Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
ACS Chem Biol ; 2020 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-32568522

RESUMEN

Targeted protein degradation (TPD) and proteolysis-targeting chimeras (PROTACs) have arisen as powerful therapeutic modalities for degrading specific proteins in a proteasome-dependent manner. However, a major limitation of TPD is the lack of E3 ligase recruiters. Recently, we discovered the natural product nimbolide as a covalent recruiter for the E3 ligase RNF114. Here, we show the broader utility of nimbolide as an E3 ligase recruiter for TPD applications. We demonstrate that a PROTAC linking nimbolide to the kinase and BCR-ABL fusion oncogene inhibitor dasatinib, BT1, selectively degrades BCR-ABL over c-ABL in leukemia cancer cells, compared to previously reported cereblon or VHL-recruiting BCR-ABL degraders that show opposite selectivity or in some cases inactivity. Thus, we further establish nimbolide as an additional general E3 ligase recruiter for PROTACs, and demonstrate the importance of expanding upon the arsenal of E3 ligase recruiters, as such molecules confer differing selectivity for the degradation of neo-substrate proteins.

2.
Nat Chem Biol ; 2020 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-32572277

RESUMEN

Molecular glues are an intriguing therapeutic modality that harness small molecules to induce interactions between proteins that typically do not interact. However, such molecules are rare and have been discovered fortuitously, thus limiting their potential as a general strategy for therapeutic intervention. We postulated that natural products bearing one or more electrophilic sites may be an unexplored source of new molecular glues, potentially acting through multicovalent attachment. Using chemoproteomic platforms, we show that members of the manumycin family of polyketides, which bear multiple potentially reactive sites, target C374 of the putative E3 ligase UBR7 in breast cancer cells, and engage in molecular glue interactions with the neosubstrate tumor-suppressor TP53, leading to p53 transcriptional activation and cell death. Our results reveal an anticancer mechanism of this natural product family, and highlight the potential for combining chemoproteomics and multicovalent natural products for the discovery of new molecular glues.

4.
Nat Chem Biol ; 15(7): 747-755, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31209351

RESUMEN

Nimbolide, a terpenoid natural product derived from the Neem tree, impairs cancer pathogenicity; however, the direct targets and mechanisms by which nimbolide exerts its effects are poorly understood. Here, we used activity-based protein profiling (ABPP) chemoproteomic platforms to discover that nimbolide reacts with a novel functional cysteine crucial for substrate recognition in the E3 ubiquitin ligase RNF114. Nimbolide impairs breast cancer cell proliferation in-part by disrupting RNF114-substrate recognition, leading to inhibition of ubiquitination and degradation of tumor suppressors such as p21, resulting in their rapid stabilization. We further demonstrate that nimbolide can be harnessed to recruit RNF114 as an E3 ligase in targeted protein degradation applications and show that synthetically simpler scaffolds are also capable of accessing this unique reactive site. Our study highlights the use of ABPP platforms in uncovering unique druggable modalities accessed by natural products for cancer therapy and targeted protein degradation applications.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Productos Biológicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Proteínas Portadoras/metabolismo , Limoninas/farmacología , Proteolisis/efectos de los fármacos , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Limoninas/química , Limoninas/aislamiento & purificación
5.
ACS Chem Biol ; 14(11): 2430-2440, 2019 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-31059647

RESUMEN

Targeted protein degradation has arisen as a powerful strategy for drug discovery allowing the targeting of undruggable proteins for proteasomal degradation. This approach most often employs heterobifunctional degraders consisting of a protein-targeting ligand linked to an E3 ligase recruiter to ubiquitinate and mark proteins of interest for proteasomal degradation. One challenge with this approach, however, is that only a few E3 ligase recruiters currently exist for targeted protein degradation applications, despite the hundreds of known E3 ligases in the human genome. Here, we utilized activity-based protein profiling (ABPP)-based covalent ligand screening approaches to identify cysteine-reactive small-molecules that react with the E3 ubiquitin ligase RNF4 and provide chemical starting points for the design of RNF4-based degraders. The hit covalent ligand from this screen reacted with either of two zinc-coordinating cysteines in the RING domain, C132 and C135, with no effect on RNF4 activity. We further optimized the potency of this hit and incorporated this potential RNF4 recruiter into a bifunctional degrader linked to JQ1, an inhibitor of the BET family of bromodomain proteins. We demonstrate that the resulting compound CCW 28-3 is capable of degrading BRD4 in a proteasome- and RNF4-dependent manner. In this study, we have shown the feasibility of using chemoproteomics-enabled covalent ligand screening platforms to expand the scope of E3 ligase recruiters that can be exploited for targeted protein degradation applications.


Asunto(s)
Complejos de Coordinación/química , Proteínas Nucleares/metabolismo , Proteolisis/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/química , Factores de Transcripción/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Complejos de Coordinación/metabolismo , Cisteína/química , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Complejo de la Endopetidasa Proteasomal/metabolismo , Unión Proteica , Dominios Proteicos , Bibliotecas de Moléculas Pequeñas/metabolismo , Relación Estructura-Actividad , Ubiquitinación , Zinc/química
6.
Cell Rep ; 25(11): 3074-3085.e5, 2018 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-30540940

RESUMEN

Intratumoral (IT) STING activation results in tumor regression in preclinical models, yet factors dictating the balance between innate and adaptive anti-tumor immunity are unclear. Here, clinical candidate STING agonist ADU-S100 (S100) is used in an IT dosing regimen optimized for adaptive immunity to uncover requirements for a T cell-driven response compatible with checkpoint inhibitors (CPIs). In contrast to high-dose tumor ablative regimens that result in systemic S100 distribution, low-dose immunogenic regimens induce local activation of tumor-specific CD8+ effector T cells that are responsible for durable anti-tumor immunity and can be enhanced with CPIs. Both hematopoietic cell STING expression and signaling through IFNAR are required for tumor-specific T cell activation, and in the context of optimized T cell responses, TNFα is dispensable for tumor control. In a poorly immunogenic model, S100 combined with CPIs generates a survival benefit and durable protection. These results provide fundamental mechanistic insights into STING-induced anti-tumor immunity.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Inmunidad , Proteínas de la Membrana/metabolismo , Neoplasias/inmunología , Animales , Antígeno CTLA-4/metabolismo , Línea Celular Tumoral , Citocinas/metabolismo , Relación Dosis-Respuesta Inmunológica , Resistencia a Antineoplásicos , Hematopoyesis , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neoplasias/patología , Receptor de Muerte Celular Programada 1/metabolismo , Proteínas S100/administración & dosificación , Proteínas S100/inmunología
7.
J Am Chem Soc ; 140(26): 8350-8356, 2018 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-29939024

RESUMEN

C(sp3)-H bond functionalization has emerged as a robust tool enabling rapid construction of molecular complexity from simple building blocks, and the development of asymmetric versions of this reaction creates a powerful methodology to access enantiopure sp3-rich materials. Herein, we report the stereoselective functionalization of C(sp3)-H bonds of cyclic ethers employing a photochemically active diaryliodonium salt in combination with an anionic phase-transfer catalyst. The synthetic strategy outlined herein allows for regio- and stereochemical control in the α-C-H acetalization of furans and pyrans using alcohol nucleophiles, thus providing the ability to control the configuration at the stereogenic exocyclic acetal carbon.


Asunto(s)
Acetales/síntesis química , Éteres Cíclicos/química , Luz , Compuestos Onio/química , Fosfatos/química , Acetales/química , Furanos/química , Estructura Molecular , Piranos/química , Estereoisomerismo
8.
Chem Sci ; 8(4): 2890-2897, 2017 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-28451354

RESUMEN

A mild palladium-catalyzed ligand-controlled regioselective 1,3-arylfluorination of 2[H]-chromenes has been developed. The products with a syn-1,3 substitution pattern were obtained with high enantiomeric excess using a PyrOx ligand, wherein the utility of these pyranyl-fluorides was further demonstrated through their participation in a diastereoselective C-C bond forming reaction. Ligand dependent divergent formation of both the 1,3- and 1,2- alkene difunctionalization products was observed. The nature of this bifurcation was investigated through experimental studies in combination with computational and statistical analysis tools. Ultimately, the site selectivity was found to rely on ligand denticity and metal electrophilicity, the electronics of the boronic acid, and the donor ability of the directing group in the substrate.

9.
J Org Chem ; 80(20): 9838-46, 2015 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-26401908

RESUMEN

(1)H NMR and computational analyses provide insight into the regiodivergent (α- and α'-) lithiation-electrophile trapping of N-thiopivaloyl- and N-(tert-butoxythiocarbonyl)-α-alkylazetidines. The magnitudes of the rotation barriers in these azetidines indicate that rotamer interconversions do not occur at the temperature and on the time scale of the lithiations. The NMR and computational studies support the origin of regioselectivity as being thiocarbonyl-directed lithiation from the lowest energy amide-like rotameric forms (cis for N-thiopivaloyl and trans for N-tert-butoxythiocarbonyl).


Asunto(s)
Azetidinas/química , Teoría Cuántica , Compuestos de Sulfhidrilo/química , Espectroscopía de Resonancia Magnética , Estructura Molecular
10.
Org Lett ; 17(2): 330-3, 2015 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-25535850

RESUMEN

tert-Butoxythiocarbonyl (Botc), the long-neglected thiocarbonyl analogue of Boc, facilitates (unlike its alkoxycarbonyl cousin) α-lithiation and electrophile incorporation on N-Botc-azetidine. N,N,N',N'-endo,endo-Tetramethyl-2,5-diaminonorbornane proved optimal as a chiral ligand, generating adducts with er up to 92:8. Facile deprotection, under conditions that left the corresponding N-Boc systems intact, was achieved using either TFA or via thermolysis in ethanol.


Asunto(s)
Aminas/química , Azetidinas/química , Diaminas/química , Ésteres del Ácido Fórmico/química , Litio/química , Norbornanos/química , Compuestos Organometálicos/química , Estructura Molecular , Estereoisomerismo
11.
Adv Synth Catal ; 356(4): 687-691, 2014 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-24839436

RESUMEN

A mild, catalytic, atom economical synthesis of imidazo[1,2-a]pyridines has been developed: catalytic PicAuCl2 in the presence of an acid produces a range imidazo[1,2-a]pyridines in good yield. This strategy is mild and forseen to be of particular use for the installation of stereogenic centers adjacent to the imidazo[1,2-a]pyridine ring without loss of enantiomeric excess.

12.
J Am Chem Soc ; 136(11): 4101-4, 2014 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-24617344

RESUMEN

A mild catalytic asymmetric direct fluoro-arylation of styrenes has been developed. The palladium-catalyzed three-component coupling of Selectfluor, a styrene and a boronic acid, provides chiral monofluorinated compounds in good yield and in high enantiomeric excess. A mechanism proceeding through a Pd(IV)-fluoride intermediate is proposed for the transformation and synthesis of an sp(3) C-F bond.


Asunto(s)
Hidrocarburos Fluorados/síntesis química , Paladio/química , Estirenos/química , Catálisis , Hidrocarburos Fluorados/química , Estructura Molecular
13.
Dermatol Surg ; 35(1): 30-3, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19018813

RESUMEN

BACKGROUND: Nonmelanoma skin cancer (NMSC) of the ear can result in large defects with significant morbidity. OBJECTIVE: To determine whether subanatomic location of NMSCs, based on ease of visualization of the ear, correlated with post-Mohs micrographic surgery (MMS) defect size. METHODS: A retrospective chart review of 142 post-MMS ear lesions was performed and categorized according to subanatomic location: the helix, antihelix, and tragus (Location 1); retroauricular (Location 2); and conchal bowl, scapha, and triangular fossa (Location 3). RESULTS: The average defect sizes were 2.50 cm(2) (Location 1), 5.76 cm(2) (Location 2), and 4.03 cm(2) (Location 3). Tumors in Location 1 were significantly smaller than those occurring in Location 2 (P<.001) and Location 3 (P<.01), but a significant difference in size was not seen between Locations 2 and 3 (P=.16). As a control group, we randomly selected 50 NMSC cases from the nose and found the average defect size of nose NMSCs to be 1.58 cm(2). CONCLUSIONS: MMS defects of the ear are larger in nonvisible parts of the ear. As a group, MMS defects on the ear were larger than those on the nose.


Asunto(s)
Neoplasias del Oído/patología , Neoplasias del Oído/cirugía , Cirugía de Mohs , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/patología , Carcinoma Basocelular/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Oído Externo/anatomía & histología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
14.
Dermatol Surg ; 34(2): 147-51, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18093206

RESUMEN

BACKGROUND: Imiquimod 5% cream has demonstrated effectiveness in the treatment of lentigo maligna (LM) in several small studies. None of the studies to date have included posttreatment surgical removal to confirm negative histologic margins. OBJECTIVE: The aim of this retrospective analysis was to assess the efficacy of topical imiquimod in LM by circumferentially examining vertically oriented sections from a geometrically designed "picture frame" margin as well as bread-loafed sections of the central portion after staged excisions of imiquimod-treated lesions of LM. METHODS: Forty patients with biopsy-confirmed LM were treated five times a week for 3 months with 5% imiquimod cream before staged excision. Tazarotene 0.1% gel was added when no clinical signs of erythema developed with imiquimod alone after 1 month (10 patients). After the course of topical therapy, patients were assessed for clinical and complete histologic clearance after staged excision. RESULTS: A total of 33 of 40 patients had a complete clinical response as determined by the absence of remaining clinical lesion on physical examination. Upon histologic review, 30 of 40 patients had no evidence of LM whereas 10 of 40 harbored residual disease. One patient was found to have histologic evidence of invasion after completing the topical protocol. After a mean follow-up of 18 months (range, 12-34 months) and after complete surgical excision of the treatment site, none of the imiquimod-treated patients had evidence of recurrence. CONCLUSIONS: Imiquimod appears to be an effective adjunctive treatment for LM but does not qualify as a replacement therapy for surgery.


Asunto(s)
Aminoquinolinas/administración & dosificación , Antineoplásicos/administración & dosificación , Peca Melanótica de Hutchinson/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Estudios de Seguimiento , Humanos , Peca Melanótica de Hutchinson/patología , Peca Melanótica de Hutchinson/cirugía , Imiquimod , Masculino , Persona de Mediana Edad , Pomadas , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Resultado del Tratamiento
15.
Dermatol Surg ; 33(1): 62-8; discussion 68, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17214680

RESUMEN

BACKGROUND: Dynamic telepathology is the real-time transmission of histologic images from one pathologist to another by means of telecommunications technology. OBJECTIVE: The objective was to determine whether dynamic telepathology can be accomplished accurately and inexpensively by use of readily available off-the-shelf consumer products and software. METHODS: We attached a standard, consumer-grade, digital video camera to a microscope in the Mohs surgery laboratory and then transmitted via the Internet real-time histologic video images and audio to a consultant dermatopathologist by means of iChat AV videoconferencing software (Apple Computer Inc., Cupertino, CA). In the first part of the study, 20 unknown formalin-fixed, paraffin-embedded slides from tumors typically seen in a Mohs practice were evaluated by the consultant dermatopathologist. In the second part of the study, the Mohs surgeon consulted the dermatopathologist on 20 Mohs frozen section slides in which the surgeon had a particular question (e.g., "Is this part of a pilosebaceous unit or is this basal cell carcinoma?"). RESULTS: The video images were adequate for pathologic interpretation. There was agreement between conventional light microscopy and dynamic telepathology diagnosis in 19 of 20 tumors. There was complete agreement for all 20 Mohs frozen section consultations. CONCLUSION: Dynamic telepathology can be accomplished accurately and inexpensively by use of readily available consumer products and software.


Asunto(s)
Consulta Remota/instrumentación , Enfermedades de la Piel/patología , Telepatología/instrumentación , Interfaz Usuario-Computador , Comunicación por Videocoferencia/instrumentación , Análisis Costo-Beneficio , Secciones por Congelación , Humanos , Cirugía de Mohs , Consulta Remota/economía , Reproducibilidad de los Resultados , Enfermedades de la Piel/cirugía , Telepatología/economía , Comunicación por Videocoferencia/economía
16.
Am J Prev Med ; 32(1): 79-85, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17184959

RESUMEN

BACKGROUND: Two of the major goals of tobacco prevention and control activities are to change social norms and influence policy. The news media can play an important role for achieving both goals. METHODS: The Centers for Disease Control and Prevention's Office on Smoking and Health created a surveillance system to track tobacco stories in the news media beginning in 2004. The system was developed based on reviewing lessons from previous news media tracking efforts, including defining the purpose of the system, using a parsimonious approach to sample media outlets, and attending to data-quality issues. Tobacco news stories were systematically identified and coded from ten newspapers, four news wire services, and seven national television networks. RESULTS: Findings indicated that from January 2004 through June 2005, tobacco-related stories were in selected major newspapers virtually every day. More than 70% of all newspaper stories contained one of only three main story themes: policy or regulation (31.0%), legal issues (23.8%), or health effects or statistics (18.1%). Television news stories on tobacco were much less common, but increased substantially during the first 6 months of 2005 compared to 2004. Health effects/statistics (50.5%) were the dominant theme for television, with policy/regulation a distant second (19.5%). CONCLUSIONS: Tobacco-related media coverage can be systematically tracked and characterized. These findings may have value to public health researchers and policymakers who wish to evaluate efforts to curb tobacco-related disease.


Asunto(s)
Medios de Comunicación de Masas , Investigación , Industria del Tabaco , Prevención del Hábito de Fumar , Estados Unidos
17.
Dermatol Surg ; 32(4): 493-504, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16681656

RESUMEN

BACKGROUND: Lentigo maligna (LM) is a subtype of melanoma in situ that typically develops on sun-damaged skin. Presentation may be quite subtle and delayed diagnosis is common. Clinical margins are often ill defined. Histologic evaluation can be difficult due to the widespread atypical melanocytes that are present in the background of long-standing sun damage. Recurrence following standard therapies is common. OBJECTIVE: To review the clinical features, histopathology, and treatment options for LM. Emphasis is placed on recent advances in the treatment of LM. METHODS AND MATERIALS: Literature review. RESULTS: The estimated lifetime risk of LM progressing to LM melanoma is 5%. Standard excision of LM with 5 mm margins is insufficient in 50% of cases. The recurrence rate with standard excision ranges from 8 to 20%. Mohs surgery and staged excision may offer better margin control and lower recurrence rates (4-5%). Estimates of recurrence rates following nonsurgical therapies such as cryosurgery, radiotherapy, electrodessication and curettage, laser surgery, and topical medications range from 20 to 100% at 5 years. CONCLUSIONS: Adequate treatment of LM requires a comprehensive knowledge of the diagnostic features, histopathology, and treatment options. Surgical modalities with meticulous evaluation of tissue margins appears to offer the lowest rates of disease recurrence.


Asunto(s)
Peca Melanótica de Hutchinson/diagnóstico , Peca Melanótica de Hutchinson/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Crioterapia , Neoplasias Faciales/diagnóstico , Neoplasias Faciales/terapia , Humanos , Peca Melanótica de Hutchinson/patología , Peca Melanótica de Hutchinson/radioterapia , Rayos Láser , Cirugía de Mohs , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/radioterapia
18.
Immunol Allergy Clin North Am ; 24(3): 399-423, vi, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15242718

RESUMEN

Cutaneous drug reactions have a variety of clinical presentations. This review focuses on the most common or severe cutaneous reaction patterns. Knowledge of the clinical morphology and the most commonly associated medication aids in rapid diagnosis and institution of the appropriate therapy.


Asunto(s)
Erupciones por Medicamentos/inmunología , Erupciones por Medicamentos/fisiopatología , Diagnóstico Diferencial , Erupciones por Medicamentos/diagnóstico , Humanos , Factores de Riesgo , Índice de Severidad de la Enfermedad
19.
Drugs Today (Barc) ; 40(12): 961-74, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15645008

RESUMEN

Recognition of psoriasis as a T-cell-mediated immune disease has led to the development of various therapeutic approaches directed against the T cell and T-cell processes such as activation, trafficking and cytokine release. The novel and selective biologic agent alefacept, with an effect of selective apoptotic reduction in memory-effector T cells, has been given FDA approval for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. The clinical profile of this novel biologic agent is presented here. Two pivotal multicenter, randomized, placebo-controlled, double-blind studies enrolling 1060 patients were designed to support the efficacy and safety of alefacept in the treatment of moderate to severe chronic plaque psoriasis. With either intramuscular or intravenous administration, well over half of patients treated with a single course of alefacept achieved a 50% reduction in PASI (Psoriasis Area and Severity Index), and a second course of therapy provided further benefit by increasing response rates and providing long-lasting off-treatment responses regardless of the route of administration. In all studies, alefacept was well tolerated. There was no evidence of an increased risk of infections or malignancies and no opportunistic infections were reported. Consistent with its composition as a fully human fusion protein, alefacept had a low incidence of immunogenicity and no evidence of an increased rate of antibody development over time. There was no evidence that primary or secondary responses to a new antigen or memory response to a recall antigen were blunted in patients treated with alefacept. In conclusion, alefacept is the first biologic therapy to demonstrate positive effects in an immune-mediated disease while maintaining immune responses to novel and recall antigens. This selective effect on the immune system distinguishes alefacept from immunosuppressive therapies that are nonselective.


Asunto(s)
Psoriasis/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Alefacept , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/farmacología , Fármacos Dermatológicos/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Inyecciones Intramusculares , Inyecciones Intravenosas , Masculino , Psoriasis/diagnóstico , Psoriasis/inmunología , Radioterapia Ayuvante , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/farmacología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
20.
Int J Dermatol ; 42(7): 549, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12839605

RESUMEN

A 65-year-old male presented for skin examination and was incidentally noted to have discoloration of the fingernails. These findings were completely asymptomatic. The patient had been taking colloidal silver supplementation (Silverzone 140 ppm silver Gifts of Nature, St. George, UT, USA) for 2 years as therapy for diabetes. He first noticed the onset of nail discoloration 1 year ago. His past medical history included type II diabetes and hypertension. His current medications were metformin, glyburide, and benazepril. Physical examination revealed slate-gray discoloration involving the lunulae of the fingernails (Fig. 1). The skin, mucous membranes, and sclerae were unaffected.


Asunto(s)
Argiria/etiología , Enfermedades de la Uña/inducido químicamente , Plata/efectos adversos , Anciano , Coloides , Diabetes Mellitus/tratamiento farmacológico , Suplementos Dietéticos/envenenamiento , Humanos , Masculino
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA