Formation of immunoglobulin light chain amyloid oligomers in primary cutaneous nodular amyloidosis.

BACKGROUND: Primary cutaneous nodular amyloidosis (PCNA) is thought to be a plasma cell dyscrasia. The amyloid deposits are found in the dermis and subcutis, and they contain clonal immunoglobulin light chains, produced by a local proliferation of plasma cells. New insights into amyloid diseases have revealed that the pathology is due more to the presence of small, misfolded protein species termed oligomers than to the deposition of fibrillar material. OBJECTIVES: To demonstrate the presence of amyloid oligomers in PCNA and to provide evidence that cutaneous amyloid diseases share a common pathogenic pathway similar to other amyloid diseases. METHODS: Immunohistochemical staining with conformation-specific and sequence-specific antibodies was used to localize different amyloid species of light chain immunoglobulins in a case of PCNA. Additionally, in vitro characterization of immunoglobulin oligomers and fibrils was performed to determine, through toxicity studies in a human keratinocyte cell line, which amyloidogenic form of the immunoglobulin is toxic in PCNA. RESULTS: Amyloid oligomers were identified in PCNA. Oligomers were mainly formed by lambda light chain immunoglobulins, and kappa light chain oligomers were detected in lesser amounts. Amyloid species were detected intra- and extracellularly. In addition, amyloid oligomers and fibrils, derived from unknown protein sources, were detected. This finding suggests that immunoglobulin amyloids can act as seeds capable of inducing the aggregation of heterogeneous proteins in the skin. Furthermore, cytotoxicity studies demonstrated that immunoglobulin oligomers, but not monomers or fibrils, are toxic to human keratinocytes. CONCLUSIONS: These data indicate that PCNA has common pathways with other amyloid diseases with respect to protein misfolding and pathogenesis. Immunoglobulin oligomers may prove to be targets for the treatment of PCNA.

Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice.

Gold nanoparticles (GNPs) offer a great promise in biomedicine. Currently, there is no data available regarding the accumulation of nanoparticles in vivo after repeated administration. The purpose of the present study was to evaluate the bioaccumulation and toxic effects of different doses (40, 200, and 400 microg/kg/day) of 12.5 nm GNPs upon intraperitoneal administration in mice every day for 8 days. The gold levels in blood did not increase with the dose administered, whereas in all the organs examined there was a proportional increase on gold, indicating efficient tissue uptake. Although brain was the organ containing the lowest quantity of injected GNPs, our data suggest that GNPs are able to cross the blood-brain barrier and accumulate in the neural tissue. Importantly, no evidence of toxicity was observed in any of the diverse studies performed, including survival, behavior, animal weight, organ morphology, blood biochemistry and tissue histology. The results indicate that tissue accumulation pattern of GNPs depend on the doses administered and the accumulation of the particles does not produce sub-acute physiological damage.

[Intravitreal injection of bevacizumab for exsudative AMD with occult or minimal classic choroidal neovascularisation (CNV)]. / Bevacizumab intravitreal zur Behandlung okkulter und minimal klassischer choroidaler Neovaskularisation (CNV) bei AMD.

PURPOSE: Systemic anti-VEGF therapy with bevacizumab was effective in neovascular AMD in the SANA study. Intravitreal bevacizumab has the advantage that a high concentration can be achieved in the eye with a low dose. First clinical studies showed a good therapeutic effect. METHODS: In a clinical study 93 patients with occult or minimal classic CNV due to neovascular AMD were treated with intravitreal injections of Bevacizumab (1.25 mg). Before, 1, 3 and 6 months after treatment visual acuity, intraocular pressure measurement, angiography and OCT examination were performed. After one day and after one week an eye examination was done and the intraocular pressure was measured. RESULTS: Bevacizumab was well tolerated and we had no complications. Mean visual acuity was 20 / 80 at baseline. Visual acuity was stabilised but not significantly improved after 1, 3 and 6 months (20 / 80). 70 (75 %) patients showed reduced leakage in fluorescein angiography after 6 month. In OCT retinal thickness was reduced significantly after 1, 3 and 6 months (OCT: mean 323 microm at baseline, 260 microm after 1, 290 microm after 3 and 275 microm after 6 months). CONCLUSIONS: Intravitreal therapy with bevacizumab was safe and well tolerated. It is a therapeutic option in treating occult choroidal neovascularisations and minimal classic CNV. Six months after intravitreal administration of bevacizumab mean visual acuity was stabilised. Retinal thickness and leakage were more reduced after 1 month than after 3 and 6 months. According to our results, a monthly injection schedule could give more favourable results.

[Photodynamic therapy with verteporfin combined with intravitreal injection of bevacizumab for occult and classic CNV in AMD]. / Photodynamische Therapie kombiniert mit intravitrealer Injektion von Bevacizumab zur Behandlung okkulter und klassischer choroidaler Neovaskularisationen bei AMD.

PURPOSE: The aim of this study is to discuss the effect and outcome of a combined photodynamic therapy and intravitreal injection of bevacizumab (1.25 mg) in occult and classic choroidal neovascularisation (CNV) due to AMD. Especially cases of occult CNV with pigment epithelium detachment (PED) are not likely to respond positively to standard photodynamic therapy, often ending up in PED enlargement or tearing of the RPE. METHODS: In a pilot study involving 23 patients, intravitreal injections of bevacizumab were administered within 12 to 24 hours after standard PDT to reduce the post-PDT increase of proangiogenic and inflammatory factors. Before and at 1, 3 and 6 month after treatment visual acuity and OCT examinations (retinal thickness) were performed. RESULTS: Mean visual acuity was significantly improved compared to baseline. (VA baseline 20/125, after 1 month 20/80, after 3 months 20/80, and 20/80 after 6 months) and an enlargement of the PED in occult CNV was prevented. We found no RPE rip. OCT findings in patients with occult and classic choroidal neovascularisation 1, 3 and 6 months after combination therapy showed a reduced retinal thickness compared to baseline. CONCLUSIONS: Photodynamic therapy combined with injection of intravitreal bevacizumab tends to be more effective compared to PDT monotherapy by reducing the post-PDT increase of vascular growth and inflammatory factors. Our short-term results are very promising. Further studies are necessary to show the long-term effect of PDT and anti-VEGF combination therapy.

[The most informative abstracts of research papers: suggestion of a model]. / Resumos mais informativos para trabalhos de pesquisa: proposta de um modelo.

Considering proposals on research work writing which point out importance elements for dissemination of scientific findings, the authors have as aims testing a structured and a more informative abstract model. For a research done in Rio de Janeiro, in 1994, the quantitative method and documental analyses in 68 abstracts published in REBEn between 1990 a 1993 was applied. It has been found that the majority of indicative abstracts whose communication doesn't facilitates findings comprehension on nursing. It has been concluded that the tested model can be applied because all essential elements have been found in the majority of works that originated the investigated abstracts. So it is recommended the implementation this structured and informative model usage among the research beginners.

[Styles of conflict management among nurses. Instrument validation]. / Estilos de administração do conflito entre enfermeiros(as): validação de instrumento.

The present study has as an object the modalities of conflict administration adopted by nurses in professional praxis. Considering the Management Grid Theory (BLAKE & MOUNTON, 1978), the conflict can be solved in different levels of quality or even, not solved, influenced by the manager behavior model. It is intended to identify nurses managing styles in conflict administration, analyzing their interactions. A questionnaire composed with 25 items, in its majority of popular adagios which express the five basic models of the Management Grid, has been tested. The research was run at the Rio de Janeiro State University Pedro Ernesto University Hospital from June, 1996 to August, 1997, and descriptive method and check-list schedule type functional analysis technique have been used. The factorial analysis of items has showed an occurrence of eight interdependent factors which designing the following styles that have been adopted by nurses: confrontation, negotiation, facing, conciliation, manipulation, acceptance, submission and withdrawing. The authors recommend data collect instrument revalidation.