Novel customized age-dependent corneal membranes and interactions with biodegradable nanoparticles loaded with dexibuprofen.

Ocular inflammation is one of the most prevalent diseases in ophthalmology and it is currently treated using eye drops of nonsteroidal antiinflammatory drugs such as dexibuprofen (DXI). However, their bioavailability is low and therefore, PLGA nanoparticles constitute a suitable approach to be administered as eyedrops. Therefore, DXI has been encapsulated into PLGA nanoparticles (DXI-NPs). Although the eye, and specifically the cornea, suffers from age-related changes in its composition, current medications are not focused on these variations. Therefore, to elucidate the interaction mechanism of DXI-NPs with the cornea in relation with age, two different corneal membrane models have been developed (corresponding to adult and elder population) using lipid monolayers, large and giant unilamellar vesicles. Interactions of both DXI and DXI-NPs were studied with these models by means of Langmuir balance technique, dipole potential, anisotropy and confocal microscopy. In addition, fluorescently labelled nanoparticles were administered to mice in order to corroborate these data obtained in vitro. It was observed that DXI-NPs interact with lipid membranes through an adhesion process, mainly in the rigid regions and afterwards DXI-NPs are internalized by a wrapping process. Furthermore, differences on the dipole potential caused by DXI-NPs in each corneal membrane have been obtained due to the increase of membrane rigidity on the ECMM. Additionally, it can be confirmed that DXI-NPs adhere to Lo phase and also inside the lipid membrane. Finally, in vitro and in vivo results corroborate that DXI-NPs are adhered to the more ordered phase. Finally, differences between interactions of DXI-NPs with the elder and adult corneal tissue were observed.

Riluzole-Loaded Nanostructured Lipid Carriers for Hyperproliferative Skin Diseases.

Nanocarriers, and especially nanostructured lipid carriers (NLC), represent one of the most effective systems for topical drug administration. NLCs are biodegradable, biocompatible and provide a prolonged drug release. The glutamate release inhibitor Riluzole (RLZ) is a drug currently used for amyotrophic lateral sclerosis (ALS), with anti-proliferative effects potentially beneficial for diseases with excessive cell turnover. However, RLZ possesses low water solubility and high light-sensibility. We present here optimized NLCs loaded with RLZ (RLZ-NLCs) as a potential topical treatment. RLZ-NLCs were prepared by the hot-pressure homogenization method using active essential oils as liquid lipids, and optimized using the design of experiments approach. RLZ-NLCs were developed obtaining optimal properties for dermal application (mean size below 200 nm, negative surface charge and high RLZ entrapment efficacy). In vitro release study demonstrates that RLZ-NLCs allow the successful delivery of RLZ in a sustained manner. Moreover, RLZ-NLCs are not angiogenic and are able to inhibit keratinocyte cell proliferation. Hence, a NLCs delivery system loading RLZ in combination with natural essential oils constitutes a promising strategy against keratinocyte hyperproliferative conditions.

Psoriasis: From Pathogenesis to Pharmacological and Nano-Technological-Based Therapeutics.

Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.

Decrease in sleep depth is associated with higher cerebrospinal fluid neurofilament light levels in patients with Alzheimer's disease.

STUDY OBJECTIVES: The majority of studies investigating the association between sleep and Alzheimer's disease (AD) biomarkers have been performed in healthy participants. Our objective was to investigate the association between sleep and several biomarkers that reflect distinct aspects of AD physiopathology. METHODS: The cohort included 104 individuals with mild-moderate AD. The participants were submitted to one-night polysomnography, and cerebrospinal fluid was collected in the following morning to measure the selected biomarkers associated with amyloid deposition, tau pathology, neurodegeneration, axonal damage, synaptic integrity, neuroinflammation, and oxidative damage. RESULTS: There was a positive correlation between neurofilament light (NF-L) and the time spent in stage 1 of non-rapid eyes movement (NREM) (N1) sleep and a negative correlation between this marker and the time spent in stage 3 of NREM (N3) sleep. Accordingly, we observed that deep sleep was associated with lower levels of NF-L, whereas light sleep increased the probability of having higher levels of this marker. Furthermore, chitinase-3-like-1 (YKL-40) was negatively correlated with sleep efficiency, the time spent in stage 2 of NREM (N2) sleep, and the time spent in N3 sleep. Conversely, there was a positive correlation between N3 sleep and the oxidative protein damage markers N-ε-(carboxyethyl)lysine and N-ε-(malondialdehyde)lysine. CONCLUSIONS: There were significant correlations between sleep parameters and AD biomarkers related to axonal damage and neuroinflammation, such as NF-L and YKL-40. A lack of deep sleep was associated with higher levels of NF-L. This highlights a potential role for NF-L as a biomarker of sleep disruption in patients with mild-moderate AD in addition to its role in predicting neurodegeneration and cognitive decline.

Raman amplification in the ultra-small limit of Ag nanoparticles on SiO2 and graphene: Size and inter-particle distance effects.

Size, shape and hot spots are crucial to optimize Raman amplification from metallic nanoparticle (NPs). The amplification from radius = 1.8 ± 0.4 nm ultra-small silver NPs was explored. Increasing NP density redshifts and widens their plasmon that, according to simulations for NPs arrays, is originated by the reduction of the interparticle distance, d, becoming remarkable for d ≤ R. Inter-particle interaction red-shifts (N130 nm) and widens (N90 nm) the standard plasmon of non-interacting spherical particles. Graphene partly delocalizes the carriers enhancing the NIR spectral weight. Raman amplification of graphene phonons is moderate and depends smoothly on d while that of Rhodamine 6G (R6G) varies almost exponentially due to their location at hotspots that depend strongly on d. The experimental correlation between amplification and plasmon position is well reproduced by simulations. The amplification originated by the ultra-small NPs is compared to that of larger particles, granular silver films with 7 < R < 15 nm grains, with similar extinction values. The amplification is found to be larger for the 1.8nm NPs due to the higher surface/volume ration that allows higher density of hot spots. It is demonstrated that Raman amplification can be efficiently increased by depositing low density layers of ultra-small NPs on top of granular films.

Trastornos del movimiento y de la conducta durante el sueño en el adulto / Sleep-related movement and behavioural disorders in adults

Los trastornos del movimiento y de la conducta durante el sueño pueden tener un impacto en la calidad del sueño del paciente y dar lugar a síntomas diurnos. En estos grupos de enfermedades se incluyen entidades como el síndrome de piernas inquietas, los movimientos periódicos de las piernas y las parasomnias del sueño de movimientos oculares rápidos (REM) y no REM. El conocimiento de sus características clínicas y nociones sobre su manejo es de gran importancia para el neurólogo y especialista en sueño por su frecuencia e impacto en la calidad del sujeto. Con frecuencia, estos pacientes son referidos a dichos especialistas, y es relevante conocer que ciertos trastornos del sueño pueden asociarse a otras enfermedades neurológicas

Sleep-related movement and behaviour disorders may have an impact on sleep quality and lead to daytime symptoms. These groups of conditions include diseases such as restless legs syndrome, periodic leg movements, and REM and NREM parasomnias. The knowledge of their clinical features and management is of utmost importance for the neurologist and sleep specialist. Frequently, these patients are referred to such specialists and it is relevant to know that certain sleep disorders may be associated with other neurological conditions

Supported Ultra-Thin Alumina Membranes with Graphene as Efficient Interference Enhanced Raman Scattering Platforms for Sensing.

The detection of Raman signals from diluted molecules or biomaterials in complex media is still a challenge. Besides the widely studied Raman enhancement by nanoparticle plasmons, interference mechanisms provide an interesting option. A novel approach for amplification platforms based on supported thin alumina membranes was designed and fabricated to optimize the interference processes. The dielectric layer is the extremely thin alumina membrane itself and, its metallic aluminum support, the reflecting medium. A CVD (chemical vapor deposition) single-layer graphene is transferred on the membrane to serve as substrate to deposit the analyte. Experimental results and simulations of the interference processes were employed to determine the relevant parameters of the structure to optimize the Raman enhancement factor (E.F.). Highly homogeneous E.F. over the platform surface are obtained, typically 370 ± (5%), for membranes with ~100 nm pore depth, ~18 nm pore diameter and the complete elimination of the Al2O3 bottom barrier layer. The combined surface enhanced Raman scattering (SERS) and interference amplification is also demonstrated by depositing ultra-small silver nanoparticles. This new approach to amplify the Raman signal of analytes is easily obtained, low-cost and robust with useful enhancement factors (~400) and allows only interference or combined enhancement mechanisms, depending on the analyte requirements.

Dexibuprofen Biodegradable Nanoparticles: One Step Closer towards a Better Ocular Interaction Study.

Ocular inflammation is one of the most prevalent diseases in ophthalmology, which can affect various parts of the eye or the surrounding tissues. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, are commonly used to treat ocular inflammation in the form of eye-drops. However, their bioavailability in ocular tissues is very low (less than 5%). Therefore, drug delivery systems such as biodegradable polymeric PLGA nanoparticles constitute a suitable alternative to topical eye administration, as they can improve ocular bioavailability and simultaneously reduce drug induced side effects. Moreover, their prolonged drug release can enhance patient treatment adherence as they require fewer administrations. Therefore, several formulations of PLGA based nanoparticles encapsulating dexibuprofen (active enantiomer of Ibuprofen) were prepared using the solvent displacement method employing different surfactants. The formulations have been characterized and their interactions with a customized lipid corneal membrane model were studied. Ex vivo permeation through ocular tissues and in vivo anti-inflammatory efficacy have also been studied.

De la fragmentación a la cohesión. Una experiencia grupal con víctimas de abuso sexual infantil / From fragmentation to cohesion. A group experience with victims of child sexual abuse / De la fragmentació a la cohesió. Una experiència grupal amb víctimes d'abús sexual infantil

Presentamos, en este artículo, una experiencia de psicoterapia psicoanalítica de grupo con tres niñas de cuatro y cinco años que habían sufrido abusos sexuales de muy pequeñas por parte de un familiar cercano y que ninguna había verbalizado. El único síntoma manifiesto era una importante inhibición, que las tres compartían. Se inició una psicoterapia semanal sin un límite predefinido de tiempo que ha durado un año y medio. Como resultado del proceso psicoterapéutico, las niñas fueron capaces de salir de la inhibición, desarrollar un juego simbólico, manifestar fantasías inconscientes y encontrar otra manera de expresarse con el cuerpo y también de comunicarse con él

In this article, we present a psychoanalytic group psychotherapy experience with three girls, aged between four and five, who had been sexually abused by a close relative. None of the victims had verbalized it. The only manifest symptom was an important inhibition, which the three of them shared. A weekly psychotherapy was started without a predefined time limit. It lasted a year and a half. As a result of the psychotherapeutic process, the girls were able to get out of inhibition, develop a symbolic play, manifest unconscious fantasies and find another way to express themselves with the body and also to communicate with it

Presentem, en aquest article, una experiència de psicoteràpia psicoanalítica de grup amb tres nenes de quatre I cinc anys que havien patit abusos sexuals de molt petites per part d'un familiar proper I que cap d'elles havia verbalitzat. L'únic símptoma manifest era una important inhibició, que totes tres compartien. Es va iniciar una psicoteràpia setmanal sense un límit predefinit de temps que ha durat un any I mig. Com a resultat del procés psicoterapèutic, les nenes van ser capaces de sortir de la inhibició, desenvolupar un joc simbòlic, manifestar fantasies inconscients I trobar una altra manera d'expressar-se amb el cos I també de comunicar-s'hi

Pautas generales en el proceso de readaptación al entrenamiento después de una lesión deportiva / General guidelines in the rehabilitation process for return to training after a sports injury

La readaptación a la práctica deportiva es el proceso interdisciplinar, específico e individualizado, que tiene como objetivo la óptima disponibilidad del deportista para la competición después de una lesión deportiva. Este proceso se lleva a cabo a partir del alta médica hasta el alta deportiva, e intervienen los diferentes profesionales del ámbito de la salud, liderados por el médico deportivo. Su planificación consta de 3 fases definidas por la acción muscular (isométrica, concéntrica y excéntrica), la cadena cinética (cerrada o abierta), la amplitud de trabajo (interna, media, externa y total) y la orientación de los ejercicios (general, dirigida y específica). La vuelta a la competición (return to play) debe ser consensuada a partir de información objetiva sobre la evolución de la lesión, el estado de forma, así como la propia percepción del deportista (AU)

Rehabilitation for return to training is an interdisciplinary, specific and individualized process that is geared towards the sportsman's optimal availability for competition after a sports injury. This process begins after medical discharge and continues up to the return to play, involving the different professionals in the field of healthcare and led by the sports physician. Planning consists of three phases, defined by muscular action (isometric, concentric and eccentric);kinetic chain (closed or open); range of movement (internal, medial, external and total);and exercise orientation (general, directed and specific). Return to play must be agreed upon on the basis of objective information on the recovery stage of the injury, the state of fitness, and the sportsman's own perception (AU)

Idiopathic REM sleep behavior disorder in the elderly Spanish community: a primary care center study with a two-stage design using video-polysomnography.

OBJECTIVE: To examine the presence and characteristics of idiopathic REM sleep behavior disorder (IRBD) in a representative Caucasian sample from the elderly community of Lleida, Spain, attending primary care centers. METHODS: Participants were individuals aged 60 years or older who underwent routine visits in two primary care centers. They underwent a two-stage study; a validated screening single question for IRBD diagnosis (RBD1Q) followed by, in those who endorsed positive answer, clinical assessment by a neurologist plus video-polysomnography (V-PSG). RESULTS: Of 539 individuals (56.4% women, mean age 72.86 ± 8.20 years), 28 (5.2%) endorsed positively the RBD1Q. Four of these 28 refused further assessments. Four of the 24 remaining subjects underwent clinical assessment but refused V-PSG. Of the 20 who underwent clinical assessment plus V-PSG, REM sleep was not recorded in four (20%, all four taking antidepressants). V-PSG ruled out RBD in 12 subjects who had obstructive sleep apnea (n = 9), periodic limb movement disorder in sleep (n = 2) and normal sleep (n = 1). IRBD was diagnosed in four individuals giving an estimated prevalence of 0.74% (95% CI = 0.29-1.89). They were three men and one woman between 74 and 82 years of age who never reported dream-enacting behaviors to their doctors because they thought they represented a normal phenomenon despite suffering sleep-related injuries. These patients had history of violent sleep behaviors with an interval between estimated RBD onset and V-PSG of 4.5 ± 4.2 years. CONCLUSIONS: IRBD is not uncommon in the elderly community and its demographic and clinical profile is similar to those diagnosed in sleep centers.

Clinical rating scale for pantothenate kinase-associated neurodegeneration: A pilot study.

BACKGROUND: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration. METHODS: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs. RESULTS: Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's α = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale. CONCLUSIONS: The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing. © 2017 International Parkinson and Movement Disorder Society.

Periodic Limb Movements During Sleep Mimicking REM Sleep Behavior Disorder: A New Form of Periodic Limb Movement Disorder.

Study Objectives: To describe a group of patients referred because of abnormal sleep behaviors that were suggestive of rapid eye movement (REM) sleep behavior disorder (RBD) in whom video-polysomnography ruled out RBD and showed the reported behaviors associated with vigorous periodic limb movements during sleep (PLMS). Aims and Methods: Clinical history and video-polysomnography review of patients identified during routine visits in a sleep center. Results: Patients were 15 men and 2 women with a median age of 66 (range: 48-77) years. Reported sleep behaviors were kicking (n = 17), punching (n = 16), gesticulating (n = 8), falling out of bed (n = 5), assaulting the bed partner (n = 2), talking (n = 15), and shouting (n = 10). Behaviors resulted in injuries in 3 bed partners and 1 patient. Twelve (70.6%) patients were not aware of displaying abnormal sleep behaviors that were only noticed by their bed partners. Ten (58.8%) patients recalled unpleasant dreams such as being attacked or chased. Video-polysomnography showed (1) frequent and vigorous stereotyped PLMS involving the lower limbs, upper limbs, and trunk (median PLMS index 61.2; median PLMS index in NREM sleep 61.9; during REM sleep only 8 patients had PLMS and their median PLMS index in REM sleep was 39.5); (2) abnormal behaviors (e.g., punching, groaning) during some of the arousals that immediately followed PLMS in NREM sleep; and (3) ruled out RBD and other sleep disorders such as obstructive sleep apnea. Dopaminergic agents were prescribed in 14 out of the 17 patients and resulted in improvement of abnormal sleep behaviors and unpleasant dreams in all of them. After dopaminergic treatment, follow-up video-polysomnography in 7 patients showed a decrease in the median PLMS index from baseline (108.9 vs. 19.2, p = .002) and absence of abnormal behaviors during the arousals. Conclusions: Abnormal sleep behaviors and unpleasant dreams simulating RBD symptomatology may occur in patients with severe PLMS. In these cases, video-polysomnography ruled out RBD and identified prominent PLMS followed by arousals containing abnormal behaviors. Our cases represent an objectively documented subtype of periodic limb movement disorder causing abnormal sleep behaviors.

Efficient Heterostructures for Combined Interference and Plasmon Resonance Raman Amplification.

The detection, identification, and quantification of different types of molecules and the optical imaging of, for example, cellular processes are important challenges. Here, we present how interference-enhanced Raman scattering (IERS) in adequately designed heterostructures can provide amplification factors relevant for both detection and imaging. Calculations demonstrate that the key factor is maximizing the absolute value of the refractive indices' difference between dielectric and metal layers. Accordingly, Si/Al/Al2O3/graphene heterostructures have been fabricated by optimizing the thickness and roughness and reaching enhancement values up to 700 for 488 nm excitation. The deviation from the calculated enhancement, 1200, is mainly due to reflectivity losses and roughness of the Al layer. The IERS platforms are also demonstrated to improve significantly the quality of white light images of graphene and are foreseen to be adequate to reveal the morphology of 2D and biological materials. A graphene top layer is adequate for most organic molecule deposition and often quenches possible fluorescence, permitting Raman signal detection, which, for a rhodamine 6G (R6G) monolayer, presents a gain of 400. Without graphene, the nonquenched R6G fluorescence is similarly amplified. The wavelength dependence of the involved refractive indices predicts much higher amplification (around 104) for NIR excitation. These interference platforms can therefore be used to gain contrast and intensity in white light, Raman, and fluorescence imaging. We also demonstrate that surface-enhanced Raman scattering and IERS amplifications can be efficiently combined, leading to a gain of >105 (at 488 nm) by depositing a Ag nanostructured transparent film on the IERS platform. When the plasmonic structures deposited on the IERS platforms are optimized, single-molecule detection can be actively envisaged.

Implementing a care bundle approach reduces ventilator-associated pneumonia and delays ventilator-associated tracheobronchitis in children: differences according to endotracheal or tracheostomy devices.

OBJECTIVE: To reduce ventilator-associated infections (VARI) and improve outcomes for children. METHODS: This prospective interventional cohort study was conducted in a paediatric intensive care unit (PICU) over three periods: pre-intervention, early post-intervention, and late post-intervention. These children were on mechanical ventilation (MV) for ≥48h. RESULTS: Overall, 312 children (11.9% of whom underwent tracheostomy) and 6187 ventilator-days were assessed. There was a significant reduction in ventilator-associated pneumonia (VAP) among tracheostomized patients (8.16, 3.27, and 0.65 per 1000 tracheostomy ventilation-days before the intervention, after the general bundle implementation, and after the tracheostomy intervention, respectively). The median time from onset of MV to diagnosis of ventilator-associated tracheobronchitis (VAT) increased from 5.5 to 48 days in the late post-intervention period (p=0.004), and was associated with a significant increase in median 28-day ventilator-free days and PICU-free days. Tracheostomy (odds ratio 7.44) and prolonged MV (odds ratio 2.75) were independent variables significantly associated with VARI. A trend towards a reduction in PICU mortality was observed, from 28.4% to 16.6% (relative risk 0.58). CONCLUSIONS: The implementation of a care bundle to prevent VARI in children had a different impact on VAP and VAT, diminishing VAP rates and delaying VAT onset, resulting in reduced healthcare resource use. Tracheostomized children were at increased risk of VARI, but preventive measures had a greater impact on them.

Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria.

Resistance to all known antibiotics is a growing concern worldwide, and has renewed the interest in antimicrobial peptides, a structurally diverse class of amphipathic molecules that essentially act on the bacterial membrane. Propelled by the antimicrobial potential of this compound class, we have designed three new lipopeptides derived from polymyxin B, sp-34, sp-96 and sp-100, with potent antimicrobial activity against both Gram positive and Gram negative bacteria. The three peptides bind with high affinity to lipopolysaccharide as demonstrated by monolayer penetration and dansyl-displacement. The interaction with the cytoplasmic membrane has been elucidated by biophysical experiments with model membranes of POPG or POPE/POPG (6:4), mimicking the Gram positive and Gram negative bacterial membrane. Trp-based fluorescence experiments including steady-state, quenching, anisotropy and FRET, reveal selectivity for anionic phospholipids and deep insertion into the membrane. All three lipopeptides induce membrane fusion and leakage from anionic vesicles, a process that is favored by the presence of POPE. The molecules bind to zwitterionic POPC vesicles, a model of the eukaryotic membrane, but in a different way, with lower affinity, less penetration into the bilayer and no fusion or permeabilization of the membrane. Results in model membranes are consistent with flow cytometry experiments in Escherichia coli and Staphylococcus aureus using a membrane potential sensitive dye (bis-oxonol) and a nucleic acid dye (propidium iodide), suggesting that the mechanism of action is based on membrane binding and collapse of membrane integrity by depolarization and permeabilization.

Langmuir monolayers and Differential Scanning Calorimetry for the study of the interactions between camptothecin drugs and biomembrane models.

CPT-11 and SN-38 are camptothecins with strong antitumor activity. Nevertheless, their severe side effects and the chemical instability of their lactone ring have questioned the usual forms for its administration and have focused the current research on the development of new suitable pharmaceutical formulations. This work presents a biophysical study of the interfacial interactions of CPT-11 and SN-38 with membrane mimetic models by using monolayer techniques and Differential Scanning Calorimetry. The aim is to get new insights for the understanding of the bilayer mechanics after drug incorporation and to optimize the design of drug delivery systems based on the formation of stable bilayer structures. Moreover, from our knowledge, the molecular interactions between camptothecins and phospholipids have not been investigated in detail, despite their importance in the context of drug action. The results show that neither CPT-11 nor SN-38 disturbs the structure of the complex liposome bilayers, despite their different solubility, that CPT-11, positively charged in its piperidine group, interacts electrostatically with DOPS, making stable the incorporation of a high percentage of CPT-11 into liposomes and that SN-38 establishes weak repulsive interactions with lipid molecules that modify the compressibility of the bilayer without affecting significantly neither the lipid collapse pressure nor the miscibility pattern of drug-lipid mixed monolayers. The suitability of a binary and a ternary lipid mixture for encapsulating SN-38 and CPT-11, respectively, has been demonstrated.

A cyclic GB virus C derived peptide with anti-HIV-1 activity targets the fusion peptide of HIV-1.

The development of peptide fusion inhibitors based on short synthetic peptides represents a promising option in the fight against HIV-1 infection, especially in individuals infected with multiresistant HIV-1 strains. GBV-C has the beneficial effect of retarding the progression of AIDS in people who are co-infected with both the GBV-C and HIV viruses. In previous works, the E1(22-39) GBV-C sequence (E1P8lin) was found to be capable of inhibiting the interaction of HIV-1 FP with bilayers and its cyclic analogue (E1P8cyc) showed a higher anti-HIV-1 activity. In the present work, in an attempt to gain a better understanding of the interaction of E1P8 peptides with HIV-1 FP, we analyzed direct interactions between peptides at the molecular level. Our results support that E1P8cyc might be more potent at blocking HIV-1 entry than E1P8lin as a consequence of the structure induced in the complex formed with HIV-1 FP, which is able to modify the conformation adopted by this functional domain of the HIV-1 gp41 protein in target cell membranes.

[Basic mechanisms: absorption and excretion of cholesterol and other sterols]. / Mecanismos básicos. Absorción y excreción de colesterol y otros esteroles.

Cholesterol is of vital importance for vertebrate cell membrane structure and function. It is obvious that adequate regulation of cholesterol homeostasis is essential. Hypercholesterolemia promotes atherosclerosis and thereby represents a major risk factor for cardiovascular disease. The liver has been considered the major site of control in maintenance of cholesterol homeostasis. The liver facilitates clearance of (very) low density lipoprotein particles and cholesterol-containing chylomicron remnants, synthesizes cholesterol, synthesizes and secretes (nascent) high density lipoprotein particles, secretes cholesterol and bile salts to bile, and is involved in reverse cholesterol transport. In recent years, however, the importance of the intestine in many aspects of cholesterol physiology is increasingly recognized. It has become apparent that direct secretion of cholesterol from the blood compartment into the intestine, or transintestinal cholesterol excretion, plays a major role in disposal of cholesterol via the feces. This review will discuss current knowledge on the physiology of cholesterol homeostasis, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and therapeutic options for hypercholesterolemia.