Complex nanoemulsion for vitamin delivery: droplet organization and interaction with skin membranes.

Lipid nanoemulsions are promising nanomaterials for drug delivery applications in food, pharmaceutical and cosmetic industries. Despite the noteworthy commercial interest, little is known about their supramolecular organization, especially about how such multicomponent formulations interact with cell membranes. In the present work, coarse-grained molecular dynamics simulations have been employed to study the self-assembly of a 15-component lipid nanoemulsion droplet containing vitamins A and E for skin delivery. Our results display aspects of the unique "onion-like" agglomeration between the chemical constituents in the different layers of the lipid nanodroplet. Vitamin E molecules are more concentrated in the center of the droplet together with other hydrophobic constituents such as the triglycerides with long tails. On the other hand, vitamin A occupies an intermediate layer between the core and the co-emulsifier surface of the nanodroplet, together with lecithin phospholipids. Coarse-grained molecular dynamics simulations were also performed to provide insight into the first steps involved in absorption and penetration of the nanodroplet through skin membrane models, representing an intracellular (hair follicle infundibulum) and intercellular pathway (stratum corneum) through the skin. Our data provide a first view on the complex organization of commercial nanoemulsion and its interaction with skin membranes. We expect our results to open the way towards the rational design of such nanomaterials.

Collision Cross Section Calculations Using HPCCS.

A technical overview of the High Performance Collision Cross Section (HPCCS) software for accurate and efficient calculations of collision cross sections for molecular ions ranging from small organic molecules to large protein complexes is presented. The program uses helium or nitrogen as buffer gas with considerable gains in computer time compared to publicly available codes under the Trajectory Method approximation. HPCCS is freely available under the Academic Use License at https://github.com/cepid-cces/hpccs .

High performance collision cross section calculation-HPCCS.

Since the commercial introduction of Ion Mobility coupled with Mass Spectrometry (IM-MS) devices in 2003, a large number of research laboratories have embraced the technique. IM-MS is a fairly rapid experiment used as a molecular separation tool and to obtain structural information. The interpretation of IM-MS data is still challenging and relies heavily on theoretical calculations of the molecule's collision cross section (CCS) against a buffer gas. Here, a new software (HPCCS) is presented, which performs CCS calculations using high perfomance computing techniques. Based on the trajectory method, HPCCS can accurately calculate CCS for a great variety of molecules, ranging from small organic molecules to large protein complexes, using helium or nitrogen as buffer gas with considerable gains in computer time compared to publicly available codes under the same level of theory. HPCCS is available as free software under the Academic Use License at https://github.com/cepid-cces/hpccs. © 2018 Wiley Periodicals, Inc.

An alternative conformation of ERß bound to estradiol reveals H12 in a stable antagonist position.

The natural ligand 17ß-estradiol (E2) is so far believed to induce a unique agonist-bound active conformation in the ligand binding domain (LBD) of the estrogen receptors (ERs). Both subtypes, ERα and ERß, are transcriptionally activated in the presence of E2 with ERß being somewhat less active than ERα under similar conditions. The molecular bases for this intriguing behavior are mainly attributed to subtype differences in the amino-terminal domain of these receptors. However, structural details that confer differences in the molecular response of ER LBDs to E2 still remain elusive. In this study, we present a new crystallographic structure of the ERß LBD bound to E2 in which H12 assumes an alternative conformation that resembles antagonist ERs structures. Structural observations and molecular dynamics simulations jointly provide evidence that alternative ERß H12 position could correspond to a stable conformation of the receptor under physiological pH conditions. Our findings shed light on the unexpected role of LBD in the lower functional response of ERß subtype.

CHARMM Force Field Parameterization of Peroxisome Proliferator-Activated Receptor γ Ligands.

The peroxisome proliferator-activated receptor γ (PPARγ) ligands are important therapeutic drugs for the treatment of type 2 diabetes, obesity and cardiovascular diseases. In particular, partial agonists and non-agonists are interesting targets to reduce glucose levels, presenting few side effects in comparison to full agonists. In this work, we present a set of CHARMM-based parameters of a molecular mechanics force field for two PPARγ ligands, GQ16 and SR1664. GQ16 belongs to the thiazolidinedione class of drugs and it is a PPARγ partial agonist that has been shown to promote the "browning" of white adipose tissue. SR1664 is the precursor of the PPARγ non-agonist class of ligands that activates PPARγ in a non-classical manner. Here, we use quantum chemical calculations consistent with the CHARMM protocol to obtain bonded and non-bonded parameters, including partial atomic charges and effective torsion potentials for both molecules. The newly parameterized models were evaluated by examining the behavior of GQ16 and SR1664 free in water and bound to the ligand binding pocket of PPARγ using molecular dynamics simulations. The potential parameters derived here are readily transferable to a variety of pharmaceutical compounds and similar PPARγ ligands.

Sepsis-Associated Outcomes in Critically Ill Patients with Malignancies.

RATIONALE: Sepsis is a major cause of mortality among critically ill patients with cancer. Information about clinical outcomes and factors associated with increased risk of death in these patients is necessary to help physicians recognize those patients who are most likely to benefit from ICU therapy and identify possible targets for intervention. OBJECTIVES: In this study, we evaluated cancer patients with sepsis chosen from a multicenter prospective study to characterize their clinical characteristics and to identify independent risk factors associated with hospital mortality. METHODS: Subgroup analysis of a multicenter prospective cohort study conducted in 28 Brazilian intensive care units (ICUs) to evaluate adult cancer patients with severe sepsis and septic shock. We used logistic regression to identify variables associated with hospital mortality. MEASUREMENTS AND MAIN RESULTS: Of the 717 patients admitted to the participating ICUs, 268 (37%) had severe sepsis (n = 142, 53%) or septic shock (n = 126, 47%). These patients comprised the population of the present study. The mean score on the third version of the Simplified Acute Physiology Score was 62.9 ± 17.7 points, and the median Sequential Organ Failure Assessment score was 9 (7-12) points. The most frequent sites of infection were the lungs (48%), intraabdominal region (25%), bloodstream as primary infection (19%), and urinary tract (17%). Half of the patients had microbiologically proven infections, and Gram-negative bacteria were the most common pathogens causing sepsis (31%). ICU and hospital mortality rates were 42% and 56%, respectively. In multivariable analysis, the number of acute organ dysfunctions (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.16-1.87), hematological malignancies (OR, 2.57; 95% CI, 1.05-6.27), performance status 2-4 (OR, 2.53; 95% CI, 1.44-4.43), and polymicrobial infections (OR, 3.74; 95% CI, 1.52-9.21) were associated with hospital mortality. CONCLUSIONS: Sepsis is a common cause of critical illness in patients with cancer and remains associated with high mortality. Variables related to underlying malignancy, sepsis severity, and characteristics of infection are associated with a grim prognosis.

Molecular Recognition of PPARγ by Kinase Cdk5/p25: Insights from a Combination of Protein-Protein Docking and Adaptive Biasing Force Simulations.

The peroxisome proliferator-activated receptor γ (PPARγ) is an important transcription factor that plays a major role in the regulation of glucose and lipid metabolisms and has, therefore, many implications in modern-life metabolic disorders such as diabetes, obesity, and cardiovascular diseases. Phosphorylation of PPARγ by the cyclin-dependent kinase 5 (Cdk5) has been recently proved to promote obesity and loss of insulin sensitivity. The inhibition of this reaction is currently being pursued to develop PPARγ ligands for type 2 diabetes treatments. The knowledge of the protein-protein interactions between Cdk5/p25 and PPARγ can be an important asset for better understanding of the molecular basis of the Cdk5-meditated phosphorylation of PPARγ and its inhibition. By means of a computational approach that combines protein-protein docking and adaptive biasing force molecular dynamics simulations, we obtained PPARγ-Cdk5/p25 structural models that are consistent with the mechanism of the enzymatic reaction and with overall structural features of the full length PPARγ-RXRα heterodimer bound to DNA. In addition to the active site, our model shows that the interacting regions between the two proteins should involve two distal docking sites, comprising the PPARγ Ω-loop and Cdk5 N-terminal lobe and the PPARγ ß-sheet and Cdk5 C-terminal lobe. These sites are related to PPARγ transactivation and directly interact with PPARγ ligands. Our results suggest that ß-sheets and Ω-loop stabilization promoted by PPARγ agonists could be important to inhibit Cdk5-mediated phosphorylation.

The use of neurovascular ultrasound versus digital subtraction angiography in acute ischemic stroke.

UNLABELLED: Cervical and intracranial arterial evaluation is an important issue for acute ischemic stroke (IS). OBJECTIVE: Compare the use of the neurovascular ultrasound examination (NVUE) to digital subtraction angiography (DSA) in acute IS patients for diagnosing significant extracranial and intracranial arteriopathy. METHOD: Nonconsecutive patients with IS or transient ischemic attack admitted within 12 hours of the onset of symptoms were evaluated retrospectively. Standardized NVUE and DSA were done in all patients within the first 120 hours of hospital admission. RESULTS: Twenty-four patients were included in the study. Compared to DSA, the NVUE demonstrated 94.7% sensitivity and 100% specificity for identifying symptomatic extracranial and/or intracranial arteriopathy. CONCLUSION: The standardized NVUE technique demonstrated high sensitivity and specificity compared to DSA for diagnosing arterial abnormalities in acute IS patients.

The use of neurovascular ultrasound versus digital subtraction angiography in acute ischemic stroke / O uso do ultrassom neurovascular comparado a angiografia digital no AVC isquêmico agudo

Cervical and intracranial arterial evaluation is an important issue for acute ischemic stroke (IS). Objective Compare the use of the neurovascular ultrasound examination (NVUE) to digital subtraction angiography (DSA) in acute IS patients for diagnosing significant extracranial and intracranial arteriopathy. Method Nonconsecutive patients with IS or transient ischemic attack admitted within 12 hours of the onset of symptoms were evaluated retrospectively. Standardized NVUE and DSA were done in all patients within the first 120 hours of hospital admission. Results Twenty-four patients were included in the study. Compared to DSA, the NVUE demonstrated 94.7% sensitivity and 100% specificity for identifying symptomatic extracranial and/or intracranial arteriopathy. Conclusion The standardized NVUE technique demonstrated high sensitivity and specificity compared to DSA for diagnosing arterial abnormalities in acute IS patients. .

A avaliação cervical e intracraniana é uma etapa importante no AVC isquêmico (AVCi) agudo. Objetivo Comparar o uso do ultrassom neurovascular (USNV) com técnica padronizada e a angiografia digital (AD) em paciente com AVCi agudo no diagnóstico de doença arterial significativa extra e/ou intracraniana. Método Pacientes com AVCi e AIT admitidos em até 12 horas do início dos sintomas foram retrospectivamente avaliados. Todos os pacientes foram submetidos a USNV e AD padronizado em até 120 horas da admissão. Resultados Vinte e quatro pacientes foram incluídos no estudo. Em comparação com a AD, o USNV apresentou sensibilidade de 94,7% e especificidade de 100% para o diagnóstico de doença arterial significativa extra e/ou intracraniana. Conclusão O uso de técnica padronizada de USNV demonstrou elevada sensibilidade e especificidade para o diagnóstico de doença arterial significativa extra e intracraniana quando comparado a AD. .

Molecular mechanism of peroxisome proliferator-activated receptor α activation by WY14643: a new mode of ligand recognition and receptor stabilization.

Peroxisome proliferator-activated receptors (PPARs) are members of a superfamily of nuclear transcription factors. They are involved in mediating numerous physiological effects in humans, including glucose and lipid metabolism. PPARα ligands effectively treat dyslipidemia and have significant antiinflammatory and anti-atherosclerotic activities. These effects and their ligand-dependent activity make nuclear receptors obvious targets for drug design. Here, we present the structure of the human PPARα in complex with WY14643, a member of fibrate class of drug, and a widely used PPAR activator. The crystal structure of this complex suggests that WY14643 induces activation of PPARα in an unusual bipartite mechanism involving conventional direct helix 12 stabilization and an alternative mode that involves a second ligand in the pocket. We present structural observations, molecular dynamics and activity assays that support the importance of the second site in WY14643 action. The unique binding mode of WY14643 reveals a new pattern of nuclear receptor ligand recognition and suggests a novel basis for ligand design, offering clues for improving the binding affinity and selectivity of ligand. We show that binding of WY14643 to PPARα was associated with antiinflammatory disease in a human corneal cell model, suggesting possible applications for PPARα ligands.

Medium chain fatty acids are selective peroxisome proliferator activated receptor (PPAR) γ activators and pan-PPAR partial agonists.

Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) γ to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPARγ ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8-C10) bind the PPARγ LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPARγ LBD, stronger partial agonists with full length PPARγ and exhibit full blockade of PPARγ phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPARγ also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/ß-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPARγ modulators with useful clinical profiles among natural products.

Helix 12 dynamics and thyroid hormone receptor activity: experimental and molecular dynamics studies of Ile280 mutants.

Nuclear hormone receptors (NRs) form a family of transcription factors that mediate cellular responses initiated by hormone binding. It is generally recognized that the structure and dynamics of the C-terminal helix 12 (H12) of NRs' ligand binding domain (LBD) are fundamental to the recognition of coactivators and corepressors that modulate receptor function. Here we study the role of three mutations in the I280 residue of H12 of thyroid hormone receptors using site-directed mutagenesis, functional assays, and molecular dynamics simulations. Although residues at position 280 do not interact with coactivators or with the ligand, we show that its mutations can selectively block coactivator and corepressor binding, and affect hormone binding affinity differently. Molecular dynamics simulations suggest that ligand affinity is reduced by indirectly displacing the ligand in the binding pocket, facilitating water penetration and ligand destabilization. Mutations I280R and I280K link H12 to the LBD by forming salt bridges with E457 in H12, stabilizing H12 in a conformation that blocks both corepressor and coactivator recruitment. The I280M mutation, in turn, blocks corepressor binding, but appears to enhance coactivator affinity, suggesting stabilization of H12 in agonist conformation.

On the denaturation mechanisms of the ligand binding domain of thyroid hormone receptors.

The ligand binding domain (LBD) of nuclear hormone receptors adopts a very compact, mostly alpha-helical structure that binds specific ligands with very high affinity. We use circular dichroism spectroscopy and high-temperature molecular dynamics simulations to investigate unfolding of the LBDs of thyroid hormone receptors (TRs). A molecular description of the denaturation mechanisms is obtained by molecular dynamics simulations of the TRalpha and TRbeta LBDs in the absence and in the presence of the natural ligand Triac. The simulations show that the thermal unfolding of the LBD starts with the loss of native contacts and secondary structure elements, while the structure remains essentially compact, resembling a molten globule state. This differs from most protein denaturation simulations reported to date and suggests that the folding mechanism may start with the hydrophobic collapse of the TR LBDs. Our results reveal that the stabilities of the LBDs of the TRalpha and TRbeta subtypes are affected to different degrees by the binding of the isoform selective ligand Triac and that ligand binding confers protection against thermal denaturation and unfolding in a subtype specific manner. Our simulations indicate two mechanisms by which the ligand stabilizes the LBD: (1) by enhancing the interactions between H8 and H11, and the interaction of the region between H1 and the Omega-loop with the core of the LBD, and (2) by shielding the hydrophobic H6 from hydration.

A new integrative weaning index of discontinuation from mechanical ventilation.

INTRODUCTION: Indexes predicting weaning outcome are frequently inaccurate. We developed a new integrative weaning index aimed at improving the accuracy of the traditional indexes. METHODS: Three hundred and thirty-one patients mechanically-ventilated for more than 24 hours were evaluated. Initially, the threshold values of each index that best discriminate between a successful and an unsuccessful weaning outcome were determined in 115 patients. In the second phase, the predictive performance of these values was tested prospectively in the other 216 patients. Frequency/tidal volume ratio (f/Vt ratio), tidal volume (Vt), tracheal airway occlusion pressure 0.1 s (P 0.1), the product of P 0.1 and f/Vt (P 0.1 x f/Vt), respiratory rate (f), static compliance of the respiratory system (Cst,rs), ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2 ratio) and the new integrative weaning index IWI (Cst,rs x arterial oxygen saturation/f/Vt ratio) were evaluated in all patients. The readiness for weaning and the decision to return to mechanical ventilation was made by the physician in charge, based on the signs of poor tolerance. The receiver operating characteristic (ROC) curves were calculated in order to evaluate the predictive performance of each index. The Bayes' theorem was used to assess the probability of each test of predicting weaning. RESULTS: In the prospective-validation set, successful weaning was observed in 183 patients (84.7%) and weaning failure in 33 (15.27%). IWI presented the highest accuracy, with the area under the ROC curves larger than that under the curves for the f/Vt ratio (0.96 x 0.85 respectively; P = 0.003), and also larger than that under the curves for the other indexes. IWI presented a higher probability of successful weaning when the test was positive (0.99) and a lower probability when the test was negative (0.14). Measurement of Cst,rs during the weaning process was considered one of the study limitations. CONCLUSIONS: IWI was the best predictive performance index of weaning outcome and can be used in the intensive care unit setting. TRIAL REGISTRATION: controlled-trials.com ISRCTN92117906.

Molecular phylogenetic analysis of the avian malarial parasite Plasmodium (Novyella) juxtanucleare.

Plasmodium (Novyella) juxtanucleare is a widely distributed parasite that primarily infects chickens (Gallus gallus domesticus). All species of Novyella are characterized by very small schizonts, which in the case of P. juxtanucleare are always found juxtaposed to the erythrocyte nucleus, hence its name. Nearly complete small-subunit ribosomal RNA sequences have been obtained from 2 isolates of this species, and comparisons with other Plasmodium species have been made. Phylogenetic analysis reveals that this parasite is closely related to other avian-infecting Plasmodium species and that molecular relationships among the avian-infecting plasmodia do not correspond to their morphology-based subgeneric classifications.

Caracterización morfológica y morfométrica de plasmodium juxtanucleares: apicomplexa plasmodiidae / Morphological and morphometrical characterization of plasmodium juxtanucleares: apicomplexa plasmodiidae

Se realizó el análisis morfométrico y morfológico de un aislado de (MSS-47) de Plasmodium juxtanucleares. Fueron evaluados, la parasitemia, las medidas del diámetro menor (dm), el diámetro mayor (DM) y el índice morfométrico (IM=dm/DM) de formas intraeritrociticas, aves inoculadas experimentalmente. En 106 trofozoítos se observaron formas puntiformes, ovoides, anilladas, elípticas, piriformes y redondeadas, con predominios de las formas ovoides y elípticas. La media de los trofozoítos fue de 1.802 ñ 0,313 x 1.230 ñ 0,2 um, con un IM = 0,623 ñ 0,110 um. En 98 esquizontes, se observaron formas ovoides, elípticas piriformes y ameboides, con predominio de formas ovoides y piriformes. La media de los esquzontes fue de 2.809 ñ 0,187 x 1.820 ñ 0,386 um, con un IM = 0,643 ñ 0,120. En 18 macrogametocitos, se observaron formas ovoides, redondeadas, elípticas y piriformes, con predominios de las formas ovoides y elípticas. La media de los macrogametocitos fue de 3.559 ñ 0,883 x 2.363 ñ 0,207 um, con un IM = 0,766 ñ 0,078 um. En 34 microgametocitos, se observaron formas ovoides, redondeadas, elípticas y piriformes, con predominio de las formas ovoides y elípticas. La media de los microgametocitos fue de 3.891 ñ 0,946 x 2.386 ñ 0,783 um, con un IM = 0,505 ñ 0,103 um. Por lo tanto, el aislado MSS-47 de P. juxtanucleares se puede caracterizar como pleomórfico

Esquizogonia exoeritrocítica plasmática en plasmodium, novyella, juxtanucleare, apicomplexa, plasmodiidae / Plasmatic exoerythrocytic merogony in plasmodium, novyella, juxtanucleare, apicomplexa, plasmodiidae

Se realizó un estudio de los esquizontes exoeritrocíticos plasmáticos de plasmodium juxtanucleare en gallinas sin raza difinida, provenientes del município de Seropédica, estado de Rio de Janeiro, Brasil. Al examen sanguíneo se pudo observar en aves con alto índice de parasitémia eritrocítica (>10 por ciento) formas esquizogónicas exoeritrocíticas libres, con un tamaño promedio de 7,492 ñ 2,308 X 5,926 ñ 2,048 µm; conteniendo una média de 15 ñ 16,92 merozoítas. Estos esquizontes se presentaron con características pleomórficas de redondeado a oval, con merozoítos de núcleo basofílico. Se observó también, formas de esquizontes rotos con merozoítas libres. Estas y otras observaciones, reportadas y discutidas, hacen inferir que la cepa de P. juxtanucleare estudiada, realiza un ciclo paraeritrocítico. Se sugiere que P. juxtanucleare es una espécie de plasmodio, evolutivamente, intermediário entre los plasmodios de reptiles y los de mamíferos

Parasitismo de leucocitos y trombocitos de gallus gallus l. por plasmodium (novyella) juxtanucleare (apicomplexa: plasmodiidae) / Parasitism of leukocytes and thrombocytes of gallus gallus L. by plasmodium (novyella) juxtanucleare (apicomplexa: plasmodiidae)

Se realizó un investigación del parasitismo de plasmodium juxtanucleare en gallinas sin razas definida, provenientes de criaderos rústicos en el municipio de Seropédica, estado de Río de Janeiro, de Brasil. Se realizaron frotis sanguíneo periféricos, los cuales fuero coloreados con giemsa diluido en tampón sorensen pH6,8. En el examen hemoscópico se puede observar en aves con alto índice de (< 10 por ciento ) formas parasitarias de trofozoítas y esquizontes en el citoplasma de células de la línea leucocitica y trofozoítas en células de la línea trombocítica. Las observaciones en el presente estudio hacen inferir que la cepa de P. juxtanuclear que ocurre en Seropédica realiza esquizogonia fanerozóica. Este trabajo constituye el primer hallazgo de formas de P. juxtanucleares en leucocitos

Tratamento cirúrgico das lesöes do seio cavernoso / Surgical treatment of cavernous sinus lesions

O comprometimento do seio cavernoso por lesoes, seja pela infiltraçao de tumores ou pela presença de patologias vasculares, sempre constituiu desafio ao neurocirurgiao, sendo, na maioria das vezes, o limite de um tratamento cirúrgico radical. O desenvolvimento de novas técnicas cirúrgicas para a base do crânio, associado a novos meios de diagnóstico por imagem, tem permitido abordagem mais segura e radical para muitas lesoes desta regiao. Neste trabalho, a experiência no tratamento de 88 pacientes com lesoes do seio cavernoso é apresentada. Esses pacientes foram atendidos entre janeiro de 1987 a junho de 1995. Meningeomas foram os tumores mais freqüentemente encontrados, seguidos dos adenomas invasivos da hipófise. Ressecçao total da lesao foi possível em todos os casos de neurinomas do trigêmeo, angiofibromas juvenis, condrossarcomas e hemangiomas cavernosos. Ressecçao radical de meningeomas invasivos e adenomas da hipófise nao foi possível em muitos casos, porém melhora dos sintomas pré-operatórios ocorreu na maioria dos pacientes. Lesoes vasculares como fístulas carótido- cavernosas e aneurismas da porçao intracavemosa da artéria carótida interna foram tratadas com técnicas endovasculares utilizando baloes e molas destacáveis.O conhecimento da anatomia cirúrgica desta regiao é fundamental para o sucesso da abordagem cirúrgica com preservaçao das estruturas vásculo-nervosas. Detalhes de dissecaçoes anatômicas realizadas no nosso serviço sao apresentados neste trabalho. A monitorizaçao intraoperatória dos nervos cranianos I, III e VI mostrou-se de utilidade na maioria dos casos em que o tumor apresentava tendência infiltrativa. A infiltraçao de nervos cranianos e da artéria carótida interna foi o fator limitante da ressecçao radical em alguns pacientes portadores de meningeomas. Com o aumento da experiência cirúrgica, nossa conduta no tratamento destes tumores tornou-se mais agressiva, com tentativa de remoçao radical na maioria dos pacientes. A preservaçao da funçao do nervo oculomotor é de fundamental importância. Neste trabalho, expomos nossos resultados e a conduta atual nos pacientes portadores de lesoes expansivas do seio cavernoso os quais apresentam funçao preservada do nervo oculomotor.