Síndrome de boca ardiente: estudio de la psicoterapia, medicación con ácido alfa- lipoico y combinación de terapias

En este estudio de 192 personas sanas con Síndrome de boca ardiente, se analizó la eficacia del control de los síntomas de la psicoterapia sola durante dos sesiones semanales de 1 hora durante dos meses, del ácido alfa lipoico (ALA, ácido tioctico, Tiobec) 600 mg al día durante dos meses, y de la combinación de la psicoterapia y los 600 mg / día de ALA durante 2 meses. Los controles solo recibieron placebo. RESULTADOS. Se obtuvo el mayor beneficio con la terapia combinada. La combinación de los tratamientos con psicoanálisis y ácido alfa lipoico (ALA, acido tioctico, Tiobec 600 mgr al día), durante 2 meses fue significativamente más beneficiosa que el psicoanálisis solo durante dos sesiones semanales de una hora durante dos meses ( p< 0.0005) o el ALA 600 mgr al día solo, durante dos meses (p< 0,0005). CONCLUSIÓN. Los resultados sugieren que el ácido alfa lipoico podría complementar la psicoterapia y ser una alternativa aceptable a los fármacos psicoactivos, por lo que estudios de comparación de ambas alternativas están actualmente justificados.-Objective and study design This open study of 192 otherwise healthy persons with burning mouth syndrome, examined the efficacy on control of symptoms of psychotherapy alone with two hour sessions weekly for two months; alpha lipoic acid (ALA, tioctic acid; Tiobec) 600 mg/ day alone for two months; or combination therapy of psychoanalysis and 600mg/day ALA for two months. Controls received placebo alone. -Results Most benefit was obtained with combination therapy. Combination therapy of psychoanalysis and alpha lipoic acid (ALA , tioctic acid; Tiobec. 600mg/day) for two months gave most benefit and significantly more than psychoanalysis alone for two 1 hour sessions weekly for two months (p<0.0005), or ALA 600 mg/day alone for two months (p<0.0005) . -Conclusion The present results suggest that alpha lipoic acid may complement psychotherapy and can be an acceptable alternative to psychoactive agents, but trials to compare the two approaches are now warranted

Burning mouth disorder (bmd) and taste : a hypothesis

Background: Burning mouth disorder (BMD) is a burning or stinging sensation affecting the oral mucosa, lips, and/ or tongue, in the absence of clinically visible mucosal lesions. There is a strong female predilection, with the age of onset being approximately 50 years. The causes of BMD are multifactorial and remain poorly understood. Often BMD patients report, in association, change in taste. In this regards, it is relevant that in central nervous system connections exist between taste and oral pain and that taste normally inhibits oral pain. Aim: The working hypothesis of this study considers a possible relationship between burning mouth disorders and alterations of taste. Several conditions or pathologies can be responsible of taste disturbances that might be the cause of oral pain in BMD patients. Subjects and methods: We have analyzed, retrospectively, 142 cases of BMD with associated taste disturbance. Possible causes that could be responsible for alterations of taste were investigated. Results and conclusions: Sixty-one subjects revealed the habitual use of drugs having a documented interference with taste perception. Thirty-five subjects, among the 81 patients who had no associated pathology or habitual use of drugs, noticed in their clinical history conditions, pathologies or use of drugs that are known to affect the gustatory system. Therefore, we propose that BMD may represent an oral phantom pain induced in susceptible individuals by alteration of taste

Burning mouth syndrome (BMS) : evaluation of thyroid and taste

Background Burning mouth syndrome (BMS) is a chronic, intraoral burning sensation seen mainly in middle-aged and post-menopausal females, without identifiable oral lesions or abnormal laboratory findings, but often associated with psychogenic disorders such as depression. The latter can have a range of causes, including hormonal. Objective Since there may be connections between BMS, psychogenic changes, hormonal changes and taste abnormalities , we have examined aspects of taste and thyroid function.. Patients and methods We selected 50 patients with BMS (study group) and 50 healthy subjects (control group) and analysed their ability to taste bitter, acid and spicy substances and analysed their thyroid function and Undertook thyroid echography. Results Taste sensation was normal in all controls. However, 30 of the patients with BMS reported ageusia for bitter taste and 2 had ageusia for acid. The use of pepper sauce ( Tabasco®) (spicy substance) produced a strong burning to the tongue in 28 patients of the BMS group but only in 10 controls. No control patients showed abnormality of thyroid function or echograpic abnormality. Five patients in the BMS group had biochemical evidence of hypothyroidism, 4 patients had raised levels of thyroid autoantibodies and, of the 41 remaining BMS patients, most (34) had thyroid echographic changes indicative of nodularity. Conclusions Hypothyroidism may be responsible for a negative influence on taste and consequent increase in trigeminal sensorial sensation (tactile, thermal and painful sensation)

Evidence of key role of Cdk2 overexpression in pemphigus vulgaris

The pathogenesis of pemphigus vulgaris (PV) is still poorly understood. Autoantibodies present in PV patients can promote detrimental effects by triggering altered transduction of signals, which results in a final acantholysis. To investigate mechanisms involved in PV, cultured keratinocytes were treated with PV serum. PV sera were able to promote the cell cycle progression, inducing the accumulation of cyclin-dependent kinase 2 (Cdk2). Microarray analysis on keratinocytes detected that PV serum induced important changes in genes coding for one and the same proteins with known biological functions involved in PV disease (560 differentially expressed genes were identified). Then, we used two different approaches to investigate the role of Cdk2. First, small interfering RNA depletion of Cdk2 prevented cell-cell detachment induced by PV sera. Second, pharmacological inhibition of Cdk2 activity through roscovitine prevented blister formation and acantholysis in the mouse model of the disease. In vivo PV serum was found to alter multiple different pathways by microarray analysis (1463 differentially expressed genes were identified). Major changes in gene expression induced by roscovitine were studied through comparison of effects of PV serum alone and in association with roscovitine. The most significantly enriched pathways were cell communication, gap junction, focal adhesion, adherens junction, and tight junction. Our data indicate that major Cdk2-dependent multiple gene regulatory events are present in PV. This alteration may influence the evolution of PV and its therapy. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

Engineering the fatty acid synthesis pathway in Synechococcus elongatus PCC 7942 improves omega-3 fatty acid production

Background: The microbial production of fatty acids has received great attention in the last few years as feedstock for the production of renewable energy. The main advantage of using cyanobacteria over other organisms is their ability to capture energy from sunlight and to transform CO2 into products of interest by photosynthesis, such as fatty acids. Fatty acid synthesis is a ubiquitous and well-characterized pathway in most bacteria. However, the activity of the enzymes involved in this pathway in cyanobacteria remains poorly explored. Results: To characterize the function of some enzymes involved in the saturated fatty acid synthesis in cyanobacteria, we genetically engineered Synechococcus elongatus PCC 7942 by overexpressing or deleting genes encoding enzymes of the fatty acid synthase system and tested the lipid profile of the mutants. These modifications were in turn used to improve alpha-linolenic acid production in this cyanobacterium. The mutant resulting from fabF overexpression and fadD deletion, combined with the overexpression of desA and desB desaturase genes from Synechococcus sp. PCC 7002, produced the highest levels of this omega-3 fatty acid. Conclusions: The fatty acid composition of S. elongatus PCC 7942 can be significantly modified by genetically engineering the expression of genes coding for the enzymes involved in the first reactions of fatty acid synthesis pathway. Variations in fatty acid composition of S. elongatus PCC 7942 mutants did not follow the pattern observed in Escherichia coli derivatives. Some of these modifications can be used to improve omega-3 fatty acid production. This work provides new insights into the saturated fatty acid synthesis pathway and new strategies that might be used to manipulate the fatty acid content of cyanobacteria.Work in the FDLC laboratory was financed by the Spanish Ministry of Economy and Competitivity (MINECO) Grant BFU2014-55534-C2-1-P. MSM. was recipientof a Ph.D. fellowship (BES-2012-057387) from MINECO

Internalization of Non-Clustered Desmoglein 1 without Depletion of Desmoglein 1 from Adhesion Complexes in An Experimental Model of the Autoimmune Disease Pemphigus Foliaceus

Serum antibodies against desmoglein 1 (Dsg1) are known to induce the clinical and histological manifestations of pemphigus foliaceus (PF), autoimmune bullous disease targeting skin. The basic pathophysiological phenomenon of PF blistering is the disruption of epithelial integrity in the granular layer of the epidermis due to separation of keratinocytes from one another, or acantholysis. In this report we investigate the changes in subcellular distribution of Dsg1 in response to serum of patients with PF by using an in vitro model of PF. Immunofluorescence analysis on HaCaT cells indicates that non-clustered Dsg1 is markedly internalized after exposure to serum. However, binding of PF IgG to Dsg1-rich adhesion complexes (desmosomes) does not cause disruption of such structures nor depletion of clustered Dsg1, as revealed by colocalization of PF IgG and Dsg1 in a punctate staining on cell membrane 24 hours after treatment. Furthermore, morphological studies demonstrate that the dramatic alterations induced by PF sera are not the result of apoptotic programs. Taken together, our data strongly suggest that anti-Dsg1 antibodies from PF serum could cause the internalization of non-clustered Dsg1 and perturb the formation of new desmosomes but not directly disrupt Dsg1-containing junctions when stable contacts are already formed

Internalization of non-clustered desmoglein 1 without depletion of desmoglein 1 from adhesion complexes in an experimental model of the autoimmune disease pemphigus foliaceus

Serum antibodies against desmoglein 1 (Dsg1) are known to induce the clinical and histological manifestations of pemphigus foliaceus (PF), autoimmune bullous disease targeting skin. The basic pathophysiological phenomenon of PF blistering is the disruption of epithelial integrity in the granular layer of the epidermis due to separation of keratinocytes from one another, or acantholysis. In this report we investigate the changes in subcellular distribution of Dsg1 in response to serum of patients with PF by using an in vitro model of PF. Immunofluorescence analysis on HaCaT cells indicates that non-clustered Dsg1 is markedly internalized after exposure to serum. However, binding of PF IgG to Dsg1-rich adhesion complexes (desmosomes) does not cause disruption of such structures nor depletion of clustered Dsg1, as revealed by colocalization of PF IgG and Dsg1 in a punctate staining on cell membrane 24 hours after treatment. Furthermore, morphological studies demonstrate that the dramatic alterations induced by PF sera are not the result of apoptotic programs. Taken together, our data strongly suggest that anti-Dsg1 antibodies from PF serum could cause the internalization of non-clustered Dsg1 and perturb the formation of new desmosomes but not directly disrupt Dsg1-containing junctions when stable contacts are already formed

Immune profiling of uveal melanoma identifies a potential signature associated with response to immunotherapy

Background To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies.Methods Relevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM. Immune gene expression profiling was conducted by NanoString analysis on pre-treatment and post-treatment tumors from patients (n=6) receiving immune checkpoint blockade or 4-1BB and OX40 dual costimulation. The immune signature of UM tumors responding to immunotherapy was further characterized by Ingenuity Pathways Analysis and validated in The Cancer Genome Atlas data set.Results Both primary and metastatic UM tumors showed detectable infiltrating lymphocytes. Compared with primary tumors, treatment-naïve metastatic UM showed significantly higher levels of CD3+, CD8+, FoxP3+ T cells, and CD68+ macrophages. Notably, levels of PD-1+ infiltrates and PD-L1+ tumor cells were low to absent in primary and metastatic UM tumors. No metastatic organ-specific differences were seen in immune infiltrates. Our NanoString analysis revealed significant differences in a set of immune markers between responders and non-responders. A group of genes relevant to the interferon-γ signature was differentially up-expressed in the pre-treatment tumors of responders. Among these genes, suppressor of cytokine signaling 1 was identified as a marker potentially contributing to the response to immunotherapy. A panel of genes that encoded pro-inflammatory cytokines and molecules were expressed significantly higher in pre-treatment tumors of non-responders compared with responders.Conclusion Our study provides critical insight into immune profiles of UM primary and metastatic tumors, which suggests a baseline tumor immune signature predictive of response and resistance to immunotherapy in UM