Characteristics of Medically Transported Critically Ill Children with Respiratory Failure in Latin America: Implications for Outcomes.

Several challenges exist for referral and transport of critically ill children in resource-limited regions such as Latin America; however, little is known about factors associated with clinical outcomes. Thus, we aimed to describe the characteristics of critically ill children in Latin America transferred to pediatric intensive care units for acute respiratory failure to identify risk factors for mortality. We analyzed data from 2,692 patients admitted to 28 centers in the Pediatric Collaborative Network of Latin America Acute Respiratory Failure Registry. Among patients referred from another facility (773, 28%), nonurban transports were independently associated with mortality (adjusted odds ratio = 9.4; 95% confidence interval: 2.4-36.3).

Síndrome de Saethre-Chotzen: a propósito de un caso / Saethre-Chotzen syndrome: a case report

El síndrome de Saethre-Chotzen es un síndrome malformativo craneofacial caracterizado por una sinostosis de las suturas coronales y alteraciones de extremidades. Tiene una prevalencia de 1 de cada 25 000-50 000 recién nacidos vivos. Se presenta el caso de un neonato sin antecedentes de interés con alteraciones craneofaciales al nacer. Ante los rasgos fenotípicos del paciente, se realizó una tomografía axial computada craneal, que mostró la fusión parcial de la sutura coronal y evidenció la presencia de huesos wormianos en localización metópica y lambdoidea derecha. Con la sospecha clínica de síndrome malformativo craneofacial, se solicitó análisis del exoma dirigido, que confirmó que el paciente era portador heterocigoto de la variante patogénica c.415C>A, que inducía un cambio de prolina a treonina en la posición 139 del gen TWIST1, responsable del síndrome. La presencia de huesos wormianos, hallazgo no descrito hasta ahora en la literatura, amplía la variabilidad fenotípica conocida de este síndrome.

The Saethre-Chotzen syndrome is a craniofacial malformation syndrome characterized by synostosis of coronal sutures and limb anomalies. The estimated prevalence of this syndrome is 1 in 25 000-50 000 live births. We present a case report of a neonate, without relevant family history, who presented craniofacial alterations at birth. Given the phenotypic features, a cranial computed tomography scan was performed, showing partial fusion of the coronal suture, evidencing the presence of wormian bones in the metopic and right lambdoid location. With the clinical suspicion of craniofacial malformation syndrome, an analysis of the directed exome was requested confirming that the patient is a heterozygous carrier of the pathogenic variant c.415C>A, which induces a change of proline to threonine at position 139 of the TWIST1 gene, responsible for Saethre-Chotzen syndrome.The presence of wormian bones, a finding not described so far in the literature, extends the well-known phenotypic variability of this syndrome.

[Saethre-Chotzen syndrome: a case report]. / Síndrome de Saethre-Chotzen: a propósito de un caso.

The Saethre-Chotzen syndrome is a craniofacial malformation syndrome characterized by synostosis of coronal sutures and limb anomalies. The estimated prevalence of this syndrome is 1 in 25 000-50 000 live births. We present a case report of a neonate, without relevant family history, who presented craniofacial alterations at birth. Given the phenotypic features, a cranial computed tomography scan was performed, showing partial fusion of the coronal suture, evidencing the presence Síndrome de Saethre-Chotzen: a propósito de un caso Saethre-Chotzen syndrome: a case report of wormian bones in the metopic and right lambdoid location. With the clinical suspicion of craniofacial malformation syndrome, an analysis of the directed exome was requested confirming that the patient is a heterozygous carrier of the pathogenic variant c.415C>A, which induces a change of proline to threonine at position 139 of the TWIST1 gene, responsible for Saethre-Chotzen syndrome. The presence of wormian bones, a finding not described so far in the literature, extends the well-known phenotypic variability of this syndrome.

El síndrome de Saethre-Chotzen es un síndrome malformativo craneofacial caracterizado por una sinostosis de las suturas coronales y alteraciones de extremidades. Tiene una prevalencia de 1 de cada 25 000-50 000 recién nacidos vivos. Se presenta el caso de un neonato sin antecedentes de interés con alteraciones craneofaciales al nacer. Ante los rasgos fenotípicos del paciente, se realizó una tomografía axial computada craneal, que mostró la fusión parcial de la sutura coronal y evidenció la presencia de huesos wormianos en localización metópica y lambdoidea derecha. Con la sospecha clínica de síndrome malformativo craneofacial, se solicitó análisis del exoma dirigido, que confirmó que el paciente era portador heterocigoto de la variante patogénica c.415C>A, que inducía un cambio de prolina a treonina en la posición 139 del gen TWIST1, responsable del síndrome. La presencia de huesos wormianos, hallazgo no descrito hasta ahora en la literatura, amplía la variabilidad fenotípica conocida de este síndrome.

3,4-Dihydropyrimidin-2(1H)-ones as Antagonists of the Human A2B Adenosine Receptor: Optimization, Structure-Activity Relationship Studies, and Enantiospecific Recognition.

We present and thoroughly characterize a large collection of 3,4-dihydropyrimidin-2(1H)-ones as A2BAR antagonists, an emerging strategy in cancer (immuno) therapy. Most compounds selectively bind A2BAR, with a number of potent and selective antagonists further confirmed by functional cyclic adenosine monophosphate experiments. The series was analyzed with one of the most exhaustive free energy perturbation studies on a GPCR, obtaining an accurate model of the structure-activity relationship of this chemotype. The stereospecific binding modeled for this scaffold was confirmed by resolving the two most potent ligands [(±)-47, and (±)-38 Ki = 10.20 and 23.6 nM, respectively] into their two enantiomers, isolating the affinity on the corresponding (S)-eutomers (Ki = 6.30 and 11.10 nM, respectively). The assessment of the effect in representative cytochromes (CYP3A4 and CYP2D6) demonstrated insignificant inhibitory activity, while in vitro experiments in three prostate cancer cells demonstrated that this pair of compounds exhibits a pronounced antimetastatic effect.

Identification and characteristics of extracellular vesicles from bovine blastocysts produced in vitro.

Extracellular vesicles (EVs) have been identified within different body fluids and cell culture media. However, there is very little information on the secretion of these vesicles during early embryonic development. The aims of this work were first to demonstrate the secretion of extracellular vesicles by pre-implantation bovine embryos and second to identify and characterize the population of EVs secreted by bovine blastocysts during the period from day seven to nine of embryo culture and its correlation with further embryo development up to day 11. Bovine embryos were produced by in vitro fertilization (IVF) or parthenogenetic activation (PA) and cultured until blastocyst stage. Blastocyst selection was performed at day 7 post IVF/PA considering two variables: stage of development and quality of embryos. Selected blastocysts were cultured in vitro for 48 hours in groups (exp. 1) or individually (exp. 2) in SOF media depleted of exosomes. At day 9 post IVF/PA the media was collected and EVs isolated by ultracentrifugation. Transmission electron microscopy revealed the presence of heterogeneous vesicles of different sizes and population: microvesicles (MVs) and exosomes (EXs) of rounded shape, enclosed by a lipid bi-layer and ranging from 30 to 385 nm of diameter. Flow cytometry analysis allowed identifying CD63 and CD9 proteins as exosome markers. Nanoparticle tracking analysis generated a large number of variables, which required the use of multivariate statistics. The results indicated that the concentration of vesicles is higher in those blastocysts with arrested development from day 9 up to day 11 of in vitro development (6.7 x 108 particles/ml) derived from IVF (p <0.05), compared to PA blastocysts (4.7 x 108 particles/ml). Likewise, the profile (concentration and diameter) of particles secreted by embryos derived from IVF were different from those secreted by PA embryos. In conclusion, we demonstrated that bovine blastocysts secrete MVs/EXs to the culture media. Data suggest that characteristics of the population of EVs vary depending on embryo competence.

Human Immunodeficiency Virus/Hepatitis C Virus Coinfection in Spain: Prevalence and Patient Characteristics.

Background. The purpose of this study was to assess the prevalence of anti-hepatitis C virus (HCV) antibodies (Abs) and active HCV infection in human immunodeficiency virus (HIV)-infected (HIV+) patients in Spain in 2015. This was a cross-sectional study. Methods. The study was performed in 41 centers in 2015. Sample size was estimated for an accuracy of 2%, the number of patients from each hospital was determined by proportional allocation, and patients were selected using simple random sampling. Results. The reference population was 35 791 patients, and the sample size was 1867 patients. Hepatitis C virus serostatus was known in 1843 patients (98.7%). Hepatitis C virus-Abs were detected in 695 patients (37.7%), in whom the main route of HIV acquisition was injection drug use (75.4%). Of these 695 patients, 402 had HCV RNA, 170 had had a sustained viral response (SVR) after anti-HCV therapy, and 102 cleared HCV spontaneously. Hepatitis C virus-ribonucleic acid results were unknown in 21 cases. Genotype distribution (known in 367 patients) was 1a in 143 patients (39.0%), 4 in 90 (24.5%) patients, 1b in 69 (18.8%) patients, 3 in 57 (15.5%) patients, 2 in 5 (1.4%) patients, and mixed in 3 (0.8%) patients. Liver cirrhosis was present in 93 patients (23.1%) with active HCV infection and in 39 (22.9%) patients with SVR after anti-HCV therapy. Conclusions. The prevalence of HCV-Abs and active HCV infection in HIV+ patients in Spain is 37.7% and 22.1%, respectively; these figures are significantly lower than those recorded in 2002 and 2009. The predominant genotypes in patients with active HCV infection were 1a and 4. A high percentage of patients had cirrhosis. Cirrhosis is also common in patients with SVR after anti-HCV therapy.

Comorbilidades y gravedad de la apnea del sueño. Estudio en una cohorte de pacientes portugueses / Co-morbidities and sleep apnoea severity. A study in a cohort of Portuguese patients

Introducción. El síndrome de apnea obstructiva del sueño (SAOS) se asocia frecuentemente a otras enfermedades que actúan como factores de riesgo que influyen en la morbilidad y mortalidad del SAOS. Objetivos. Analizar la presencia de comorbilidades en pacientes con SAOS, seleccionados en una clínica del sueño ambulatoria en el norte de Portugal y clasificados atendiendo a la gravedad del SAOS. Pacientes y métodos. Una cohorte de 319 pacientes con trastornos del sueño fueron evaluados mediante estudios clínicos y registro videopoligráfico durante el sueño. Del total de pacientes (n = 209) con distrés respiratorio durante el sueño, 145 tenían SAOS con gravedad definida según el índice de apnea/hipopnea (IAH); 64 presentaban ronquidos primarios o distrés respiratorio con IAH < 5; y 110 tenían otros trastornos del sueño. Resultados. La presencia de comorbilidades fue del 75% en todos los pacientes con SAOS y del 79,5% en el grupo de pacientes con SAOS grave; 47 pacientes presentaban una única comorbilidad, la más común de las cuales fue la obesidad (56,3%), seguida de hipertensión, diabetes y otros trastornos cardiovasculares. La obesidad estuvo presente en el 84% de los casos más graves de SAOS y en el 100% de casos con múltiples comorbilidades. En comparación con el grupo de pacientes con distrés respiratorio durante el sueño, la comorbilidad aparece normalmente relacionada con el SAOS (p = 0,0196). Conclusión. Las comorbilidades se asocian con frecuencia al SAOS, independientemente de la gravedad de la enfermedad. Entre las comorbilidades presentes, la obesidad resultó ser la más común en los casos más graves de SAOS (AU)

Introduction. Obstructive sleep apnoea syndrome (OSAS) is frequently associated to other morbid conditions that act as risk factors influencing OSAS morbidity and mortality. Aim. To analyse the presence of co-morbidities in OSAS patients, recruited from a sleep outpatient clinic in Northern Portugal, stratified as a function of OSAS severity. Patients and methods. A cohort of 319 sleep-disordered patients was assessed by clinical and sleep video-polygraphic recording. Patients (n = 209) with sleep respiratory distress had OSAS (n = 145) and severity defined according to Apnoea/ Hypopnea Index (AHI); 64 had primary snoring or respiratory distress with AHI < 5; and 110 had other sleep disorders. A full individual background study was possible in 128 OSAS patients. The association to unique or multiple co-morbidities was assessed by clinical and analytical studies in general group or as a function of OSAS severity. Results. The presence of co-morbidities was of 75% in all OSAS patients and of 79.5% in the severe group of OSAS. Forty seven of patients had only one co-morbidity. The most common was obesity (56.3%) followed by high blood pressure, diabetes and other cardiovascular disorders. Obesity was present in 84% among the most severe OSAS cases and always present in those with multiple co-morbidities. When compared with the group of patients without sleep respiratory distress the co-morbidity condition was more frequently related to OSAS (p = 0.0196). Conclusion. Comorbidities are commonly associated to OSAS independently of disease severity. Among the comorbidities present obesity was the most common in the most severe OSAS cases (AU)

Exposición a fluidos corporales en trabajadores de salud del Hospital Universitario de Caracas: primer reporte: años 1991-1999 Caracas República de Venezuela / Exposure to body fluids in health workers the Hospital Universitario de Caracas: first report: years 1991-1999 Caracas República de Venezuela

Estudio prospectivo diseñado con el fin de evaluar a los trabajadores de salud del Hospital Universitario de Caracas que notificaran exposición a fluidos corporales al Sistema de Vigilancia de Virus de Inmunodeficiencia Humana y Hepatitis Viral, desde los años 1991 hasta 1999. Las variables estudiadas fueron: fecha y sitio del accidente, categoría del personal, edad, género, fluido involucrado, tipo de exposición, instrumento utilizado, serología basal para Virus de Inmunodeficiencia Humana y hepatitis viral del paciente índice y del TS, tipo de profilaxis antirretroviral, efectos adversos y seroconversión al Virus de Inmunodeficiencia Humana. Se utilizó el método descriptivo serie de casos los cuales fueron analizados por Epi-info. Versión 5. Durante el período de estudio fueron evaluados 242 trabajadores de la salud con exposición a fluidos corporales, 65% accidentes fueron notificados los dos últimos años. Ciento sesenta y tres femeninos y 79 masculinos, edad promedio 43 años (rango de 21-65 años). Los trabajadores de la salud que notificaron exposición a fluidos corporales procedían principalmente de los servicios de medicina interna, emergencia y cirugía. El mayor número de los accidentes correspondió a los médicos, principalmente residentes de posgrado. Exposición de tipo parenteral fue observada en 197 casos (179 percutáneas, y 18 salpicaduras en mucosas). Exposición cutánea se observó en 14 y combinada (piel y mucosas) 23 casos. El instrumento utilizado en 179 exposiciones percutáneas fue aguja con lumen en 48%. El fluido corporal involucrado fue la sangre en el 73% de los casos. La fuente fue conocida en 65% de las exposiciones. La profilaxis antirretroviral posexposición fue indicada inicialmente en 52% de los TS. Los efectos adversos se presentaron en 40%, en 7 casos fue motivo de abandono de tratamiento. El seguimiento se realizó en el 80% de los casos. Un trabajador de salud presentó Virus de Inmunodeficiencia Humana ocupacional...

Prospective study designed to assess the health workers at the Hospital Universitario de Caracas to notify body fluid exposure to Human Immunodeficiency Virus Surveillance System and Viral Hepatitis, from the years 1991-1999. The variables studied were: date and place of the accident, staff category, age, gender, fluid involved, type of exposure, instrument used, and baseline serology for Human Immunodeficiency Virus and Viral Hepatitis of health workers and index patient, type of prophylaxis antiretroviral, side effects and Human Immunodeficiency Virus seroconversion. Descriptive method was used series of cases which were analyzed by Epi-info. Version 5. During the study period were evaluated health workers 242 with body fluid exposure, 65% accidents were reported the past two years. 163 female and 79 male, mean age 43 years (range 21-65 years). Health workers who reported exposure to body fluids were mainly of Internal Medicine, Emergency and Surgery. The greatest numbers of injuries were doctors, mainly postgraduate residents. Parenteral exposure rate was observed in 197 cases (179 percutaneous, splash to mucous membranes 18). Dermal exposure was observed in 14 and combined (skin and mucosa) 23 cases. The instrument used in 179 percutaneous exposures was needle lumen in 48%. The body fluid blood was involved in 73% of cases. The source was known in 65% of exposures. Antiretroviral prophylaxis post exposure was initially indicated in 52% of the TS. Adverse events occurred in 40 %, in 7 cases was cause for withdrawals. The monitoring was performed in 80%. A case of Human Immunodeficiency Virus occupational in which it ruled out other risk factors

Hamamelitannin from witch hazel (Hamamelis virginiana) displays specific cytotoxic activity against colon cancer cells.

Hamamelis virginiana (witch hazel) bark is a rich source of condensed and hydrolyzable tannins reported to exert a protective action against colon cancer. The present study characterizes different witch hazel tannins as selective cytotoxic agents against colon cancer. To cover the structural diversity of the tannins that occur in H. virginiana bark, the hydrolyzable tannins, hamamelitannin and pentagalloylglucose, together with a proanthocyanidin-rich fraction (F800H4) were selected for the study. Treatment with these compounds reduced tumor viability and induced apoptosis, necrosis, and S-phase arrest in the cell cycle of HT29 cells, with hamamelitannin being the most efficient. Owing to polyphenol-mediated H(2)O(2) formation in the incubation media, the antiproliferative effect was determined in the presence and absence of catalase to rule out any such interference. The presence of catalase significantly changed the IC(50) only for F800H4. Furthermore, at concentrations that inhibit the growth of HT29 cells by 50%, hamamelitannin had no harmful effects on NCM460 normal colonocytes, whereas pentagalloylglucose inhibited both cancerous and normal cell growth. Using the TNPTM assay, we identified a highly reactive phenolic position in hamamelitannin, which may explain its efficacy at inhibiting colon cancer growth.

Procyanidins from grape pomace are suitable inhibitors of human endothelial NADPH oxidase.

Procyanidins have been associated with a reduced risk of cardiovascular diseases such as atherosclerosis. However, the molecular mechanisms underlying this benefit are not fully understood. Increased reactive oxygen species (ROS) production generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a common problem in different cardiovascular diseases. Our objective was to evaluate the effects of procyanidin-rich fractions from distilled grape pomace on NADPH oxidase activity in human umbilical vein endothelial cells (HUVEC). Three differently polymerized and galloylated procyanidin fractions were analyzed for their NADPH oxidase inhibitory activity in cell lysates and in HUVEC cultures. All of the three fractions, up to 1 µg/ml, equally inhibited isolated NADPH oxidase in HUVEC lysates in a concentration-dependent manner and independently of any superoxide anion scavenging activities. The procyanidin fractions even blocked NADPH oxidase activity in intact HUVEC, inhibiting ROS production at both extra- and intracellular levels. The fractions achieved the same effects that known NADPH oxidase inhibitors, such as diphenylene iodonium and apocynin, but they presented better hydrosolubility. Our results demonstrated that procyanidin from grape pomace inhibit human endothelial NADPH oxidase regardless of their polymerization degree and galloylation percentage. Therefore, procyanidins are suitable NADPH oxidase inhibitors which could serve as models for therapeutic alternatives for cardiovascular diseases.

The antioxidant potential of alprazolam on the redox status of peripheral blood leukocytes in restraint-stressed mice.

AIMS: Stress can cause adverse reactions in the body that induce a wide range of biochemical and behavioral changes. Oxidative damage is an established outcome of stress that has been implicated in the pathogenesis of mood and anxiety disorders. Anxiolytic drugs are widely prescribed to treat these conditions; however, no animal study has investigated the effect of benzodiazepines on the levels of intracellular reactive oxygen species (ROS) in the peripheral blood leukocytes of stressed mice. MAIN METHODS: Mice were immobilized for a period of 6h. Alprazolam (0.1-0.8 mg/kg of body weight) was administered 30 min before subjecting the animals to acute stress. The level of intracellular ROS in lymphocytes, granulocytes, and monocytes in the peripheral blood of stressed mice was investigated by using a 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe. KEY FINDINGS: Our results show that restraint stress significantly increases the generation of ROS in peripheral defense cells. Treatment with alprazolam partially reverses the adverse effects of stress. SIGNIFICANCE: Our findings suggest that the therapeutic efficacy of alprazolam may be mediated, at least partially, by the reversal of oxidative damage as demonstrated by the protective enhancement of antioxidant status following a stress-induced decline. Because alprazolam is used for the treatment of anxiety in patients with cancer, neurodegenerative disease, inflammatory bowel diseases, and other diseases, these results may have important clinical implications.

El infectológo y su labor en el hospital: 10 años de gestión, 2000-2009 / The infectious disease and its work in the hospital: 10 years of management, 2000-2009

El infectológo es de gran importancia en los hospitales; realiza funciones en atención ambulatoria, hospitalización, control de infecciones hospitalarias, docencia, investigación, asesoria en epidemias y pandemias entre otras. Precisar el cumplimiento de las funciones del infectológo, investigando la carga laboral y académica en HUC durante la última década. Se analizaron los registros de atención al paciente y programas académicos cumplidos desde el 1 de enero 2000 al 31 de diciembre 2009, calculando el número de pacientes evaluados en cada una de las actividades asistenciales y horas académicas. Se evaluaron 110 691 pacientes atendidos a través de los años. La distribución de las actividades correspondió a 72 521 (65 %) de atención en consultas ambulatorias (35 % pacientes viviendo con VIH y 30 % no VIH); 18 682 interconsultas de pacientes hospitalizados para control de antimicrobianos (17 %); 12 792 (12 %) cursos de tratamiento administrados en la sala de tratamiento ambulatorio (STA); 3 764 (3 %) egresos del SEIA y 2 932 personas atendidas por exposición de riesgo biológico. La actividad académica fue regular durante la década, cumpliendose los programas correspondientes. El número de horas empleadas en las revistas a los pacientes hospitalizados en el SEIA fue > 300/año. Seis miembros del servicio participaron en el programa del control de infecciones del HUC. Residentes y especialistas del SEIA cumplieron las funciones del infectológo en la última década;El mayor número de pacientes fue atendido de forma ambulatoria (consultas y la STA).

Hospital role of infectious diseases (ID) specialists is important. They participate in outpatient and inpatient care, hospital infection control, academic and research activities, and also pandemic and epidemic issues. This study's aim was to assess the number of activities, booth academic and im patients care, and fulfillment of ID physicians'roles at HUC during the last decade. Analysis of records for patient care and academic programs during January 1, 2000 to December 31, 2009. The number of patients clinically assessed and academic hours spent was calculated. During the decade, 110 691 patients were evaluated. There was a progessive increase of patients cared fir throughout they years. The activities distribution was as follows: 72 521 (65 %) outpatients (35 % HIV infected patients y % non HIV); 18 682 inpatients assessed following HUC policy on antibiotic control (17 %); 12 792 (12 %) courses of treatment administered at the outpatient treatment clinic (OTC); 3 764 (3 %) discharged patients fron SEIA y 2 932 people evaluated because of biologic risk exposition. Academic activities were fulfilled according to the fellowship program. Physicians dedicated more than 300 hour/year for inpatient rounds at SEIA. Six specialist form the ID Service also Were Members of HUC Infection Control Committee. Physicians at SEIA have accomplished the role of ID doctors during the last decade; most patients were evaluated outpatients and at OTC.

Antiradical activity, phenolics profile, and hydroxymethylfurfural in espresso coffee: influence of technological factors.

The influence of technological factors (decaffeination, brew volume, coffee species, and roast degree) on antiradical activity and phenolics content of espresso coffee is described. The screenings of phenolics profile and other compounds (caffeine and trigonelline), as well as the quantification of hydroxymethylfurfural, were performed by LC-DAD-ESI-MS. Significantly lower (p < 0.05) scavenging activities and phenolics contents were found in decaffeinated espressos when compared with regular ones (32 vs 38% and 324 vs 410 mg/30 mL cup, respectively). A long espresso (70 mL) offers more than twice the phenolics amount of a short one (20 mL). Robusta brews showed higher (p < 0.05) antiradical activity and phenolic contents than arabica ones, for all roast degrees (light, medium, and dark). No significant differences (p > 0.05) were observed for scavenging activities of differently roasted robusta brews, whereas an increase in medium-dark brews was observed for arabica samples. Total phenolics in robusta espressos decreased (p < 0.05) with the increase of roast degree, but no significant differences (p > 0.05) were found between arabica espressos from different roasts. By LC-DAD-ESI-MS, 23 hydroxycinnamic derivatives were found, including chlorogenic acids, lactones, and cinnamoyl-amino acid conjugates. The amount of each compound was differently affected by species and roast. Robusta brews presented superior levels of caffeine and chlorogenic acids, whereas arabica ones contained more trigonelline. Hydroxymethylfurfural contents in the brew (30 mL) varied from 2.60 to 0.84 mg for light- and dark-roasted arabicas and from 1.29 to 0.68 mg for light- and dark-roasted robustas, respectively.

Effects of resveratrol on expression of vascular endothelial growth factor in human gingival fibroblasts stimulated by periodontal pathogens.

OBJECTIVE: To investigate the effects of resveratrol, a naturally occurring polyphenol, on the expression of vascular endothelial growth factor (VEGF) in human gingival fibroblast culture in response to vesicles and outer membrane proteins from periodontopathic bacteria. MATERIAL AND METHODS: Human gingival fibroblasts were stimulated with vesicles and outer membrane proteins from Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. In human gingival fibroblast cultures treated with or without resveratrol, VEGF production was evaluated by means of enzyme-linked immunosorbent assay and VEGF mRNA expression by means of reverse transcription polymerase chain reaction analysis. Vascular permeability enhancement was measured by the leakage of intravenously injected dye at the injection site of supernatant from cultures of human gingival fibroblasts stimulated by vesicles and outer membrane proteins. RESULTS: Resveratrol significantly inhibited the increased production of VEGF by human gingival fibroblasts in response to vesicles and outer membrane proteins from periodontopathic bacteria, as shown by the detection of these proteins and their mRNA in vitro. Moreover, resveratrol treatment significantly decreased vascular permeability enhancement induced by supernatant from human gingival fibroblast cultures stimulated by vesicles and outer membrane proteins. CONCLUSIONS: Overall, these findings suggest that resveratrol inhibits production of VEGF by stimulated human gingival fibroblasts and can inhibit vascular permeability, suggesting a therapeutic role for it in pathogenic bacteria-induced periodontal inflammation.

Effects of psychological stress and fluoxetine on development of oral candidiasis in rats.

Psychological stress has been found to suppress cell-mediated immune responses that are important for limiting the proliferation of Candida albicans. Fluoxetine has been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on its effects on oral candidiasis. We designed experiments to evaluate the effects of fluoxetine on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Stress application and treatment with drugs (placebo or fluoxetine) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments, on day 15 postinoculation. Establishment of C. albicans infection was evaluated on days 2 and 15 after inoculation. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results showed that stress exacerbates C. albicans infection in the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by hyphae were found in stressed rats compared to the nonstressed ones. Treatment with fluoxetine significantly reversed these adverse effects of stress. Besides the psychopharmacological properties of fluoxetine against stress, it has consequences for Candida infection.

Identification of polymeric procyanidins from pine bark by mass spectrometry.

Pine bark is an important source of polyphenolic compounds, mainly procyanidins, with reported protective effects against disease. In previous works, barks of two varieties of pine (P. pinaster and P. radiata) were extracted with ethanol, and partially purified to obtain the aqueous fractions (FA), that contained mainly polymeric procyanidins. The mean degree of polymerization was 7.9 for radiata (rFA) and 10.6 for pinaster (pFA). FAs were chromatographed on Sephadex LH-20 by using a gradient of methanol, water and acetone, to render a series of sub-fractions. In this work, the procyanidin compositions of these sub-fractions were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The mass spectra of sub-fractions from FA of P. pinaster showed signals of procyanidin polymers up to tridecamers, whereas for those from P. radiata the maximum degree of polymerization was 15. For this latter case, the MALDI-TOF mass spectra detected the presence of prodelphinidins in a small amount.

[Parotid pneumocele in Down's syndrome]. / Neumocele parotídeo en el síndrome de Down.

Pneumoparotiditis is related to the cause of an infrequent increase in the size of the parotid gland due to the entrance of air through the Stenon duct following an increase in the pressure in the oral cavity. It is observed in musicians who play wind instruments, glass blowers, patients undergoing diagnostic or therapeutic techniques, in adolescents that provoke it intentionally, and in mentally handicapped people as found in the clinical case reported here. The symptoms are usually non-specific and the diagnosis is confirmed with an axial tomography. The interest in this clinical case lies in the peculiar form of presentation and its diagnostic confirmation through the use of CT imaging.

Neumocele parotídeo en el síndrome de Down / Parotid pneumocele in Down's syndrome

La neumoparotiditis supone una causa infrecuente de aumento de tamaño de la glándula parótida debido a la entrada de aire por el conducto de Stenon secundaria al incremento de presión en la cavidad oral. Se observa en músicos de instrumentos de viento, sopladores de vidrio, pacientes sometidos a técnicas diagnósticas y/o terapéuticas y, de forma intencionada, en adolescentes y disminuidos psíquicos, como en el caso clínico que presentamos. La clínica suele ser inespecífica y el diagnóstico se confirma mediante tomografía computarizada. El interés del caso clínico radica en la particular forma de presentación y la confirmación diagnóstica mediante la imagen de la tomografía

Pneumoparotiditis is related to the cause of an infrequent increase in the size of the parotid gland due to the entrance of air through the Stenon duct following an increase in the pressure in the oral cavity. It is observed in musicians who play wind instruments, glass blowers, patients undergoing diagnostic or therapeutic techniques, in adolescents that provoke it intentionally, and in mentally handicapped people as found in the clinical case reported here. The symptoms are usually non-specific and the diagnosis is confirmed with an axial tomography. The interest in this clinical case lies in the peculiar form of presentation and its diagnostic confirmation through the use of CT imaging

Effects of amphetamine and cocaine on the development of acute experimental allergic encephalomyelitis in Lewis rats.

The present experiment deals with the effects of amphetamine and cocaine on the development and course of experimental allergic encephalomyelitis (EAE) induced in Lewis rats. Rats were immunized at the age of eight weeks with purified myelin basic protein isolated from guinea pig brain in complete Freund's adjuvant. Drug administration and recording of EAE clinical signs was performed daily since day 1 post-immunization (PI). On day 14 and 28 PI, six rats per group were bled and sacrificed. Spinal cord was examined histologically for EAE lesions. In vivo administration of 0.5 and 1 mg/Kg of amphetamine or cocaine resulted in a dose-related enhancement of neurological and histological signs of acute EAE in comparison with control rats. Both drugs caused a reduction of latent period together with a delayed regression of neurological signs along with an increase in inflammation in the central nervous system in comparison with placebo. Human & Experimental Toxicology (2007) 26, 637-643.

Effects of fluoxetine on cellular immune response in stressed mice.

We studied the effects of fluoxetine, a non-tricyclic antidepressant drug that selectively inhibits re-uptake of serotonin by presinaptic neurons in the brain, on cellular immune responses in mice exposed to a chronic auditory stressor. The natural killer (NK) cell activity was reduced after 4, 8, 12, 16 and 20 days of stress exposure with a partial recovery on days 16 and 20. Daily treatment with fluoxetine partially reversed these adverse effects of stress in a dose-dependent manner. Significant differences appeared when fluoxetine was administered at 2 mg/kg and maximum effect was reached at doses of 5 mg/kg. The capacity of T cells to generate cytotoxic T-lymphocytes (CTL) in mixed lymphocyte cultures and in vivo was reduced after 4 days of stress application and this effect was partially reduced when mice were injected with 5 mg/kg of fluoxetine. Nevertheless, in our experiments, fluoxetine did not significantly affect the cellular immunity in unstressed mice. In conclusion, fluoxetine seems to partially recover the adverse effects of chronic stress on cellular immune response.