An updated review on pathophysiology and management of burning mouth syndrome with endocrinological,psychological and neuropathic perspectives

Burning mouth syndrome (BMS) is a chronic oro‐facial pain disorder of unknown cause. It is more common in peri‐ and post‐menopausal women, and sex hormone dysregulation is believed to be an important causative factor. Psychosocial events often trigger or exacerbate symptoms, and persons with BMS appear to be predisposed towards anxiety and depression. Atrophy of small nerve fibres in the tongue epithelium has been reported, and potential neuropathic mechanisms for BMS are now widely investigated. Historically, BMS was thought to comprise endocrinological, psychosocial and neuropathic components. Neuroprotective steroids and glial cell line–derived neurotrophic factor family ligands may have pivotal roles in the peripheral mechanisms associated with atrophy of small nerve fibres. Denervation of chorda tympani nerve fibres that innervate fungiform buds leads to alternative trigeminal innervation, which results in dysgeusia and burning pain when eating hot foods. With regard to the central mechanism of BMS, depletion of neuroprotective steroids alters the brain network–related mood and pain modulation. Peripheral mechanistic studies support the use of topical clonazepam and capsaicin for the management of BMS, and some evidence supports the use of cognitive behavioural therapy. Hormone replacement therapy may address the causes of BMS, although adverse effects prevent its use as a first‐line treatment. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) may have important benefits, and well‐designed controlled studies are expected. Other treatment options to be investigated include brain stimulation and TSPO (translocator protein 18 kDa) ligands.     

Cosolvency of Dimethyl Isosorbide for Steroid Solubility

Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI–PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant.     

Effects of topical anti-inflammatory drugs on eosinophil survival primed by epithelial cells. Additive effect of glucocorticoids and nedocromil sodium

Background Eosinophil infiltration is a hallmark of the inflammatory response in rhinitis and in nasal polypcsis. Objective We studied the effect of steroids and nedocromil sodium on eosinophil survival primed by epithelial cells from healthy (nasal mucosa) and inflamed (nasal polyp) respiratory tissue. Methods Blood eosinophils were incubated with increasing concentrations (10^-11 10^-5 M) of topical steroids (fiuticasone propionate, budesonide, triamcinolone acetonide and beclomethasone dipropionate) and/or nedocromil sodium prior to the addition of human epithelial cell conditioned media (HECM), eosinophil viability was measured and IC₅₀ for each drug was calculated. Results All four steroids and nedocromil sodium caused a dose-related inhibition of HECM-induced eosinophil survival. The IC₅₀ of steroids were lower in eosinophils primed by mucosa HECM than on those primed by polyp HECM (fluticasone, 4nM vs 114nM: budesonide, 21 nM vs 280 nM; triamcinolone, 7 nM vs 853 nM; and beclomethasone, 171 nM vs 181 nM). The combined inhibitory effect of 10^-7M budesonide plus 10^-5M nedocromil (43.8 ± 10.8%, P < 0.03) was significantly higher than budesonide (28.5 ± 9.2%) or nedocromil (16.7 ± 5.4%) alone and close to 10^-5M budesonide (52.3 ± 11%). No differences were found in cytokine (IL-8, IL-6, GM-CSF, TNFα, IL-lβ and RANTES) concentrations between HECM from mucosa and polyps. Conclusion These results suggest that topical anti-inflammatory drugs may diminish airway eosinophilic infiltration by decreasing eosinophil viability, that nasal polyp epithelial cell secretions may induce steroid resistance in eosinophils, and that nedocromil sodium has additive effects with steroids.     

Successful Treatment of Kasabach-Merritt Syndrome with Prednisone and Epsilon-Aminocaproic Acid

The Kasabach-Merritt syndrome is characterized by thrombocytopenia and localized coagulopathy associated with a hemangioma. Most techniques applied to eradicate the tumor or accelerate its involution (surgery, radiation therapy, embolization) are invasive and require transfusion of large amounts of blood products. In some cases, medical treatment is the only alternative. Efficacy of steroids and antifibronolytic agents has already been described, but even this approach is associated with the administration of blood products. We report two cases of infants with Kasabach-Merritt syndrome associated with cardiac and hepatic hemangiomas. At admission, both had signs of cardiac failure. They were successfully treated with prednisone and epsilon-aminocaproic acid (EACA). Blood products were not required once the diagnosis was made. These observations have important implications for the management of patients with Kasabach-Merritt syndrome because they show that even in severe cases blood transfusions can be avoided by the use of prednisone and EACA.     

Testosterone Enhances GABA and Taurine but not N-Methyl-D,L-Aspartate Stimulation of Gonadotropin Secretion in the Goldfish: Possible Sex Steroid Feedback Mechanisms

The effects of gonadal steroids on GABA-, taurine (TAU)- and N-methyl-D, L-aspartate (NMA)-induced gonadotropin-II (GTH-II) release were investigated in male and female goldfish in vivo. In sexually regressed goldfish (both sexes mixed), intraperitoneal implantation for 5 to 10 days with solid Silastic pellets containing testosterone (100 μg/g), oestradiol (100 μg/g) or progesterone (100 μg/g) was previously shown to elevate serum sex steroid levels to values comparable to those in sexually mature animals, and to potentiate gonadotropin-releasing hormone-stimulated GTH-II release. In the present study, testosterone but not oestradiol or progesterone enhanced the stimulatory effects of exogenous GABA (100 μg/g) on GTH-II release in vivo. TAU (1 mg/g) stimulated GTH-II release in sexually regressed mixed sex and sexually recrudescent male goldfish, and both testosterone and oestradiol implantation enhanced GTH-II release induced by TAU. The glutamate agonist NMA (25 to 50 μg/g) was also found to stimulate GTH-II release; however it was relatively less effective in elevating serum GTH-II levels than GABA and TAU, and its effects were not modulated by sex steroid treatments. Pretreatment of goldfish with α-methyl-p-tyrosine to deplete brain and pituitary catecholam-ines did not affect NMA action on GTH-II release. Our results indicate that GABA, TAU and NMA are involved in the neuroendocrine regulation of GTH-II release in goldfish, and support the idea that testosterone participates in the positive feedback regulation of pituitary gonadotropin release in a non-mammalian vertebrate by enhancing GABA- and TAU-stimulated GTH release in vivo.     

Liver pathology associated with the use of anabolic-androgenic steroids

Abstract: This review examines the liver-damaging side effects of anabolic-androgenic steroids (AAS). It seems that AAS can cause development of peliosis hepatis, subcellular changes of hepatocytes, hepatocellular hyperplasia and hepatocellular adenomas. On the other hand, it has not been convincingly proved that AAS can cause development of hepatocellular carcinomas when used in the usual therapeutic doses. Tumours reported as hepatocellular carcinomas caused by AAS seem to be hyperplastic lesions of a benign nature able to regress with withdrawal of the putative agent. The effects of untraditional combinations and high-dose AAS are not yet known, leaving the possibility of a carcinogenic effect in those cases.