In vitro effects of wound-dressings on key wound healing properties of dermal fibroblasts.

Healing of complex wounds requires dressings that must, at least, not hinder and should ideally promote the activity of key healing cells, in particular fibroblasts. This in vitro study assessed the effects of three wound-dressings (a pure Ca2+ alginate: Algostéril®, a Ca2+ alginate + carboxymethylcellulose: Biatain alginate® and a polyacrylate impregnated with lipido-colloid matrix: UrgoClean®) on dermal fibroblast activity. The results showed the pure calcium alginate to be non-cytotoxic, whereas the other wound-dressings showed moderate to strong cytotoxicity. The two alginates stimulated fibroblast migration and proliferation, whereas the polyacrylate altered migration and had no effect on proliferation. The pure Ca2+ alginate significantly increased the TGF-ß-induced fibroblast activation, which is essential to healing. This activation was confirmed by a significant increase in Vascular endothelial growth factor (VEGF) secretion and a higher collagen production. The other dressings reduced these fibroblast activities. The pure Ca2+ alginate was also able to counteract the inhibitory effect of NK cell supernatants on fibroblast migration. These in vitro results demonstrate that tested wound-dressings are not equivalent for fibroblast activation. Only Algostéril was found to promote all the fibroblast activities tested, which could contribute to its healing efficacy demonstrated in the clinic.

Gas exchange and osmotic adjustment in cotton cultivars subjected to severe salt stress.

Salinity is harmful to crops when the concentration of soluble salts overcomes the salinity threshold of the crop, causing osmotic stress and limitations in plant growth. In this scenario, adopting tolerant cultivars is the most adequate strategy to minimize agricultural losses. However, the inheritance of tolerance depends on the genotype. From this perspective, this study assessed the tolerance to severe salt stress in 11 cotton cultivars based on gas exchange parameters and the free proline content. The cultivars were grown in a greenhouse and subjected to 34 days of saline irrigation (10 dS m-1), starting 45 days after seedling emergence (B1 phase). Plant growth was monitored weekly until the end of the salt stress period. The treatments consisted of a combination of two factors: eleven cultivars associated with two electrical conductivity levels of irrigation water (ECw: 0.3 and 10.0 dS m-1). The experimental design was in randomized blocks in a 11 × 2 factorial arrangement with three replications (66 plots), with the experimental unit consisting of one plant per plot. Salinity impacted plant growth, being reflected on the gas exchange and free proline data of most cultivars. However, BRS 286, FMT 705, BRS 416, and BRS Acácia, and CNPA 7MH withstood the effects of stress and osmotically adjusted to the salt stress conditions, thus minimizing the damage to growth. Those cultivars are the most indicated for improvement programs aiming at tolerance to salt stress based on the results found in this research.

Evaluation of maximal exercise capacity through the incremental shuttle walking test in lymphangioleiomyomatosis.

BACKGROUND: The cardiopulmonary exercise test (CPET) is the gold standard for assessing aerobic fitness; however, it is expensive, not widely available, and requires specialized equipment and staff. The incremental shuttle walking test (ISWT) is an exercise field test used to evaluate exercise capacity and may be an alternative to CPET in patients with lymphangioleiomyomatosis (LAM). OBJECTIVE: To investigate whether the ISWT can be used to assess maximal aerobic capacity in patients with LAM. METHODS: Forty-five women were evaluated on two days, and they randomly performed the CPET and ISWT. The maximum oxygen uptake (peak VO2) was evaluated using gas analyzers in both tests. The carbon dioxide production (VCO2), respiratory exchange ratio (RER), and heart rate (HR) were compared during peak exercise. Pearson's correlation and Bland-Altman assessed the association and agreement, respectively. The intraclass correlation coefficient (ICC) was used to assess the reliability of the data. RESULTS: All patients (46.1 ± 10.2 years) presented similar peak VO2, RER, and peak HR during the CPET and ISWT (15.6 ± 4.6 vs. 15.7 ± 4.4 ml·kg-1·min-1; 1.15±0.09 vs. 1.17±0.12; and 142.2 ± 18.6 vs. 141.5 ± 22.2 bpm, respectively; p>0.05). A good linear correlation (r = 0.79; p<0.001) and ICC (0.86; 95%CI 0.74-0.93) were observed between the peak VO2 in both tests. Predictive peak VO2 equations based on the ISWT performance are also presented. CONCLUSION: Our results suggest that the ISWT can be used to assess maximal exercise performance in patients with LAM, and it is a valuable option to be used as an alternative to the CPET and predict maximal exercise capacity.

[MRI of the axial skeleton for evaluation of prostate cancer extent in french Guyana]. / IRM du squelette axial pour le bilan du cancer de prostate en Guyane française.

INTRODUCTION: Spread evaluation of Prostate Cancer (PC) in French Guyana is bothered by the lack of bone scintigraphy. The availability of 4 MRI allows to develop alternatives using Axial Skeleton MRI (AS MRI). We report the related results. MATERIAL: AS MRI was done in patients with diagnosis of high risk PC: PSA>=10ng/ml and/or Gleason Score>=7 (predominant Gleason grade 4) and/or clinical T2b and/or T2b/T3 MRI and/or >50% positive biopsies. AS MRI was including spine, pelvis and skull assessement.The results were systematically compared to the clinical, biological and biopsy features. RESULTS: Amongst 163 AS MRI performed, 30 were positive and 133 negative. Of these 133 patients, 60 were submited to radical prostatectomy with or without lymphadenectomy. In these 133 patients with negative AS MRI, median PSA was 11ng/ml (1-51) and 27 (20,3%) had PSA>20ng/ml. In patients with positive AS MRI, only 1 had PSA<20ng/ml and predominant Gleason grade 3. CONCLUSION: Our study shows that AS MRI assessement is especially usefull in patients who are most likely to have bone metastasis that is to say those with PSA>20ng/ml and/or predominant Gleason grade 4. LEVEL OF EVIDENCE: 3.

Immunization against gonadotropin-releasing factor (GnRF) in market gilts: Effect on growth and carcass parameters, and impact of immunization timing.

Reproductive cycling in fattening gilts can be associated with undesirable effects, such as estrus-related aggressive behavior, reduced feed intake and, in production systems where gilts are co-housed with entire males, unwanted pregnancy. Immunization against Gonadotrophin Releasing Factor (IM) can temporarily suppress ovarian activity, including related negative consequences on animal welfare and productivity. Feed intake has been shown to be higher after IM, resulting in both increased growth and increased carcass fat. A series of studies was conducted to confirm these effects on production and look at their dynamics over time. Three trials were performed to a similar design, each involving 240 gilts divided into 4 experimental groups at 12 weeks of age. One group remained untreated while the others had the two dose, IM course completed 8, 6 or 4 weeks before harvest, which was on a single day at 24, 25 or 26 weeks of age depending on the study. Feed intake was measured daily and bodyweight weekly, allowing growth parameters to be calculated on a weekly basis and for specific longer periods. Carcass weight, backfat depth and lean meat percentage were recorded at harvest. No effects were observed before the second application of the immunological product (V2) and completion of the IM course. Starting in the second week after V2 all IM groups showed a marked and consistent increase in Average Daily Feed Intake (ADFI), typically peaking at over 120% of the control group 3 to 4 weeks after V2 and then slowly declining, but still remaining elevated at 8 weeks. Weekly Average Daily Gain (ADG) showed a similar pattern but with a faster decline, resulting in the initially favorable impact on feed efficiency becoming less favorable as the V2 to harvest interval (V2H) progressed. Carcass weights were higher in IM gilts and backfat depths were greater, with the effects increasing with increasing V2H. Correspondingly, carcass lean meat percentage tended to decrease, although the higher carcass weights meant that the absolute weight of lean meat remained similar or higher. Carcass yield was generally unaffected by IM, but some between-group differences were statistically significant, and it is possible that different factors predominated at different times after V2, creating a complex relationship with V2H duration. The optimum IM protocol will depend on local conditions and production objectives but, as a generalization and assuming ad libitum feeding, a shorter V2H will favor efficient growth, while a longer duration will maximize carcass changes, such as increased fat coverage. It is suggested that the growth performance changes seen after IM in gilts might be viewed as a process of adjustment to a heavier and fatter target body type.

[A long distance between home and hospital does not bother ambulatory surgery for ureteroscopy in French Guyana]. / Une grande distance entre le domicile et l'hôpital ne contre-indique pas l'ambulatoire pour urétéroscopie en Guyane française.

INTRODUCTION: French Guyana is 83,500 km2 wide (equivalent to 1/6 of France). Communes are distant. Public urology is set in Kourou only. These particularities led to develop ambulatory urological surgery including for patients living far away from the reference centre. We report our experience with patient ureteroscopy (URS). MATERIAL: The study is retrospective (2018-2019), and includes 125 patients. Among these patients, 19.2% live in Kourou, 71.1% live 40 to 100km from the hospital and 9.7% beyond 100km. Every patient had an outpatient procedure for rigid and/or flexible URS to treat stone disease, including in lower calyx [LC] (38.4%). Ambulatory surgery was also proposed to the patients living away with the usual restrictions. Complications, results and switch to conventional hospitalisation (CH) were studied. RESULTS: Mean stone size was 10,5mm (4-30), stone density was 1030 UH (470-1700). The postoperative complication rate was 4%. There were 90.4% 'stone free' patients (85.4% for LC). One patient was rehospitalised within 48hours for acute flank pain and 9 patients had a switch of ambulatory to CH: 6 for discharge too late and 3 for complication (fever and/or pain). Distance between home and hospital was linked neither to complication rate, nor to switch to CH. CONCLUSION: Ambulatory URS is possible without further complications in selected patients living beyond 100km from the hospital, because of a specific organisation and an appropriate training of the caregivers involved in postoperative patient care. LEVEL OF PROOF: 3.

Cinnamyl Schiff bases: synthesis, cytotoxic effects and antifungal activity of clinical interest.

The aim of this study was to synthesize and investigate the in vitro antifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2 min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains of Candida, Aspergillus, Fonsecaea and, particularly, Cryptococcus species. Indeed, cinnamyl Schiff bases 1 and 23 exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all the Cryptococcus neoformans strains (MIC = 1·33, 1·4 and 5·2 µg ml-1 , respectively) and Cryptococcus gattii strains (MIC = 5·3, 2·8 and 9·2 µg ml-1 , respectively) (12 strains of each species) while cinnamyl Schiff base 11 was as potent as FCZ against all strains from both Cryptococcus species. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially 1 and 23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1 and 23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.

Secondary origin, hybridization and sexual reproduction in a diploid-tetraploid contact zone of the facultatively apomictic orchid Zygopetalum mackayi.

The production of triploids and apomictic reproduction are important processes for polyploid establishment and cytotype coexistence, but we know little about the interaction between triploids and facultatively apomictic plants. To bridge this gap, we studied the pollen-dependent, facultatively apomictic orchid Zygopetalum mackayi from high-elevation outcrops of southeast Brazil. We described the nature of the contact between Z. mackayi cytotypes and patterns of genetic diversity and structure based on eight microsatellite markers and 155 individuals of pure tetraploid, pure diploid and mixed cytotype populations. Our results revealed high values of genetic and genotypic diversity within all populations of Z. mackayi. Each cytotype emerged as a genetic distinct cluster, combining individuals from different populations. Triploids clustered in an intermediate position between diploids and tetraploids. Most genetic variance is associated with individuals within populations and genetic differentiation is high among populations. Mixed cytotype populations of Z. mackayi originate from secondary contact. Triploids are hybrids between diploids and tetraploids and likely act as a bridge. Our results point to the predominance of sexual reproduction in all populations but do not corroborate previous basic chromosome number for this species. Polyploidy rather than facultative apomixis may explain the larger geographic distribution of tetraploids of Z. mackayi.

[Epidemiology of prostate cancer (PCa) in French Guyana (FG) - Preliminary results]. / Épidémiologie du cancer de la prostate en Guyane française ­ Données préliminaires.

INTRODUCTION: Epidemiology of prostate cancer (PCa) in French Guyana (FG) is not well documented yet. It differs from the reported one in French West Indies due to a younger population, less exposed to agricultural pesticides with also much lower level of medical information and care. MATERIAL: The incidence and mortality rates available in the regional register of cancers are reported for the period 2010-2014. The characteristics of 242 consecutive prostate biopsy series performed between 2017 January and 2019 October for abnormal digital rectal examination (DRE) and/or PSA>4ng/mL are also described. RESULTS: PCa incidence in FG is 94.4°/°°°° and specific mortality 16.9°/°°°°. Among the biopsies, 77.7% (188/242) are positive with a mean PSA of 72.6ng/mL (1-4000) at a mean age of 66years (50-89), 34% (64/188) with an abnormal DRE, 12.3% (23/188) with a PSA>50ng/mL and 28.2% (53/188) with a Gleason score≥8. CONCLUSION: In spite of young population, less exposure to environmental risk factors and high rate of racial mixing, the early PCa diagnosis is still a challenge in FG. The observed incidence and mortality rates suggest underestimation of PCa cases and too late specific care what is also suggested by adverse pathological and biological characteristics of the tumors at the time of diagnosis. LEVEL OF EVIDENCE: 3.

Co-delivery of immunomodulators in biodegradable nanoparticles improves therapeutic efficacy of cancer vaccines.

To improve the efficacy of cancer vaccines we aimed to modulate the suppressive tumor microenvironment. In this study, the potential of intratumoral immune modulation with poly (I:C), Resiquimod (R848) and CCL20 (MIP3α) was explored. Biodegradable polymeric nanoparticles were used as delivery vehicles for slow and sustained release of these drugs in the tumor area and were combined with specific immunotherapy based on therapeutic peptide vaccination in two aggressive murine carcinoma and lymphoma tumor models. Whereas nanoparticle delivery of poly (I:C) or R848 improved therapeutic efficacy, the combination with MIP3α remarkably potentiated the cancer vaccine antitumor effects. The long-term survival increased to 75-100% and the progression free survival nearly doubled on mice with established large carcinoma tumors. The potent adjuvant effects were associated with lymphoid and myeloid population alterations in the tumor and tumor-draining lymph node. In addition to a significant influx of macrophages into the tumor, the phenotype of the suppressor tumor-associated macrophages shifted towards an acute inflammatory phenotype in the tumor-draining lymph node. Overall, these data show that therapeutic cancer vaccines can be potentiated by the combined nanoparticle mediated co-delivery of poly (I:C), R848 and MIP3α, which indicates that a more favorable milieu for cancer fighting immune cells is created for T cells induced by therapeutic cancer vaccines.

In vitro anthelmintic activity of Siparuna guianensis extract and essential oil against Strongyloides venezuelensis.

New therapeutic approaches are necessary to control strongyloidiasis due to the side effects of, and resistance to, currently available drugs thiabendazole, albendazole, and ivermectin. This study examined the anthelmintic properties of extracts and isolated compounds from Siparuna guianensis against Strongyloides venezuelensis eggs and larvae, using the egg hatching test (EHT) and larval motility test (LMT). Albendazole (0.025 mg/ml) and ivermectin (0.316 mg/ml) were used as the positive controls for the EHT and LMT assays, respectively. Strongyloides venezuelensis eggs or larvae (±50 specimens) were treated with ethanol extract (0.05-1.0 mg/ml), ethyl acetate and aqueous fractions (0.05-0.8 mg/ml), essential oil (0.2-1.0 mg/ml) and α-bisabolol (0.2-1.0 mg/ml) from S. guianensis, and analysed by optical microscopy after 48 h (EHT), or after 24, 48 and 72 h (LMT). All the tested compounds exhibited ovicidal activity equivalent to the positive control and changed the morphology of the eggs. The S. guianensis ethanol extract and aqueous fraction were as effective as the positive control. Phytochemical analysis of the ethanol extract and fractions revealed the presence of phenolic compounds, tannins and flavonoids. Therefore, S. guianensis is effective against S. venezuelensis eggs and larvae in vitro, and can be considered as a potential alternative treatment for strongyloidiasis.

Combinatory therapy adopting nanoparticle-based cancer vaccination with immune checkpoint blockade for treatment of post-surgical tumor recurrences.

Cancer immunotherapy is emerging as a candidate treatment modality for treating post-surgical metastasis and recurrences. Despite the great promises with therapeutic cancer vaccines and checkpoint blocking antibodies in pre-clinical studies, response rates in the clinic still remain unsatisfactory. The evaluation of immunotherapy after surgery in patients could confront significant unexpected hurdles. Surgery itself tends to cause immune suppression, while wound healing factors also stimulate tumor cell outgrowth and metastasis. Regarding the marked changes in the post-surgical tumor microenvironment, one can anticipate that better tumor growth control is attainable by combining cancer vaccines with immune checkpoint blockade. However, it is important that vaccines and checkpoint blocking antibodies are delivered efficiently to their target cells, are released sustained and locally and do not induce cytotoxic effects. The generation of effective anti-tumor immunity and durable response rates could largely depend on these parameters. In the last decade, researchers spend tremendous effort in optimizing the delivery of immunotherapeutic compounds with the use of nanomedicine. Biocompatible nanoparticle based delivery systems demonstrated intriguing results with regard to specific immune cell activation, improved drug delivery, cell targeting, limiting off target toxicity and improving treatment outcome. It therefore makes sense, to speculate on the promises of combined cancer vaccination and immune checkpoint blocking immunotherapy with the aid of nanomedicine. A powerful nanoparticle combination immunotherapy conferring durable therapeutic benefit whilst leaving healthy tissue untouched represents the base for more efficient post-surgical cancer treatment.

In Vitro and In Vivo Studies of the Trypanocidal Effect of Novel Quinolines.

Therapies for human African trypanosomiasis and Chagas disease, caused by Trypanosoma brucei and Trypanosoma cruzi, respectively, are limited, providing minimal therapeutic options for the millions of individuals living in very poor communities. Here the effects of 10 novel quinolines are evaluated in silico and by phenotypic studies using in vitro and in vivo models. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties revealed that most molecules did not infringe on Lipinski's rules, which is a prediction of good oral absorption. These quinolines showed high probabilities of Caco2 permeability and human intestinal absorption and low probabilities of mutagenicity and of hERG1 inhibition. In vitro screens against bloodstream forms of T. cruzi demonstrated that all quinolines were more active than the reference drug (benznidazole [Bz]), except for DB2171 and DB2192, with five (DB2187, DB2131, DB2186, DB2191, and DB2217) displaying 50% effective concentrations (EC50s) of <3 µM (4-fold lower than that of Bz). Nine quinolines were more effective than Bz (2.7 µM) against amastigotes, showing EC50s ranging from 0.6 to 0.1 µM. All quinolines were also highly active in vitro against African trypanosomes, showing EC50s of ≤0.25 µM. The most potent and highly selective candidates for each parasite species were tested in in vivo models. Results for DB2186 were promising in mice with T. cruzi and T. brucei infections, reaching a 70% reduction of the parasitemia load for T. cruzi, and it cured 2 out of 4 mice infected with T. brucei DB2217 was also active in vivo and cured all 4 mice (100% cure rate) with T. brucei infection.

Skin cancer prevention campaign in childhood: survey based on 3676 children in Brazil.

BACKGROUND AND OBJECTIVES: Primary skin cancer prevention campaigns are essential and more effective among children, not only because of the importance of sun exposure effects during this period, but also because this age is when individuals are developing behaviours. The Brazilian Society of Dermatology - Regional State of Sao Paulo developed and conducted the programme named 'The Sun, Friend of Childhood', a school health education and disease prevention project for children and parents. Our objective was to evaluate the cognitive and behavioural effects of the children and parents before and after an education model-based intervention of sun protection. METHODS: We carried out a study on a school population of Social Service of Industry - Regional State of São Paulo, from the first to the fifth years of the regular course (6-10 years). Our educational project was planned to be based on two children's learning tools (comic magazine and a DVD cartoon). Questionnaires in relation to habits and knowledge in sun exposure were applied to the children (3776) before and (2748) after the intervention. A questionnaire was applied to 3663 parents regarding personal details and habits of their children. RESULTS: According to the McNemar's statistical test, all changes in the children in acquiring new knowledge about good practices for sun exposure were statistically significant. CONCLUSIONS: Educative sun exposure programmes in childhood are a relevant tool to modify the history of life for next generations, to concern the skin cancer and good health practices.

Is the adjustable transobturator system ATOMS® useful for the treatment of male urinary incontinence in low to medium volume urological centers? / ¿Es útil el sistema transobturatriz ajustable ATOMS® para el tratamiento de la incontinencia urinaria masculina en centros urológicos de bajo y medio volumen?

INTRODUCTION: Urinary incontinence (UI) is a complication of radical prostatectomy (RP) and transurethral resection of the prostate (TURP). The gold-standard treatment is the artificial urinary sphincter, however, new treatments have been investigated. OBJECTIVE: To examine the outcome of an adjustable transobturator male system (ATOMS®) in men with UI after prostatic surgery in a low to medium volume continence center. MATERIALS AND METHODS: Twenty-five men with UI were implanted with ATOMS® system between 2012 and 2014. The most common indication was UI after RP (92%), followed by UI after TURP (8%). Eleven patients (44%) had received adjuvant external beam radiotherapy (RT). Patients were considered to be 'dry' if they stopped wearing pads or needed just one protective pad per day; and improved if the daily number of pads used decreased by at least half. The Incontinence Quality of Life questionnaire (ICIQ-SF) was used, adding a verbal question about the satisfaction of the patient considering the outcome. RESULTS: After a mean follow-up of 21.56 months, 64% were dry and 8% revealed a significant improvement. The success of the procedure was negatively correlated with the severity of the previous UI and with previous treatment with RT. Concerning patients satisfaction, 84% of the patients would repeat the procedure. CONCLUSION: ATOMS® offers good rates of cure and improvement of UI after prostatic surgery with a reasonable rate of minor complications. The results of this study, performed in a low to medium volume continence center, are comparable to the results achieved in high volume continence centers.

Stallion spermatozoa surviving freezing and thawing experience membrane depolarization and increased intracellular Na.

In order to gain insight of the modifications that freezing and thawing cause to the surviving population of spermatozoa, changes in the potential of the plasma membrane (Em) and intracellular Na+ content of stallion spermatozoa were investigated using flow cytometry. Moreover, caspase 3 activity was also investigated and the functionality of the Na+ -K+ ATPase pump was investigated before and after freezing and thawing. Cryopreservation caused a significant (p < 0.001) increase in the subpopulation of spermatozoa with depolarized sperm membranes, concomitantly with an increase (p < 0.05) in intracellular Na+ . These changes occurred in relation to activation of caspase 3 (p < 0.001). Cryopreservation reduced the activity of the Na-K+ pump and inhibition of the Na+ -K+ ATPase pump with ouabain-induced caspase 3 activation. It is concluded that inactivation of Na+ -K+ ATPase occurs during cryopreservation, an inhibition that could play a role explaining the accelerated senescence of the surviving population of spermatozoa.

The potential of multi-compound nanoparticles to bypass drug resistance in cancer.

PURPOSE: The therapeutic efficacy of conventional chemotherapy against several solid tumors is generally limited and this is often due to the development of resistance or poor delivery of the drugs to the tumor. Mechanisms of resistance may vary between cancer types. However, with current development of genetic analyses, imaging, and novel delivery systems, we may be able to characterize and bypass resistance, e.g., by inhibition of the right target at the tumor site. Therefore, combined drug treatments, where one drug will revert or obstruct the development of resistance and the other will concurrently kill the cancer cell, are rational solutions. However, drug exposure of one drug will defer greatly from the other due to their physicochemical properties. In this sense, multi-compound nanoparticles are an excellent modality to equalize drug exposure, i.e., one common physicochemical profile. In this review, we will discuss novel approaches that employ nanoparticle technology that addresses specific mechanisms of resistance in cancer. METHODS: The PubMed literature was consulted and reviewed. RESULTS: Nanoparticle technology is emerging as a dexterous solution that may address several forms of resistance in cancer. For instance, we discuss advances that address mechanisms of resistance with multi-compound nanoparticles which co-deliver chemotherapeutics with an anti-resistance agent. Promising anti-resistance agents are (1) targeted in vivo gene silencing methods aimed to disrupt key resistance gene expression or (2) protein kinase inhibitors to disrupt key resistance pathways or (3) efflux pumps inhibitors to limit drug cellular efflux.

Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation.

The initiation of the mucosal immune response in Peyer's patch (PP) relies on the sampling, processing, and efficient presentation of foreign antigens by dendritic cells (DCs). Among PP DCs, CD11b+ conventional DCs (cDCs) and lysozyme-expressing DCs (LysoDCs) have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here we show that both DN and CD11b+ cDCs belong to a unique SIRPα+ cDC subset. At steady state, cDCs and TIM-4+ macrophages are mainly located in T-cell zones, i.e., interfollicular regions, whereas a majority of subepithelial phagocytes are monocyte-derived cells, namely, LysoDCs and TIM-4- macrophages. Finally, oral administration of a Toll-like receptor 7 ligand induces at least three TNF-dependent events: (i) migration of dome-associated villus cDCs in interfollicular regions, (ii) increase of CD8α+ interfollicular cDC number, and (iii) activation of both CD11b+ and CD8α+ interfollicular cDCs. The latter is marked by a genetic reprograming leading to the upregulation of type I interferon-stimulated and of both immuno-stimulatory and -inhibitory gene expression.

l-Arginine supplementation improves rats' antioxidant system and exercise performance.

Reactive species have great importance in sports performance, once they can directly regulate energy production, muscular contraction, inflammation, and fatigue. Therefore, the redox control is essential for athletes' performance. Studies demonstrated that l-arginine has an important role in the synthesis of urea, cell growth and production of nitric oxide, moreover, there are indications that it is also able to induce benefits to muscle antioxidant system through the upregulation of some antioxidant enzymes, and by inhibiting some pathways of reactive species production. Therefore, the aim of this study was to evaluate the effects of l-arginine supplementation on performance and oxidative stress of male rats (trained or not), submitted to a single session of high intensity exercise. Forty male Wistar rats were divided into four groups, control (C), control+l-arginine (C + A), trained (T), and trained+l-arginine (T + A). The aerobic training was conducted for 8 weeks. Data of maximum speed and time from tests were used as indicators of performance. Variables related to oxidative stress and antioxidant system were also evaluated. Aerobic training was capable to induce enhancements on animals' exercise performance and on their redox state. Additionally, supplementation improved rats' physical performance on both groups, control and trained. Different improvements between groups on the antioxidant capacity were observed. Nevertheless, considering the ergogenic effect of l-arginine and the lack of all positive adaptations promoted by the exercise training, untrained animals may be more exposed to oxidative damages after the practice of intense exercises.

Prevalencia de enfermedad arterial periférica con la determinación del índice tobillo-brazo en pacientes con artritis reumatoide / Prevalence of peripheral arterial disease measured with the ankle-arm index in rheumatic patients suffering from rheumatoid arthritis

La enfermedad arterial periférica (EAP) afecta 15-20% de las personas mayores de 70 años. Objetivo: Establecer la prevalencia de enfermedad arterial periférica mediante la determinación del índice tobillo brazo (ITB) en pacientes con Artritis Reumatoide que acuden a la consulta de reumatología, en el Hospital Universitario "Ángel Larralde" Valencia-Venezuela durante el periodo Enero-Abril 2016. Métodos: Estudio descriptivo, transversal y de campo. Se estudiaron 50 pacientes. La recolección de los datos personales y familiares, así como el registro de las medidas antropométricas, se hizo mediante un formulario prediseñado, utilizando una entrevista estructurada. Resultados: El promedio de edad fue de 54,6 ± 11 años, con un rango de 50 a 60 años; predominio del sexo femenino 76%; índice isquémico promedio de 0,74 ± 0,38 siendo normal en 20%, 42% con EAP leve a moderada, 28% con EAP grave y 10% vaso no compresible; la edad sigue siendo el marcador principal de riesgo de EAP. Entre los factores de riesgo cardiovascular (FRCV) modificables la dislipidemia se observó en 38%,obesidad 12%, sedentarismo 100%, consumo de alcohol 2%, tabaquismo 32%, hipertensión arterial 32% y Diabetes Mellitus (DM) 22%. El 74% de los pacientes han utilizado terapia biológica como tratamiento para Artritis Reumatoide dada por Adalimumab/Leflunomida 24%, Metrotrexate/ Etarnecept 10%, Metrotrexate /Adalimumab 8%. Al correlacionar los FRCV no modificables (edad, sexo) y modificables (dislipidemia, obesidad, sedentarismo, consumo de alcohol, tabaquismo, antecedentes de HTA y DM) con el uso de la terapia biológica sólo se observó relación estadísticamente significativa con el tabaquismo (P=0.04) y, con una relación inversa muy baja (-0.293) pero estadísticamente significativa (P=0.039), con el valor bioquímico de la glicemia. Conclusiones: En vista de la poca asociación entre la alteración del ITB con los factores de riesgo cardiovascular, podría plantearse la posibilidad que la Artritis Reumatoide per se sea un factor independiente para desarrollar EAP(AU)

Peripheral arterial disease (PAD) affects 15-20% of people older than 70 years. Objectives: to determine the prevalence of peripheral arterial disease measuring the ankle-brachial index in ambulatory patients who had Rheumatoid Arthritis, at the Hospital Universitario Angel Larralde in Valencia-Venezuela during the period 2015-2016. Methods: This is a descriptive, transversal study, with a sample of 50 patients who attended the rheumatology clinic of the hospital. The collection of personal and family data as well as the registration of anthropometric measurements were done through a pre-designed form with a structured interview. The average age was 54.6 ± 11 years. Results: gender: 76% were female; the average age was between 50 and 60 years, mean 0.74 ± 0.38; the Ischemic index was normal in 20%, 42% had mild to moderate PAD, in 28% it was severe and 10% non compressible. Age remains as the main risk marker for EAP; among the modifiable risk factors, dyslipidemia was observed in 38%, obesity 12%, sedentarism 100%, alcohol consumption 2%, smoking 32%, hypertension 32% and Diabetes Mellitus 22%. 74% of patients had received biological therapy as a treatment for rheumatoid arthritis: Adalimumab / Leflunomide 24%, Metrotrexate / Etarnecept 10%, Metrotrexate / Adalimumab 8%. When correlating non-modifiable CVD (age, sex) and modifiable (dyslipidemia, obesity, sedentary lifestyle, alcohol consumption, smoking, history of hypertension and DM) and use of biological therapy, a statistically significant relationship with smoking (P=0.04), and with a very low inverse (-0.293) statistically significant (P = 0.039) with the biochemical value of glycemia. Conclusions: Rheumatoid Arthritis per se may be an independent factor in the development of PAD. Recommendation: there is a need to routinely perform ABI in patients with asymptomatic RA from a cardiovascular point of view.(AU)