Mesenchymal Lineage Heterogeneity Underlies Nonredundant Functions of Pancreatic Cancer-Associated Fibroblasts.

Cancer-associated fibroblast (CAF) heterogeneity is increasingly appreciated, but the origins and functions of distinct CAF subtypes remain poorly understood. The abundant and transcriptionally diverse CAF population in pancreatic ductal adenocarcinoma (PDAC) is thought to arise from a common cell of origin, pancreatic stellate cells (PSC), with diversification resulting from cytokine and growth factor gradients within the tumor microenvironment. Here we analyzed the differentiation and function of PSCs during tumor progression in vivo. Contrary to expectations, we found that PSCs give rise to a numerically minor subset of PDAC CAFs. Targeted ablation of PSC-derived CAFs within their host tissue revealed nonredundant functions for this defined CAF population in shaping the PDAC microenvironment, including production of specific extracellular matrix components and tissue stiffness regulation. Together, these findings link stromal evolution from distinct cells of origin to transcriptional heterogeneity among PDAC CAFs and demonstrate unique functions for CAFs of a defined cellular origin. SIGNIFICANCE: By tracking and ablating a specific CAF population, we find that a numerically minor CAF subtype from a defined cell of origin plays unique roles in establishing the pancreatic tumor microenvironment. Together with prior studies, this work suggests that mesenchymal lineage heterogeneity and signaling gradients diversify PDAC CAFs.See related commentary by Cukierman, p. 296.This article is highlighted in the In This Issue feature, p. 275.

RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair.

Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair and damage tolerance pathways in which gap-filling DNA synthesis is required. In this work, we show that human Polλ is conjugated with Small Ubiquitin-like MOdifier (SUMO) proteins both in vitro and in vivo, with Lys27 being the main target of this covalent modification. Polλ SUMOylation takes place in the nuclear pore complex and is mediated by the E3 ligase RanBP2. This post-translational modification promotes Polλ entry into the nucleus, which is required for its recruitment to DNA lesions and stimulated by DNA damage induction. Our work represents an advance in the knowledge of molecular pathways that regulate cellular localization of human Polλ, which are essential to be able to perform its functions during repair of nuclear DNA, and that might constitute an important point for the modulation of its activity in human cells.

Fibroblast Heterogeneity in the Pancreatic Tumor Microenvironment.

The poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) impels an improved understanding of disease biology to facilitate the development of better therapies. PDAC typically features a remarkably dense stromal reaction, featuring and established by a prominent population of cancer-associated fibroblasts (CAF). Genetically engineered mouse models and increasingly sophisticated cell culture techniques have demonstrated important roles for fibroblasts in PDAC progression and therapy response, but these roles are complex, with strong evidence for both tumor-supportive and tumor-suppressive or homeostatic functions. Here, we review the recent literature that has improved our understanding of heterogeneity in fibroblast fate and function in this disease including the existence of distinct fibroblast populations, and highlight important avenues for future study. SIGNIFICANCE: Although the abundant stromal reaction associated with pancreatic cancer has long been appreciated, the functions of the CAF cells that establish this stromal reaction remain unclear. An improved understanding of the transcriptional and functional heterogeneity of pancreatic CAFs, as well as their tumor-supportive versus tumor-suppressive capacity, may facilitate the development of effective therapies for this disease.

Quercetin repressed the stress response factor (sigB) and virulence genes (prfA, actA, inlA, and inlC), lower the adhesion, and biofilm development of L. monocytogenes.

The present study explored the effect of quercetin on the expression of virulence genes actA, inlA, inlC, and their regulatory components, sigB and prfA, in L. monocytogenes. Furthermore, the physicochemical changes on the surface, membrane permeability, and biofilm formation of quercetin-treated bacteria were evaluated. An inhibitory dose-dependent effect of quercetin (0.1-0.8 mM) was observed on the cell attachment on stainless steel at 2 and 6 h at 37 °C. Quercetin at 0.8 mM prevented the biofilm formation on stainless steel surfaces after 6 h of incubation at 37 °C, while the untreated bacteria formed biofilms with a cell density of 5.1 Log CFU/cm2. The microscopic analysis evidenced that quercetin at 0.2 mM decreased the biovolume and covered area of the attached micro-colonies. Also, sigB, prfA, inlA, inlC, and actA genes were downregulated by 7-29 times lower compared to untreated bacteria. In addition, quercetin decreased the superficial cell charge, increased the membrane permeability, and its surface hydrophobicity. These results demonstrated that quercetin prevented biofilm formation, repressed the genes of stress and virulence of L. monocytogenes and also altered the physicochemical cell properties.

A Molecular Reporter for Monitoring Autophagic Flux in Nervous System In Vivo.

The relevance of autophagy in neuronal health has been extensively reported in a plethora of conditions affecting the nervous system, such as neurodegenerative diseases, cancer, diabetes, and tissue injury, where altered autophagic activity may contribute to the pathological process. Autophagy is a dynamic pathway involving the formation of a membrane surrounding and enclosing cargoes that are delivered to lysosomal compartments for degradation. Cargoes can include large protein aggregates, organelles, or even pathogens. Traditionally, autophagy assessment relies on the measurement of LC3-II protein levels or the visualization of LC3-positive puncta. However, these approaches represent a static measurement of autophagy markers, making difficult the dissection of the actual changes in the autophagy process (activation, inhibition, or no effects), due to the dynamic regulation of LC3 viral levels. To circumvent this limitation, we previously developed an adeno-associated vector (AAV) to deliver a molecular autophagy sensor to the neuronal compartment in vivo. Here, we describe the detailed design and methods to use an engineered AAV harboring the monomeric tandem mCherry-GFP-LC3 to determine autophagic fluxes in the nervous system. Key methodological details to succeed in the use of this reporter are provided.

Decoding astrocyte heterogeneity: New tools for clonal analysis.

The importance of astrocyte heterogeneity came out as a hot topic in neurosciences especially over the last decades, when the development of new methodologies allowed demonstrating the existence of big differences in morphological, neurochemical and physiological features between astrocytes. However, although the knowledge about the biology of astrocytes is increasing rapidly, an important characteristic that remained unexplored, until the last years, has been the relationship between astrocyte lineages and cell heterogeneity. To fill this gap, a new method called StarTrack was recently developed, a powerful genetic tool that allows tracking astrocyte lineages forming cell clones. Using StarTrack, a single astrocyte progenitor and its progeny can be specifically labeled from its generation, during embryonic development, to its final fate in the adult brain. Because of this specific labeling, astrocyte clones, exhibiting heterogeneous morphologies and features, can be easily analyzed in relation to their ontogenetic origin. This review summarizes how astrocyte heterogeneity can be decoded studying the embryonic development of astrocyte lineages and their clonal relationship. Finally, we discuss about some of the challenges and opportunities emerging in this exciting area of investigation.

Damage response involves mechanisms conserved across plants, animals and fungi.

All organisms are constantly exposed to adverse environmental conditions including mechanical damage, which may alter various physiological aspects of growth, development and reproduction. In plant and animal systems, the damage response mechanism has been widely studied. Both systems posses a conserved and sophisticated mechanism that in general is aimed at repairing and preventing future damage, and causes dramatic changes in their transcriptomes, proteomes, and metabolomes. These damage-induced changes are mediated by elaborate signaling networks, which include receptors/sensors, calcium (Ca(2+)) influx, ATP release, kinase cascades, reactive oxygen species (ROS), and oxylipin signaling pathways. In contrast, our current knowledge of how fungi respond to injury is limited, even though various reports indicate that mechanical damage triggers reproductive processes. In fungi, the damage response mechanism has been studied more in depth in Trichoderma atroviride. Interestingly, these studies indicate that the mechanical damage response involves ROS, Ca(2+), kinase cascades, and lipid signaling pathways. Here we compare the response to mechanical damage in plants, animals and fungi and provide evidence that they appear to share signaling molecules and pathways, suggesting evolutionary conservation across the three kingdoms.

Measurement of autophagy flux in the nervous system in vivo.

Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases. Moreover, strategies to modulate autophagy have been shown to provide protection against neurodegeneration. Here we describe a novel and simple strategy to express an autophagy flux reporter in the nervous system of adult animals by the intraventricular delivery of adeno-associated viruses (AAV) into newborn mice. Using this approach we efficiently expressed a monomeric tandem mCherry-GFP-LC3 construct in neurons of the peripheral and central nervous system, allowing the measurement of autophagy activity in pharmacological and disease settings.

Loss of PKCδ results in characteristics of Sjögren's syndrome including salivary gland dysfunction.

OBJECTIVES: Chronic infiltration of lymphocytes into the salivary and lacrimal glands of patients with Sjögren's syndrome (SS) leads to destruction of acinar cells and loss of exocrine function. Protein kinase C-delta (PKCδ) is known to play a critical role in B-cell maintenance. Mice in which the PKCδ gene has been disrupted have a loss of B-cell tolerance, multiple organ lymphocytic infiltration, and altered apoptosis. To determine whether PKCδ contributes to the pathogenesis of SS, we quantified changes in indicators of SS in PKCδ-/- mice as a function of age. Salivary gland histology, function, the presence of autoantibodies, and cytokine expression were examined. MATERIALS AND METHODS: Submandibular glands were examined for the presence of lymphocytic infiltrates, and the type of infiltrating lymphocyte and cytokine deposition was evaluated by immunohistochemistry. Serum samples were tested by autoantibody screening, which was graded by its staining pattern and intensity. Salivary gland function was determined by saliva collection at various ages. RESULTS: PKCδ-/- mice have reduced salivary gland function, B220+ B-cell infiltration, anti-nuclear antibody production, and elevated IFN-γ in the salivary glands as compared to PKCδ+/+ littermates. CONCLUSIONS: PKCδ-/- mice have exocrine gland tissue damage indicative of a SS-like phenotype.

Loss of flower bud vigour in the Mediterranean shrub, Cistus albidus L. at advanced developmental stages.

To better understand aging in perennials, age-related changes in the physiology of leaves and flower buds of the Mediterranean shrub, Cistus albidus L. were evaluated. Two groups of different ages (5 and 10 years old), both at advanced developmental stages but of similar size, were compared. Total plant biomass, biomass produced per apical meristem and levels of cytokinins, abscisic acid and jasmonic acid in leaves and flower buds, as well as flower production, were measured. No differences in plant size, vegetative growth rates and levels of phytohormones in leaves were observed between 5- and 10-year-old plants. However, they showed significant differences in flower bud development; the older plants having reduced vigour, with 29.6% of flowers reaching anthesis compared to 52.5% in the younger plants. Furthermore, endogenous concentrations of zeatin and abscisic acid in flower buds at stage I (start of flower organ formation) were 61% and 41%, respectively, smaller in 10- than in 5-year-old plants. At stage II (with all flower organs formed), zeatin and abscisic acid concentrations decreased by ca. 90% and 80%, respectively, but differences between age groups were still evident (60% and 29% for zeatin and abscisic acid, respectively). Jasmonic acid levels in flower buds decreased by 80% from stage I to II, but did not differ between age groups. Despite reductions in flower bud vigour, total number of flowers per individual was not significantly different between age groups, so that an age-related loss in reproductive vigour at the organ level did not lead to a decrease in flower production at the whole plant level.

Meristem aging is not responsible for age-related changes in growth and abscisic acid levels in the Mediterranean shrub, Cistus clusii.

To obtain new insights into the mechanisms underlying aging in perennials, we measured abscisic acid levels, growth and other stress indicators in leaves of Cistus clusii Dunal plants of different ages grown under Mediterranean field conditions. Recently emerged leaves from 9-year-old plants were compared to those of 1-year-old plants (obtained from cuttings from 9-year-old plants) to evaluate the effects of meristem aging on plant aging. Rooting and successful establishment of the cuttings allowed us to compare the physiology of plants with old meristems, but of different size. Plants obtained from cuttings were rejuvenated, with new leaves displaying a higher leaf area and chlorophyll content, but smaller leaf mass per unit area ratios and endogenous abscisic acid levels than those of 9-year-old plants. A comparative study in 1-, 4- and 9-year-old plants revealed that abscisic acid levels increase during the early stages of plant life (with increases of 90% between 1- and 4-year-old plants), but then remain constant at advanced developmental stages (between 4- and 9-year-old plants). Although leaf biomass was 53% smaller in 9-year-old compared to 4-year-old plants, the dry matter produced per shoot apical meristem was equivalent in both plant groups due to an increased number of leaves per shoot in the former. It is concluded that (i) C. clusii plants maintain the capacity to rejuvenate for several years; (ii) newly emerged leaves accumulate higher amounts of abscisic acid during early stages of plant life, but the levels of this phytohormone later remain constant; and (iii) although plant aging leads to the production of smaller leaves, the amount of biomass produced per shoot apical meristem remains constant at advanced developmental stages.

Descenso ponderal y calidad de vida mediante la cirugía de Bypass gástrico con y sin anillo de calibración / Weight loss in patients subjected to gastric bypass with or without calibration ring

Hay evidencias de que en la técnica habitual de bypass gástrico, la gastroyeyunostomía se puede dilatar. Por esta razón la técnica de bypass de Capella y Fobi, incluye la instalación de una banda de silastix u otro material alrededor del bolsillo gástrico, con el objeto de evitar que la pasada se dilate y permita una ingesta más rápida y abundante. El objetivo de este estudio prospectivo es comparar bypass gástrico con bypass gástrico anillado, en cuanto a baja de peso y calidad de vida. Material y Método: Seleccionamos 244 pacientes con bypass anillado (Grupo A) y 194 sin anillo (Grupo B). Los dos grupos son clínicamente comparables. Se analizó el por ciento de baja de exceso de peso ( por ciento EWL) a los 3, 6, 12, 18, 24 y 36 meses. Se consideró significativo p<0,05, con prueba t de Student. Se controlaron las comorbilidades y se efectuó encuesta BAROS II, para calidad de vida. Resultados: A veinticuatro meses el por ciento EWL es de 80,5 y 69,6 y respectivamente, y a los 36 meses 81 y 63,9, diferencias significativas entre ambos grupos. Encuesta BAROS II es similar en los grupos. En grupo A se mantuvo por más tiempo un grado de disfagia. En grupo B, hubo más estenosis de gastroyeyunoanastomosis. Conclusiones: EWL es mejor en el largo plazo en los pacientes con bypass anillado, en cuanto a la baja de peso y tienen menos estenosis porque permiten hacer una gastroenteroanastomosis más amplia ya que la calibración está dada por el anillo. La calidad de vida y corrección de comorbilidades, son similares en ambos grupos.

Background: In gastric bypass, the diameter of gastrojejunal anastomosis may increase with time. It is not clear if a higher weight reduction can be achieved if a ring is added to the pouch. Aim: To compare the results of gastric bypass with and without the addition of a ring. Material and methods: Prospective study of patients subjected to gastric bypass using Capella and Fobi technique. In a group of 244 patients (201 women), operated in one surgical center, a 6 cm ring was attached around the gastric pouch. In 194 patients (163 women) operated in other two centers, the ring was not used. Patients were followed for 36 months. Excess weight loss (EWL) and quality of life using BAROS II score were evaluated in both groups. Results: EWL at 24 months were 80.8 + 17 and 69.6 + 19 percent in groups with and without ring, respectively (p < 0.05). The figures at 36 months were 81+16 and 71.9 + 14 percent, respectively (p <0.05). Strictures of thegastrojejunal anastomosis were observed in 12 patients without ring (6.1 percent) and in 2 patients with ring (0.8 percent). Patients with ring had higher rates of disphagia. Quality of life scores were similar in both groups. Conclusions: Patients with banded bypass had a higher weight loss but a higher frequency of disphagia. Patients without band had a higher frequency of gastrojejunal anastomosis strictures.

[Is efalizumab a safe treatment for a chronic disease?]. / Efalizumab: un tratamiento seguro para una enfermedad crónica?

Psoriasis is a chronic disease that has a very negative impact on the quality of life of those suffering it. Therefore, treatments that make it possible to satisfactorily control the disease in the long term and maintain a good safety profile are needed. Efalizumab fulfills both requirements. In this article, the potential risks involved in treatment with efalizumab, specifically the acute flu-like syndrome, alterations in laboratory data (leukocytosis, lymphocytosis, thrombocytopenia, hemolytic anemia, elevation of alkaline phosphatase and hepatic biochemistry), infections, neoplasms, skin disorders related with psoriasis (localized papular rash, generalized inflammatory rash, changes in the morphology of psoriasis, rebound phenomenon), joint manifestations, acute inflammatory polyradiculoneuropathy and hypersensitivity reactions are reviewed. The contraindications, presence of antiefalizumab antibodies, their drug interactions, use of vaccines and relationship with pregnancy and breast-feeding are also discussed. An adequate selection of the patient, detailed information to the patient on the benefits and risks and correct knowledge of the potential adverse effects by the clinician are essential requirements for satisfactory use of efalizumab in long-term continued therapy.

Experiencia de 10 años con el bypass gástrico / Long term results of gastric bypass for morbid obesity

Introducción: El bypass gástrico es el estándar para el obeso mórbido. Es importante un seguimiento apropiado para conocer su real utilidad. Material y método: 1000 pacientes operados con bypass y seguidos entre Mayo 1996 y Marzo 2006. 545 pacientes tuvieron un seguimiento prolongado, algunos hasta 10 años. Controles de peso periódicos, midiendo el porcentaje de baja del exceso de peso ( por ciento EWL). Evolución de las comorbilidades, complicaciones postoperatorias. Encuesta BAROS II, para la calidad de vida. Resultados: por ciento EWL se estabiliza entre 72 y 79 por ciento entre los 12 y 84 meses. Pero a más largo plazo, a los 120 meses los pocos pacientes que hay recuperan peso, manteniendo el EWL en 55 por ciento. BAROS muestra un 84 por ciento de excelentes y buenos resultados 14 por ciento regular y 2 por ciento disconforme. Complicaciones: Tromboembolismo 0,2 por ciento, hemorragia digestiva 0,3 por ciento (3 casos); uno requirió gastrectomía, filtraciones 2 por ciento (11 casos), 6 requirieron reoperación, un caso de fasceítis necrotizante grave, hemoperitoneo 0,3 por ciento, neumopatía aguda 2 por ciento, un fallecido, por tromboembolismo pulmonar masivo. Infección herida operatoria 1 por ciento. En el largo plazo hernias 4 por ciento, colecistolitiasis 3 por ciento, caída del cabello 15 por ciento, anemia hipocroma 5 por ciento, úlcera de boca anastomótica 2 por ciento, una úlcera perforada, obstrucción intestinal 1,5 por ciento, 3 por estenosis mesocolon, 1 por hernia interna 2 por bridas, 1 por migración anillo de PTFE, 2 migraciones de anillo al interior del estómago. Estenosis de anastomosis gastroyeyunal 2 por ciento. Las complicaciones son más frecuentes en bypass laparoscópico. Reducción comorbilidades cercano 100 por ciento. Conclusiones: La evolución del peso es excelente en el bypass, pero hay una tendencia a recuperar peso en el largo plazo, especialmente en los pacientes que no se someten a control periódico. Las comorbilidades y la...

Background: Gastric bypass is the standard surgical procedure for morbid obesity. Aim: To evaluate long term results of gastric bypass. Patients and methods: Prospective follow up of 1000 consecutive patients (800 women) subjected to gastric bypass between May 1996 and March 2006. A long term follow up was achieved in 545 patients. Percentage of excess weight loss ( percent EWL), postoperative complications and evolution of complications associated to obesity were studied. Quality of life was assessed using the BAROS II test . Results: percent EWL stabilizes in a range from 72 to 79 percent and between 12 to 84 months after operation. However, patients followed for 120 months, gain weight and percent EWL is reduced to 55 percent. According to BAROS II, 84 percent of patients considered results as excellent or good, 14 percent considered results regular and 2 percent were dissatisfied with surgical outcome. Complications recorded were thromboembolism in 0.5 percent, gastrointestinal bleeding in 0.1 percent, leaks in 2 percent, necrotizing fasciitis in 0.1 percent, hemoperitoneum in 0.3 percent acute pneumonia in 2 percent and wound infection in 1 percent. One patient died due to a massive pulmonary embolism. As late complications, hernias appeared in 4 percent, cholelithiasis in 3 percent, hair loss in 15 percent, hypocromic anemia 5 percent, anastomotic ulcers in 2 percent, intestinal Obstruction in 1.5 percent, PTFE ring migration and anastomosis obstruction in 2 percent. Complications were more common in laparoscopic bypass. In all patients there was a reduction of complications associated to obesity. Conclusions: percent EWL is excellent with gastric bypass, but there is weight gain in the long term follow up. Complications associated to obesity are almost always corrected.

Plasma trough levels of mycophenolic acid do not correlate with efficacy and safety of mycophenolate mofetil in psoriasis.

BACKGROUND: Mycophenolate mofetil (MMF) has been shown to be effective for systemic treatment of psoriasis. MMF is the prodrug of mycophenolic acid (MPA), the pharmacologically active compound. The measurement of plasma MPA levels could be useful for optimizing therapeutic management using MMF. OBJECTIVES: To investigate whether plasma trough levels of MPA correlate with the efficacy and safety of oral MMF in the treatment of patients with psoriasis. METHODS: Six patients (four women and two men, mean age 58 years) with severe chronic plaque-type psoriasis were treated with oral MMF 1 g twice daily. The Psoriasis Area and Severity Index (PASI), routine laboratory examinations and plasma MPA trough levels, measured by an enzyme-multiplied immunoassay (EMIT), were determined at 2 weeks and 1, 3, 5 and 7 months. RESULTS: All the patients experienced a marked improvement within the first 15 days and continued to do so for 5-7 months. Two patients achieved complete remission. MMF was well tolerated. MPA levels showed a wide intra- and interindividual variability. There was no significant correlation between MPA trough levels and the reduction of the PASI or the presence of adverse effects, but a good correlation with therapeutic compliance. CONCLUSIONS: The monitoring of MPA trough levels with EMIT appears to be a poor predictor of efficacy or toxicity. In contrast, it is a useful tool to evaluate the degree of therapeutic compliance.

Evolution of synaptic body numbers in the pineal gland of the cat over a 24-hour period in spring / Evolución del número de cuerpos sinápticos en la glándula pineal del gato en un periodo de 24 horas en primavera: análisis descriptivo, morfométrico y estadístico

Eighteen cross-bred male cats (2650±750 g) were kept for three weeks with environmental lighting and under the same feeding (ad libitum) and temperature conditions (18-22°C). The animals were sacrificed in the spring in groups of three at 4 h intervals with the following GMT time sequence: 06:00, 10:00, 14:00, 18:00, 22:00, and 02:00 hours. During the circadian cycle, significant variations were observed in the number of synaptic ribbons and synaptic spherules in the pineal glands of the animals, with maximum and minimum values at 02:00 and 14:00 hours, and at 10:00 and 02:00 hours, respectively. Analysis of variance (ANOVA) showed these differences to be statistically significant (F-ratio: 43.513; p<0.0001 for synaptic ribbons, and F-ratio: 6.0; p<0.005 for synaptic spherules). The number of synaptic ribbons was found to be significantly higher (p<0.0001) at night (67.3%) than in the daytime (32.6%), while the number of synaptic spherules was 59.1% and 40.8% in the daytime and at night, respectively. The polynomial correlation between the evolution of the synaptic ribbons and the time point was very positive (R = 0.8). The circadian variations observed in the intermediate synaptic bodys (ISBS) population were not significant, either for triangular synaptic bodies (TSB) (p<0.07) or for rectangular synaptic bodies (RSB) (p<02). Finally, the total number of synaptic ribbons observed in the photophase merged to form "fields" of three or more elements. These fields were more commonly observed in pinealocyte prolongations than in areas close to the nucleus (AU)

Se mantuvieron dieciocho gatos machos de cepa cruzada (2650ñ750 g) durante tres semanas con luz ambiental y bajo las mismas condiciones de alimentación (ad libitum) y temperatura (18-22º C). Los animales fueron sacrificados en primavera en grupos de tres a intervalos de 4 horas en las siguientes secuencias horarias: 06:00, 10:00, 14:00, 18:00, 22:00 y 02:00 horas. Durante el ciclo circadiano se observaron variaciones significativas en el número de botones sinápticos y esférulas sinápticas en las glándulas pineales de los animales, con valores máximos y mínimos a las 02:00 y 14:00 horas, y a las 10:00 y 02:00 horas, respectivamente. El análisis de la varianza (ANOVA) demostró que estas diferencias fueron estadísticamente significativas (F-ratio: 43.513; p<0.0001 para los botones sinápticos y F-ratio: 6.0; p<0.005 para las esférulas sinápticas). El número de botones sinápticos fue significativamente mayor (p<0.0001) por la noche (67.3 por ciento) que durante el día (32.6 por ciento), mientras que el número de esférulas sinápticas fue del 59.1 por ciento y 40.8 por ciento durante el día y durante la noche, respectivamente. La correlación polinómica entre la evolución de los botones sinápticos y el punto horario fue muy positiva (R = 0.8). Las variaciones circadianas observadas en la población de cuerpos sinápticos intermedios (ISBS) no fueron significativas, bien para los cuerpos sinápticos triangulares (TSB) (p<0.07) o bien para los cuerpos sinápticos rectangulares (RSB) (p<0.2). Finalmente, el número total de botones sinápticos observados en la fase de luz se combinaron para formar "campos" de tres o más elementos. Estos campos se observaron generalmente más en las prolongaciones de los pinealocitos que en las áreas próximas al núcleo (AU)

Tumor carcinoide duodenal / Duodenum carcinoid tumor

El tumor carcinoide duodenal es un tumor infrecuente. Por esta razón es una patología poco conocida por el cirujano general. Sin embargo, se ha observado un aumento de su frecuencia en los últimos 20 años. Es conveniente tener un conocimiento claro sobre la estrategia diagnóstica en las diferentes etapas de la enfermedad. Esto permitiría adecuar la conducta terapéutica a cada caso en particular. Se revisan los casos de tumor carcinoide duodenal entre 1954 y 1997 en el Hospital San Juan de Dios. Se presenta la experiencia con el tratamiento quirúrgico en los dos únicos pacientes portadores de esta lesión, atendidos en los últimos dos años, con un seguimiento postoperatorio de 12 y 30 meses

Litotripsia extracorpórea en litiasis renal: evaluación de resultados en 499 pacientes / Extracorporeal lithotripsy in renal lithiasis: assessment of the results in 499 patients

La litiasis urinaria constituye una patología de alta prevalencia. Los avances más importantes han ocurrido en su tratamiento quirúrgico. Presentamos nuestra experiencia con la aplicación de la tecnología de ondas de choque en 499 pacientes quienes han completado un tiempo mínimo de seguimiento de 3 meses. Su margen de edad fue de 1 a 83 años. En estos pacientes se trataron 619 cálculos de los cuales 72,9 porciento se encontraba en el riñón. Para el tratamiento utilizamos la máquina Sonolith 300 que tiene un sistema de localización con ultrasonido y una generación de la onda de choque de tipo electrohidráulico. En el control alejado 389 pacientes (77,95 porciento) se encontraban libres de cálculos y 41 pacientes (8,25 porciento) con fragmentos de menos de 3 mm. El porcentaje de retratamiento fue de 11,8 porciento. La litotripsia extracorpórea es el tratamiento de elección de la litiasis renal en la mayoría de los pacientes con indicación quirúrgica