RESUMEN
The utilization of biocatalytic oxidations has evolved from the niche applications of the early 21st century to a widely recognized tool for general chemical synthesis. One of the major drawbacks that hinders commercialization is the dependence on expensive nicotinamide adenine dinucleotide (NAD(P)+) cofactors, and so, their regeneration is essential. Here, we report the design of carbon-supported Pt catalysts that can regenerate NAD(P)+ by proton-driven NAD(P)H oxidation with concurrent hydrogen formation. The carbon support was modified to tune the electronic nature of the Pt nanoparticles, and it was found that the best catalyst for NAD(P)+ regeneration (TOF = 581 h-1) was electron-rich Pt on carbon. Finally, the heterogeneous Pt catalyst was applied in the biocatalytic oxidation of a variety of alcohols catalyzed by different alcohol dehydrogenases. The Pt catalyst exhibited good compatibility with the biocatalytic system. Its NAD(P)+ regeneration function successfully supported biocatalytic conversion from alcohols to corresponding ketone or lactone products. This work provides a promising strategy for chemical synthesis via NAD(P)+-dependent pathways utilizing a cooperative inorganic-enzymatic catalytic system.
Asunto(s)
NAD , Platino (Metal)/química , Protones , Alcoholes , Carbono , Catálisis , NAD/metabolismo , Oxidación-Reducción , RegeneraciónRESUMEN
This study demonstrates a novel method to quantify selective (1,4-NADH) and unselective products (1,2- and 1,6-NADH) in NADH regeneration using combined UV-Vis spectroscopy and biological assays. The validity of the proposed method was tested in the Pt/C promoted NAD+ hydrogenation using hydrogen as reducing agent.
RESUMEN
A 3-year 10-month-old child initially developed locally recurrent cutaneous eruptions within the first 2 weeks after sustaining a jellyfish sting to her lower extremities. After 5 asymptomatic weeks, she developed unilateral orbital inflammation that did not respond to systemic antibiotics, antihistamines, or steroids. Imaging revealed a rapidly growing mass of the right lacrimal gland. Urgent anterior orbitotomy was performed and the lacrimal gland was biopsied. Histopathologic diagnosis revealed sclerosing dacryodenitis consistent with orbital inflammatory syndrome and/or an immune response to an antigen challenge.
Asunto(s)
Mordeduras y Picaduras/complicaciones , Dacriocistitis/etiología , Pierna , Seudotumor Orbitario/etiología , Escifozoos , Animales , Preescolar , Venenos de Cnidarios , Dacriocistitis/patología , Femenino , Humanos , Aparato Lagrimal/patología , Imagen por Resonancia Magnética , Seudotumor Orbitario/diagnóstico , EsclerosisRESUMEN
Envenomation syndromes induced by Atlantic cnidaria have been tabulated and their therapy discussed. The pharmacokinetics of the venom has been emphasized. Pain occurs instantly and reaches a zenith rapidly in the surf. The nematocysts have already penetrated the dermis and disease proceeds before help can arrive. This fact plus the relative impermeability of human epidermis hampers the efficacy of topical agents. Oral analgesics, the agents of choice, are seldom offered and systemic administration of these drugs is usually not necessary. The use of hot or cold applications has not been settled. Measures to inactivate nematocysts within tentacles adherent to skin post-sting have been demonstrated in vitro, but the clinical significance of these actions has not been shown. Using an abrader (sand, crystalline papain) to counter-irritate nearby skin might provide relief. Antivenoms for Atlantic cnidaria are not available. The instances when verapamil might be employed are very rare. The reasons for the increasing case load of these injuries are discussed and the need to discover more effective therapeutic agents is emphasized.
Asunto(s)
Analgésicos/uso terapéutico , Mordeduras y Picaduras/terapia , Venenos de Cnidarios/antagonistas & inhibidores , Fármacos Dermatológicos/uso terapéutico , Analgésicos/farmacología , Animales , Mordeduras y Picaduras/tratamiento farmacológico , Venenos de Cnidarios/envenenamiento , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Fármacos Dermatológicos/farmacología , Humanos , Dolor/tratamiento farmacológicoRESUMEN
BACKGROUND: Patients with stem cell transplantation (SCT) develop erythematous eruptions (SCTE) that are often misdiagnosed and poorly treated. Latent herpes simplex virus (HSV) is likely to be reactivated by SCT-associated immunosuppression. Therefore, one of the differential diagnostic possibilities for SCTE is HSV-associated erythema multiforme (HAEM) in which HSV genetic fragments localize in stem cells that deliver them to the skin on differentiation. OBSERVATIONS: Lesional skin from patients with SCTE, HAEM, HSV, or drug-induced erythema (DIEM) was stained with antibodies to the HSV antigen DNA polymerase (Pol) and the major capsid protein, virion protein 5 (VP5). The HSV DNA polymerase Pol was expressed in 79% of patients with SCTE and 75% of those with HAEM. The protein VP5 was not expressed in these patients, indicative of the absence of virus replication. Findings in patients with DIEM were negative for both antigens, and those with HSV lesions were positive for both antigens. CONCLUSIONS: There is a growing problem with SCTE, related to the increasing numbers of performed SCT. The greater frequency of SCT-generated circulating stem cells in patients with hematological malignant neoplasms (who have latent HSV infection) may result in a widespread SCTE characterized by skin deposition of HSV DNA fragments, notably those expressing Pol antigen. This HAEM-like presentation should be considered in the differential diagnosis of SCTE. Prolonged high-dosage antiviral chemotherapy during and after hospitalization may be warranted.
Asunto(s)
Eritema Multiforme/virología , Herpes Simple/complicaciones , Simplexvirus/aislamiento & purificación , Trasplante de Células Madre , Enfermedad Aguda , Adulto , Antígenos CD34/análisis , ADN Viral/análisis , ADN Polimerasa Dirigida por ADN/genética , Eritema Multiforme/etiología , Eritema Multiforme/patología , Exodesoxirribonucleasas/genética , Humanos , Simplexvirus/enzimología , Simplexvirus/genética , Simplexvirus/inmunología , Proteínas Virales/genéticaAsunto(s)
Mordeduras y Picaduras/complicaciones , Venenos de Cnidarios/efectos adversos , Tratamiento de Urgencia , Eritema Nudoso/etiología , Hidrozoos , Corticoesteroides/uso terapéutico , Animales , Mordeduras y Picaduras/terapia , Humanos , Hipersensibilidad Tardía/tratamiento farmacológico , Hipersensibilidad Tardía/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunologíaAsunto(s)
Mordeduras y Picaduras/complicaciones , Venenos de Cnidarios/toxicidad , Dermatitis por Contacto/tratamiento farmacológico , Dermatitis por Contacto/etiología , Escifozoos , Tacrolimus/uso terapéutico , Animales , Niño , Humanos , Inmunosupresores/uso terapéutico , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Herpes-simplex-virus-associated erythema multiforme (HAEM) is characterized by lesional skin expression of the viral protein Pol and localized inflammation. The objective of this study is to examine the mechanism whereby Pol induces localized inflammation. METHODS: A431 cells transfected with Pol or an empty vector and lesional skin from HAEM or drug-induced erythema multiforme patients were examined for expression of the transcription factor SP1 and SP1-regulated genes by immunoblotting, immunohistochemistry and immunofluorescence. RESULTS: SP1, TGF-beta, p21(waf1) and Hsp27 were upregulated in A431 cells transfected with Pol but not the empty vector. Expression was further increased by exposure to IFN-gamma. Pol+ HAEM lesional skin expressed SP1, Hsp27, TGF-beta and p21(waf1). Normal skin and drug-induced erythema multiforme lesional skin were negative. CONCLUSION: The data indicate that Pol activates SP1, causing upregulation of SP1 target genes (notably TGF-beta) involved in localized inflammation. Upregulation is potentiated by IFN-gamma.
Asunto(s)
Eritema Multiforme/genética , Genes pol/fisiología , Inflamación/genética , Simplexvirus/genética , Factor de Transcripción Sp1/metabolismo , Adulto , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Citocinas/metabolismo , Erupciones por Medicamentos/genética , Erupciones por Medicamentos/patología , Eritema Multiforme/etiología , Eritema Multiforme/patología , Humanos , Immunoblotting , Inflamación/etiología , Inflamación/metabolismo , Interferón gamma/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Queratinocitos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Simplexvirus/metabolismo , Factor de Transcripción Sp1/genética , Transfección , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia ArribaRESUMEN
A 16-year-old girl was seriously stung on her abdomen by a jellyfish as she jumped on her small surfboard. She and her mother identified the animal from photographs as Chrysaora fuscescens. Within several minutes the girl developed a massive abdominal cutaneous eruption composed of hundreds of punctuate erythematous papules and macules, which persisted for 5 to 7 days. Persistent urinary incontinence and biliary dyskinesia appeared over the following night. It is theorized that a systemic uptake of venom occurred percutaneously after contact of the jellyfish tentacles with her abdominal skin. The result was an injury to the urinary and biliary bladders. This is the first case report of such sequellae after topical contact with a marine animal. The causal relationship of these abnormalities with the sting is suggested by their temporal association. The gallbladder disorder required surgical intervention, but spontaneous resolution of the urinary bladder dysfunction occurred within 20 months.
Asunto(s)
Discinesia Biliar/etiología , Venenos de Cnidarios/efectos adversos , Escifozoos , Incontinencia Urinaria/etiología , Adolescente , Animales , Discinesia Biliar/cirugía , Mordeduras y Picaduras , Femenino , Humanos , Factores de TiempoRESUMEN
BACKGROUND: The heat shock protein H11 is silenced in melanoma cell lines, where its forced expression by demethylation with Aza-C triggers apoptosis. OBJECTIVE: To examine whether H11 is silenced by aberrant DNA methylation in melanoma as compared to nevi and normal skin tissues. METHODS: Cell suspensions from benign intradermal nevi, atypical nevi and malignant melanoma tissues were used in reverse-transcriptase PCR and methylation-specific PCR. Paraffin-embedded tissues were stained with H11 antibody. RESULTS: H11 is methylated in 60-75% of melanoma and atypical nevi, but not in normal skin or most benign nevi. Methylation is inversely correlated with H11 expression. CONCLUSION: The heat shock protein H11 is silenced by aberrant DNA methylation in melanoma, but not benign melanocytic lesions or normal skin melanocytes. The data suggest that H11 is a promising target for the molecular therapy of melanoma.
Asunto(s)
Metilación de ADN , Proteínas de Choque Térmico/genética , Melanocitos/patología , Melanoma/genética , Proteínas Serina-Treonina Quinasas/genética , Neoplasias Cutáneas/genética , Apoptosis , Síndrome del Nevo Displásico/genética , Síndrome del Nevo Displásico/metabolismo , Síndrome del Nevo Displásico/patología , Técnica del Anticuerpo Fluorescente , Regulación Neoplásica de la Expresión Génica , Proteínas de Choque Térmico/metabolismo , Humanos , Técnicas para Inmunoenzimas , Melanocitos/metabolismo , Melanoma/metabolismo , Melanoma/patología , Chaperonas Moleculares , Nevo Intradérmico/genética , Nevo Intradérmico/metabolismo , Nevo Intradérmico/patología , Nevo Pigmentado/genética , Nevo Pigmentado/metabolismo , Nevo Pigmentado/patología , Reacción en Cadena de la Polimerasa , Proteínas Serina-Treonina Quinasas/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaAsunto(s)
Mordeduras y Picaduras/diagnóstico , Escifozoos , Trastornos de la Voz/etiología , Adulto , Animales , Mordeduras y Picaduras/complicaciones , Mordeduras y Picaduras/patología , Mordeduras y Picaduras/terapia , Diagnóstico Diferencial , Tratamiento de Urgencia , Humanos , Masculino , NataciónRESUMEN
Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) is a recurrent disease characterized by the presence and expression of HSV DNA fragments in lesional skin. Our studies examined the mechanism of viral DNA transport to the skin of HAEM patients. CD34+ cells were isolated from the blood of normal subjects and HSV and HAEM patients during acute lesions and at quiescence. They were cultured with cytokines that favor their differentiation into Langerhans cells (LC) precursors (CD1a+/CD14-) and examined for HSV replication, HSV-induced cellular alterations, viral DNA fragmentation, and clearance. CD34+ cells from all study groups were non-permissive for HSV replication but infection favored their differentiation into CD1a+/CD14- LC precursors and upregulated E-cadherin expression, thereby assisting LC targeting to the skin. Only HAEM patients had CD34+ cells that retained viral DNA fragments, notably polymerase DNA, for at least 7 d of in vitro culture. The percentages of circulating CD34+ (and CD34+/CLA+) cells were significantly higher in HAEM patients at the time of acute lesions. A similar increase was not seen for HSV patients. The data are the first report implicating CD34+ cells in HAEM pathogenesis, likely by transporting HSV DNA fragments to lesional skin.
Asunto(s)
Antígenos CD34/metabolismo , Células Sanguíneas/metabolismo , ADN Viral/metabolismo , Eritema Multiforme/metabolismo , Simplexvirus/genética , Piel/metabolismo , Adulto , Apoptosis , Transporte Biológico , Recuento de Células , Diferenciación Celular , Eritema Multiforme/genética , Eritema Multiforme/fisiopatología , Eritema Multiforme/virología , Genes pol , Herpes Simple/complicaciones , Herpes Simple/metabolismo , Herpes Simple/patología , Humanos , Células de Langerhans/patología , Células Madre/patologíaAsunto(s)
Antinematodos/uso terapéutico , Mordeduras y Picaduras/prevención & control , Hidrozoos , Protectores Solares/uso terapéutico , Administración Cutánea , Animales , Antinematodos/administración & dosificación , Combinación de Medicamentos , Humanos , Masculino , Protectores Solares/administración & dosificación , Insuficiencia del TratamientoRESUMEN
A separation of toxic components from the upside down jellyfish Cassiopea xamachana (Cx) was carried out to study their cytotoxic effects and examine whether these effects are combined with a binding activity to cell membrane receptors. Nematocysts containing toxins were isolated from the autolysed tentacles, ruptured by sonication, and the crude venom (CxTX) was separated from the pellets by ultracentrifugation. For identifying its bioactive components, CxTX was fractionated by gel filtration chromatography into six fractions (named fraction I-VI). The toxicity of CxTX and fractions was tested on mice; however, the hemolytic activity was tested on saline washed human erythrocytes. The LD50 of CxTX was 0.75 microg/g of mouse body and for fraction III, IV and VI were 0.28, 0.25 and 0.12 microg/g, respectively. Fractions I, II and V were not lethal at doses equivalent to LD50 1 microg/g. The hemolytic and phospholipase A2 (PLA2) activities of most fractions were well correlated with their mice toxicity. However, fraction VI, which contains the low molecular mass protein components (< or =10 kDa), has shown no PLA2 activity but highest toxicity to mice, highest hemolytic activity, and bound significantly to the acetylcholine muscarinic receptors (mAChRs) isolated from rat brain. The results suggested that fraction VI contains proteinaceous components contributing to most of cytolysis as well as membrane binding events. Meanwhile, fraction IV has shown high PLA2 that may contribute to the venom lethality and paralytic effects.
Asunto(s)
Venenos de Cnidarios/farmacología , Receptores Muscarínicos/metabolismo , Animales , Encéfalo/enzimología , Venenos de Cnidarios/aislamiento & purificación , Venenos de Cnidarios/metabolismo , Masculino , Ratones , Puerto Rico , Ratas , Ratas Sprague-Dawley , Escifozoos/químicaAsunto(s)
Mordeduras y Picaduras/tratamiento farmacológico , Venenos de Cnidarios/antagonistas & inhibidores , Venenos de Cnidarios/toxicidad , Cubomedusas , Cardiopatías/tratamiento farmacológico , Verapamilo/uso terapéutico , Animales , Antivenenos/uso terapéutico , Cardiopatías/inducido químicamenteRESUMEN
Chrysaora quinquecirrha (sea nettle) nematocyst venom is lethal to rainbow killifish (Adina xenica) when injected intraperitoneally or topically applied to the exposed brain or denuded epithelium. The lethal activity is thermostable requiring 100 degrees C heat for inactivation. This paper reports here for the first time that the venom also activates the complement system with the subsequent formation of the C5b-9 terminal complement complex. The events are associated with both a strong chemoattractant release and the tissue damage. These are also, at least in part, responsible for the pathogenesis of some clinical signs and symptoms associated to the jellyfish stings.
Asunto(s)
Encéfalo/efectos de los fármacos , Venenos de Cnidarios/toxicidad , Activación de Complemento/efectos de los fármacos , Ciprinodontiformes/fisiología , Ortiga de Mar de la Costa Este/química , Administración Cutánea , Animales , Venenos de Cnidarios/administración & dosificación , Venenos de Cnidarios/química , Humanos , Técnicas In Vitro , Dosificación Letal Mediana , ConejosRESUMEN
Irukandji syndrome is a constellation of delayed severe local and systemic symptoms occurring after a Carukia barnesi box jellyfish sting involving any exposed skin. These cases are limited to Australia, the habitat of that animal. Numerous other cases of an Irukandji-like syndrome after other small Carybdeid genus envenomations have been reported elsewhere in the world. There have yet been no reports of Irukandji-like syndrome occurring in continental US coastal waters. We describe 3 cases of marine envenomation causing such a symptom complex in US military combat divers off Key West, FL. It is unclear what species caused the injuries, but a member of the Carybdeid genus seems most likely.