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https://www.readbyqxmd.com/read/29782307/cutaneous-manifestations-of-tuberous-sclerosis
#1
Mirjana Bakić, Marina Ratković, Branka Gledović, Balsa Vujović, Danilo Radunović, Vera Babić, Vladimir Prelević
Dear Editor, Tuberous sclerosis (TS) is an autosomal dominant multisystem disease, which occurs due to genetically determined hyperplasia of ectodermal and mesodermal cells. Clinical manifestations present on the skin and in the nervous system, kidneys, heart, and other organs. Recent studies estimate the incidence of TS at 1/6000 to 1/10,000 live births, and a prevalence in the general population of approximately 1 in 20,000 (1). There are two different genetic loci responsible for TS: 9q34 (TSC1-hamartin) and 16p13...
April 2018: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/29559887/topical-dexamethasone-administration-impairs-protein-synthesis-and-neuronal-regeneration-in-the-olfactory-epithelium
#2
Umberto Crisafulli, André M Xavier, Fabiana B Dos Santos, Tavane D Cambiaghi, Seo Y Chang, Marimélia Porcionatto, Beatriz A Castilho, Bettina Malnic, Isaias Glezer
Chronic inflammatory process in the nasal mucosa is correlated with poor smell perception. Over-activation of immune cells in the olfactory epithelium (OE) is generally associated with loss of olfactory function, and topical steroidal anti-inflammatory drugs have been largely used for treating such condition. Whether this therapeutic strategy could directly affect the regenerative process in the OE remains unclear. In this study, we show that nasal topical application of dexamethasone (DEX; 200 or 800 ng/nostril), a potent synthetic anti-inflammatory steroid, attenuates OE lesion caused by Gram-negative bacteria lipopolysaccharide (LPS) intranasal infusion...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29432811/rapamycin-attenuates-th2-driven-experimental-allergic-conjunctivitis
#3
Soojung Shin, Ji Hyun Lee, Hyun Jung Lee, Sun Young Chang, So-Hyang Chung
Allergic conjunctivitis is mediated by eosinophilic infiltration and Th2 type immune responses. This study aims to elucidate the role of rapamycin, mTOR inhibitor, on OVA-induced experimental allergic conjunctivitis (EAC). Rapamycin administration intraperitoneally markedly reduced clinical signs, total and OVA-specific IgE and IgG1/G2a ratio in serum, and conjunctival eosinophilic infiltration. Infiltrations of CD11c+ dendritic cells and CD4+ T cells, and the expressions of chemokines and adhesion molecules in the conjunctiva were attenuated in rapamycin-treated mice, as well as decreased Th1 and Th2 cytokines in the cervical lymph nodes compared to non-treated mice...
May 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29233869/mtorc1-as-the-main-gateway-to-autophagy
#4
REVIEW
Yoana Rabanal-Ruiz, Elsje G Otten, Viktor I Korolchuk
Cells and organisms must coordinate their metabolic activity with changes in their environment to ensure their growth only when conditions are favourable. In order to maintain cellular homoeostasis, a tight regulation between the synthesis and degradation of cellular components is essential. At the epicentre of the cellular nutrient sensing is the mechanistic target of rapamycin complex 1 (mTORC1) which connects environmental cues, including nutrient and growth factor availability as well as stress, to metabolic processes in order to preserve cellular homoeostasis...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29189123/anti-aging-drugs-prospect-of-longer-life
#5
Blanka Klimova, Michal Novotny, Kamil Kuca
BACKGROUND: Aging is a natural part of human life. However, recent discoveries indicate that pharmacological approaches used for the improvement and possibly, for the delay of the aging process, might shed a new light on this topic. This might obviously contribute to the extension of the active life of older people and maintenance of their quality of life, which could consequently reduce both social and economic burden of each country, especially the developed ones. OBJECTIVE: The purpose of this study is to explore pharmacological discoveries which may help to the delay or improvement of the aging process...
November 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29146131/dysregulation-of-autophagy-in-melanocytes-contributes-to-hypopigmented-macules-in-tuberous-sclerosis-complex
#6
Fei Yang, Lingli Yang, Mari Wataya-Kaneda, Junya Hasegawa, Tamotsu Yoshimori, Atsushi Tanemura, Daisuke Tsuruta, Ichiro Katayama
BACKGROUND: Tuberous sclerosis complex (TSC) gene mutations lead to constitutive activation of the mammalian target of rapamycin (mTOR) pathway, resulting in a broad range of symptoms. Hypopigmented macules are the earliest sign. Although we have already confirmed that topical rapamycin treatment (an mTOR inhibitor) protects patients with TSC against macular hypopigmentation, the pathogenesis of such lesions remains poorly understood. OBJECTIVE: Recently emerging evidence supports a role for autophagy in skin pigmentation...
February 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28811001/topical-rapamycin-an-additional-therapeutic-option-for-tufted-angioma-in-adults
#7
M M Escudero-Góngora, O Corral-Magaña, C Gómez, A Martín-Santiago
No abstract text is available yet for this article.
March 2018: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/28694031/in-vivo-induction-of-regulatory-t-cells-promotes-allergen-tolerance-and-suppresses-allergic-contact-dermatitis
#8
Stephen C Balmert, Cara Donahue, John R Vu, Geza Erdos, Louis D Falo, Steven R Little
Allergic contact dermatitis (ACD) is a common T-cell mediated inflammatory skin condition, characterized by an intensely pruritic rash at the site of contact with allergens like poison ivy or nickel. Current clinical treatments use topical corticosteroids, which broadly and transiently suppress inflammation and symptoms of ACD, but fail to address the underlying immune dysfunction. Here, we present an alternative therapeutic approach that teaches the immune system to tolerate contact allergens by expanding populations of naturally suppressive allergen-specific regulatory T cells (Tregs)...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28690858/topical-rapamycin-for-facial-angiofibromas-in-tuberous-sclerosis-complex
#9
Gilles Safa
Facial angiofibromas are a common cutaneous manifestation of tuberous sclerosis complex. Although angiofibromas are usually asymptomatic, they can be highly disfiguring and can have a significant impact on patient quality of life. Treatment for facial angiofibromas is challenging. Recently, topical rapamycin has been proposed as an effective option to treat angiofibromas. Herein is reported a case of a 27-year-old woman whose facial angiofibromas were successfully treated with topical rapamycin without relevant side effects...
July 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/28677234/anti-aging-pharmacology-in-cutaneous-wound-healing-effects-of-metformin-resveratrol-and-rapamycin-by-local-application
#10
Pan Zhao, Bing-Dong Sui, Nu Liu, Ya-Jie Lv, Chen-Xi Zheng, Yong-Bo Lu, Wen-Tao Huang, Cui-Hong Zhou, Ji Chen, Dan-Lin Pang, Dong-Dong Fei, Kun Xuan, Cheng-Hu Hu, Yan Jin
Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects...
October 2017: Aging Cell
https://www.readbyqxmd.com/read/28597024/blocking-mtor-signalling-with-rapamycin-ameliorates-imiquimod-induced-psoriasis-in-mice
#11
Claudia Bürger, Nitesh Shirsath, Victoria Lang, Sandra Diehl, Roland Kaufmann, Andreas Weigert, Ying-Ying Han, Christian Ringel, Peter Wolf
The mTOR (mechanistic target of rapamycin) inhibitor rapamycin has long been known for its immune suppressive properties, but it has shown limited therapeutic success when given systemically to patients with psoriasis. Recent data have shown that the mTOR pathway is hyperactivated in lesional psoriatic skin, which probably contributes to the disease by interfering with maturation of keratinocytes. This study investigated the effect of topical rapamycin treatment in an imiquimod-induced psoriatic mouse model...
October 2, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28557723/microcystic-lymphatic-malformation-successfully-treated-with-topical-rapamycin
#12
Pablo García-Montero, Javier Del Boz, Miguel Sanchez-Martínez, Isabel María Escudero Santos, Eulalia Baselga
Microcystic lymphatic malformations (MLM) are low-flow vascular malformations composed of multiple small cysts. MLM usually affect deep-lying structures, which makes their treatment even more difficult and complex. A novel and interesting treatment is rapamycin, a mammalian target of rapamycin inhibitor that when orally administrated has offered favorable results. However, until recently, topical rapamycin had not been used in the treatment of MLM. Case 1 is a girl aged 13 years with extensive MLM affecting the muscles in the right buttock...
May 2017: Pediatrics
https://www.readbyqxmd.com/read/28469076/stat3-regulates-desmoglein-3-transcription-in-epithelial-keratinocytes
#13
Xuming Mao, Michael Jeffrey T Cho, Christoph T Ellebrecht, Eric M Mukherjee, Aimee S Payne
Pemphigus vulgaris (PV) is an epithelial blistering disease caused by autoantibodies to the desmosomal cadherin desmoglein 3 (DSG3). Glucocorticoids improve disease within days by increasing DSG3 gene transcription, although the mechanism for this observation remains unknown. Here, we show that DSG3 transcription in keratinocytes is regulated by Stat3. Treatment of primary human keratinocytes (PHKs) with hydrocortisone or rapamycin, but not the p38 MAPK inhibitor SB202190, significantly increases DSG3 mRNA and protein expression and correspondingly reduces phospho-S727 Stat3...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28388374/summary-points-and-consensus-recommendations-from-the-international-protein-summit
#14
Ryan T Hurt, Stephen A McClave, Robert G Martindale, Juan B Ochoa Gautier, Jorge A Coss-Bu, Roland N Dickerson, Daren K Heyland, L John Hoffer, Frederick A Moore, Claudia R Morris, Douglas Paddon-Jones, Jayshil J Patel, Stuart M Phillips, Saúl J Rugeles, Menaka Sarav Md, Peter J M Weijs, Jan Wernerman, Jill Hamilton-Reeves, Craig J McClain, Beth Taylor
The International Protein Summit in 2016 brought experts in clinical nutrition and protein metabolism together from around the globe to determine the impact of high-dose protein administration on clinical outcomes and address barriers to its delivery in the critically ill patient. It has been suggested that high doses of protein in the range of 1.2-2.5 g/kg/d may be required in the setting of the intensive care unit (ICU) to optimize nutrition therapy and reduce mortality. While incapable of blunting the catabolic response, protein doses in this range may be needed to best stimulate new protein synthesis and preserve muscle mass...
April 2017: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/28351834/cutaneous-manifestations-of-tuberous-sclerosis-complex-and-the-paediatrician-s-role
#15
REVIEW
Michael A Cardis, Cynthia Marie Carver DeKlotz
Tuberous sclerosis complex (TSC) is a multisystem genetic disorder stemming from unregulated activation of the mammalian target of rapamycin (mTOR) pathway, resulting in the growth of hamartomas in multiple organs. TSC-related skin lesions often develop early in life and can be disfiguring, emotionally distressful and even painful at times. Recognition of TSC-associated skin features by paediatricians can be a catalyst for facilitating early implementation of treatment strategies and establishing appropriate follow-up care...
September 2017: Archives of Disease in Childhood
https://www.readbyqxmd.com/read/28285560/prospective-pilot-study-on-combined-use-of-pulsed-dye-laser-and-1-topical-rapamycin-for-treatment-of-nonfacial-cutaneous-capillary-malformation
#16
Eun Jin Doh, Jungyoon Ohn, Min Ji Kim, Young Gull Kim, Soyun Cho
BACKGROUND: The regeneration or revascularization of blood vessels after pulsed dye laser (PDL) treatment is one of the causes of treatment failures of cutaneous capillary malformations (CM). Recently, topical administration of rapamycin was introduced as a possible adjunctive therapeutic option to minimize postlaser revascularization in facial CM. OBJECTIVES: We evaluated the effect of combined use of 1% topical rapamycin with PDL compared to PDL alone in cutaneous CM of trunk or extremities and tried to identify the optimal duration of topical rapamycin application...
November 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28203158/a-28-year-old-male-patient-with-nail-tumors-skin-lesions-and-epilepsy
#17
Deepak M W Balak, Bernard A Zonnenberg, Juliette M J Spitzer-Naaijkens, Mieke M Hulshof
BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of benign hamartomas in multiple organs. Most patients with TSC exhibit cutaneous manifestations. METHODS: We report a 28-year-old patient with multiple pink papules at the proximal nail fold of several toes. RESULTS: Histopathological analysis of a biopsy of a papule was consistent with an ungual fibroma. Histopathological analysis of a biopsy of an elevated skin-colored plaque at the lower back was diagnostic for a Shagreen patch...
January 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28195079/update-on-etiopathogenesis-and-treatment-of-acne
#18
REVIEW
Yasmeen Jabeen Bhat, Insha Latief, Iffat Hassan
Acne, the most common skin disease, is a disorder of pilosebaceous units that affects adolescents mainly and adults occasionally. The pathogenesis is multifactorial. Besides genetic predisposition, other major factors include the action of androgens, pro-inflammatory lipids acting as ligands of peroxisome proliferator-activated receptors in the sebocytes, toll-like receptor-2 acting on keratinocytes, recognition of pathogen-associated molecular patterns, cytokines, chemokines, inflammasomes, neuroendocrine regulatory mechanisms, diet and other pro-inflammatory targets implicated in the activation of immune detection and response...
May 2017: Indian Journal of Dermatology, Venereology and Leprology
https://www.readbyqxmd.com/read/28186992/autophagy-is-highly-targeted-among-host-comparative-proteomes-during-infection-with-different-virulent-rabv-strains
#19
Ling Li, Hongli Jin, Hualei Wang, Zengguo Cao, Na Feng, Jianzhong Wang, Yongkun Zhao, Xuexing Zheng, Pengfei Hou, Nan Li, Hang Chi, Pei Huang, Cuicui Jiao, Qian Li, Lina Wang, Tiecheng Wang, Weiyang Sun, Yuwei Gao, Changchun Tu, Guixue Hu, Songtao Yang, Xianzhu Xia
Rabies virus (RABV) is a neurotropic virus that causes serious disease in humans and animals worldwide. It has been reported that different RABV strains can result in divergent prognoses in animal model. To identify host factors that affect different infection processes, a kinetic analysis of host proteome alterations in mouse brains infected with different virulent RABV strains was performed using isobaric tags for a relative and absolute quantification (iTRAQ)-liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach, and this analysis identified 147 differentially expressed proteins (DEPs) between the pathogenic challenge virus standard (CVS)-11 strain and the attenuated SRV9 strain...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28181194/topical-rapamycin-for-facial-angiofibromas-in-a-child-with-tuberous-sclerosis-complex-tsc-a-case-report-and-long-term-follow-up
#20
Daniel Ebrahimi-Fakhari, Cornelia Sigrid Lissi Müller, Sascha Meyer, Marina Flotats-Bastardas, Thomas Vogt, Claudia Pföhler
Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with prominent skin involvement including facial angiofibromas that often appear in early childhood. Here we report the case of a 12-year-old girl with widespread disfiguring facial angiofibromas that were successfully treated with topical rapamycin, a mTOR inhibitor. A sustained remission of skin lesions was documented in detail over a 3-year follow-up. This case highlights the fact that topical rapamycin is a useful option in treating TSC-associated skin lesions...
March 2017: Dermatology and Therapy
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