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1.
Biomolecules ; 13(7)2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37509158

RESUMO

Beta-2 microglobulin (B2M) is an immune system protein that is found on the surface of all nucleated human cells. B2M is naturally shed from cell surfaces into the plasma, followed by renal excretion. In patients with impaired renal function, B2M will accumulate in organs and tissues leading to significantly reduced life expectancy and quality of life. While current hemodialysis methods have been successful in managing electrolyte as well as small and large molecule disturbances arising in chronic renal failure, they have shown only modest success in managing plasma levels of B2M and similar sized proteins, while sparing important proteins such as albumin. We describe a systematic protein design effort aimed at adding the ability to selectively remove specific, undesired waste proteins such as B2M from the plasma of chronic renal failure patients. A novel nanoparticle built using a tetrahedral protein assembly as a scaffold that presents 12 copies of a B2M-binding nanobody is described. The designed nanoparticle binds specifically to B2M through protein-protein interactions with nanomolar binding affinity (~4.2 nM). Notably, binding to the nanoparticle increases the effective size of B2M by over 50-fold, offering a potential selective avenue for separation based on size. We present data to support the potential utility of such a nanoparticle for removing B2M from plasma by either size-based filtration or by polyvalent binding to a stationary matrix under blood flow conditions. Such applications could address current shortcomings in the management of problematic mid-sized proteins in chronic renal failure patients.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/terapia , Qualidade de Vida , Diálise Renal , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/terapia , Microglobulina beta-2/metabolismo , Microglobulina beta-2/farmacologia , Nanopartículas/uso terapêutico
2.
Rev. chil. infectol ; 37(4): 463-469, ago. 2020. graf
Artigo em Espanhol | LILACS | ID: biblio-1138571

RESUMO

Resumen Bartonella henselae es el agente etiológico de la enfermedad por arañazo de gato (EAG), infección endémica en Chile. Típicamente se presenta como una linfadenopatía regional autolimitada y menos frecuentemente con compromiso sistémico y manifestaciones extraganglionares: en hígado, bazo, hueso, ojo, entre otros. Se presentan tres casos de infección atípica por Bartonella henselae en las que se evidenció compromiso ocular, manifestado como una neurorretinitis. Esta revisión destaca la importancia de la búsqueda activa de complicaciones oculares en pacientes con compromiso sistémico por Bartonella henselae, implicando un cambio en el tratamiento y pronóstico de la enfermedad.


Abstract Bartonella henselae is cat scratch disease's etiological agent, which is considered an endemic infection in Chile. It typically presents as a self-limited regional lymphadenopathy and less frequently with systemic involvement and extranodal or atypical manifestations: hepatosplenic, ocular or musculoskeletal involvement, among others. We present three cases of atypical cat scratch disease with ocular compromise, as neurorretinitis. This review highlights the importance of the active search for ocular complications in patients with disseminated cat scratch disease, leading to possible change in treatment and prognosis of the disease.


Assuntos
Humanos , Retinite/diagnóstico , Bartonella henselae , Doença da Arranhadura de Gato/complicações , Doença da Arranhadura de Gato/diagnóstico , Chile
3.
Rev Chilena Infectol ; 37(4): 463-469, 2020 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-33399668

RESUMO

Bartonella henselae is cat scratch disease's etiological agent, which is considered an endemic infection in Chile. It typically presents as a self-limited regional lymphadenopathy and less frequently with systemic involvement and extranodal or atypical manifestations: hepatosplenic, ocular or musculoskeletal involvement, among others. We present three cases of atypical cat scratch disease with ocular compromise, as neurorretinitis. This review highlights the importance of the active search for ocular complications in patients with disseminated cat scratch disease, leading to possible change in treatment and prognosis of the disease.


Assuntos
Bartonella henselae , Retinite , Doença da Arranhadura de Gato/complicações , Doença da Arranhadura de Gato/diagnóstico , Chile , Humanos , Retinite/diagnóstico
4.
PLoS One ; 14(6): e0218651, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220168

RESUMO

Community marine reserves are geographical areas closed to fishing activities, implemented and enforced by the same fishermen that fish around them. Their main objective is to recover commercial stocks of fish and invertebrates. While marine reserves have proven successful in many parts of the world, their success near important marine predator colonies, such as the California sea lion (Zalophus californianus) and the Pacific harbor seal (Phoca vitulina richardii), is yet to be analyzed. In response to the concerns expressed by local fishermen about the impact of the presence of pinnipeds on their communities' marine reserves, we conducted underwater surveys around four islands in the Pacific west of the Baja California Peninsula: two without reserves (Todos Santos and San Roque); one with a recently established reserve (San Jeronimo); and, a fourth with reserves established eight years ago (Natividad). All these islands are subject to similar rates of exploitation by fishing cooperatives with exclusive rights. We estimated fish biomass and biodiversity in the seas around the islands, applying filters for potential California sea lion and harbor seal prey using known species from the literature. Generalized linear mixed models revealed that the age of the reserve has a significant positive effect on fish biomass, while the site (inside or outside of the reserve) did not, with a similar result found for the biomass of the prey of the California sea lion. Fish biodiversity was also higher around Natividad Island, while invertebrate biodiversity was higher around San Roque. These findings indicate that marine reserves increase overall fish diversity and biomass, despite the presence of top predators, even increasing the numbers of their potential prey. Community marine reserves may help to improve the resilience of marine mammals to climate-driven phenomena and maintain a healthy marine ecosystem for the benefit of both pinnipeds and fishermen.


Assuntos
Biomassa , Espécies em Perigo de Extinção , Phoca/fisiologia , Comportamento Predatório , Leões-Marinhos/fisiologia , Animais , Biodiversidade , Peixes/fisiologia , Cadeia Alimentar
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