previously unreported 2'-(2-fluoro-4-pyridyl)-11beta,17,21-trihydroxy-16alpha-methyl-20-oxo-pregn-4-eno-[3,2-c]-pyrazole, which was evaluated for biological activity.

Plasma cell granuloma of the maxillary sinus: a case report and literature review.

BACKGROUND: Plasma cell granulomas are rare and heterogeneous tumor-like lesions of mixed inflammatory cell infiltrates of unknown etiology. Although they have the potential to occur in sites throughout the body, their occurrence in the paranasal sinuses and nasal cavity is uncommon and often associated with unique clinical characteristics and natural history. METHODS: We present a case of an aggressive plasma cell granuloma of the maxillary sinus and a review of the literature (28 cases). RESULTS: The patient was treated with definitive radiotherapy (45 Gy in 25 fractions) and experienced a local recurrence 2 years later. The lesion initially responded to corticosteroids and then progressed. Resection was performed and was followed by another recurrence. The patient was treated with radiosurgery and is disease free 8 years after initial treatment. CONCLUSIONS: Review of the literature indicates that the optimal first line of treatment is high-dose corticosteroids. Surgery is indicated if the lesion fails to respond. Radiotherapy is indicated if complete resection is not feasible.

[The action of sublethal doses of ionizing radiation on the endogenous radioresistance background]. / Issledovanie deistviia subletal'nykh doz ioniziruiushchego izlucheniia na éndogennyi fon radiorezistentnosti.

Sublethal doses of X radiation (0.5 Gy and 1 Gy) caused the alterations in levels of main components of endogenous radioresistance background in rat tissues. There were demonstrated the decrease of serotonin content in stomach mucosa and spleen, adrenalin, noradrenalin and corticosteroid contents in adrenal glands, nonprotein thiols content in spleen, and the increase of lipid peroxide level in serum on the 3-14 days after irradiation. The recovery of the investigated parameters was occurred to the 21 day after exposure.

[The coupling of the contrariwise changes in the steroid-secreting activity of the adrenals and the steroid-metabolizing activity of the liver in rats after x-ray irradiation]. / Sopriazhennost' protivonapravlennykh izmenenii steroidsekretiruiushchei aktivnosti nadpochechnikov i steroidmetaboliziruiushchei aktivnosti pecheni krys pri rentgenovskom obluchenii.

The rat adrenal cortex activation is accompanied by inhibition of steroid metabolism in liver and vice versa at acute radiation disease caused by X-ray irradiation. A coupling of contrary changes of corticosteroid secretion and metabolism evidences that there is common regulation of these functions. The possible ACTH participation in coupling of adrenals and liver functions and the liver role in radiation hypercorticism genesis are discussed.

[The light sensitivity of corticosteroids in crystalline form. Photochemical studies. 59. (1)]. / Lichtempfindlichkeit von Corticosteroiden in kristallinem Zustand. Photochemische Studien, 59. Mitt. [1].

The light sensitivity of corticosteroids in the solid state have been investigated and the photodecomposition rates of the compounds have been estimated by HPLC. After 48 h UV-irradiation desoxycortone acetate, hydrocortisone, hydrocortisone acetate, prednisolone, methylprednisolone, dexamethasone, betamethasone and triamcinolone acetonide decompose between 20 and 50%. Cortisone acetate, prednisone and fluocinolone acetonide show photostability in contrast to requirements of the Pharmacopeia for light protections.

[The immunomodulating action of microwaves in the induction of an immune response to Vi antigen]. / Immunomoduliruiushchee deistvie mikrovoln pri induktsii immunnogo otveta na Vi-antigen.

In this work the possibility of using microwaves for immunomodulation in the immunization of animals with thymus-independent antigen was studied. The projection zones of the thymus and adrenal glands of the test animals were subjected to the action of decimeter, or ultrahigh frequency (UHF), waves, while the corresponding zones of the control animals were subjected to imitation UHF irradiation. Vi-antigen was shown to be a thymus-independent antigen for rabbits (according to the results of the evaluation of the functional state of thymocytes, as manifested by the adsorption of acridine orange by the chromatin of thymocyte nuclei and by the content of RNA and DNA in the thymus). The action of UHF waves on the projection zone of the thymus was accompanied by a decrease in the glucocorticoid activity of the adrenal cortex, observed simultaneously with a pronounced immunostimulating effect. The UHF irradiation of the zone of the adrenal glands was accompanied by immunosuppression in combination with enhanced glucocorticoid activity of the adrenal cortex.

Radiolytic degradation scheme for 60Co-irradiated corticosteroids.

The cobalt 60 radiolytic degradation products have been identified in the following corticosteroids: cortisone, cortisone acetate, hydrocortisone, hydrocortisone acetate, hydrocortisone sodium succinate, isoflupredone acetate, methylprednisolone, methylprednisolone acetate, prednisolone, prednisolone acetate, and prednisone. Two major types of degradation processes have been identified: loss of the corticoid side chain on the D-ring to produce the C-17 ketone and conversion of the C-11 alcohol, if present, to the C-11 ketone. Minor degradation products derived from other changes affecting the side chain are also identified in several corticosteroids. These compounds are frequently associated in corticosteroids as process impurities or degradation compounds. No new radiolytic compounds unique to 60Co-irradiation have been found. The majority of corticosteroids have been shown to be stable to 60Co-irradiation. The rates of radiolytic degradation ranged from 0.2 to 1.4%/Mrad.