The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior.

In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism.

The HERC1 E3 Ubiquitin Ligase is essential for normal development and for neurotransmission at the mouse neuromuscular junction.

The ubiquitin-proteasome system (UPS) plays a fundamental role in protein degradation in neurons, and there is strong evidence that it fulfills a key role in synaptic transmission. The aim of the present work was to study the implication of one component of the UPS, the HERC1 E3 Ubiquitin Ligase, in motor function and neuromuscular transmission. The tambaleante (tbl) mutant mouse carries a spontaneous mutation in HERC1 E3 Ubiquitin Ligase, provoking an ataxic phenotype that develops in the second month of life. Our results show that motor performance in mutant mice is altered at postnatal day 30, before the cerebellar neurodegeneration takes place. This defect is associated with by: (a) a reduction of the motor end-plate area, (b) less efficient neuromuscular activity in vivo, and (c) an impaired evoked neurotransmitter release. Together, these data suggest that the HERC1 E3 Ubiquitin Ligase is fundamental for normal muscle function and that it is essential for neurotransmitter release at the mouse neuromuscular junction.

Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model.

Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain's white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrow-derived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft.

Analysis of CXCL12 3'UTR G>A polymorphism in colorectal cancer.

Colorectal cancer is one of the most prevalent cancers in developed countries. However, the genetic factors influencing its appearance remain far from being fully characterized. Recently, a G>A functional transition mapping the 3' untranslated region of the CXCL12 gene (rs1801157) has been found to be under-represented among rectal cancer patients when compared to colon cancer patients from a Swedish series. Here we present the results from an independent analysis of CXCL12 rs1801157 in a larger CRC series of Spanish origin in order to analyse the robustness of this association within a different European population. No significant difference was observed between controls and colon or rectal cancer patients. We were also unable to find a correlation between rs1801157 and different prognostic markers such as metastasis development or disease-free survival time. The epidemiologic data involving CXCL12 rs1801157 in colorectal cancer risk are discussed.

Diagnostic yield and safety of capsule endoscopy.

INTRODUCTION: the capsule endoscopy (CE), from his approval, has become a first line diagnostic procedure for the study of the small bowel disease. The aim of this study is to report our experience since the implantation of this technique in our hospital. MATERIAL AND METHODS: retrospective review of the CE undertaken in Department of Endoscopy. There was gathered in every case the age, sex, motive of consultation, previous diagnostic procedures, capsule endoscopy findings and complication of the technique. One took to end a descriptive and analytical analysis. RESULTS: there was achieved a total of 416 explorations in 388 patients. The obscure gastrointestinal bleeding was the most frequent indication (83.30%) followed by suspected Crohn s disease (7.5%). Angiodisplasia was the endoscopic lesion more frequently detected (42.2%), especially, in patients with digestive bleeding of obscure origin (OR 3.13 p < 0.001), followed by the flebectasia (10.6%) and the ulcer suspicious of Crohn s disease (9.9%). The global diagnostic yield as for the detection of injuries was 77.34% with a case of "not defecation of the capsule" and therefore need of laparotomy. CONCLUSIONS: the capsule endoscopy is a technique consolidated and as his potential is known, his indications are extended. The obscure gastrointestinal bleeding is the most frequent indication and the angiodisplasia the most identified injury. Once known his diagnostic yield, larger studies are needed that assess the influence of capsule endoscopy on clinical outcoumes.

Rendimiento diagnóstico seguridad de la cápsula endoscópica / Diagnostic yield and safety of capsule endoscopy

Introducción: la cápsula endoscópica desde su aprobación seha convertido en un procedimiento diagnóstico de primera líneapara el estudio del intestino delgado. El objetivo del estudio es exponerla experiencia desde la implantación de esta técnica ennuestro hospital.Material y métodos: se hizo una revisión retrospectiva de losestudios realizados en el Servicio de Endoscopia. Se recogió encada caso la edad, sexo, motivo de consulta, procedimientos diagnósticosprevios, diagnósticos endoscópicos e incidencias inherentesa la técnica y se llevó a cabo un análisis descriptivo y analítico.Resultados: se realizaron un total de 416 exploraciones en388 pacientes. La hemorragia digestiva de origen oscuro fue la indicaciónmás frecuente (83,30%) seguida de la sospecha de enfermedadde Crohn (7,5%). La angiodisplasia fue la lesión endoscópicamás detectada (42,2%) cuando se analizó la hemorragiadigestiva oscura (OR 3.13 p < 0,001) seguida de la flebectasia(10,6%) y las úlceras sugerentes de enfermedad de Crohn (9,9%).La rentabilidad global en cuanto a la detección de lesiones fue del77,34% con un caso de “no defecación de la cápsula” y por lotanto de necesidad de laparotomía.Conclusiones: la cápsula endoscópica es una técnica consolidaday a medida que se conoce su potencial, se van ampliando susindicaciones. La hemorragia digestiva de origen oscuro es la indicaciónmás frecuente y la angiodisplasia la lesión más identificada.Una vez conocida su eficacia diagnóstica se hace necesario determinarmediante estudios a gran escala y con metodología precisala rentabilidad clínica de la misma

Introduction: the capsule endoscopy (CE), from his approval,has become a first line diagnostic procedure for the study of thesmall bowel disease. The aim of this study is to report our experiencesince the implantation of this technique in our hospital.Material and methods: retrospective review of the CE undertakenin Department of Endoscopy. There was gathered inevery case the age, sex, motive of consultation, previous diagnosticprocedures, capsule endoscopy findings and complication ofthe technique. One took to end a descriptive and analytical analysis.Results: there was achieved a total of 416 explorations in388 patients. The obscure gastrointestinal bleeding was the mostfrequent indication (83.30%) followed by suspected Crohn's disease(7.5%). Angiodisplasia was the endoscopic lesion more frequentlydetected (42.2%), especially, in patients with digestivebleeding of obscure origin (OR 3.13 p < 0.001), followed by theflebectasia (10.6%) and the ulcer suspicious of Crohn´s disease(9.9%). The global diagnostic yield as for the detection of injurieswas 77.34% with a case of “not defecation of the capsule” andtherefore need of laparotomy.Conclusions: the capsule endoscopy is a technique consolidatedand as his potential is known, his indications are extended.The obscure gastrointestinal bleeding is the most frequent indicationand the angiodisplasia the most identified injury. Once knownhis diagnostic yield, larger studies are needed that assess the influenceof capsule endoscopy on clinical outcoumes

Calbindin, calretinin and parvalbumin immunoreactivity in the retina of the chameleon (Chamaeleo chamaeleon).

Apart from the pioneering studies of Ramon y Cajal [1893] and Rochon-Duvigneaud [1943], few studies have been devoted to the detailed study of the cytological and biochemical structure of the chameleon retina. In the present study we analyzed the expression of calbindin (CB), calretinin (CR) and parvalbumin (PV) immunoreactivities in the chameleon retina, and compared their distribution with those found in the retinas of other vertebrate species. CB immunoreactivity is dense in photoreceptors, horizontal and some lower amacrine cells. The most intense immunoreactivity was observed for calretinin; CR-ir amacrine cells are distributed throughout the inner nuclear, inner plexiform, and ganglion cell layers of the retina. Horizontal cells also display immunoreactivity to CR. A few retinal interneurons are weakly PV-ir. Double-labeling shows that all PV-ir or CB-ir cells, except the photoreceptors, are also strongly CR-ir. The distributions of these calcium-binding proteins in the chameleon retina share similarities with those observed in mammalian and avian retinas. In addition, the widespread distribution and co-localization of CB and CR reinforces the idea that these proteins play a general role in buffering the intracellular calcium levels in retinal cells. Furthermore, CB- and CR-immunoreactivities have enabled us to identify for the first time axon-bearing horizontal cells in the peripheral retina of the chameleon, very similar to those described in mammals.

¿Quién debe responsabilizarse de la realización de las técnicas de sedación en endoscopia digestiva? / Who should be responsible for sedation techniques in digestive endoscopy?

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Gamma-aminobutyric acid-synthesizing cells in the retina of the chameleon Chamaeleo chameleon.

Antibodies directed against gamma-aminobutyric acid (GABA) and L-glutamic acid decarboxylases 65 and 67 kDa (GAD65 and -67) were used to study the GABAergic cell populations of the chameleon retina. GABA immunoreactivity was found in the two main types of retinal interneurons, amacrine and horizontal cells. Amacrine, displaced amacrine, and intra- and interplexiform cells displayed the strongest GABA immunoreactivity of all the retinal cell types. Horizontal cells formed a continuous GABA-immunoreactive cell layer lying against the outermost portion of the inner nuclear layer. In contrast to previous studies (Quesada et al. [1996] Cell Biol. Int. 20:395-400; [1999] Eur. J. Anat. 3:13-25), the present results demonstrate that the horizontal cells of the chameleon retina are GABA immunoreactive and that a subpopulation of these is immunolabelled by an antibody against GAD65. These results indicate that GABAergic synaptic transmission plays a key role in the outer plexiform layer of the vertebrate retina.

Cleaning and disinfection practices in digestive endoscopy in spain: results of a national survey.

BACKGROUND AND STUDY AIMS: Disinfection and surveillance of it are important for ensuring safety in gastrointestinal endoscopy. The aim of this survey was to assess the current status of disinfection in gastrointestinal endoscopy units in Spain. MATERIALS AND METHODS: An anonymous questionnaire on cleaning and disinfection methods was sent to gastrointestinal endoscopy units at 244 public hospitals in Spain. A minimum standard of disinfection (MSD) was defined to evaluate the appropriateness of disinfection practices. RESULTS: A total of 144 centers responded (58 %). All units perform manual washing of endoscopes before disinfection. Automatic washers are available in only 23 % of the centers. Selective cleaning of internal channels is systematically performed in 85 % of the centers. Glutaraldehyde-based disinfectants are the most commonly employed (84 % of units). The time of exposure to the disinfectant is at least 10 min in 97 % of units, but 20 min or more in only 36 % of them. Endoscopic accessories are sterilized in 57 % of centers. The MSD was complied with by 79 % of the units evaluated. Compliance with the MSD was significantly lower in small units (P = 0.0005) performing small numbers of examinations per month. Quality control tests on the efficacy of disinfection methods are conducted at 66 % of the centers. Specialized personnel record disinfection procedures in 85 % of the centers and supervise them in 55 % of the centers. Half of the units have inadequate equipment and facilities. CONCLUSIONS: This survey suggests that cleaning and disinfection practices in gastrointestinal endoscopy units in Spain have improved in recent years, and that there is a good compliance with standard guidelines. Most units should improve their equipment and facilities in order to provide better comfort and safety for patients and staff.

Endoscopic ultrasonography features of calcified gastric cancer.

Calcifications are a rare finding described in benign and malignant tumors located in any site of the body. Their presence in stomach and colon carcinomas is very rare. Most of the cases described are mucinous adenocarcinomas. We present the case of one patient with this disease studied with endoscopic ultrasonography. There were punctate calcifications in the submucosa layer that tended to take on a crown-like shape in the outer-most area, producing an acoustic shadow. The pathological study of the surgical specimen showed amorphic calcifications inside some mucin lakes. More cases need to be studied with this technique in order to define their endosonographic characteristics.

Phenylethanolamine N-methyltransferase-immunoreactive neurons in the medulla oblongata of the pigeon (Columba livia) projecting to the hypothalamic paraventricular nucleus.

The distribution and ascending projections to the hypothalamic paraventricular nucleus of phenylethanolamine N-methyltransferase (PNMT)-immunoreactive perikaria were studied in adult pigeons using a combination of retrograde transport of Fluorogold injected into the paraventricular nucleus, and double immunohistochemical procedures for PNMT, tyrosine hydroxylase and neuropeptide Y. PNMT-immunoreactive cell bodies were found in the subtrigeminal reticular nucleus of the ventrolateral medulla and in the nucleus of the solitary tract, mainly in the subnuclei: medialis superficialis, pars posterior, and medialis ventralis, pars posterior. PNMT-immunoreactive perikaria were also tyrosine hydroxylase immunoreactive, and are located within the rostral tyrosine hydroxylase immunoreactive cell groups of these areas. No perikaria double-labeled for neuropeptide Y and PNMT were found. Retrograde labeled cell bodies were observed in the subtrigeminal reticular nucleus and in the nucleus of the solitary tract. PNMT-immunoreactive retrogradely labeled cells were mainly observed in the subtrigeminal reticular nucleus. These data suggest the presence in the pigeon of medullary adrenergic cell groups partially comparable to mammalian C1 and C2 groups. Comparison of these results with data previously obtained in amphibians and reptiles suggests that the presence of a hypothalamically-projecting C1-like group might be a plesiomorphic medullary attribute in amniotes, whereas the variable presence of C2 and C3-like groups, as well as the content of NPY in the putative adrenergic perikaria, seem to be species-specific.

[Microbiologic diagnosis of Helicobacter pylori and its resistance to antibiotics]. / Diagnóstico microbiológico de Helicobacter pylori y su resistencia a los antimicrobianos.

From March 1995 to February 1996 a total of 386 gastroduodenal biopsies were processed for microbiological diagnosis of Helicobacter pylori which included culture, Gram staining and urease test. For susceptibility studies to five antimicrobial agents, 35 additional gastroduodenal biopsies (n = 421) were added. There were 272 (70.4%) positive cultures, 220 (56.9%) samples with positive urase test and 244 (63.2%) with positive result in Gram-staining; both tests were statistically significant compared with culture (p < 0.05). Considering culture as the reference method, sensitivity and specificity values for the urease test were 77.0% and 92.1% and for Gram staining 86.7% and 92.9%, respectively. A total of 11 isolates were recovered from the 35 biopsies processed only for culture. Susceptibility testing of 283 isolates (272 + 11) was performed to the following antimicrobials: amoxicillin, metronidazole, clarithromycin, azythromycin and tetracycline. Resistance to metronidazole was 25.4% and the corresponding values for clarithromycin and azithromycin 9.5%. No resistance to amoxicillin or tetracycline was observed. Urease test and Gram staining are two easy-to-perform tests and when taken together allow the microbiological diagnosis of Helicobacter pylori infection. Culture should be performed to know the evolution of resistance to antimicrobials used for treatment of this infection.

[Endoscopic diagnosis of an ileocolic intussusception in an adult]. / Diagnóstico endoscópico de una intususcepción ileocólica en un adulto.

Although intussusception is the most frequent cause of intestinal obstruction in children, it only represents 5-10% of all adults. The preoperative diagnosis is difficult and it is rarely done by endoscopy. We present a case of adult ileocolic intussusception caused by an ileon terminal hamartoma. The diagnosis was done by colonoscopy.

Cellular and functional recovery of Parkinsonian rats after intrastriatal transplantation of carotid body cell aggregates.

We have tested the suitability of chromaffin-like carotid body glomus cells for dopamine cell replacement in Parkinsonian rats. Intrastriatal grafting of cell aggregates resulted in almost optimal abolishment of motor asymmetries and deficits of sensorimotor orientation. Recovery of transplanted animals was apparent 10 days after surgery and progressed throughout the 3 months of the study. The behavioral effects were correlated with the long survival of glomus cells in the host brain. In host tissue, glomus cells were organized into glomerulus-like structures and retained the ability to secrete dopamine. Several weeks after transplantation, dopaminergic fibers emerged from the graft, reinnervating the striatal gray matter. The special durability of grafted glomus cells in the conditions of brain parenchyma could be related to their sensitivity to hypoxia, which is known to induce cell growth, excitability, and dopamine synthesis. This work should stimulate research on the clinical applicability of carotid body autotransplants in Parkinson's disease.

Antibodies to macrophage inflammatory protein-1beta in preoptic area of rats fail to suppress PGE2 hyperthermia.

This study determined whether macrophage inflammatory protein-1beta (MIP-1beta) plays a role in the hyperthermia caused by prostaglandin E2 (PGE2) given intracerebroventricularly (i.c.v.) in the rat. In these experiments, anti-murine MIP-1beta antibody (anti-MIP-1beta) was micro-injected in the anterior hypothalamic, preoptic area (AH/POA) just before i.c.v. PGE2. The results showed that anti-MIP-1beta failed to alter the PGE2 hyperthermia. However, immunocytochemical studies revealed MIP-1beta immunoreactivity detectable in both the organum vasculosum laminae terminalis (OVLT) and AH/POA in the febrile rat. These data thus demonstrate that MIP-1beta is sequestered in diencephalic structures underlying thermoregulation even though it is not involved in PGE2 hyperthermia. This dissociation supports the viewpoint that at least two distinct systems exist in the brain which underlie a febrile response: MIP-1beta underlies one component whereas PGE2 comprises the other.