Antiparasitic Derivatives of the Furoquinoline Alkaloids Kokusaginine And Flindersiamine.

We report the synthesis of 16 new compounds obtained from kokusaginine and flindersiamine, the main alkaloids isolated from the bark of Balfourodendron riedelianum. The activity of the compounds against axenic cultures of Trypanosoma cruzi epimastigtotes and trypomastigotes, as well as intracellular amastigotes, is described, together with their cytotoxic activity against three different human cell lines. The synthetic strategy for the preparation of the new compounds was based on the reactivity at the C4 position of the furoquinoline core towards nucleophiles. The new derivatives were synthesized by a Buchwald-Hartwig reaction, in most cases under green, solvent-free conditions. Compounds 1 c and 1 e displayed better in-vitro activity against trypomastigotes than benznidazole and nifurtimox (positive controls) with IC50 <4 µM. In addition, both compounds were not cytotoxic against the three human cell lines K562 (erytroleukimia), LM2 (breast cancer), and HaCat (keratinocyte). Interestingly, when evaluated against intracellular amastigotes, compound 1 c was able to significantly reduce the number of this parasite form, compared to the negative control.

Self-reported executive function, and not performance-based measures, strongly associates with symptoms of premenstrual syndrome/premenstrual dysphoric disorder / Autorreporte de funciones ejecutivas, y no medidas de desempeño, fuertemente se asocia con síntomas de síndrome premenstrual/trastorno disfórico premenstrual

Abstract Introduction Premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD) may be neuropsychologically understood as impairments of executive functions (EF), since these are related to the regulation of complex behavior and cognition. Objective To test the utility of self-report of EF versus performance-based measures, for the understanding of PMS/PMDD, and to analyze interactive effects between symptoms of these pathologies and EF on daily-life functionality. Method Mexican women were recruited through non-probabilistic procedures. The Premenstrual Symptoms Screening Tool (PSST) was used to determine severity of symptoms and functional impairment in daily-life activities, and the Behavioral Rating Inventory of Executive Functions-Adults (BRIEF-A) (short Spanish-translated version) adapted to collect information on EF during luteal versus follicular phases. Performance was evaluated with Stroop, Trail Making Test and Letter-Number Sequencing. Results A total of 157 were analyzed. Three groups were formed: No diagnosis ( n = 78); PMS ( n = 67) and PMDD ( n = 12). Between-group differences were observed for both BRIEF-A-Luteal and BRIEF-A-Follicular. Bivariate correlations between these measures and the PSST were found, with double the magnitude relative to BRIEF-A-Luteal. Only two indicators of performance-based measures were weakly associated to the PSST. The regression model showed high multicollinearity between self-reported EF and PMS/PMDD symptoms, and no interaction was found. Discussion and conclusion Self-report probed a better association than based-performance tests for the assessment of EF in PMS/PMDD. EF deficits and PMS/PMDD symptoms, particularly during luteal phase, may be as closely link as to allow for the consideration of these diagnoses as partial forms of dysexecutive syndrome.

Resumen Introducción El síndrome premenstrual/trastorno disfórico premenstrual (SPM/TDPM) pueden entenderse neuropsicológicamente como alteraciones de las funciones ejecutivas (FE), ya que éstas permiten la regulación del comportamiento complejo y la cognición. Objetivo Evaluar la utilidad del autorreporte de las FE versus pruebas de desempeño para comprender el SPM/TDPM, y analizar los efectos interactivos entre los síntomas de estas patologías y las FE sobre el funcionamiento diario. Método Mujeres mexicanas fueron reclutadas por medio de procedimientos no probabilísticos. El Instrumento de Detección de Síntomas Premenstruales (PSST) se utilizó para determinar la gravedad de los síntomas y el deterioro funcional en las actividades de la vida diaria, y el Inventario de Evaluación Conductual de la Función Ejecutiva-Adultos (BRIEF-A) (versión breve traducida al español) para recopilar información sobre EF durante las fases lútea versus folicular. Se emplearon también las pruebas de desempeño: Stroop, Trail Making Test y Secuencia de Letras y Números. Resultados Se analizó un total de 157 participantes. Se formaron tres grupos: sin diagnóstico ( n = 78); SPM ( n = 67) y TDPM ( n = 12). Se observaron diferencias entre los grupos para BRIEF-A-Lútea y BRIEF-A-Folicular. Se encontraron correlaciones bivariadas entre estas medidas y el PSST, con el doble de magnitud en relación con BRIEF-A-Lútea. Solo dos indicadores de medidas basadas en el desempeño mostraron una asociación débil con el PSST. El modelo de regresión mostró alta multicolinealidad entre el autorreporte de FE y SPM/TDPM, y no se encontró la interacción esperada. Discusión y conclusión El autorreporte mostró una mejor asociación que las pruebas de rendimiento para la evaluación de FE en SPM/TDPM. Los déficits de EF y los síntomas de SPM/TDPM, particularmente durante la fase lútea, pueden estar tan estrechamente vinculados como para permitir la consideración de estos diagnósticos como formas parciales de síndrome disejecutivo.

Inflicted versus unintentional injury: towards improved detection and surveillance of supervisory neglect.

BACKGROUND: Many children evaluated for child abuse have non-inflicted injuries due to supervisory neglect. Despite its prevalence, supervisory neglect has received minimal attention. METHODS: We performed a retrospective review of patients maintained in a hospital forensic registry. Text analytics software was used to classify types of supervisory neglect from reported mechanism of injury (MOI). Logistic regression was used to assess risks associated with supervisory neglect. RESULTS: For 1185 eligible patients, 553 were classified as having unintentional injuries. Text analysis identified four types of supervisory neglect for falls (N = 376): interrupted supervision (53.4%); failure to adapt the home (26.7%); safety equipment non-compliance (12.8%); inadequate substitute care (7.0%); a fifth category was identified for non-falls (N = 54): rough handling (32.0%). Supervisory neglect was associated with MOI consistent with the injury (AOR = 15.5[p < 0.001]), no loss of consciousness (AOR = 6.8(p < 0.001]), no bruising away from the injury site (AOR = 3.7[p < 0.001]), and direct hospital presentation (AOR = 1.8[p < 0.05]). Of the 553 with unintentional injury, 62% had isolated head injuries; 20%, however, had evidence of prior head trauma. CONCLUSIONS: Interrupted supervision was the most common form of supervisory neglect. Twenty percent of forensics patients with head injury found to have non-inflicted injuries had evidence of prior head injury. Supervisory neglect suggests a high-risk population. LEVEL OF EVIDENCE: Level II, Prognosis.

Effects of Post Anthesis Foliar Application of Sodium Selenite to Soybeans (Glycine max): Lipid Composition and Oil Stability.

This study aimed at determining whether applying selenium to soybean plants affected composition and oil oxidative stability of the seeds. Soybean was cultivated and sodium selenite (Selenite) added by foliar application (0, 200, or 300 g Selenite/Ha). Physical and chemical characterization was performed on the harvested seeds (thousand seed weight, bulk and true densities, fat, fiber, ash, protein, nitrogen free extract and selenium content). Soybean oil was tested in terms of Oxidation Induction Time (OIT), fatty acid, tocopherols, phytosterols, density, refractive index and saponification and iodine values. All seeds showed similar composition: crude fat (around 20%) and crude fiber (from 8.4 to 9.3%). Control seeds and those treated with 200 g Selenite/Ha contained higher protein concentration (37%), compared to the 300 g treatment (35.9%). All seeds showed similar ash content (7%). OIT values for both treatments were slightly lower (from 39.1 to 43.7 min) compared with 45.02 min in the control. Polyunsaturated fatty acids were higher for the 300 g Se/Ha (50.2%) compared with 48.2 to 49.4%of the other treatments. All samples showed similar phytosterols and tocopherols concentrations. Results showed that OIT values maintained an inverse relationship with selenium content, suggesting that foliar fertilization enhanced oil oxidation or acted as a pro-oxidant at the applied rates.

Drug Development in Conformational Diseases: A Novel Family of Chemical Chaperones that Bind and Stabilise Several Polymorphic Amyloid Structures.

The increasing prevalence of conformational diseases, including Alzheimer's disease, type 2 Diabetes Mellitus and Cancer, poses a global challenge at many different levels. It has devastating effects on the sufferers as well as a tremendous economic impact on families and the health system. In this work, we apply a cross-functional approach that combines ideas, concepts and technologies from several disciplines in order to study, in silico and in vitro, the role of a novel chemical chaperones family (NCHCHF) in processes of protein aggregation in conformational diseases. Given that Serum Albumin (SA) is the most abundant protein in the blood of mammals, and Bovine Serum Albumin (BSA) is an off-the-shelf protein available in most labs around the world, we compared the ligandability of BSA:NCHCHF with the interaction sites in the Human Islet Amyloid Polypeptide (hIAPP):NCHCHF, and in the amyloid pharmacophore fragments (Aß17-42 and Aß16-21):NCHCHF. We posit that the merging of this interaction sites is a meta-structure of pharmacophore which allows the development of chaperones that can prevent protein aggregation at various states from: stabilizing the native state to destabilizing oligomeric state and protofilament. Furthermore to stabilize fibrillar structures, thus decreasing the amount of toxic oligomers in solution, as is the case with the NCHCHF. The paper demonstrates how a set of NCHCHF can be used for studying and potentially treating the various physiopathological stages of a conformational disease. For instance, when dealing with an acute phase of cytotoxicity, what is needed is the recruitment of cytotoxic oligomers, thus chaperone F, which accelerates fiber formation, would be very useful; whereas in a chronic stage it is better to have chaperones A, B, C, and D, which stabilize the native and fibril structures halting self-catalysis and the creation of cytotoxic oligomers as a consequence of fiber formation. Furthermore, all the chaperones are able to protect and recondition the cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP20-29 fragment or by a low potassium medium, regardless of their capacity for accelerating or inhibiting in vitro formation of fibers. In vivo animal experiments are required to study the impact of chemical chaperones in cognitive and metabolic syndromes.

Estrés oxidativo en las cardiopatías congénitas cianóticas / Oxidative stress in cyanotic congenital heart disease

Las cardiopatías y el infarto agudo de miocardio son procesos en cuya fisiopatología están presentes los radicales libres, que causan daños severos en la estructura del miocardio e involucran una cascada de eventos asociados con la pérdida de la integración de las membranas. Con el propósito de determinar la presencia de estrés oxidativo en las cardiopatías congénitas cianóticas, en un grupo de 20 pacientes pediátricos con esta afección se determinaron los niveles de antioxidantes séricos, como albúmina, ceruloplasmina, vitamina C, bilirrubina, ácido úrico, y de LDLox como marcador de daño oxidativo. Los resultados demostraron niveles bajos de vitamina C, hiperbilirrubinemia e hiperuricemia; las cifras de albúmina y ceruloplasmina no se modificaron, a diferencia de la LDLox, que evidenció la presencia de estrés oxidativo en estos pacientes.

Heart diseases and acute myocardial infarct are processes where free radicals are present in the pathophysiology, causing severe damage to myocardial structure and involving a cascade of events associated with membrane integration loss. Aimed at assessing the presence of oxidative stress in cyanotic congenital heart disease in a group of 20 pediatric patients with this condition, serum levels of antioxidatives such as albumin, ceruloplasmin, vitamin C, bilirubin, uric acid, and LDLox as oxidative damage marker were assessed. Results showed low levels of vitamin C, hyperbilirubinemia, and hyperuricemia; albumin and ceruloplasmin levels remained stable unlike LDLox, which showed the presence of oxidative stress in these patients.

Perfil lipídico en niños con cardiopatías congénitas cianóticas / Lipidic profile in children with cyanotic congenital heart disease

La oxidación de lipoproteínas desempeña un papel importante en la aterogénesis y en el daño endotelial y, por lo tanto, en las cardiopatías. Con el objetivo de evaluar el perfil lipídico en niños con cardiopatías congénitas cianóticas, en un grupo de 20 niños con esta afección se determinaron niveles de colesterol total, colesterol HDL, colesterol LDL, triglicéridos y LDL oxidada (LDLox) y se compararon con los de un grupo control conformado por 50 niños supuestamente sanos. Se demostró que la oxidación de la LDL está asociada con el grado de estrés oxidativo, del 100% en los pacientes enfermos, con cifras elevadas de colesterol LDL (65%) y con niveles bajos de colesterol HDL (70%), lo cual hace al endotelio más sensible ala aterogénesis.

Lipoprotein oxidation plays an important role in atherogenesis and endothelial damage, therefore in heart disease. In order to assess the lipidic profile in children with cyanotic congenital heart disease, determinations of HDL, LDL, total cholesterol, triglycerides, and oxidative LDL (LDLox) were assessed in a group of 20 children with this condition. Results were compared with those of a control group formed by 50 children supposedly healthy. It was shown that LDL oxidation is associated to the degree of oxidative stress in 100% of the ill patients, with elevated levels of LDL cholesterol (65%) and low levels of HDL cholesterol (70%), which makes the endothelium more sensitive to atherogenesis.

c-fos and estrogen receptor gene expression pattern in the rat uterine epithelium during the estrous cycle.

Different studies in ovariectomized estrogen treated animals support the idea that c-fos plays a role in the proliferation of uterine epithelial cells. However, these studies invite us to reassess the role played by c-fos in epithelial cell types of the endometrium during the estrous cycle. The present study was undertaken to determine the c-fos and estrogen receptor (ER) gene expression pattern in the rat uterine epithelium during the estrous cycle in which natural and cyclic changes of steroid hormones occur, and correlate these changes with the proliferation status of this cellular types. Proliferation was assessed during the estrous cycle using bromodeoxyuridine incorporation to DNA. ERalpha and beta proteins were assessed by immunohistochemistry. The regulation of c-fos gene expression in the uterus of intact animals during the estrous cycle was evaluated using both in situ hybridization and immunohistochemistry. Estradiol (E(2)) and progesterone (P(4)) plasma levels were assessed by radioimmunoassay. The results indicated that luminal (LE) and glandular epithelia (GE) presented maximal proliferation during the metestrus (M) and the diestrus (D) days. However, during the proestrus (P) day only LE presented proliferation, and during the estrus (E) day only the stromal cells proliferated. A marked immunostaining for ERalpha was detected in both LE and GE cells during the early phases of the cycle but diminished on the P and the E day. In contrast, ERbeta was undetectable in both epithelia during all stages of the cycle. The highest c-fos mRNA level was detected in both epithelia on the M day, followed by a significant reduction during the other days of the cycle. The highest protein content was observed on the M and D days, and the minimal value was detected on the E day. The c-Fos protein level in LE was increased during M and D days, presenting a high correlation with the cellular proliferation pattern of this cell type. In conclusion, the overall results indicate that c-Fos protein presented a good correlation with uterine epithelial cell proliferation of LE. In the case of GE, the same tendency was observed, although no significant correlation was found. Both in LE and GE, c-fos mRNA did not strictly correlate with its protein levels. c-fos seems to have a postranscriptional regulation in uterine epithelial cells during the rat's estrous cycle.

Nitrito de sodio en productos cárnicos elaborados en Cienfuegos / Sodium nitrite in meat products manufactured in Cienfuegos

Se analizó el contenido de nitrito residual en productos cárnicos curados, elaborados en la provincia de Cienfuegos durante la década de 1991 al 2000, con el objetivo de evaluar el uso del nitrito de sodio en 3 fuentes de producción: un combinado cárnico, centros de elaboración y trabajadores por cuenta propia. El uso del aditivo no fue adecuado en ninguna de las fuentes, pues en todas se hallaron muestras con contenidos superiores al límite máximo de residuo permisible; la situación fue peor en los productores por cuenta propia

Fisiología y técnicas de estudio anorrectal / Physiology and techniques of anorectal study

La compleja función anorrectal normal envuelve la acción coordinada de una serie de nervios y músculos, reflejos y acciones voluntarias. El correcto balance de estructuras anatómicas y procesos fisiológicos resulta en una defecación y continencia normal. Se efectúa una revisión de la literatura sobre la fisiología anorrectal y sus técnicas de estudio

Localization of intranuclear RNA by electron microscopy in situ hybridization using a genomic DNA probe

Background. The presence of RNA in the cell nucleus is well known. However, a high resolution in situ hybridization evidence for the presence of RNA in some nuclear particles is still lacking. The aim of this work is to localize RNA in subnuclear particles using a novel ultrastructural in situ hybridization procedure. In this study, biotinylated genomic mouse DNA as a probe to localiza total RNA in the nuclei of mouse hepatocytes was used. Methods. The procedure is based on Paraformaldehyde fixation and embedding in lowicryl resin. Thin sections are mounted in formvar-coated gold grids. Hybridization is performed on non-denatured thin sections. DNA-RNA hybrids are detected with streptavidin-10 mm gold particles complex. By controlling the time of nick-translation during incorporation of biotin into the probe, labeling in the fibrillar portions of the nucleoplasm is obtained. More digested probes generate more labeling in the granular components. Nucleoli were similarly labeled. Results. As expected, no label was observed in the compact chromatin clumps. These results indicate that granular components as perichromatin granules in the nucleus contain more processed RNA than fibrillar portions. As a comparison, viral DNA sequences on denatured RNase-treated thin sections of adenovirus-2 (Ad-2)-infected human cells were detected. As previously reported, at late stages DNA was observed in the viral particles and surrounding nucleoplasm, where Ad-2 DNA is synthesized. Conclusions. The present procedure allows the study of intranuclear RNA distribution and will be useful fo the analysis of RNA processing in several types of cells

Control infeccioso en el consultorio odontológico. Estudio sobre conocimientos y actitudes / Infection control in the dental office. A study on knowledges and attitudes

Una encuesta fue realizada entre profesionales con más de tres años de ejercicio para ponderar su conocimiento y actitudes sobre el control infeccioso. Los resultados encontrados demuestran que se requiere un mayor conocimiento de los propósitos y recursos que se requieren para la adecuada ejecución de un programa óptimo de control infeccioso. Dos datos fueron claros: conocimiento parcial y falsa seguridad

Paralisis cerebral infantil: tratamiento médico / Infantile cerebral palsy: medical treatment

Presentamos los resultados del tratamiento médico en 27 pacientes con parálisis cerebral infantil (PCI). Inicialmente todos recibieron clonazepam y piracetam y dos a tres meses después, carbamazepina (CBZ) y/o difenilhidantoína (DFH). Los pacientes con supresión de las crisis epilépticas, transtornos del sueño, falta de atención e hiperquinesia, mostraron mejoría de la capacidad intelectual, actividad motora y del EEG. Creemos que estos resultados fueron debidos al control de los focos epileptógenos, fisioterapia y terapia educacional.

Prevalencia del síndrome de Sjögren en diabetes mellitus / Prevalence of Sjögren's syndrome in diabetes mellitus

El objetivo del presente estudio fue conocer si el síndrome de Sjögren presenta una mayor prevalencia en los pacientes con diabetes mellitus que la población general. Se realizó un estudio prospectivo, ciego simple, comparativo en 50 pacientes con diabetes mellitus tipo I, 50 pacientes con diabetes mellitus tipo II y 50 sujetos control a los que se le diagnosticó síndrome de Sjögren definitivo o probable en base a criterios universalmente aceptados. Los pacientes con síndrome de Sjögren definitivo y probable en el grupo con diabetes mellitos tipo I fueron cinco, en el tipo II y en los controles dos sujetos, sin existir diferencia estadísticamente significativa entre ellos (x2=1.53, p=NS). Se puede concluir que la prevalencia del síndrome de Sjögren en los pacientes con diabetes mellitus no es mayor que en la población general