Lysophosphatidylinositol Promotes Chemotaxis and Cytokine Synthesis in Mast Cells with Differential Participation of GPR55 and CB2 Receptors.

Mast cells (MCs) are the main participants in the control of immune reactions associated with inflammation, allergies, defense against pathogens, and tumor growth. Bioactive lipids are lipophilic compounds able to modulate MC activation. Here, we explored some of the effects of the bioactive lipid lysophosphatidylinositol (LPI) on MCs. Utilizing murine bone marrow-derived mast cells (BMMCs), we found that LPI did not cause degranulation, but slightly increased FcεRI-dependent ß-hexosaminidase release. However, LPI induced strong chemotaxis together with changes in LIM kinase (LIMK) and cofilin phosphorylation. LPI also promoted modifications to actin cytoskeleton dynamics that were detected by an increase in cell size and interruptions in the continuity of the cortical actin ring. The chemotaxis and cortical actin ring changes were dependent on GPR55 receptor activation, since the specific agonist O1602 mimicked the effects of LPI and the selective antagonist ML193 prevented them. The LPI and O1602-dependent stimulation of BMMC also led to VEGF, TNF, IL-1α, and IL-1ß mRNA accumulation, but, in contrast with chemotaxis-related processes, the effects on cytokine transcription were dependent on GPR55 and cannabinoid (CB) 2 receptors, since they were sensitive to ML193 and to the specific CB2 receptor antagonist AM630. Remarkably, GPR55-dependent BMMC chemotaxis was observed towards conditioned media from distinct mouse and human cancer cells. Our data suggest that LPI induces the chemotaxis of MCs and leads to cytokine production in MC in vitro with the differential participation of GPR55 and CB2 receptors. These effects could play a significant role in the recruitment of MCs to tumors and the production of MC-derived pro-angiogenic factors in the tumor microenvironment.

Relationship between median nerve vascularization before tourniquet release and the Boston Carpal Tunnel Questionnaire: a cohort study.

The results of this study suggest that a decreased vascularization of the median nerve after releasing the carpal tunnel predicts an inferior clinical improvement assessed by the Boston Carpal Tunnel Questionnaire.

Mast Cell-Tumor Interactions: Molecular Mechanisms of Recruitment, Intratumoral Communication and Potential Therapeutic Targets for Tumor Growth.

Mast cells (MCs) are tissue-resident immune cells that are important players in diseases associated with chronic inflammation such as cancer. Since MCs can infiltrate solid tumors and promote or limit tumor growth, a possible polarization of MCs to pro-tumoral or anti-tumoral phenotypes has been proposed and remains as a challenging research field. Here, we review the recent evidence regarding the complex relationship between MCs and tumor cells. In particular, we consider: (1) the multifaceted role of MCs on tumor growth suggested by histological analysis of tumor biopsies and studies performed in MC-deficient animal models; (2) the signaling pathways triggered by tumor-derived chemotactic mediators and bioactive lipids that promote MC migration and modulate their function inside tumors; (3) the possible phenotypic changes on MCs triggered by prevalent conditions in the tumor microenvironment (TME) such as hypoxia; (4) the signaling pathways that specifically lead to the production of angiogenic factors, mainly VEGF; and (5) the possible role of MCs on tumor fibrosis and metastasis. Finally, we discuss the novel literature on the molecular mechanisms potentially related to phenotypic changes that MCs undergo into the TME and some therapeutic strategies targeting MC activation to limit tumor growth.

Síndrome compartimental del brazo tras cirugía por fractura supracondilea de húmero / Compartment syndrome of the arm after surgery for supracondylar fracture of the humerus

Presentamos un síndrome compartimental en el brazo que es una localización muy poco frecuente y de la que apenas existe bibliografía. El caso se presentó 48 h después de una cirugía de humero a través de abordaje posterior, aunque afecto al compartimento anterior. Queremos con este caso resaltar la importancia del diagnóstico diferencial al no tratarse de una localización habitual.

We present a compartment syndrome in the arm that is a very rare location and for which there is hardly any literature. The case presented 48 hours after humerus surgery through a posterior approach, although it affected the anterior compartment. With this case we want to highlight the importance of differential diagnosis as it is not a common location.

Mortality and antibody responses of mice to three successive episodes of experimental scorpion (Centruroides limpidus limpidus) envenomation and immunological rescue.

Mortality rates of mice and their levels of anti-venom and anti-F(ab')2 antibodies were assessed after three episodes of subcutaneous envenomations with or without treatment with horse F(ab')2. Soluble venom from the Mexican scorpion Centruroides limpidus limpidus was used for these experiments. Repetition of episodes did not induce different mortality rates in untreated mice. F(ab')2 rescued about 85% of the mice in the first two episodes and 66% in the third, without distinction of gender or ostensible side-effects: a suggestion of selection of the most resistant mice. Surviving mice produced in vitro neutralizing antibodies to the scorpion venom and also antibodies to F(ab')2, when injected alone but more so if combined: a possible immunological adjuvant or alarm effect of the venom or of the cascading physiopathology of envenomation. In the few surviving mice, both anti-venom and anti-F(ab')2 antibodies increased significantly after the first envenomation but not thereafter, showing no correlation with mortality rates: a suggestion of their clinical irrelevance, the few hard-to kill mice appeared to resist envenomation by mechanisms other than antibody response. Injection of F(ab')2 alone induced production of detectable anti-venom antibodies in a few mice and injection of venom alone induced that of anti-F(ab')2 antibodies, perhaps due to trace amounts of venom in the high affinity fraction of F(ab')2 and to anti-idiotypic antibodies or polyclonal activity in the envenomation episode, respectively.

Experimental envenoming of mice with venom from the scorpion Centruroides limpidus limpidus: differences in mortality and symptoms with and without antibody therapy relating to differences in age, sex and strain of mouse.

C57Bl/6J and BALB/cAnN inbred strains of mice differed significantly in mortality and symptoms when intoxicated subcutaneously with one LD(50) of venom from Centruroides limpidus limpidus. Higher mortality was observed in C57Bl/6J than in BALB/cAnN. Also, C57Bl/6J mice more quickly developed muscular and respiratory collapse whilst BALB/cAnN mice were hyperactive before dying. Also, the symptoms in the survivors lasted for 24 h in C57Bl/6J and for 2 h in BALB/cAnN. The age and sex of mice were also related to mortality: younger mice were more resistant than older mice and females were more susceptible than males, especially in the younger groups. Antivenom (horse F(ab')(2)) administration 5-10 min after envenoming of mice with one LD(50) rescued 60% of BALB/cAnN and 52% of C57Bl/6J mice, respectively. Results indicate that genetic background, gender and age differences are of consequence in the pathogenesis of C. limpidus scorpion envenomation in mice, and that timely treatment with active antivenom F(ab')(2) saves a significant fraction of intoxicated mice without statistically significant distinction of strains.

An atypical protein disulfide isomerase from the protozoan parasite Leishmania containing a single thioredoxin-like domain.

In higher eukaryotes, secretory proteins are under the quality control of the endoplasmic reticulum for their proper folding and release into the secretory pathway. One of the proteins involved in the quality control is protein disulfide isomerase, which catalyzes the formation of protein disulfide bonds. As a first step toward understanding the endoplasmic reticulum quality control of secretory proteins in lower eukaryotes, we have isolated a protein disulfide isomerase gene from the protozoan parasite Leishmania donovani. The parasite enzyme shows high sequence homology with homologs from other organisms. However, unlike the four thioredoxin-like domains found in most protein disulfide isomerases, of which two contain an active site, the leishmanial enzyme possesses only one active site present in a single thioredoxin-like domain. When expressed in Escherichia coli, the recombinant parasite enzyme shows both oxidase and isomerase activities. Replacement of the two cysteins with alanines in its active site results in loss of both enzymatic activities. Further, overexpression of the mutated/inactive form of the parasite enzyme in L. donovani significantly reduced their release of secretory acid phosphatases, suggesting that this single thioredoxin-like domain protein disulfide isomerase could play a critical role in the Leishmania secretory pathway.

The quality in the radiology department.

In the last three years, the Spanish juridical ordinance has regulated (mostly the radiologic protection area) the essential quality that every radiodiagnostic and dentistry unit should comply with. This quality, as in every service, rests on the competence of the professional's who perform it. This means that in advanced countries much time and effort is dedicated to forming these people and therefore the academic charge for teaching dentistry radiology in Venezuela results 15 times higher than what is dedicated in our environment. Also, the supply of graduates or specialized radiologists is very poor; for example, it does not exist in Barcelona while in Merida the radiology service staff has 4 licentiates exclusively dedicated to oral radiology assistance and teaching (apart from two other people who work as technicians). This wealth influences positively in the quality of the service. Among other things, it allows the readjustment of the incoming petitions and also to justify them better and makes possible that all the explorations go out with the corresponding judgment. The academic quality in this discipline is also high due to the fact that it is a university teaching service. Our goal, through this work, is to show the situation of the problem comparing 2 different university services of oral radiology and reveal the lacks found with its solutions.

Análisis numérico de imágenes digitalizadas de western blot. El caso del VIH / Numeric analysis of digitalized images of western blot. The case of VIH

El presente trabajo explora la digitalización de imágenes de "western blot" (WB) para extraer mayor información acerca de la respuesta inmune humoral del paciente infectado por el virus de la inmunodeficiencia adquirida humana (VIH) y analizar de manara multivariada los datos obtenidos. Se realizó la digitalización y análisis de las imágenes de WB de 115 sueros. Con estos datos se hicieron análisis tanto cualitativos: dendograma y análisis de componentes principales (ACP), como cuantitativos: ACP con el total de bandas tomando sólo los antígenos propios del virus o utilizando los antígenos que no pertenecen al virus. Los resultados demuestran la factibilidad de diagnosticar de forma mecánica un número grande de imágenes de WB. Tanto el dendograma como el ACP cualitativo separaron, de manera adecuada, imágenes blancas, imágenes con menos de cuatro bandas e imágenes con patrones más complejos. El análisis cuantitativo, que conserva más información, separa perfectamente imágenes de diagnóstico negativo, indeterminado y positivo. Además, se encontró que las imágenes con patrones complejos correlacionan más con individuos asintomáticos. Este análisis reveló también la existencia de banda que no parecen corresponder a proteínas virales, mismas que pudieran corresponder a autoantígenos o antígenos cruzados entre el VIH y el ser humano, dando cauce a autoinmunidad. El análisis digital de imágenes de WB en el caso del VIH, prueba así su gran utilidad en el diagnóstico de caso y en el seguimiento de la evolución y patogenia de la enfermedad

Heridas del duodeno: ¿Qué hacer? / Duodenal wounds: What to do?

Con el objetivo primordial de documentar nuestra experiencia con las "heridas duodenales" en el Hospital Escuela de Tegucigalpa, Honduras, C.A.-en primer lugar- y de hacer una revisión bibliográfica, con el respectivo análisis crítico de ella, para así detectar cual es la experiencia foránea con éste tipo de lesiones traumáticas -en segundo lugar-, se hizo una "investigación clínica" orientada esencialmente a determinar cual procedimiento quirúrgico debe ser utilizado en cada caso, de acuerdo al grado de "lesión duodenal", para así disminuir la alta tasa de mortalidad postoperatoria de estas heridas. La investigación retrospectiva hecha en el Hospital Escuela entre 1987 y 1992 reveló que la mortalidad global fue de aproximadamente 17 por ciento y que la operación más usada fue la "duodenorrafía", también con una mortalidad postoperatoria de aproximadamente 17 por ciento, es decir 6 en 35 casos. Por otro lado, al revisar también retrospectivamente los casos personales de uno de los autores, encontramos que entre 1991 y 1999 operó 12 casos y en todos ellos practicó "solo duodenorrafia" con sonda nasogástrica-duodenal y drenajes periduodenales obteniendo similares resultados, es decir: una mortalidad de aproximadamente 17 por ciento (2 en 12 casos). La otra operación utilizada en la primera parte de nuestra investigación fue la "exclusión pilórica", la cual también resultó tener idéntico porcentaje de mortalidad operatoria, aproximadamente 17 por ciento, pero sólo en 6 casos. En base a nuestra experiencia y a los resultados encontrados en la revisión y análisis de bibliografía que se hizo, creemos que ambas operaciones pueden ser utilizadas en "heridas duodenales" que son correctamente clasificadas como "grado III", durante la parte inicial del acto quirúrgico; pero así mismo recomendamos muy enfáticamente que en aquellas otras heridas que igualmente son clasificadas por el cirujano como "grado II", sólo debe hacerse una o más duodenorrafias, toda vez que técnicamente sea posible, para evitar hacer algún otro procedimiento más difícil y más largo, que podría aumentar la morbimortalidad postoperatoria...