Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder.

INTRODUCTION: Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD. METHODS: We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck's Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies. RESULTS: Clinical scores decreased in both groups (p = 0.0001); Beck's presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks. CONCLUSION: Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.

Gastrointestinal neuroendocrine tumor with unresectable liver metastases: an example of multimodal therapeutic approach.

Gastrointestinal neuroendocrine tumors (NET) frequently present with unresectable hepatic metastases, which poses a barrier for curative treatment. Resection of the primary tumor and subsequent orthotopic liver transplantation (OLT) has been proposed as a treatment approach but available data in this regard is limited. We present a clinical case of an otherwise asymptomatic 44-yo man complaining of abdominal pain and dyspepsia that was diagnosed of a 10 cm duodenal tumor with multiple hepatic metastases. A CT-guided biopsy confirmed a NET. He underwent first a Whipple's procedure, and then was listed for liver transplantation. During the waiting time a multimodal therapeutic approach was used including the use of radioactive 177lutetium-labeled somatostatin analogues, long-acting somastostatin analogues and antiangiogenic antibodies (bevacizumab) in order to keep neoplastic disease under control. Two years after Whipple's procedure and given disease stability he underwent OLT with an uneventful postoperative evolution. Patient condition and graft function are optimal after a 4-year follow-up period with no evidence of recurrence. This case report underscores how a multimodal approach involving careful patient selection, resective surgery as well as use of somatostatin analogues and antiangiogenic biological therapy followed by liver transplantation can achieve excellent long-term results in this difficult patient population.

In situ microscopic cytometry enables noninvasive viability assessment of animal cells by measuring entropy states.

Current state of the art to determine the viability of animal cell suspension cultures is based on sampling and subsequent counting using specific staining assays. We demonstrate for the first time a noninvasive in situ imaging cytometry capable of determining the statistics of a morphologic transition during cell death in suspension cultures. To this end, we measure morphometric inhomogeneity--defined as information entropy--in cell in situ micrographs. We found that the cells are partitioned into two discrete entropy states broadened by phenotypical variability. During the normal course of a culture or by inducing cell death, we observe the transition of cells between these states. As shown by comparison with ex situ diagnostics, the entropy transition happens before or while the cytoplasmatic membrane is loosing its ability to exclude charged dyes. Therefore, measurement of morphometric inhomogeneity constitutes a noninvasive assessment of viability in real time.

Aerobic physical training does not condition against strenuous exercise-induced changes in immune function but modulates T cell proliferative responses.

BACKGROUND: Exercise-induced stress induces considerable changes in the immune system. To better understand the mechanisms related to these immune changes during acute and chronic physical stress, we studied the effects of aerobic physical training (APT) on several parameters of the immune system. METHODS: Previously untrained males (18-25 years of age) were divided into a group that was subjected to 6 months of APT (N.=10) and a sedentary control group (N.=7). The subjects performed a cardiopulmonary exercise test (CET) at 0, 3, and 6 months of the APT program. B cell (CD19+), T cell (CD4+ and CD8+), and natural killer cell (CD56+) levels, and mitogen-induced T cell proliferation and cytokine production (interleukin-1, interleukin-4, interleukin-12, and interferon-γ) were evaluated before and at 30 seconds and 24 hours after the CET. RESULTS: There was a significant increase in CD4+ T cells and natural killer cells and a significant reduction in T cell proliferation in both groups 30 seconds after the CET at 0, 3 and 6 months of the APT program. Of note, the trained group showed significantly lower resting T cell proliferation (before and 24 hour after the CET) than the sedentary control groups at 0, 3 and 6 months of the APT program. There were no significant differences in cytokine production after the CET between both groups at any time point of the APT program. CONCLUSIONS: These data show that APT does not condition against strenuous exercise-induced immune changes but significantly modulates T cell proliferative responses.

Changes in regional cerebral blood flow are associated with endothelial dysfunction markers in cocaine-dependent patients under recent abstinence.

OBJECTIVES: Cocaine is a known risk factor for several vascular ischemic events. The underlying mechanisms leading to the complications are not fully understood, although thrombus formation and accelerated atherosclerosis are prominent findings. Evidence of endothelial dysfunction (ED), a key phenomenon in the pathogenesis of atherogenesis, has been demonstrated in cocaine-dependent individuals. Abnormal regional cerebral blood flow (rCBF) is a common finding among chronic cocaine users. The aim of this study was to evaluate whether brain perfusion changes were associated with ED markers in cocaine-dependent individuals. METHODS: Circulating endothelial cells (CECs), soluble intercellular cell adhesion molecule, and the chemokine regulated on activation normal T cells expressed and secreted were measured in 27 DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) cocaine-dependents patients. Regional cerebral blood flow was assessed using single-photon emission computed tomography at baseline (after recent cocaine consumption) and after 4 weeks of strict abstinence under standard benzodiazepine or antipsychotic therapy. We used statistical parametric mapping analysis to evaluate the covariates. RESULTS: Endothelial cell damage/activation markers were significantly higher in cocaine-dependent individuals after recent consumption and were reduced after 1-month abstinence (P < 0.05). Global rCBF exhibited no significant difference between baseline and after abstinence. When regional perfusion was analyzed in association with ED covariates, significant differences were observed in bilateral cortical areas, including the limbic lobes. CONCLUSIONS: We demonstrated an association between systemic ED markers and rCBF in cocaine-dependent patients. These findings suggest that vascular injury may play a role in the pathogenesis of abnormal rCBF.

[Tityus asthenes scorpion stings: epidemiological, clinical and toxicological aspects]. / Picaduras por escorpión Tityus asthenes en Mutatá, Colombia: aspectos epidemiológicos, clínicos y toxinológicos.

INTRODUCTION: Scorpion stings are a public health problem in many countries. However, in Colombia, very few epidemiological, clinical or toxicological studies have been undertaken. OBJECTIVE: Ecological and epidemiological aspects were related to the prevalence of scorpion stings by Tityus asthenes. The clinical features of envenomization were described in patients and in an experimental animal model. MATERIALS AND METHODS: The study was conducted in four localities of Mutatá and Urabá Counties in the province of Antioquia, Colombia. The sample consisted of 1,593 (929 urban, 664 rural) of the 5,305 exposed people, inhabitating 324 households (188 urban (58%); 136 rural (42%) of 1,448 houses total in the study area. An interview survey was performed in every selected family for a more realistic estimate of sting prevalence. Additionally, a prospective study was directed toward patients presenting scorpion stings at care at the local hospital over an 18-month period. RESULTS: The probability was 12.9 times greater of finding T. asthenes inside or around houses in places near to forest and high agrarian plantations (odds ratio = 13). Eighty scorpion stings were reported in the retrospective study (4.1% prevalence [95% CI 3.3-4.8%] ), but only 14 of the patients (17.5%) sought care in the local hospital (an 82.5% underreportage). Seventy percent of the stings occurred in rural places; 50% occurred in the locality of Caucheras, with an attack rate of 10.6%. The overall household infestation rate was 269% (95% CI 22.9-30.8%) and an area dispersion ratio of 100%. Signs of systemic envenomization occurred mainly in children (67%). The 50% lethal dose of T. asthenes venom was 121.6 µg for 18-20 g Swiss Webster rats (95% CI 103.7-139.6). Immunodetection of T. asthenes and Centruroides gracilis/C.margantatus venoms in the experimental animals was possible when were tested by Western blot against Alacramyn (Instituto Bioclón, México) and Soro antiaracnídico (Instituto Butantan, Brasil) antivenoms. Scorpion interspecific differences were noted. CONCLUSIONS: The prevalence of stings by T. asthenes were common and their presence was associated with tropical rainforests. Envenomization at low density can be neutralized efficiently by anti-scorpion antivenoms produced in México and Brazil but with differing specificities for the venom of each scorpion species.

Cervical metastases of glucagonoma in a patient with multiple endocrine neoplasia type 1: report of a case.

Multiple endocrine neoplasia type 1 (MEN 1) is a syndrome characterized by tumors of the parathyroid glands, pancreatic islet cells, duodenum, and pituitary gland. We report a case of cervical metastases of glucagonoma with MEN 1. The patient was a 34-year-old woman admitted to our hospital with epigastric pain. Her medical history included two resections of prolactinoma and two upper GI hemorrhages secondary to duodenal ulcers. Computed tomography (CT) showed two hypervascular lesions in the tail of the pancreas and cervical ultrasound showed multiple hypoechogenic ovoid images in the neck. A cervical CT scan confirmed two 15-mm lymph nodes in the left cervical region and 111In-DOTATOC imaging showed focal abnormal somatostatin expression in the pancreatic tail and the cervical nodes. The patient had asymptomatic hypoglycemic episodes, with blood sugar levels as low as 30 mg/dl, which raised our suspicion of MEN 1 associated with pancreatic insulinoma. Thus, we performed a distal pancreatectomy with bilateral cervical dissection and parathyroid gland resection. Histopathological examination revealed 12 pancreatic tumors as well as metastases in four cervical lymph nodes. The resected parathyroid glands had normal structure, suggesting parathyroid hyperplasia. A follow-up CT scan, 18 months after surgery, showed new tumors in the head of the pancreas and in the duodenal wall. A pancreatoduodenectomy was performed and histopathological examination revealed nine nonfunctioning endocrine tumors in the pancreas, one tumor in the duodenal wall, and metastases in two peripancreatic lymph nodes. The patient recovered well and remains asymptomatic.

A novel, inexpensive method of image coregistration for applications in image-guided surgery using augmented reality.

OBJECTIVE: Augmented reality (AR) is a technique in which an overlay of a virtual image to a live picture is performed to create a new image in which both original images coexist as a single image. This results in the visualization of internal structures through overlying tissues. The objective was to describe an easy, inexpensive, and successful method to coregister with AR in an image-guided surgery setting using the resources at hand. METHODS: Cortical information was obtained with a volumetric acquisition of 200 0.8-mm thick, cerebral magnetic resonance imaging scans in an axial T1-weighted sequence. For the venous anatomy, a contrast phase at 7 mm/s velocity was used. This data was reconstructed in a three-dimensional fashion using MRIcro software (v. 1.37, freeware, courtesy of Chris Rorden) and was overlaid to a digital image of the cerebral cortex either pre- or intraoperatively. RESULTS: Eight patients were studied. There was an adequate coregistration in seven of the patients as confirmed by intraoperative ultrasound, frame-based stereotaxy, or obvious anatomic homology between the three-dimensional magnetic resonance imaging scan virtual reconstruction and the live image obtained during surgery. AR was not possible in one case of a cerebellar lesion. CONCLUSION: AR coregistration capabilities are adequate when revised by other intraoperative guidance devices. When performed with "freeware" software and conventional digital cameras, it is relatively inexpensive, which makes it a potential tool for surgical planning and noncontinuous intraoperative guidance in neurosurgery. Its largest drawbacks are the inability to function in deep-seated lesions and its lack of tracking devices, which gives it a noncontinuous coregistration nature.

Efectos inhibitorios de compuestos fenólicos de plantas sobre la actividad enzimática y citotoxica inducida por una fosfolipasa A2 de veneno de serpiente / Inhibitory effects of plant phenolic compounds on enzymatic and cytotoxic activities induced by a snake venom phospholipase A2

Los compuestos fenólicos han mostrado inhibir los efectos tóxicos inducidos por proteínas de veneno de serpiente. En éste trabajo, nosotros demostramos que el ácido gálico, el ácido ferúlico, el ácido cafeico, el propilgalato y el epigalocatequingalato inhiben la actividad enzimática de una fosfolipasa A2 (PLA2) usando yema de huevo como sustrato. Los valores de IC50 están entre 0,38 – 3,93 mM. Los compuestos mencionados también inhiben la actividad enzimática cuando un sustrato sintético es usado. Además, estos compuestos polifenólicos disminuyen el efecto citotóxico inducido por la fosfolipasa A2 miotóxica, el epigalocatequingalato exhibe la mejor capacidad inhibitoria con 90,92 ± 0,82%, mientras que el ácido ferúlico muestra la menor actividad inhibitoria con 30,96 ± 1,42%. Con el fin de determinar los posibles mecanismos de acción de los compuestos fenólicos, realizamos estudios de modelamiento molecular. Todos los polifenoles muestran puentes de hidrogeno con el sitio activo de la enzima; además el epigalocatequingalato presenta una unión más fuerte con la PLA2 que los otros compuestos. Adicionalmente, un análisis preliminar de relación estructura actividad muestra una correlación entre los valores de IC50 y el área superficial polar topológica (p = 0,0491, r = -0,8079 (-0,9878 a -0,2593)), la cual indica el área superficial requerida por cada molécula para unirse a la enzima. Además, nuestros resultados muestran al propilgalato y el epigalocatequingalato como dos nuevos productos naturales con potencial antimiotóxico. La aplicación tópica de estos polifenoles en el sitio de mordedura podría llevar a la prevención de la miotoxicidad; sin embargo, posteriores investigaciones in vivo serían necesarias para confirmar los resultados in vitro.

Picaduras por escorpión Tityus asthenes en Mutatá, Colombia: aspectos epidemiológicos, clínicos y toxinológicos / Tityus asthenes scorpion stings: epidemiological, clinical and toxicological aspects

Introducción. El escorpionismo afecta a países tropicales como Colombia.Objetivo. Determinar los indicadores ecológicos y epidemiológicos de las picaduras por Tityus asthenes en cuatro localidades de Mutatá, Colombia, y las características clínicas del envenenamiento y toxinológicas del veneno. Materiales y métodos. Es un estudio prospectivo/retrospectivo descriptivo y experimental; se visitaron aleatoriamente 324 de las 1.448 viviendas del municipio: 188 urbanas (58,0%) y 136 rurales (42,0%), con 1.593 habitantes. En 18 meses se estudiaron prospectivamente los pacientes picados por T. asthenes que ingresaron al hospital local y, retrospectivamente en encuestas domiciliarias, se determinó el subregistro. Se recolectaron escorpiones vivos y se realizaron experimentos con el veneno. Resultados. Hubo 12,9 más probabilidades de hallar ejemplares de T. asthenes en el área rural (OR=6,5; IC95% 3,9-10,8), en el intradomicilio y peridomicilio cercano a bosques y plantaciones agrarias altas (OR=13,0; IC95% 7,5-23,0). Se reportaron 80 picaduras ocurridas en los dos últimos años (prevalencia de 4,1%; IC95% 4,8-3,3); sólo 14 personas (17,5%) consultaron al hospital (subregistro de 82,5%). La prevalencia ponderada de infestación por escorpiones en las viviendas encuestadas fue de 26,9% (112 casas) (IC95% 30,8-22,9). El 50% de los accidentes ocurrió en la localidad de Caucheras: 10,6% de proporción de ataque. El envenenamiento sistémico fue más frecuente en niños (67%). La dosis letal 50 del veneno en ratones de 18 a 20 g, fue 121,6 μg (IC95% 103,7-139,6). Hubo reactividad inmunológica por Western blot de los antivenenos del Instituto Bioclón, México (Alacramyn®) y del Instituto Butantan, Brasil (Soro antiaracnídico®)...

Introduction. Scorpion stings are a public health problem in many countries. However, in Colombia, very few epidemiological, clinical or toxicological studies have been undertaken. Objective. Ecological and epidemiological aspects were related to the prevalence of scorpion stings by Tityus asthenes. The clinical features of envenomization were described in patients and in an experimental animal model. Materials and methods. The study was conducted in four localities of Mutatá and Urabá Counties in the province of Antioquia, Colombia. The sample consisted of 1,593 (929 urban, 664 rural) of the 5,305 exposed people, inhabitating 324 households (188 urban (58%); 136 rural (42%) of 1,448 houses total in the study area. An interview survey was performed in every selected family for a more realistic estimate of sting prevalence. Additionally, a prospective study was directed toward patients presenting scorpion stings at care at the local hospital over an 18-month period. Results. The probability was 12.9 times greater of finding T. asthenes inside or around houses in places near to forest and high agrarian plantations (odds ratio=13). Eighty scorpion stings were reported in the retrospective study (4.1% prevalence [95% CI 3.3-4.8%] ), but only 14 of the patients (17.5%) sought care in the local hospital (an 82.5% underreportage). Seventy percent of the stings occurred in rural places; 50% occurred in the locality of Caucheras, with an attack rate of 10.6%. The overall household infestation rate was 269% (95% CI 22.9-30.8%) and an area dispersion ratio of 100%. Signs of systemic envenomization occurred mainly in children (67%). The 50% lethal dose of T. asthenes venom was 121.6 μg for 18-20 g Swiss Webster rats (95% CI 103.7-139.6). Immunodetection of T. asthenes and Centruroides gracilis/C.margantatus venoms in the experimental animals was possible when were tested by Western blot against Alacramyn® (Instituto Bioclón, México) and Soro antiaracnídico®...

Evaluación fitoquímica preliminar de Heliconia psittacorum y Heliconia rostrata y de la potencial actividad inhibitoria de algunos de los efectos del veneno de Bothrops asper (mapaná X) / Preliminary phytochemistry assessment of Heliconia psittacorum and Heliconia rostrata and the potential inhibitory activity of some effects of the Bothrops asper (mapaná X) venom

Algunas especies de la familia Heliconaceae han demostrado capacidad neutralizante parcial/total de las actividades letal, hemolítica indirecta, hemorrágica, proteolítica, coagulante, mionecrosante y edematizante del veneno de Bothrops asper (mapaná equis). Este trabajo evalúa dos especies de heliconias: Heliconia psittacorum y Heliconia rostrata, contra las actividades hemolítica indirecta, proteolítica y coagulante del veneno de B. asper, sin que ninguna de ellas ejerza inhibición sobre la actividad hemolítica indirecta y proteolítica. Por el contrario, sus extractos retardan el efecto coagulante del veneno con respecto al controlpositivo hasta 45.59 segundos. Al realizar el perfil electroforético, se observa una banda perteneciente al extracto de H. psittacorum, y además se evidencia disminución y aumento en la intensidad de algunas bandas (66 y 31 KDa respectivamente), que pueden indicar una posible degradación por parte de los extractos. La evaluación fitoquímica de los extractos muestra la presencia de metabolitos primarios de carácter glúcido y protéico; y secundarios como compuestos fenólicos, terpenoides y cumarinas, algunos de los cuales han sido reportados en otras especies vegetales como responsables de la actividad antiofídica.

Inhibición de las actividades proteolítica, coagulante y hemolítica indirecta inducidas por el veneno de Bothrops asper por extractos etanólicos de tres especies de heliconias / Inhibition of proteolitic, coagulant and indirect hemolytic activity induced by Bothrops asper venom for ethanolic extracts from three species of Heliconias

En Colombia Bothrops asper (mapaná) es la especie causante del 70 al 90 por ciento de los cerca de 3.000 accidentes ofídicos informados cada año. Durante varios siglos, la medicina tradicional ha utilizado plantas para el tratamiento de la mordedura de serpiente. En nuestro país, el 60 por ciento de las mordeduras son atendidas inicialmente por curanderos o chamanes, que usan al menos 100 especies de plantas medicinales en diferentes formas, de acuerdo al estado clínico del paciente. En este estudio se evaluó la capacidad inhibitoria de tres especies de la familia Heliconiaceae, H. latispatha Benth, H. wagneriana Petersen y H. curtispatha Petersen, sobre los efectos proteolítico, coagulante y hemolítico indirecto inducido por el veneno de Botrhops asper. La primera indujo un mayor porcentaje de inhibición del efecto hemolítico indirecto del veneno de B. asper que la Heliconia wagneriana, así como una reducción en la intensidad en las proteínas del veneno con masa molecular de 14 KDa, mientras que el extracto de la segunda planta mostró una mayor inhibición del efecto proteolítico inducido por el veneno de B. asper, así como mayores cambios en las bandas de proteína del veneno con masas moleculares entre 95 y 110 KDa. El extracto de Heliconia curtispatha, mostró la mayor capacidad inhibitoria de los efectos hemolítico, proteolítico y coagulante; además indujo una degradación de todas las proteínas del veneno completo de B. asper, como había sido reportado previamente

Establecimiento de suspensiones celulares de Bixa orellana L. productoras de compuestos fenólicos, potencialmente antiofídicos / Celular suspensions establishment of Bixa orellana L., fenolics compounds producers with potential antiophidic activity

Se ha desarrollado un protocolo para la producción y masificación de células de achiote en suspensión, a partir de callos friables obtenidos de tejidos de hojas, como estrategia para la obtención de metabolitos antiofídícos, especialmente compuestos fenólicos, y para ello se ha evaluado el efecto de las concentraciones de inóculo, glucosa, fósforo y nitrógeno sobre la cinética de crecimiento celular, en el medio ½MS+2,4-D (5 ppm)+BAP (1 ppm), almacenados a 25º C, en oscuridad y a 140 rpm, utilizando un diseño factorial completamente aleatorizado de cuatro factores y dos niveles, con evaluación a los 20 y 40 días de establecimiento. El tratamiento que presenta la mayor producción de biomasa de células de achiote en suspensión tiene una concentración inicial de biomasa 4 g/l, 20 g/l de glucosa, 0.13 g/l de fósforo y 2.52 g/l de nitrógeno. La cinética de crecimiento de las células de achiote en suspensión, a las condiciones de cultivo de este tratamiento, presenta una fase exponencial bien definida de 25 días; a partir de allí se establece una fase estacionaria hasta el tiempo final de la evaluación (40 días). Se comparan los contenidos de fenoles totales entre el material obtenido in vitro y el material vegetal proveniente de plantas crecidas ex-vitro, como criterio válido para justificar posteriores trabajos de producción metabólica in-vitro en esta especie vegetal