Glucocorticoids in Freshwaters: Degradation by Solar Light and Environmental Toxicity of the Photoproducts.

The photodegradation process of seven glucocorticoids (GCs), cortisone (CORT), hydrocortisone (HCORT), betamethasone (BETA), dexamethasone (DEXA), prednisone (PRED), prednisolone (PREDLO) and triamcinolone (TRIAM) was studied in tap and river water at a concentration close to the environmental ones. All drugs underwent sunlight degradation according to a pseudo-first-order decay. The kinetic constants ranged from 0.00082 min-1 for CORT to 0.024 min-1 for PRED and PREDLO. The photo-generated products were identified by high-pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The main steps of the degradation pathways were the oxidative cleavage of the chain 17 for CORT, HCORT and the rearrangement of the cyclohexadiene moiety for the other GCs. The acute and chronic toxicity of GCs and of their photoproducts was assessed by the V. fischeri and P.subcapitata inhibition assays. The bioassays revealed no significant differences in toxicity between the parent compounds and their photoproducts, but the two organisms showed different responses. All samples produced a moderate acute toxic effect on V. fisheri and no one in the chronic tests. On the contrary, evident hormesis or eutrophic effect was produced on the algae, especially for long-term contact.

Kenalog modified by ionizing radiation induces intrinsic apoptosis mediated by elevated levels of reactive oxygen species in melanoma cancer.

Kenalog is a synthetic glucocorticoid drug used to treat various cancers including ocular and choroidal melanoma. However, the drug achieves rarely sustainable results for patients. To overcome this difficulty, the structure of Kenalog was altered by ionizing radiation (IR) to develop a more effective anticancer agent for treatment of various skin cancers. The anticancer effect of modified Kenalog (Kenalog­IR) was assessed in melanoma cancer cells in vitro. The assessment of mitochondrial functions by MTT assay revealed significant inhibition of melanoma cancer cell viability by Kenalog­IR compared to Kenalog. Moreover, Kenalog­IR­induced apoptotic cell death was associated with the intrinsic mitochondrial pathway by triggering the release of intrinsic apoptosis molecules through activation of caspase­related molecules in concentration and time­dependent manners. Furthermore, it was observed that Kenalog­IR­induced apoptosis was associated with the generation of reactive oxygen species (ROS) with increased G2/M cell cycle arrest. Collectively, Kenalog­IR may be a potential suppressor of skin­related cancer in particular melanoma cancer.

Ultraviolet radiation regulates cortisol activity in a waveband-dependent manner in human skin ex vivo.

BACKGROUND: 11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1), 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), and glucocorticoids (GC) and their receptor (GR) play a key role in tissue-specific regulation of GC action. OBJECTIVES: To determine the expression of genes encoding 11ß-HSD1 (HSD11B1), 11ß-HSD2 (HSD11B2) and GR (GRα; also known as NC3R1) and their protein products, and levels of cortisol in human skin explants and/or cocultured keratinocytes/melanocytes after treatment with ultraviolet (UV) A, B or C wavebands. METHODS: Skin from foreskins and/or cocultured human keratinocytes/melanocytes were irradiated with UVA, UVB or UVC (skin) and incubated for 12 and 24 h. Methods of reverse transcription-polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and immunohistochemistry (IHC) were used to determine expression and localization of corresponding genes or antigens. RESULTS: UVB enhanced the HSD11B1 gene and protein expression in a dose-dependent manner, while UVA had no effect. Similarly, UVC increased 11ß-HSD1 protein product as measured by IHC. UVB and UVC enhanced cortisol production and decreased epidermal GR expression, while UVA had no detectable effects. Although both UVA and UVB stimulated HSD11B2 gene expression, only UVA increased 11ß-HSD2 protein product levels with UVB and UVC having no effect. CONCLUSIONS: We suggest that these differential, waveband-dependent effects of UV radiation on the expression of cutaneous HSD11B1, HSD11B2 and GRα genes and their corresponding protein products, and cortisol production are to protect and/or restore the epidermal barrier homeostasis against disruption caused by the elevated cortisol level induced by UVB and UVC.

[The behavioral effects of a single adverse exposure in a number of rat generations: the role of maternal glucocorticoids]. / Povedencheskie éffekty odnokratnogo neblagopriiatnogo vozdeistviia v riadu pokolenii krys: rol' gliukokortikoidov materi.

The ionizing irradiation of rat fetuses during the last third of intrauterine development increased blood corticosterone level adulthood and decreased the open field locomotion of their adult offsprings of the next first nonirradiated generation. Treatment of the pregnant rats with glucocorticoids also decreased the offspring locomotion. Irradiation of fetuses in the middle of embryogenesis decreased blood corticosterone level in adulthood and shortened the open-field freezing reaction of their adult offsprings of the next first nonirradiated generation. Adrenalectomy of females before mating decreasing the blood corticosterone level had a similar effect on freezing duration of their adult offsprings. Irradiation of the ancestors within the last third of their intrauterine development had no effect on blood corticosterone level of their adult offsprings of the first generation and produced no behavioral alterations in their descendants of the next second nonirradiated generation. Irradiation of the ancestors in the middle of their embryogenesis decreased the stress-induced corticosterone response in their adult offsprings of the first generation and increased rearings and locomotion in their descendants of the next second nonirradiated generation. The data suggest that a single noxious treatment may have behavioral effects throughout two consequent generations of rats. Mother's glucocorticoid hormones may be one of the factors which transmit the effect.

[The effect of radon baths at Khmel'nik health resort on the central hemodynamic indices, on thyroid function and on adrenal glucocorticoid function in hypertension patients]. / Vliianie radonovykh vann kurorta Khmel'nik na pokazateli tsentral'noi gemodinamiki, funktsiiu shchitovidnoi zhelezy i gliukokortikoidnuiu funktsiiu nadpochechnikov u bol'nykh gipertonicheskoi bolezn'iu.

As many as 63 patients with stage I, II hypertensive disease were examined. Characteristics of central hemodynamics were studied by means of tetrapolar thoracic rheography, the content of thyroid-stimulating hormone, thyroxin, triiodothyranine, hydrocortisone were determined by radioimmunologic method. All investigations were done before and after the patients having radon baths. Hypotensive effect of radon baths in hyperkinetic type hemodynamics was manifested by a significant drop in cardiac index and increase in specific peripheral resistance. In hypokinetic type hemodynamics there was a significant fall in average hemodynamic pressure, and improvement of the arteriole patency. The levels of thyroxin and hydrocortisone have raised significantly. The Khmel'nik health resort radon baths have hypotensive effect in HD patients, enhance the function of the thyroid gland and glucocorticoid function of the adrenals.

[The circadian rhythm of the adrenal glucocorticoid function in female rats selected for the reaction of the estrous cycle to constant illumination]. / Sutochnyi ritm gliukokortikoidnoi funktsii nadpochechnikov samok krys, selektsionirovannykh po reaktsii éstral'nogo tsikla k postoiannomu osveshcheniiu.

Studies have been made of the circadian rhythms of a glucorticoid hormone, corticosterone, in the adrenals and blood serum in female Wistar rats from two substrains selected for high (ESTH) and low (ESTL) ability to develop permanent oestrus under constant illumination. Significant changes in parameters of the circadian rhythm of the hormone were observed in animals of the 26th generation of selection. Total alleviation of corticosterone rhythm in the blood was on observed in ESTL rats, while in ESTH animals maximum level of the hormone in the blood was shifted to the dark time. Comparison of a high corticosterone content of the adrenals in ESTL rats with a low concentration in the blood plasma indicates the increase in metabolic clearance of the hormone in animals from this strain. It is suggested that the decreased corticosteroid production in the adrenals of ESTH rats facilitates the development of permanent oestrus under constant illumination.

[Kininogenesis and the effect of bradykinin on the level of blood plasma glucocorticoids in irradiated rats]. / Sostoianie kininogeneza i vliianie bradikinina na soderzhaniie gliukokortikoidov plazmy krovi obluchennykh krys.

Kininogenesis is activated after irradiation as well as after the injection of hydrocortisone. Bradykinin, the main component of the kinin system, is a factor that limits the level of blood plasma 11-oxycorticosteroids after its intravenous injection to exposed rats.

[Glucocorticoids and the blood anticoagulation system under the effect of SHF-range electromagnetic waves]. / Gliukokortikoidy i protivosvertyvaiushchaia sistema krovi pod vliianiem élektromagnitnykh voln SVCh-diapazoma.

With an increase in the strength of the ultrahigh frequency field the sensitivity of the hypophyseal-adrenal system increases and activity of the anticoagulatory blood system decreases. Functional changes in these systems repeatedly exposed to ultrahigh frequency effects can be considered as adaptive reactions with a delayed resistance at a flux density of 50--80 Mwt/cm2.