Immunomodulatory effect and clinical outcome in Parkinson's disease patients on levodopa-pramipexole combo therapy: A two-year prospective study.

Parkinson's disease (PD), the second most frequent neurodegenerative disease, has been linked to increased central and peripheral inflammation. Although the response of the immune system to dopaminergic treatment remains to be fully understood, dopaminergic agonists are known to exhibit immunoregulatory properties which may, at least in part, explain their therapeutic effect in PD. This highlights the need of analyzing immune parameters in longitudinal studies on PD patients receiving specific therapeutic regimes. In this work, PD patients were included in a two-year prospective study comparing the effect of levodopa alone and a levodopa/pramipexole combo therapy on several regulatory and pro-inflammatory immune cell populations. We demonstrated that PD patients show decreased circulating levels of several important regulatory subpopulations, as determined by flow cytometry. Notably, when administered alone, levodopa decreased the levels of functional Bregs and SLAMF1+ tolerogenic DCs and increased the levels of total and HLA-DR+ classical monocytes, while the pramipexole/levodopa combo may promote Treg- and tolerogenic DC-mediated regulatory responses. These results suggest that a regime based on levodopa alone may promote a pro-inflammatory-type response in PD patients, but when combined with pramipexole, it promotes a clinically beneficial regulatory-type environment.

Low-fat sodium-reduced sausages: Effect of the interaction between locust bean gum, potato starch and κ-carrageenan by a mixture design approach.

A mixture design approach was used to evaluate interactions between potato starch, locust bean gum and κ-carrageenan and their effect on cooking yield, expressible moisture, texture and color in low-fat sodium-reduced sausages formulated with potassium and calcium chloride. Starch had a notable influence on cooking yield and texture, increasing product hardness and resilience as starch proportion increased. The added salt did not allow complete starch granule gelatinization and swelling, which negatively affected water retention, cohesiveness and lightness. Locust bean gum and κ-carrageenan improved cooking yield and reduced expressible moisture in formulations containing higher proportions of potato starch. The presence of other ions could have enhanced κ-carrageenan functionality and its synergistic interaction with locust bean gum, improving texture and water retention, with only minor effects on sausage color. At the lower tested proportions starch can be used as an extender in low-fat cooked meat products if κ-carrageenan and locust bean gum are included in similar proportions.

Development of a Parenteral Formulation of NTS-Polyplex Nanoparticles for Clinical Purpose.

Neurotensin (NTS)-polyplex is a nanoparticle system for targeted gene delivery that holds great promise for treatment of Parkinson's disease and various types of cancer. However, the high instability in aqueous suspension of NTS-polyplex nanoparticles is a major limitation for their widespread clinical use. To overcome this obstacle, we developed a clinical formulation and a lyophilization process for NTS-polyplex nanoparticles. The reconstituted samples were compared with fresh preparations by using transmission electron microscopy, dynamic light scattering, electrophoretic mobility, circular dichroism and transfection assays in vitro and in vivo. Our formulation was able to confer lyoprotection and stability to these nanoparticles. In addition, transmission electron microscopy (TEM) and size exclusion-high performance liquid chromatography (SEC-HPLC) using a radioactive tag revealed that the interaction of reconstituted nanoparticles with fetal bovine or human serum did not alter their biophysical features. Furthermore, the formulation and the lyophilization procedure guaranteed functional NTS-polyplex nanoparticles for at least six months of storage at 25 °C and 60% relative humidity. Our results offer a pharmaceutical guide for formulation and long-term storage of NTS-polyplex nanoparticles that could be applied to other polyplexes.

Delayed diagnosis in X-linked agammaglobulinemia and its relationship to the occurrence of mutations in BTK non-kinase domains.

BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by the absence of immunoglobulin and B cells. Patients suffer from recurrent bacterial infections from early childhood, and require lifelong immunoglobulin replacement therapy. Mutations in BTK (Bruton's Tyrosine Kinase) are associated with this phenotype. Some patients that present XLA do not show typical clinical symptoms, resulting in delayed diagnosis due to the lack of a severe phenotype. This study presents a report of five XLA patients from four different families and attempts to determine a relationship between delayed diagnosis and the occurrence of BTK mutations. METHODS: Samples from patients with antibody deficiency were analyzed to determine BTK expression, immunophenotyping and mutation analysis. Clinical and laboratory data was analyzed and presented for each patient. RESULTS: Most patients presented here showed atypical clinical and laboratory data for XLA, including normal IgM, IgG, or IgA levels. Most patients expressed detectable BTK protein. Sequencing of BTK showed that these patients harbored missense mutations in the pleckstrin homology and Src-homology-2 domains. When it was compared to public databases, BTK sequencing exhibited a new change, along with three other previously reported changes. CONCLUSIONS: Delayed diagnosis and atypical manifestations in XLA might be related to mutation type and BTK expression.

A methodology to study intracellular distribution of nanoparticles in brain endothelial cells.

Cell internalisation and intracellular distribution of PEG-coated polyhexadecylcyanoacrylate (PEG-PHDCA) nanoparticles in rat brain endothelial cells (RBEC) have been investigated. A cell fractionation method has been developed based on the selective permeabilisation of RBEC plasma membrane by digitonin. By interacting with membrane cholesterol, digitonin creates pores allowing the release of soluble and diffusible species outside the cell. The selectivity of plasma membrane permeabilisation was controlled by using compartment markers such as lactate dehydrogenase (LDH) for cytoplasm and cathepsin B for lysosomes. An optimal digitonin concentration of 0.003% (w/v) has been identified to induce a pattern of membrane permeabilisation corresponding to the extraction of 72% LDH and less than 15% of Cathepsin B. Membrane permeabilisation at this digitonin concentration allows one to distinguish between the cell cytoplasm and its endo/lysosomal fraction. This methodology was applied to investigate the intracellular distribution of the nanoparticles after their incubation with the RBEC. The results showed that PEG-PHDCA nanoparticles were able to be internalised to a higher extent than PHDCA nanoparticles (after 20 min incubation). Additionally, these nanoparticles displayed different patterns of intracellular capture, depending on their specific surface composition: PEG-PHDCA nanoparticles were 48% in the plasma membrane, 24% in the cytoplasm, 20% in vesicular compartments and 8% associated with the fraction of the nucleus, the cytoskeleton and caveolae suggesting that PEG-PHDCA nanoparticle uptake by RBEC is specific and presumably due to endocytosis. Confocal microscopy studies confirmed the cellular uptake of PEG-PHDCA nanoparticles.

Designing and evaluation of sodium selenite nanoparticles in vitro to improve selenium absorption in ruminants.

Sodium selenite is used to prevent selenium deficiency known as nutritional muscular dystrophy or white muscle disease. In ruminants, selenium supplements are transformed partiality in insoluble form by ruminal microorganisms and its process decrease the selenium absorption in digestive gastrointestinal. However, the objective in this research was focused in encapsulated sodium selenite to be release into of a pH less than four, similarity to an intestinal environment. It was encapsulated by nanoprecipitation and emulsion-evaporation methods, within polymeric nanoparticles. The effect of these methods, polymer proportion (Eudragit RL and RS) and solvent (ethanol and acetone) on the physicochemical (drug entrapment, polidispersity index (PDI) and z potential) and morphological characteristics (particle morphology and particle size) were evaluated. Particle size from each nanoparticles, formulation ranged from 36.64 to 213.86 nm. Particle size, z potential and PDI increased (P 0.05) were observed when different polymeric proportions were used. Selenium entrapment was 26% when emulsion-evaporation method was used and 78% with nanoprecipitation. Nanoparticles produced by nanoprecipitation were spherical and had a great variation in particle size; on the other hand, nanoparticles produced by emulsion-evaporation were spherical as well as amorphous and presented a homogeneous nanopartcicle size distribution. The release of selenium from nanoparticles was higher in acid pH (less than 4), this condition may represent a better availability of the mineral in the small intestine.

Satisfacción usuaria respecto a competencia de comunicación del profesional de enfermería / Customer satisfaction regarding communication quality by the nursing professional

El modelo de relación de persona a persona, de Joyce Travelbee, sustenta el estudio cuyo objetivo es determinar apreciación usuaria respecto a la competencia de comunicación del profesional de enfermería, considerando las dimensiones: proactividad, actitud profesional, comunicación verbal, comunicación no verbal y apoyo emocional. Estudio cuantitativo, descriptivo, transversal. Universo: 305 personas hospitalizadas, 3 servicios públicos, V Región, Chile, octubre y diciembre 2013. Unidades Mediana Complejidad. Muestra151, > 18 años; estadía > 5 días; Glasgow = 15. Aceptación comité ética, consentimiento informado. Cuestionario satisfacción usuaria autoaplicado 17 ítemes escala Lickert 1-4. Alfa de Cronbach 0.943. Resultados: Alto grado de satisfacción global respecto de competencia de comunicación, las mujeres perciben una mayor insatisfacción que los hombres. Aumenta grado de satisfacción con mayor estadía; los jóvenes y quienes tienen mayor nivel de instrucción, mayor insatisfacción. La comunicación no verbal refleja menor nivel de satisfacción, en comparación con el resto de variables. La actitud profesional y proactividad se perciben en menor nivel que las otras dimensiones, siendo el apoyo emocional mejor valorado. Conclusiones: La comunicación y la visualización del otro como un ser único, autónomo, que tiene derecho a ser informado, tomar decisiones respecto a su salud, son dimensiones que deben ser respetadas. El centro del quehacer de la enfermera(o) como generador de cuidados a través de la comunicación, resaltando la relación persona a persona.

Joyce Travelbee's interpersonal relationship model sheds light on the study to measure customer rating regarding the quality of communication by the nursing professional, especially considering initiative, professional attitude, verbal communication, non-verbal communication and emotional support. Quantitative, descriptive, transversal study. Universe: 305 hospitalized persons at 3 public institutions, moderate complexity units. Sample size 151, > 18 years old; stay > 5 days; Glasgow=15. Ethics Committee acceptance, informed consent, signed. Customer satisfaction self-questionnaire 17 items, Lickert scale 1-4. Cronbach alpha 0.943. Results: High degree of overall satisfaction regarding the quality of communication. However, female patients are relatively less satisfied than male patients. The degree of satisfaction increases with the hospitalization length. Young and well educated patients show the lowest relative satisfaction level. Non-verbal communication is less well developed than verbal communication. Professional attitude and initiative are the least developed aspects and emotional support the highest developed parameter. Conclusions: Communication and patient perception as a unique, autonomous being with the right to be well informed and make his/her own health decisions are all dimensions to be respected. These should be the focus of the nursing professional and also a source of patient care thus enhancing the interpersonal relationship.