Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington's disease.

Huntington's disease (HD) has traditionally been described as a disorder purely of the brain; however, evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction and preservation of GI emptying and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.

Optimization of the Promega PowerSeq™ Auto/Y system for efficient integration within a forensic DNA laboratory.

The application of massively parallel sequencing (MPS) is growing in the forensic DNA field, as forensic DNA laboratories are continuously seeking methods to gain information from a limited or degraded forensic sample. However, the laborious nature of current MPS methodologies required for successful library preparation and sequencing leave opportunities for improvement to make MPS a practical option for processing forensic casework. In this study, the Promega PowerSeq™ Auto/Y System Prototype, a MPS laboratory workflow that incorporates multiplex amplification, was selected for optimization with the objectives to introduce automation for relieving manual processing, and to reduce the number of steps recommended by the standard protocol. Successful changes in the optimized workflow included a switch from column-based PCR purification to automatable bead-based purification, adoption of the library preparation procedures by a liquid handling robot platform, and removal of various time-consuming quality checks. All data in this study were found to be concordant with capillary electrophoresis (CE) data and previously-generated MPS results from this workflow. Read abundance and allele balance, metrics related to sample interpretation reliability, were not significantly different when compared to samples processed with the manufacturer's protocol. All the modifications implemented resulted in increased laboratory efficiency, reduced the protocol steps associated with risk of contamination and human error events, and decreased manual processing time by approximately 12h. These findings provide forensic DNA laboratories a more streamlined option when considering implementation of a MPS workflow.

Validación del método de formación de coágulo para la determinación de endotoxinas bacterianas en inmunoglobulinas (IgG) nacionales / Method validation clot formation for determining bacterial endotoxins national immunoglobulin (IgG)

Las endotoxinas bacterianas son lipopolisacáridos (LPS) localizados exclusivamente en la membrana externa de las bacterias gramnegativas, su ingreso al organismo a través de productos parenterales puede causar fiebre, taquicardia, aumento de presión sanguínea y en algunos casos ocasiona la muerte. Existen normativas internacionales acerca del límite de endotoxina para productos farmacéuticos inyectables, tal como las inmunoglobulinas (IgG), que pueden estar expuestas a contaminación durante el proceso de producción y por lo tanto es necesario realizar pruebas para la determinación de endotoxinas bacterianas. El método del lisado de amebocitos de Limulus (LAL) es una de ellas.Este método se fundamenta en la reacción del LAL, el cual es un extracto de células sanguíneas que interaccionan con endotoxinas, activando la cascada del proceso de coagulación y originando la formación de la coagulina. En diversas ocasiones algunas proteínas intervienen en la activación o desactivación de esta cascada, bien sea potenciando o inhibiendo la formación del coágulo. En el caso de la potenciación, el calentamiento es uno de los métodos recomendados por la farmacopea estadounidense (USP) para eliminar interferencias, puesto que desnaturaliza las proteínas que causan la potenciación sin pérdida de endotoxinas. En este trabajo se validó la determinación de endotoxinas bacterianas en IgG mediante el método LAL, el cual es un método rápido y de fácilejecución, por lo que puede implementarse como ensayo de rutina en control de calidad y por ende nos permite agilizar las Liberaciones de Lotes de estos productos.

Bacterial endotoxins are lipopolysaccharides (LPS) located exclusively in the outer membrane of gram-negative bacteria, their entry into the body through parenteral products can cause fever, tachycardia, increased blood pressure and in some cases cause death. There are international standards for endotoxin limit for injectable pharmaceuticals, such as immunoglobulins (IgG), which may be exposed to contamination during the production process and therefore it is necessary to test for determination of bacterial endotoxins. The method of the Limulus amebocyte lysate (LAL) is one of them. This method is based on the LAL reaction, which is an extract of blood cells which interact with endotoxin, triggering the cascade of the coagulation process and causing the formation of coagulin. On several occasions some proteins involved in the activation or deactivation of this waterfall, either by enhancing or inhibiting clot formation. In the case of empowerment, the warming is one of those recommended by the US Pharmacopoeia (USP) to eliminate interference, since denatures proteins that cause endotoxin enhancement lossless methods. In this paper the determination of bacterial endotoxins in IgG was standardized by the LAL method, which is quick and easy to implement method, which can be implemented as a routine test in quality control and thus allows us to streamline releases Lots of these products.

Effects on the metabolism, growth, digestive capacity and osmoregulation of juvenile of Sub-Antarctic Notothenioid fish Eleginops maclovinus acclimated at different salinities.

In this study we assessed the influence of three different environmental salinities (5, 15 and 31 psu during 90 days) on growth, osmoregulation, energy metabolism and digestive capacity in juveniles of the Notothenioid fish Eleginops maclovinus. At the end of experimental time samples of plasma, liver, gill, intestine, kidney, skeletal muscle, stomach and pyloric caeca were obtained. Growth, weight gain, hepatosomatic index and specific growth rate increased at 15 and 31 psu and were lower at 5 psu salinity. Gill Na(+), K(+)-ATPase (NKA) activity presented a "U-shaped" relationship respect to salinity, with its minimum rates at 15 psu, while this activity correlated negatively with salinity at both anterior and posterior intestinal portions. No significant changes in NKA activity were observed in kidney or mid intestine. Large changes in plasma, metabolite levels and enzymatic activities related to energy metabolism in liver, gill, intestine, kidney and muscle were generally found in the groups exposed to 5 and 31 psu compared to the 15 psu group. Only the pepsin activity (digestive enzymes) assessed enhanced with environmental salinity, while pyloric caeca trypsin/chymotrypsin ratio decreased. This study suggests that juvenile of E. maclovinus presents greater growth near its iso-osmotic point (15 psu) and hyperosmotic environment (31 psu). Acclimation to low salinity increased the osmoregulatory expenditure as seen by the gill and anterior intestine results, while at high salinity, branchial osmoregulatory activity was also enhanced. This requires the mobilization of lipid stores and amino acids, thereby holding the growth of fish back. The subsequent reallocation of energy sources was not sufficient to maintain the growth rate of fish exposed to 5 psu. Thus, E. maclovinus juveniles present better growth efficiencies in salinities above the iso-osmotic point and hyperosmotic environment of this species, showing their best performance at 15 psu as seen by the main osmoregulatory and energy metabolism enzymatic activities.

Propiedades psicométricas del cuestionario de calidad de vida relacionada con la salud KIDSCREEN-27 en adolescentes chilenos / Psychometric properties of the quality of life questionnaire health related KIDSCREEN-27 in Chilean adolescents

Background: KIDSCREEN-52, which assesses health related quality of life in adolescents, has been adapted and validated in Chile showing excellent psychometric properties. There is a shorter version of the instrument, whose psychometric properties must be assessed. Aim: To evaluate the psychometric properties of the instrument KIDSCREEN-27 in Chilean adolescents. Material and Methods: A secondary analysis of the database obtained for the adaptation and validation of KIDSCREEN-52. Results: The reliability, calculated through Cronbach’s alpha, for the entire instrument (five dimensions) was 0.89. For physical well-being, psychological well-being, autonomy and relationship with parents and peer social support dimensions, scores were higher than 0.75 while for school environment, the score was 0.69. The confirmatory factor analysis showed that the indices obtained to assess the goodness of fit in this study were a χ2 (314) = 10521.4, a Root Mean Square Error of Approximation = 0.064 and a Comparative Fit index = 0.96. KIDSCREEN-27 scores were higher among men in the physical well-being, psychological well-being, autonomy and relationship with parents dimensions and among women in social support and peers and school environment dimensions. Scores were higher in younger age groups. Conclusions: The Chilean version of KIDSCREEN-27 instrument has adequate reliability and validity.

[Psychometric properties of the quality of life questionnaire health related KIDSCREEN-27 in Chilean adolescents]. / Propiedades psicométricas del cuestionario de calidad de vida relacionada con la salud KIDSCREEN-27 en adolescentes chilenos.

BACKGROUND: KIDSCREEN-52, which assesses health related quality of life in adolescents, has been adapted and validated in Chile showing excellent psychometric properties. There is a shorter version of the instrument, whose psychometric properties must be assessed. AIM: To evaluate the psychometric properties of the instrument KIDSCREEN-27 in Chilean adolescents. MATERIAL AND METHODS: A secondary analysis of the database obtained for the adaptation and validation of KIDSCREEN-52. RESULTS: The reliability, calculated through Cronbach’s alpha, for the entire instrument (five dimensions) was 0.89. For physical well-being, psychological well-being, autonomy and relationship with parents and peer social support dimensions, scores were higher than 0.75 while for school environment, the score was 0.69. The confirmatory factor analysis showed that the indices obtained to assess the goodness of fit in this study were a χ2 (314) = 10521.4, a Root Mean Square Error of Approximation = 0.064 and a Comparative Fit index = 0.96. KIDSCREEN-27 scores were higher among men in the physical well-being, psychological well-being, autonomy and relationship with parents dimensions and among women in social support and peers and school environment dimensions. Scores were higher in younger age groups. CONCLUSIONS: The Chilean version of KIDSCREEN-27 instrument has adequate reliability and validity.

Adaptación transcultural y validación de un instrumento de calidad de vida relacionada con la salud en adolescentes chilenos / Validation of an instrument to measure health-related quality of life in Chilean children and adolescents

Background: KIDSCREEN-52 is an instrument to assess health related quality of life in children and adolescents. Aim: To culturally adapt and validate the KIDSCREEN-52 questionnaire in Chileans. Material and Methods: Two independent translations from the English Spanish language were conciliated and retranslated to English. The conciliated version was tested during a cognitive interview to adolescents of different socioeconomic levels. The final version was validated in 7,910 school attending adolescents. Results: In the cross-cultural adaptation, 50 of the 52 items presented low or medium levels of difficulty and a high semantic equivalence. Distribution according to gender, grades and types of schools was similar to the sample. Single ages were not affected by sex distribution. The Confirmatory Factor Analyses were: X² (1229) = 20996.7, Root Mean Square Error of Approximation = .045 and Comparative Fit Index = .96. The instrument had a Cronbach’s alpha of .93. The domains had scores over 0.70 points, with the exception of the "Selfperception" domain, with a score of 0.62. Conclusions: The Chilean version of KIDSCREEN-52 is culturally appropriate and semantically equivalent in its English and Spanish versions (from Spain). Its reliability and validity were adequate.

Robust site-resolvable quantum gates in an optical lattice via inhomogeneous control.

The power of optical lattices for quantum simulation and computation is greatly enhanced when atoms at individual lattice sites can be accessed for measurement and control. Experiments routinely use high-resolution microscopy to obtain site-resolved images in real time, and site-resolved spin flips have been implemented using microwaves resonant with frequency-shifted target atoms in focused light fields. Here we show that methods adapted from inhomogeneous control can greatly increase the performance of such resonance addressing, allowing the targeting of arbitrary single-qubit quantum gates on selected sites with minimal cross-talk to neighbouring sites and significant robustness against uncertainty in the atom position. We further demonstrate the simultaneous implementation of different gates at adjacent sites with a single global microwave pulse. Coherence is verified through two-pulse experiments, and the average gate fidelity is measured to be 95±3%. Our approach may be useful in other contexts such as ion traps and nitrogen-vacancy centres in diamond.

[Validation of an instrument to measure health-related quality of life in Chilean children and adolescents]. / Adaptación transcultural y validación de un instrumento de calidad de vida relacionada con la salud en adolescentes chilenos.

BACKGROUND: KIDSCREEN-52 is an instrument to assess health related quality of life in children and adolescents. AIM: To culturally adapt and validate the KIDSCREEN-52 questionnaire in Chileans. MATERIAL AND METHODS: Two independent translations from the English Spanish language were conciliated and retranslated to English. The conciliated version was tested during a cognitive interview to adolescents of different socioeconomic levels. The final version was validated in 7,910 school attending adolescents. RESULTS: In the cross-cultural adaptation, 50 of the 52 items presented low or medium levels of difficulty and a high semantic equivalence. Distribution according to gender, grades and types of schools was similar to the sample. Single ages were not affected by sex distribution. The Confirmatory Factor Analyses were: X² (1229) = 20996.7, Root Mean Square Error of Approximation = .045 and Comparative Fit Index = .96. The instrument had a Cronbach's alpha of .93. The domains had scores over 0.70 points, with the exception of the "Selfperception" domain, with a score of 0.62. CONCLUSIONS: The Chilean version of KIDSCREEN-52 is culturally appropriate and semantically equivalent in its English and Spanish versions (from Spain). Its reliability and validity were adequate.

Association between leptin, LH and its receptor and luteinization and progesterone accumulation (P4) in bovine granulosa cell in vitro.

A full understanding of the cellular events that occur during in vitro luteinization of bovine granulosa cells, stimulated by LH and by leptin, is a complex goal that has not been completely achieved. The aim of this work was to study the effects of leptin, LH and leptin + LH on progesterone accumulation (P4) and on the expression of LH receptors (LHR) in bovine granulosa cells in culture. The results confirm that this in vitro model is representative of functional and morphological luteinization/differentiation. The pattern of expression of LHR with time of incubation was an important marker of in vitro luteinization, with 50-90% of cells expressing LHR by 96 h in culture. Cytoplasmic lipidic droplets were highly abundant in granulosa cells, suggesting a sufficient source of precursors for steroid hormone synthesis: P4 accumulation ranged between 40 and 550 ng/ml. In addition, a positive correlation (r = 0.58, p < 0.05) between the expression of LHR and accumulation of P4 throughout the time of incubation was observed. The expression of LHR was inhibited by LH and leptin + LH treatment. In conclusion, we found an inverse modulation between the expression of LHR and the concentration of LH, and the expression of LHR could be regulated by P4 produced by the luteinized granulosa cells. These findings are contributing to elucidate further the panoply of interactions during the differentiation of granulosa cells into luteal cells in vitro.

Reducción de la mortalidad por infarto del miocardio en hospitales chilenos / Reduction of acute myocardial infarction mortality in Chilean hospitals

Background: The characteristics of patients with acute myocardial infarction (MI) admitted to 37 Chilean hospitals (GEMI Registry Group), have been analyzed in the periods 1993-1995 and 1997-1998. Aim: To report the changes in hospital mortality between these 2 periods, with a particular emphasis on the impact of treatment. Patients and methods: Between 1993-1995 we collected information from 2,957 patients and between 1997-1998 we registered 1,981 patients with MI. Analysis of the changes in mortality between periods was adjusted by demographic variables, coronary risk factors, MI location, Killip class on admission and the different therapeutic strategies utilized. The effects of different treatments on hospital mortality were adjusted by the previously determined mortality risk variables. Results: Hospital mortality decreased from 13.3 percent to 10.8 percent between both periods (Odds Ratio (OR) 0.78, confidence intervals (95 percent) (CI) 0.65-0.93). A significant reduction in mortality was observed among patients below 60 years of age, in men, in diabetics and in subjects with an infarction classified as Killip class over II. The use of beta blockers (OR 0.65, CI 0.42-0.99) and intravenous nitrates (OR 0.78, CI 0.61-0.99) and the lower use of calcium channel blockers (OR 0.72, CI 0.60-0.87) were significantly associated with a lower mortality. The administration of angiotensin converting enzyme inhibitors was associated with a 29.3 percent mortality reduction (OR 0.69, CI 0.47-1.02). Conclusions: There has been a significant reduction in the mortality rate for MI in Chilean hospitals during the 2 registry periods analyzed, which was significant among some high risk patients and was related to treatment changes, according to evidence based guidelines

An interpersonal analysis of Rorschach aggression variables in a normal sample.

This study investigated the relationship between Rorschach aggression variables and a self-report measure of interpersonal control and aggression (Structural Analysis of Social Behavior), rated for best and worst states, with 50 college students using forward stepwise regression analyses. Aggressive Movement (AG) was related to the report of self-attack for the best state ratings. The following findings were significant for the worst state ratings. AG was related to viewing the other as reacting as if attacked but the self as acting more affiliatively to the other. Aggressive Past (AgPast) was related to reacting to the other more submissively. A combined Aggressive Potential (AgPot)/Aggressive Content (AgC) variable was related to viewing the other as reacting less submissively and acting more dominantly. AgC was related to viewing the other as reacting less submissively. Methodological limitations are discussed, including potential problems regarding social desirability for the self-report aggression measure.

Paragonimíase pulmonar e pleural: relato de dois casos / Pulmonary and pleural paragonimiasis: report of two cases

A paragonimíase é uma infecção pulmonar crônica causada por um trematóide do gênero Paragonimus, sendo o Paragonimus westermani o que mais infecta o homem. É uma doença endêmica da Asia Oriental, mas também é vista na América. Relatamos dois casos de paragonimíase, em que um dos pacientes apresentava antecedentes e características clínicas e radiológicas sugestivas da doença, diagnosticada pela presença de ovos do P. westermani no escarro, e o outro, um empiema pós-trauma torácico cujo diagnóstico de paragonimíase foi um achado histopatológico pleural após uma decorticação. Este diagnóstico foi confirmado pela presença de ovos do P. westermani em escarro.

P-glycoprotein expression in circulating blood leukocytes of patients with steroid-resistant asthma.

P-Glycoprotein is a transmembrane efflux pump for different lipophilic drugs including glucocorticosteroids. Thus, upregulation of P-glycoprotein may provide a mechanism for reduced glucocorticosteroid responses as they occur in steroid-resistant asthma. To address this issue, we have examined freshly isolated peripheral blood mononuclear cells and granulocytes with regards to P-glycoprotein functional and surface expression. Using two-color immuno fluorescence techniques, we demonstrated a direct correlation between the efflux of the fluorescent dye Rh 123 and P-glycoprotein surface expression in lymphocytes, NK (natural killer) cells, monocytes and granulocytes. P-Glycoprotein levels varied widely between different leucocytes, with NK cells and CD8+ T cells having high, and granulocytes having no detectable levels. There was no evidence for upregulation of P-glycoprotein expression in any cell type from patients with steroid-resistant asthma compared to patients with steroid-sensitive or mild asthma. These results suggest that increased P-glycoprotein expression can be excluded as a mechanism for steroid resistance. Interestingly, a down regulation of P-glycoprotein expression in B cells was associated with systemic glucocorticosteroid treatment in vivo and in vitro. Whether this phenomenon may account for reduced immunoglobulin levels associated with oral glucocortico-steroid therapy remains to be determined.

[Functional IgG subclass determinations in patients with suspected humoral immune defects using the LIBA technique]. / Funktionelle IgG-Subklassenuntersuchungen bei Patienten mit Verdacht auf humoralen Immundefekt mittels LIBA-Technik.

In patients with recurrent infections, "intrinsic" asthma and lymphoma the specific binding capacity of IgG subclass 2 against pneumococcus was determined by line-immuno-binding-assay (LIBA). The results show that LIBA represents a simple and specific test system suitable as diagnostic parameter in patients with a suspected humoral defect.

Differential cytokine profiles in peripheral blood lymphocyte supernatants and skin biopsies from patients with different forms of atopic dermatitis, psoriasis and normal individuals.

There is increasing evidence that the activation of a selected T helper cell population producing a Th2-related cytokine pattern with IL-4 and IL-5 but not IL-2 and interferon-gamma (IFN-gamma) may be involved in the pathogenesis of IgE-mediated atopic diseases and in particular of atopic dermatitis (AD). However, the existence of a 'nonatopic' (intrinsic) form of AD (NAD) with normal serum IgE levels, negative RAST tests, negative immediate type skin reactions towards environmental allergens and a negative patients and family history for IgE-mediated allergies raised the question whether this form may be explained by a different T cell activation and cytokine pattern. In the present study we compared the distribution of peripheral blood leukocyte and lymphocyte subpopulations, their activation state and cytokine production in peripheral blood lymphocyte supernatants and skin biopsies of patients with AD (n = 19), NAD (n = 14), psoriasis (n = 6) and normal individuals (n = 13). A characteristic eosinophilia was present in AD and NAD but not in psoriasis and normal controls. The three patient groups showed significantly increased numbers of activated CD4+ and CD8+ cells as measured by IL-2R and HLA-DR expression. Determination of spontaneously released IL-2, IL-4, IL-5 and IFN-gamma from peripheral blood lymphocytes demonstrated a Th2-related cytokine pattern with elevated levels for IL-4 and IL-5 in AD patients only. Increasingly enough, patients with NAD displayed high IL-5 but low IL-4 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone mineral content, 25-hydroxycalciferol and zinc serum levels in insulin-dependent (type I) diabetic patients.

To determine the relationship between bone mineral content (BMC), 25-Hydroxycalciferol (25OHD) and zinc serum levels in young insulin-dependent diabetics, we performed photon absorptiometry on a poorly controlled group of 22 patients. Zinc, 25OHD and alkaline phosphatase were measured in fasting serum. Ca, P, Mg, glucose and cAMP were determined in serum and in 24 hours urine collection. The diabetic group showed a significant decrease in BMC (less than 0.001) with raised urinary excretion rate of calcium (p less than 0.001). On the other hand, serum levels of zinc and 25OHD showed a significant decrease (p less than 0.001, both). We found a positive and significant correlation between glycosuria and urinary excretion rate of calcium (r = 0.77; p less than 0.001) and negative one for 25OHD and urinary excretion rate of calcium (r = -0.77; p less than 0.001). We conclude that decreased zinc and 25OHD serum levels in poorly controlled insulin-dependent (Type I) diabetic patients, in addition to raised urinary excretion rate of calcium, as result of the osmotic diuresis, contribute to bone loss in these patients.