ABSTRACT
Fungal infections cause 1.7 million deaths annually, which can be attributed not only to fungus-specific factors, such as antifungal resistance and biofilm formation, but also to drug-related challenges. In this study, the potential of Amphotericin (AmB) loaded polymeric nanoparticles (AmB-NPs) combined with murine monoclonal antibodies (mAbs) (i.e., CC5 and DD11) was investigated as a strategy to overcome these challenges. To achieve this goal, AmB-NPs were prepared by nanoprecipitation using different polymers (polycaprolactone (PCL) and poly(D,L-lactide) (PLA)), followed by comprehensive characterization of their physicochemical properties and in vitro biological performance. The results revealed that AmB-loaded NPs exhibited no cytotoxicity toward mammalian cells (baby hamster kidney cells-BHK and human monocyte cells-THP-1). Conversely, both AmB-NPs demonstrated a cytotoxic effect against C. albicans, C. neoformans, and H. capsulatum throughout the entire evaluated range (from 10 µg/mL to 0.1 µg/mL), with a significant MIC of up to 0.031 µg/mL. Moreover, the combination of AmB-NPs with mAbs markedly intensified antifungal activity, resulting in a synergistic effect that was two to four times greater than that of AmB-NPs alone. These findings suggest that the combination of AmB-NPs with mAbs could be a promising new treatment for fungal infections that is potentially more effective and less toxic than current antifungal treatments.
ABSTRACT
Epidermoid cysts (ECs) of the central nervous system (CNS) constitute benign circumscribed lesions that aremore common in lateral than in midline sites. Epidermoid cysts of the CNS arise more frequently in the cerebellopontine angle, around the pons, near the sella, within the temporal lobe, in the diploe, and in the spinal canal. Most common tumoral lesion of sellar region is pituitary adenoma, and sellar cystic epithelial masses may be difficult to differentiate based only on clinical and imaging findings. Epidermoid cysts are covered by keratinized squamous epithelium and are usually filled with keratin lamellae. The process is, for the most part, maldevelopmental in origin, presumably arising from trapped surface ectodermal elements in association with the developing CNS during the closure of the neural groove or formation of the secondary cerebral vesicles. In the present study, the authors describe a case of sellar epidermoid cyst producing endocrine alterations and visual disturbance in a 35 years woman, and review the physiopathological and diagnostic criteria of this lesion.
Subject(s)
Humans , Female , Adult , Sella Turcica/abnormalities , Epidermal Cyst/surgery , Epidermal Cyst/physiopathology , Epidermal Cyst/diagnostic imaging , Central Nervous System CystsABSTRACT
OBJECTIVE: To analyze the cumulative effect of risk factors associated with early major complications in postoperative spine surgery. METHODS: Retrospective analysis of 583 surgically-treated patients. Early "major" complications were defined as those that may lead to permanent detrimental effects or require further significant intervention. A balanced risk score was built using multiple logistic regression. RESULTS: Ninety-two early major complications occurred in 76 patients (13%). Age > 60 years and surgery of three or more levels proved to be significant independent risk factors in the multivariate analysis. The balanced scoring system was defined as: 0 points (no risk factor), 2 points (1 factor) or 4 points (2 factors). The incidence of early major complications in each category was 7% (0 points), 15% (2 points) and 29% (4 points) respectively. CONCLUSIONS: This balanced scoring system, based on two risk factors, represents an important tool for both surgical indication and for patient counseling before surgery.
Subject(s)
Postoperative Complications/etiology , Risk Assessment/methods , Spine/surgery , Adult , Age Factors , Aged , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Operative Time , Postoperative Period , Reproducibility of Results , Retrospective Studies , Risk FactorsABSTRACT
ABSTRACT Objective To analyze the cumulative effect of risk factors associated with early major complications in postoperative spine surgery. Methods Retrospective analysis of 583 surgically-treated patients. Early “major” complications were defined as those that may lead to permanent detrimental effects or require further significant intervention. A balanced risk score was built using multiple logistic regression. Results Ninety-two early major complications occurred in 76 patients (13%). Age > 60 years and surgery of three or more levels proved to be significant independent risk factors in the multivariate analysis. The balanced scoring system was defined as: 0 points (no risk factor), 2 points (1 factor) or 4 points (2 factors). The incidence of early major complications in each category was 7% (0 points), 15% (2 points) and 29% (4 points) respectively. Conclusions This balanced scoring system, based on two risk factors, represents an important tool for both surgical indication and for patient counseling before surgery.
RESUMO Objetivo Analisar os efeitos cumulativos dos fatores de risco associados com complicações precoces graves relacionadas à cirurgia da coluna. Métodos Análise retrospectiva de 583 pacientes tratados cirurgicamente. Complicações graves foram definidas como as que pudessem levar a danos permanentes ou que necessitassem de reinterveção. Um escore foi construído usando modelo de regressão logística. Resultados Noventa e duas complicações precoces graves ocorreram em 76 pacientes (13%). Idade > 60 anos e cirurgia > 3 níveis foram identificadas como fatores de risco independentes na análise multivariada. O escore foi definido como: 0 pontos (nenhum fator de risco), 2 pontos (1 fator) ou 4 pontos (2 fatores). A incidência de complicação grave precoce em cada categoria foi 7% (0 pontos), 15% (2 pontos) e 29% (4 pontos). Conclusões Esse escore balanceado baseado em 2 fatores de risco representa uma ferramenta útil na indicação cirúrgica e para o aconselhamento dos pacientes antes da cirurgia.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Postoperative Complications/etiology , Spine/surgery , Risk Assessment/methods , Postoperative Period , Logistic Models , Multivariate Analysis , Reproducibility of Results , Retrospective Studies , Risk Factors , Age Factors , Operative TimeABSTRACT
The effects and molecular mechanisms of RGD-disintegrins isolated from snake venoms on the growth and metastatic potential of B16F10-melanoma cells were investigated. Jarastatin (JT) from Bothrops jararaca is a ligand of alpha(5)beta(1), alpha(v)beta(3) and alpha(m)beta(2) integrins, flavoridin (FL) from Trimeresurus flavoridis binds preferentially to alpha(5)beta(1) and kistrin (KR) from Calloselasma rhodostoma is a selective ligand of alpha(v)beta(3). When injected simultaneously with melanoma cells in mice, the three disintegrins significantly reduced tumor lung colonization. On the other hand, JT and FL, but not KR, inhibited B16F10 cell growth in vitro. Interaction of JT or FL with melanoma cells induced actin cytoskeleton rearrangement, increasing actin polymerization and FAK phosphorylation. The effect of FL correlates with the decrease in the constitutively high nuclear content of c-Fos, whereas JT interfered with NF-kappaB translocation in melanoma cells. None of the disintegrins produced alterations in the nuclear Erk-2. The results provide further evidence to suggest RGD-disintegrins as potent anti-metastatic agents in vivo, and indicate that their interaction with alpha(5)beta(1) integrin interfere with integrin-couple signaling, down-regulating transcription factors and negatively modulating cell proliferation. These effects may contribute to inhibition of melanoma cell invasion in vivo.