RESUMO
Depression is associated with hyperactivity of the hypothalamo pituitary adrenal axis. Cortisol is a steroid hormone, released from the adrenal gland and is considered to be a biological marker of stress and anxiety. Serum or plasma cortisol levels have been previously studied in depressive patients but reported contradictory results. The present meta analysis aims to assess the serum or plasma concentration of cortisol in depressive patients compared with controls. We have conducted a systematic review with sequential meta analysis according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Web of Science, PubMed, Scopus, and PsycINFO databases, and published reference lists were searched up to January 2021. We have conducted a systematic review on PubMed for the following search (MeSH) terms ("Hydrocortisone"[Mesh]) AND "Depressive Disorder"[Mesh]). The RevMan 5.3 and Open Meta Analyst software was used with the standard mean difference (SMD) and 95% confidence intervals (CIs). The Jamovi and Open Meta Analyst Software were used to evaluate the publication bias, sensitivity analysis, and meta regression as possible sources of heterogeneity. Seventeen studies having a combined population (n) of 1400 (743 depressive patients and 657 controls) had satisfied the inclusion criteria for serum or plasma cortisol. The pooled SMD of the serum or plasma cortisol levels in depressive patients compared with controls was 1.18, (95% CI: 0.84, 1.52; P < 0.00001) with I2 = 85% (Ph < 0.00001). This meta analysis indicates a statistically significant mean difference in serum or plasma cortisol between depressed patients and controls. Meta analysis concluded that serum or plasma cortisol can differentiate depressed patients from nondepressed controls.
RESUMO
The carboxylic group responsible for the gastric side-effects of the propionic acid derivative, flurbiprofen, was masked temporarily to overcome these side-effects and to accomplish colon-specific delivery of the drug. An amide prodrug (FLU-GLY) was synthesized by coupling flurbiprofen with L-glycine. Confirmation and characterization of the structure of the synthesized prodrug included elemental analysis, Fourier transform (FT)-IR, FT-NMR, mass (FAB) spectroscopy, and determinations of R(f), R(t) and R(M) values, respectively. Aqueous solubility and lipophilicity (logP) value were determined at pH 1.2, 4.0, 6.8 and 7.4. In-vitro reversion of FLU-GLY to flurbiprofen was measured at different pHs and in a simulated colonic environment. Acute toxicity and ulceration potential were evaluated in-vivo in albino rats. Pre-formulation studies showed increased hydrophilicity but a non-significant increase in lipophilicity of the prodrug. In-vitro reversion studies suggested that the prodrug remained intact until colonic pH was attained, when the colonic microfloral enzymes (amidase) hydrolysed the FLU-GLY amide linkage, releasing the free drug. In-vivo evaluation indicated that the prodrug was much less toxic and had less ulcerogenic activity than the parent drug. Selective delivery of drugs to the colon can be useful in terms of reducing the dose administered and reducing undesirable side-effects.
