Designing an anti-inflammatory and tissue-adhesive colloidal dressing for wound treatment.

Wound dressing materials are widely used to protect wounds from the external environment and to promote wound healing. However, conventional wound dressings lack tissue adhesive properties and anti-inflammatory functions, which lead to fibrosis and stricture, in cases such as gastrointestinal wounds after endoscopic surgery. In the current study, we report tissue-adhesive and anti-inflammatory properties of a wound dressing composed of corticosteroid-modified gelatin particles. Hydrocortisone (HC), which is a class of anti-inflammatory corticosteroid, was used to modify Alaska-pollock gelatin (ApGltn) to synthesize HC-modified ApGltn (HC-ApGltn). Microparticles (MPs) of HC-ApGltn were fabricated by adding ethanol in HC-ApGltn aqueous solution and performing thermal crosslinking (TC) without the use of toxic surfactants and crosslinking reagents. Modification of ApGltn with hydrophobic HC containing cholesterol backbone structure improved its adhesion strength to gastric submucosal tissues under wet conditions owing to hydrophobic interactions. This retention of adhesive property under wet conditions allows for stable protection of wounds from the external environment. We found that HC-ApGltn MPs were taken up by macrophages and they effectively suppressed morphological changes of LPS-activated macrophages and the expression level of the inflammatory cytokine. Robust tissue adhesive and anti-inflammatory MPs may serve as an advanced wound dressing that can protect wounds and suppress inflammatory responses for promoting wound healing.

Spectroscopic evaluation of synthesized 5ß-dihydrocortisol and 5ß-dihydrocortisol acetate binding mechanism with human serum albumin and their role in anticancer activity.

Our study focus on the biological importance of synthesized 5ß-dihydrocortisol (Dhc) and 5ß-dihydrocortisol acetate (DhcA) molecules, the cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. Further experiment proved that Dhc and DhcA induced 35.6 and 37.7% early apoptotic cells and 2.5, 2.9% late apoptotic cells, respectively, morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA-Dhc and HSA-DhcA were observed as static quenching, and the binding constants (K) was 4.7 ± .03 × 104 M-1 and 3.9 ± .05 × 104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4 ± .05 × 104 M-1 replaced Dhc, and phenylbutazone 1.5 ± .05 × 104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, FT-IR, synchronous spectroscopy, and CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular size of the HSA-Dhc and HSA-DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported greater stability of HSA-Dhc and HSA-DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for further development of steroid derivative with improved pharmacological significance as novel anti-cancer drugs.

Cationic lipid-conjugated hydrocortisone as selective antitumor agent.

Hydrocortisone, the endogenously expressed steroidal, hormonal ligand for glucocorticoid receptor (GR), is body's natural anti-inflammatory and xenobiotic metabolizing agent. It has both palliative as well as adverse effects in different cancer patients. Herein, we show that conjugation product of C16-carbon chain-associated cationic lipid and hydrocortisone (namely, HYC16) induces selective toxicity in cancer (e.g. melanoma, breast cancer and lung adenocarcinoma) cells with least toxicity in normal cells, through induction of apoptosis and cell cycle arrest at G2/M phase. Further, significant tumor growth inhibition was observed in syngeneic melanoma tumor model with considerable induction of apoptosis in tumor-associated cells. In contrast to hydrocortisone, significantly higher anti-angiogenic behavior of HYC16 helped in effective tumor shrinkage. This is the first demonstration to convert natural hormone hydrocortisone into a selective bioactive entity possessing anti-tumor effect.

Thiobenzothiazole-modified Hydrocortisones Display Anti-inflammatory Activity with Reduced Impact on Islet ß-Cell Function.

Glucocorticoids signal through the glucocorticoid receptor (GR) and are administered clinically for a variety of situations, including inflammatory disorders, specific cancers, rheumatoid arthritis, and organ/tissue transplantation. However, glucocorticoid therapy is also associated with additional complications, including steroid-induced diabetes. We hypothesized that modification of the steroid backbone is one strategy to enhance the therapeutic potential of GR activation. Toward this goal, two commercially unavailable, thiobenzothiazole-containing derivatives of hydrocortisone (termed MS4 and MS6) were examined using 832/13 rat insulinoma cells as well as rodent and human islets. We found that MS4 had transrepression properties but lacked transactivation ability, whereas MS6 retained both transactivation and transrepression activities. In addition, MS4 and MS6 both displayed anti-inflammatory activity. Furthermore, MS4 displayed reduced impact on islet ß-cell function in both rodent and human islets. Similar to dexamethasone, MS6 promoted adipocyte development in vitro, whereas MS4 did not. Moreover, neither MS4 nor MS6 activated the Pck1 (Pepck) gene in primary rat hepatocytes. We conclude that modification of the functional groups attached to the D-ring of the hydrocortisone steroid molecule produces compounds with altered structure-function GR agonist activity with decreased impact on insulin secretion and reduced adipogenic potential but with preservation of anti-inflammatory activity.

[The synthesis and immunosuppressive effects of steroid-peptide linkers].

Hydrocortisone was coupled with urotoxin tripeptide UTP-A, UTP-B and UTP-C respectively yielding 4 linkers. Their bioactivities such as prolongation of heterotopic transplanted cardiac tissue survival, inhibitory effects on phagocytosis of mouse peritoneal macrophages and the influence on Con A induced proliferation of spleen lymphocytes of mouse were observed. Compared with UTP-A, UTP-B, UTP-C or hydrocortisone the linkers were more potent immunosuppressants. The results suggest that the linker of steroid-peptide may simulate the permissive action.

Hiperplasia suprarrenal congénita secundaria a deficiencia de 21-hidroxilasa: informe de un caso / Congenital adrenal hyperplasia secondary to 21-hydroxilase deficiency: case report

La hiperplasia suprarrenal congénita es un padecimiento poco frecuente. Su causa más común es la deficiencia de la 21-hidroxilasa, lo cual provoca una alteración en la síntesis de cortisol y aumenta la concentración de esteroides que preceden al bloqueo enzimático; la virilización de los órganos genitales externos femeninos es una de las principales características de este transtorno. Se presenta el caso de una paciente portadora de este síndrome y se destaca la importancia del diagnóstico y tratamiento oportuno, con lo cual mejora el pronóstico a corto y largo plazó, incluyendo el de la fertilidad futura de estas pacientes. También se mencionan los actuales recursos para el diagnóstico y tratamiento prenatales con los cuales es posible evitar, en mayor grado, las complicaciones y consecuencias de este síndrome