233 research outputs found

    Successful treatment of co-existent SAPHO syndrome and hidradenitis suppurativa with adalimumab and methotrexate

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    SAPHO syndrome, namely Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis, is a rare autoinflammatory chronic disease presenting with non-infectious inflammatory osteitis, sterile joint inflammation and skin manifestations, including palmoplantar pustulosis and severe acne. The case of a 15-year-old boy affected by SAPHO syndrome and hidradenitis suppurativa (HS) is presented and discussed. Coexistence of these two diseases may represent a therapeutic challenge and this case confirms literature data reporting the efficacy of the combination of methotrexate and adalimumab in SAPHO complicated by HS

    Effects of pharmacological treatments on emotional tasks in borderline personality disorder: A review of functional magnetic resonance imaging studies

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    Background: Borderline personality disorder (BPD) is a common mental disorder characterized by instability in interpersonal relationships, impaired self-image, impulsivity and aggressive behaviors that often requires pharmacological treatments. Neuroimaging alterations have been extensively reported in BPD, especially in regions within the fronto-limbic system. Although medications can be an important confounding factor in functional Magnetic Resonance Imaging (fMRI) studies, their role on brain function in BPD patients still remains uncertain. Therefore, this review aims to improve our understanding on the potential effect of the most commonly prescribed drugs for BPD on brain function during processing of emotional tasks. Methods: A search on PubMed, Scopus and Web of Science of fMRI studies exploring the effect of antipsychotics, antidepressants and mood stabilizers on brain activity during processing of emotional tasks on BPD was conducted. Results: Overall the studies showed small or no effect of pharmacological treatments on brain activity and connectivity in BPD patients during processing of emotional tasks. Limitations: The small sample size, the observational design, the elevated percentage of women, the concomitant use of psychostimulants, anticholinergics and opioids substitute treatments and the high rate of comorbidities limit the conclusion of this review. Conclusions: Pharmacological treatments seem to have minor role on brain activity/connectivity in BPD patients during emotional tasks, ultimately suggesting that in BPD patients brain deficits seem not be influenced by medications. This might be due to functional brain specificities of BPD and to the differences in pharmacological regimens and compliance to therapy between BPD and other common psychiatric disorders

    Epigenetic Mechanisms of Epidermal Differentiation

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    Keratinocyte differentiation is an essential process for epidermal stratification and stratum corneum formation. Keratinocytes proliferate in the basal layer of the epidermis and start their differentiation by changing their functional or phenotypical type; this process is regulated via induction or repression of epidermal differentiation complex (EDC) genes that play a pivotal role in epidermal development. Epidermal development and the keratinocyte differentiation program are orchestrated by several transcription factors, signaling pathways, and epigenetic regulators. The latter exhibits both activating and repressive effects on chromatin in keratinocytes via the ATP-dependent chromatin remodelers, histone demethylases, and genome organizers that promote terminal keratinocyte differentiation, and the DNA methyltransferases, histone deacetylases, and Polycomb components that stimulate proliferation of progenitor cells and inhibit premature activation of terminal differentiation-associated genes. In addition, microRNAs are involved in different processes between proliferation and differentiation during the program of epidermal development. Here, we bring together current knowledge of the mechanisms controlling gene expression during keratinocyte differentiation. An awareness of epigenetic mechanisms and their alterations in health and disease will help to bridge the gap between our current knowledge and potential applications for epigenetic regulators in clinical practice to pave the way for promising target therapies

    Structural and functional brain imaging after treatment with selective-serotonin reuptake-inhibitors in obsessive-compulsive disorder: A mini review

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    Background: Obsessive-compulsive disorder (OCD) is a psychiatric disorder whose etiopathogenesis, according to various neuroimaging studies, seems to be linked to selective dysfunctions in regions within the cortico-striatal-thalamo-cortical circuit. Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line therapy for OCD but their neurobiological effects on the brain is only partially understood. Therefore, the aim of this review is to highlight structural and functional brain imaging modifications induced by SSRIs treatment. Methods: A literature search on PubMed, Psych-Info and Embase database was performed. Studies including patients with OCD that analyzed the effect of SSRIs through structural and functional Magnetic Resonance Imaging were selected. Seven relevant studies were considered eligible for the present review. Results: Overall, the results of the reviewed studies showed that SSRIs treatment seems to normalize structural, in terms of the white matter and gray matter volumes, and functional activity alterations observed in OCD patients, especially in regions within the prefrontal cortex and striatum. Limitations: The poor design of the studies, the small and heterogeneous samples, differences in age, gender, illness course, comorbidities, treatment protocols and the different magnetic fields used make it difficult to generalize the results. Conclusions: From the available evidence it emerged that SSRIs treatment has proven to be effective in normalizing brain structural and functional alterations observed in OCD patients. However, future neuroimaging investigations should focus on long-term effects of drugs on brain structure and function in OCD patients through longitudinal approaches in order to identify more effective treatments for these patients

    NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies

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    The NLRP3 inflammasome is one of the NOD-like receptor family members with the most functional characterization and acts as a key player in innate immune system, participating in several physiological processes including, among others, the modulation of the immune system response and the coordination of host defences. Activation of the inflammasome is a crucial signaling mechanism that promotes both an acute and a chronic inflammatory response, which can accelerate the production of pro-inflammatory cytokines, mainly Interleukin (IL)-1β and IL-18, leading to an exacerbated inflammatory network. Cryopyrin associated periodic syndrome (CAPS) is a rare inherited autoinflammatory disorder, clinically characterized by cutaneous and systemic, musculoskeletal, and central nervous system inflammation. Gain-of-function mutations in NLRP3 gene are causative of signs and inflammatory symptoms in CAPS patients, in which an abnormal activation of the NLRP3 inflammasome, resulting in an inappropriate release of IL-1β and gasdermin-D-dependent pyroptosis, has been demonstrated both in in vitro and in ex vivo studies. During recent years, two new hereditary NLRP3-related disorders have been described, deafness autosomal dominant 34 (DFN34) and keratitis fugax hereditaria (KFH), with an exclusive cochlear- and anterior eye- restricted autoinflammation, respectively, and caused by mutations in NLRP3 gene, thus expanding the clinical and genetic spectrum of NLRP3-associated autoinflammatory diseases. Several crucial mechanisms involved in the control of activation and regulation of the NLRP3 inflammasome have been identified and researchers took advantage of this to develop novel target therapies with a significant improvement of clinical signs and symptoms of NLRP3-associated diseases. This review provides a broad overview of NLRP3 inflammasome biology with particular emphasis on CAPS, whose clinical, genetic, and therapeutic aspects will be explored in depth. The latest evidence on two “new” diseases, DFN34 and KFH, caused by mutations in NLRP3 is also described
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