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Aimee Vasconcelos,1 Estefania Vega,2 Yolanda Pérez,3 María J Gómara,1 María Luisa García,2 Isabel Haro1 1Unit of Synthesis and Biomedical Applications of Peptides, Department of Biomedical Chemistry, Institute for Advanced Chemistry of Catalonia, Consejo Superior de Investigaciones Científicas (IQAC-CSIC), 2Department of Physical Chemistry, Institute of Nanoscience and Nanotechnology, Faculty of Pharmacy, University of Barcelona, 3Nuclear Magnetic Resonance Unit, IQAC-CSIC, Barcelona, Spain Abstract: In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)–polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test–chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery. Keywords: peptide for ocular delivery, flurbiprofen, controlled release, ocular tolerance, anti-inflammatory

Amyloid β-peptide (Aβ) misfolding into β-sheet structures triggers neurotoxicity inducing Alzheimer's disease (AD). Molecules able to reduce or to impair Aβ aggregation are highly relevant as possible AD treatments since they should protect against Aβ neurotoxicity. We have studied the effects of the interaction of dynorphins, a family of opioid neuropeptides, with Aβ 40 the most abundant species of Aβ. Biophysical measurements indicate that Aβ 40 interacts with Big Dynorphin (BigDyn), lowering the amount of hydrophobic aggregates, and slowing down the aggregation kinetics. As expected, we found that BigDyn protects against Aβ 40 aggregates when studied in human neuroblastoma cells by cell survival assays. The cross-interaction between BigDyn and Aβ 40 provides insight into the mechanism of amyloid pathophysiology and may open up new therapy possibilities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Background: A restricted response against citrullinated peptides/proteins, with less isotype usage, has been found in palindromic rheumatism (PR) in comparison with rheumatoid arthritis (RA). We hypothesized that this different antibody response may be observed for other post-translational modified proteins. We compared the prevalence and isotype usage of two specificities of anti-carbamylated peptide/protein antibodies (Anti-CarP) in patients with PR and RA., Methods: Cross-sectional study including 54 patients with pure PR and 53 patients with RA, matched by sex, age, disease duration and ACPA. Anti-CarP specificities were determined by home-made enzyme-linked immunosorbent assay tests using a synthetic chimeric fibrin/filaggrin homocitrullinated peptide (CFFHP) and fetal calf serum (FCS) homocitrullinated protein as antigens. IgG, IgA and IgM isotypes were measured., Results: Anti-CarP were positive (CFFHP or FCS) in 24% and 64% of patients with PR and RA, respectively ( p  < 0.005). All Anti-CarP isotype proportions were significantly lower in PR than in RA: Anti-CarP-IgG (24% versus 51%), Anti-CarP-IgA (7% versus 34%) and Anti-CarP-IgM (7% versus 36%). Mean titers of Anti-CarP isotypes were also lower in PR. In Anti-CarP positive patients, the isotype distribution differed between PR and RA: IgG Anti-CarP was used in all PR patients and in 79% of RA patients. By contrast, a significantly lower isotype usage of both IgA (31% versus 53%) and IgM (31% versus 56%) was observed in PR patients. No significant differences in clinical or demographic characteristics were observed according to Anti-CarP status in PR patients, except for a higher prevalence of ACPA and higher mean titers of ACPA and rheumatoid factor in Anti-CarP positive patients., Conclusion: Anti-CarP are found in patients with PR but in a lower proportion and with a different isotype usage from in RA, suggesting a distinct B cell response to homocitrullinated antigens in PR., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Purpose: To investigate the efficacy and tolerability of perampanel (PER) when administered as a first add-on therapy to patients with focal epilepsy or idiopathic generalized epilepsy (IGE) taking one other antiseizure drug (ASD)., Methods: This multicentre, retrospective, one-year observational study collected data from patients (≥12 years) who initiated treatment with PER as first add-on therapy. Patients had to be experiencing inadequate seizure control on ASD monotherapy and tried ≤3 ASD monotherapies before initiating PER. Multivariate logistic regression analyses were performed, adjusted for the number and type of previous seizures, duration and aetiology of epilepsy., Results: Of the 149 patients included in the study (mean age 41 years; 54.4 % male), 118 (79.2 %) were still receiving PER as first add-on treatment after 12 months. Mean PER dose was 6.2 mg/day. At 12 months, 45.6 % were seizure-free and 84.6 % responders. A significant difference in seizure freedom rate was found between patients with IGE and patients with focal epilepsy, but not in responders. Reduced seizure control was observed when PER was administered with strong enzyme-inducing ASDs; conversely, increased seizure control was seen when the same dose of PER was combined with enzyme-inhibiting ASDs. The most frequent adverse events were dizziness (15.4 %), irritability (14.1 %) and drowsiness (14.1 %); no differences in tolerance were observed among different combinations., Conclusion: PER demonstrated a good efficacy and safety profile when used as a first add-on therapy in patients who did not respond to monotherapy. PER dose adjustments may optimize seizure control when combined with strong enzyme-inducing or enzyme-inhibiting ASDs., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Based on the structure of an HIV-1 entry inhibitor peptide two stapled- and a retro-enantio peptides have been designed to provide novel prevention interventions against HIV transmission. The three peptides show greater inhibitory potencies in cellular and mucosal tissue pre-clinical models than the parent sequence and the retro-enantio shows a strengthened proteolytic stability. Since HIV-1 fusion inhibitor peptides need to be embedded in the membrane to properly interact with their viral target, the structural features were determined by NMR spectroscopy in micelles and solved by using restrained molecular dynamics calculations. Both parent and retro-enantio peptides demonstrate a topology compatible with a shared helix-turn-helix conformation and assemble similarly in the membrane maintaining the active conformation needed for its interaction with the viral target site. This study represents a straightforward approach to design new targeted peptides as HIV-1 fusion inhibitors and lead us to define a retro-enantio peptide as a good candidate for pre-exposure prophylaxis against HIV-1.

Objective: To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients., Methods: Cross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies., Results: We enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample., Conclusions: Anti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Novel strategies in the design of HIV-1 fusion/entry inhibitors are based on the construction of dual-targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual-targeting peptides composed of peptide domains of E2 and E1 envelope proteins from Human Pegivirus with the aim of targeting both the loop region and the fusion peptide domains of HIV-1 gp41. In a previous work, we described the inhibitory role of a highly conserved fragment of the E1 protein (domain 139-156) which interacts with the HIV-1 fusion peptide at the membrane level. Here, two different dual-targeting peptides, where this E1 peptide is located on the N- or the C-terminus respectively, have been chemically synthesized and their antiviral activities have been evaluated with HIV pseudotyped viruses from different clades. The study of the functional behaviour of peptides in a membranous environment attending to the peptide recognition of the target sites on gp41, the peptide conformation as well as the peptide affinity to the membrane, demonstrate that antiviral activity of the dual-targeting peptides is directly related to the peptide affinity and its subsequent assembly into the model membrane. The overall results point out to the necessity that fusion inhibitor peptides that specifically interfere with the N-terminal region of gp41 are embedded within the membrane in order to properly interact with their viral target.

Despite the great effort to decrease the HIV infectivity rate, current antiretroviral therapy has several weaknesses; poor bioavailability, development of drug resistance and poor ability to access tissues. However, molecules such as peptides have emerged asa new expectative to HIV eradication. The vaginal mucosa is the main spreading point of HIV. There are natural barriers such as the vaginal fluid which protects the vaginal epithelium from any foreign agents reaching it. This work has developed and characterized Nanoparticles (NPs) coated with glycol chitosan (GC), loaded with an HIV-1 inhibitor peptide (E2). In vitro release and ex vivo studies were carried out using the vaginal mucosa of swine and the peptide was determined by HPLC MS/MS validated method. Moreover, the peptide was labeled with 5(6)-carboxyfluoresceine and entrapped into the NPs to carried out in vivo studies and to evaluate the NPs penetration and toxicity in the vaginal mucosa of the swine. The mean size of the NPs, ξ and the loading percentage were fundamental features for to reach the vaginal tissue and to release the peptide within intercellular space. The obtained results suggesting that the fusion inhibitor peptides loaded into the NPs coated with GC might be a new way to fight the HIV-1, due to the formulation might reach the human epithelial mucosa and release peptide without any side effects., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: To analyze differences in the recognition of anti-citrullinated peptide/protein antibody (ACPA) citrullinated epitopes and isotypes in patients with palindromic rheumatism (PR) and rheumatoid arthritis (RA)., Methods: ACPA fine specificities (citrullinated peptides of enolase, fibrin, and vimentin) and isotypes (IgG, IgM, and IgA) were analyzed in 54 patients with longstanding PR and 54 patients with established RA., Results: CCP2 tested positive in 66.7% of patients with PR and RA. The ACPA distribution of fine specificities and isotypes differed between PR and RA patients. PR patients had a lower frequency of fine ACPA specificities than RA patients, which was significant in the case of a peptide derived from vimentin (PR 24.1% vs. 59.3% RA; p < 0.001). The mean number of ACPA specificities was lower in PR than in RA patients, and only 25.9% of PR patients recognized ≥2 additional specificities compared with 46.3% of RA patients. Significantly less isotype usage, especially IgA, was observed in PR patients., Conclusion: The ACPA immune response differed in patients with PR and RA, with fewer fine specificities and isotype usage in patients with PR. Some patients with PR may have impaired maturation of the B-cell response against citrullinated peptides with no progression to RA.

Introduction: Patients with chronic migraine (CM) and medication abuse are difficult to treat, and have a greater tendency towards chronification and a poorer quality of life than those with other types of headache., Aim: To evaluate whether the presence of medication abuse lowers the effectiveness of topiramate., Patients and Methods: A series of patients with CM were grouped according to whether they met abuse criteria or not. They were advised to stop taking the drug that they were abusing. Treatment was adjusted to match their crises and preventive treatment with topiramate was established from the beginning. The number of days with headache and intense migraine in the previous month and at four months of treatment was evaluated., Results: In all, 262 patients with CM criteria were selected and 167 (63.7%) of them fulfilled abuse criteria. In both groups there was a significant reduction in the number of days with headache/month and number of migraine attacks/month at the fourth month of treatment with topiramate. The percentage of reduction in the number of days with headache/month in CM without abuse was 59.3 ± 36.1%, and with abuse, 48.7 ± 41.7% (p = 0.0574). The percentage of reduction in the number of days with intense migraine/month in CM without abuse was 61.2%, and with abuse, 50% (p = 0.0224). Response rate according to the number of days with headache/month in CM without abuse was 69%, and with abuse, 57%. Response rate according to the number of intense migraines/month in CM without abuse was 76.8%, and in CM with abuse, 61% (p = 0.0097)., Conclusions: Topiramate was effective in patients with CM with and without medication abuse, although effectiveness is lower in the latter case.

Introduction: Topiramate and onabotulinumtoxin A have proven to be effective in chronic migraine with or without medication abuse according to recent criteria of the International Headache Society's Headache Classification., Aims: To show that flunarizine is as effective as topiramate in cases of chronic migraine without medication abuse., Patients and Methods: We conducted a prospective, non-randomised, comparative study of two groups of patients paired by age and sex, with chronic migraine without abuse, who had been treated preventively for the first time with topiramate or flunarizine., Results: Forty patients treated with flunarizine were assigned a patient of their same sex and age who was being treated with topiramate. The mean rate of reduction in intense migraines in the topiramate group was 59% and in the flunarizine group, 58.5% (p = 0.9444); the responder rate at four months of treatment did not show any significant differences either, the figures being 75% for topiramate and 70% for flunarizine (p = 0.6236). The mean reduction of other headaches in the topiramate group was 57% and in the flunarizine group, 64% (p = 0.4261); the responder rate at four months of treatment was similar in the two groups: 76%. The percentage of dropouts from treatment was higher with topiramate (19.5%) than with flunarizine (10%) (p = 0.3493). No serious side effects occurred in either of the groups. In all, 78.9% of the patients who took topiramate said they were satisfied with the drug versus 75% of those in the flunarizine group (p = 0.7903)., Conclusions: Flunarizine proved to be as effective as topiramate in the treatment of chronic migraine without medication abuse.

INTRODUCTION. Flunarizine, with level of evidence A, and nadolol, with evidence level C, would be indicated as preventive treatment of migraine. Yet, no previous studies have been conducted to compare the effectiveness of the two drugs. AIM. To compare the effectiveness parameters in independent groups of patients treated preventively with one of the pharmaceuticals from the study, the same protocol being applied in both cases. PATIENTS AND METHODS. The subjects selected for the study were patients with episodic migraine (according to 2004 International Headache Society criteria) who had undergone preventive treatment for the first time, with flunarizine (5 mg/day) or nadolol (20-40 mg/day). The main effectiveness variables (reduction in the number of seizures at four months of treatment and responder rates) were analysed. RESULTS. The study included 227 patients who intended to receive treatment: 155 with flunarizine (80.5% females; mean age: 38.3 ± 12.1 years) and 72 with nadolol (63.8% females; mean age: 37.1 ± 12.0 years). The mean number of seizures prior to treatment was 6.09 ± 2.6 in the flunarizine group and 5.1 ± 1.7 in the nadolol group (p = 0.0079); at four months of treatment it was 2.61 ± 2.4 in the flunarizine group and 2.77 ± 2.4 in the nadolol group (p = NS). Percentage of reduction of migraines: 55.2% with flunarizine and 50.4% with nadolol (p = NS). The responder rate was 69% with flunarizine and 67% with nadolol (p = NS). The excellent response rate (reduction in the number of seizures by 75% or more) was 52.2% with flunarizine and 36.1% with nadolol (p = 0.0077). Percentage of adverse side effects: 48.3% with flunarizine and 25% with nadolol (p = 0.0009). The satisfaction rate was similar in both groups, 68%. CONCLUSIONS. Both flunarizine and nadolol proved to be effective in the preventive treatment of episodic migraine. Flunarizine is used more often in our milieu and was less well tolerated.

This work reports on the fabrication and performance of a simple amperometric immunosensor device to be potentially used for the detection of serum anti-citrullinated peptide antibodies (ACPAs), which are specific for rheumatoid arthritis (RA) autoimmune disease. Sera of RA patients contain antibodies to different citrullinated peptides and proteins such as fibrin or filaggrin. Herein, a chimeric fibrin-filaggrin synthetic peptide (CFFCP1) was used as a recognition element anchored to the surface of a multiwalled carbon nanotube-polystyrene (MWCNT-PS) based electrochemical transducer. The transducer fabrication process is described in detail together with its successful electrochemical performance in terms of repeatability and reproducibility of the corresponding amperometric response. The resulting immunosensor approach was initially tested in sera of rabbits previously inoculated with the synthetic peptide and eventually applied to the detection of ACPAs in human sera. A comparative study was carried out using control serum from a blood donor, which demonstrated the selectivity of the immunosensor response and its sensitivity for the detection of anti-CFFCP1 antibodies present in RA patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: The drop-out rate among patients receiving preventive treatment for migraine is higher than 30%. This situation is not very widely known and the risk factors that lead patients to drop out from treatment have yet to be identified., Aim: To evaluate some of the factors that can predispose patients to drop out of preventive treatment., Patients and Methods: We conducted a prospective study of patients suffering from migraine who required preventive treatment for the first time with one of what are considered the top three first-choice drugs, i.e. a beta-blocker (nadolol), a neuromodulator (topiramate) or a calcium antagonist (flunarizine). Two groups were established according to whether patients dropped out of treatment or not. Different demographic and clinical variables were analysed and compared in the two groups., Results: Of 800 patients with migraine who required preventive treatment for the first time, the drop-out rate was 19.7%. In the drop-out group, the variables 'age', 'number of seizures', 'number of seizures prior to preventive treatment' and 'side effects' showed significant differences with those from the group of patients who did not drop out of preventive treatment., Conclusions: The drug used as preventive treatment, the side effects, a younger age and a lower number of seizures before starting the preventive treatment favoured higher drop-out rates. Whether the migraine was episodic or chronic, the presence of medication abuse and the drugs used to treat the seizures were not related with dropping out of preventive treatment., (© 2011 Revista de Neurología)

Introduction: Patients with headache and medication abuse (HMA) are difficult to treat, have a greater tendency towards chronification and a poorer quality of life than those with other types of headache. AIM. To evaluate the indicators showing that these patients are responding to ambulatory treatment., Patients and Methods: From a series of patients with migraine, we selected those who satisfied HMA criteria according to the appendix of the 2006 International Classification of the Headache Disease (ICHD-2) and who had never previously undergone treatment. As outpatients, they were advised to stop taking the drug that they were abusing. The treatment of their seizures was adjusted with the most efficient drugs and preventive treatment was started from the outset with topiramate or flunarizine. Patients were grouped according to whether they continued with HMA or not. Comparisons were made between the number of days with headache during the previous month and after four months of treatment and the persistence of abuse., Results: HMA criteria were met by 178 patients (mean age 40.9; 88.7% females). Results showed that 68.5% (122 patients) responded and no longer met HMA criteria after treatment. The treatment used for their seizures (triptans, nonsteroidal antiinflammatory drugs, analgesics) and preventive treatment (topiramate or flunarizine) were similar in both groups. The average number of days with headache prior to treatment was 18.52 in the group that responded and 20.87 (p = 0.0263) in the group that did not respond to treatment. In the group of responders 7.3% dropped out of preventive treatment compared with 35% (p = 0.0001) in the group of non-responders., Conclusions: A higher number of days with headache during the previous month and withdrawing from preventive treatment were indicators of a bad progression.

The GB virus C or hepatitis G virus (GBV-C/HGV) is a single-stranded positive sense RNA virus that belongs to the Flaviviridae family. Recent years have seen the publication of numerous works in which coinfection with GBV-C/HGV and HIV has been associated with slower progression of the illness and a higher survival rate of patients once AIDS has developed. The mechanism by which the GBV-C/HGV virus has a "protective effect" in patients with HIV has still not been defined. Study of the interaction of the GBV-C/HGV and HIV viruses could lead to the development of new therapeutic agents for the treatment of AIDS. Given that the mechanism responsible for the beneficial effect exercised by the GBV-C/HGV virus in the course of HIV infection has not been defined, the present work is intended as a study of the structure and interactions between the fusion peptide of HIV-1, gp41(1-23), and synthetic peptide sequences of the E2 envelope protein of GBV-C/HGV using biophysical techniques. Our results highlight that the E2(269-286) sequence interacts with the target fusion peptide of HIV-1 and modifies its conformation.

Introduction: Management of cerebral vascular pathologies by means of clinical pathways allows us to make cost effective use of resources, to enhance health care quality and to obtain a greater degree of satisfaction in patients., Aims: To assess the efficiency of applying a clinical pathway designed for the treatment of transient ischemic attacks (TIA) by monitoring a series of indicators that enable us to detect existing problems, to introduce any corrections that are needed and to draw conclusions that can be useful in the future., Patients and Methods: To this end, a clinical pathway was drawn up with the general agreement of the members of our service and the different professionals involved in caring for these patients. Analyses were performed to study the data from 1998 to 2001, prior to implementation of the pathway, and from 2002 and 2003, which were the first years in which it was being applied. Altogether 1,433 patients with a diagnosis of TIA were hospitalised during this period, 554 of whom were admitted during the years 2002 and 2003., Results: Of this group, the pathway was initially applied in 123 cases and 62 completed it. The mean stay in hospital was reduced from 9.2 days in 2000 to 5.7 days in 2003. The mean stay of patients who fulfilled all the requirements of the pathway was only 2.9 days. As far as the survey on satisfaction is concerned, 97% of patients said they were satisfied or very satisfied with the care they had received., Conclusions: The application of a clinical pathway in the treatment of TIA resulted in a high degree of satisfaction among the patients who were treated and a notable reduction in the mean stay in hospital.

Introduction: Sexual dysfunction is a frequent disorder associated to multiple sclerosis, that contributes to the worsening of life quality of these patients., Aim: To ascertain how it is managed in a demyelinating disease unit., Patients and Methods: It was done an anonymous poll to multiple sclerosis patients in a demyelinating disease unit. The following variables were analysed: age, sex, marital status, education degree, sexual dysfunction, vesical dysfunction, gait disturbances and duration of illness., Results: 67 of 97 patients answered. 74.6% females. Average age was 43.7 years. Average developing time was 11.3 years. 58% of the patients had vesical dysfunction. 43% had sexual dysfunction. There was relation with statistical significance between sexual and vesical dysfunction but not among the rest of variables. 63% of the patients with sexual dysfunction had never talked about this problem with their doctors. That the patient talked about sexual dysfunction was related with the fact that the neurologist asked for or not, and if sexual dysfunction was an important problem for the patient. The neurologist had asked for dysfunction sexual symptoms to 30% of the patients, and this was more frequent if the patient was male and if he or she had gait disturbances., Conclusions: Sexual dysfunction is a frequent and important problem for patients with multiple sclerosis. According to our results, this problem is raised up in an insufficient manner as much for patients as for neurologists.

Clay-vesicle systems exhibit a potential for environmental applications, such as herbicide formulations for reduced leaching. Clay-vesicle interactions were addressed by combining adsorption and XRD measurements with fluorescence studies for didodecyldimethylammonium bromide (DDAB), dioctadecyldimethylammonium bromide (DDOB), and montmorillonite. XRD and adsorption data indicated that the adsorbing vesicles were transformed after 3 days into paraffinic and bilayer structures. Fluorescence studies revealed that adsorption was almost complete within 5 min for a loading below the cation exchange capacity (CEC). Aggregation and sedimentation of clay-surfactant particles occurred within several minutes. Fluorescent measurements of supernatants indicated decomposition of vesicles at a high clay/surfactant ratio due to rapidly adsorbing cationic monomers. The kinetics of energy transfer between vesicles labeled by NBD-PE (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl)) and montmorillonite labeled by rhodamine-B follows that of aggregation of surfactant-clay particles and structural changes of the vesicles at times of minutes to hours. Experiments following the reduction of NBD fluorescence by addition of dithionite indicate faster permeabilization of DDOB than DDAB vesicles, which was confirmed by leakage experiments. The faster permeabilization of DDOB vesicles in the presence of clay was correlated with their inferior suitability for the preparation of clay-based formulations of anionic herbicides for slow release.

Interest in synthetic immunogenic peptides is increasingly growing due to the continuous achievements in the understanding of the molecular basis of the immune response. Moreover, the use of peptide fragments to generate antibodies capable of recognizing and neutralizing viral particles could be a valuable alternative to conventional vaccines: they are safe, they can be designed to induce defined immune responses and they can be synthesised in large quantities in high purity. However, their relatively low immunogenicity requires the development of effective adjuvants and/or their incorporation into controlled release formulations. Several different strategies have been used for the induction and analysis of protective immune responses induced by short peptides against infectious diseases. In the present article we summarise the different approaches used to potentiate the immune response induced by a continuous epitope of hepatitis A virus: co-linear link of T-cell epitopes in different orientations, incorporation into liposomes, and preparation of homogeneous and heterogeneous Multiple Antigenic Peptides.