The coelomic fluid of the sea urchin Tripneustes depressus shows antiviral activity against Suid herpesvirus type 1 (SHV-1) and rabies virus (RV).

Several studies have reported that molecules extracted from invertebrates have activity against different viruses, even against those that do not infect these organisms in their environment. One of the main mechanisms against pathogens in these organisms is the production of antimicrobial peptides. The objective of this study was to determine whether the coelomic fluid (CF) of the sea urchin Tripneustes depressus has activity against Suid herpesvirus type 1 (SHV-1) and/or rabies virus (RV). We tested the antiviral activity of CF in neutralizing assays and observed 50% inhibition against SHV-1 lytic plaque formation using 33 µg of CF, whereas 21 µg CF was sufficient to obtain more than 90% inhibition for RV. Cytotoxicity to MDBK and BHK-21 cells was found with whole CF yet was eliminated by heating at 56 or 72 °C (even when using 50 µg of heat-inactivated CF supernatant [SN or thermostable fraction]), and SN retained the antiviral effect. In both cases, the antiviral effect was direct and thermostable (SN 56 and 72 °C), and the best inhibition was observed when CF + virus was incubated prior to the addition of the cells. Therefore, the coelomic fluid of T. depressus has antiviral activity against SHV-1 and RV that is direct and stable at 72 °C. We suggest that further assays should be performed using more accurate methods to characterize new molecules with antiviral activity that may result in new drugs.

Near-barrier fusion of Sn + Ni and Te + Ni systems: examining the correlation between nucleon transfer and fusion enhancement.

The fusion excitation functions for radioactive (132)Sn + (58)Ni and stable (130)Te + (58,64)Ni were measured at energies near the Coulomb barrier. The coupling of transfer channels in heavy-ion fusion was examined through a comparison of Sn + Ni and Te + Ni systems, which have large variations in the number of positive Q-value nucleon transfer channels. In contrast with previous experimental comparisons, where increased sub-barrier fusion cross sections were observed in systems with positive Q-value neutron transfer channels, the reduced excitation functions were equivalent for the different Sn + Ni and Te + Ni systems. The present results suggest a dramatically different influence of positive Q-value transfer channels on the fusion process for the Sn + Ni and Te + Ni systems.

Anti-baculovirus activity in a protein extracted from the exoskeleton of Pleuroncodes planipes [Decapoda: Galatheidae].

Antiviral activity (99.5% inhibition) against the Autographa californica polyhedrosis nuclear virus AcNPV+GFP was shown by a polypeptide of approximately 10 kDa, isolated from the exoskeleton of Pleuroncodes planipes, the pelagic red crab. This thermo-stable polypeptide retained its anti-viral properties after being exposed to 76 °C for 30 min and showed no apparent cytotoxic effect. Its anti-viral activity was observed when incubated with the virus, previous to the inoculation of cells. Using Tandem Mass Spectrometry (LC/ESI-MS/MS), this polypeptide showed sequence identity to a fragment of a myohemeritrin-like metalloprotein found in the Scoloplos armiger sea worm (VFYANLDEEHK).

Prolactin effect on CD69 and CD154 expression by CD4+ cells from systemic lupus erythematosus patients.

OBJECTIVE: The aim was to explore the role of prolactine (PRL) in the lymphocyte activation process in active and inactive systemic lupus erythematosus (SLE) patients in an in vitro model. METHODS: Peripheral blood mononuclear cells (PBMNC) were isolated from SLE patients and healthy individuals. The mRNA for prolactine and its receptor, obtained by standard techniques with an appropriate primer, were subjected to PCR and visualised. The PBMC were cultured with: a) medium alone as a negative control, b) unspecific mitogen as a positive control (PMA-ionomycin for CD154 or concanavalin A for CD69), c) PRL alone, d) mitogen plus PRL, e) mitogen plus antibody anti-PRL (1:50) and f) mitogen plus an unrelated antibody. Then CD69 and CD154 were determined by flow cytometry analysis. RESULTS: Twelve inactive and 15 active SLE patients were studied. 25% of the active patients displayed hyperprolactinemia. Under basal conditions, CD69 expression was associated with disease activity. In contrast, CD154 did not show this association. The PBMNC activated in vitro were capable of producing and secreting prolactine as measured by mRNA and Nb2 assay. In the same way the mRNA for prolactine receptor was visualized. Cells from SLE patients cultivated with PRL alone did not display increased CD69 or CD154 expression. The addition of PRL to the unspecific stimulated culture did not have an additive effect. In contrast, the addition of antibodies against PRL, in order to block the autocrine prolactine, resulted in a striking reduction in CD69 and CD154 expression. CONCLUSIONS: PRL is produced and secreted by the immune cell and acts just after the first trigger signal of activation in an autocrine way. The expression of CD69 and CD154 molecules depend partially on the prolactine.

Persistence of macroprolactinemia due to antiprolactin autoantibody before, during, and after pregnancy in a woman with systemic lupus erythematosus.

A woman with systemic lupus erythematosus (SLE) with marked increases in circulating 150-kDa PRL was studied from before conception, throughout pregnancy, and after pregnancy. The clinical features of the patient included idiopathic hyperprolactinemia without clinical symptoms such as amenorrhea and galactorrhea before pregnancy. No clinical lupus activity was present during follow-up. Serum PRL increase during pregnancy in this patient was considerably higher at weeks 27 and 33 than in normal pregnant women. In contrast, serum-free PRL levels were considerably lower at weeks 20, 27, and 33 than in normal pregnant women. A 150-kDa PRL (big big PRL) species persisted as the predominant circulating form of PRL throughout each measurement in this woman with SLE. In contrast, the predominant form of PRL in serum from healthy pregnant women was little PRL (or monomeric PRL). The nature of big big PRL was due to the presence of anti-PRL autoantibodies forming an IgG-23 kDa PRL complex, in accordance with the studies by affinity chromatography for IgG and Western blot analysis. The IgG-PRL complex was fully bioactive in vitro (Nb2 rat lymphoma cell assay). Injection of the serum into the rats demonstrated that the IgG-PRL complex was cleared more slowly than serum containing predominantly monomeric PRL. The data suggest that the IgG-PRL complex has biological activity; the absence of symptoms in this woman may be attributed to the fact that due to its large molecular weight, big big PRL does not easily cross the capillary walls. Delayed clearance may account for increased serum PRL levels in this SLE patient with anti-PRL autoantibodies.

Frequency of macroprolactinemia due to autoantibodies against prolactin in pregnant women.

The frequency of macroprolactinemia related to the presence of anti-PRL autoantibodies in the serum of 209 healthy women at different stages of pregnancy was studied. Measurements were taken of serum PRL concentrations before and after chromatographic separation (gel filtration and affinity with proteins A and G) and extraction of free PRL with polyethylene glycol (PEG). Sera from 8 of the 209 women (3.8%) were found to have a significantly high proportion of precipitated PRL by PEG (macroprolactinemia); in these patients, gel filtration showed that a substantial amount of big big PRL (molecular mass >100 kDa) was present (19.0--78.2% vs. 3.8-4.9%, P = 0.009 in normal pregnant women with a normal proportion of precipitated PRL by PEG). The presence of macroprolactinemia was attributable to anti-PRL autoantibodies in 5 of the 8 women. Comparison of serum levels of direct and free PRL between women with macroprolactinemia related to anti-PRL autoantibodies and women without macroprolactinemia showed significant differences (direct PRL: 270.2 +/- 86.9 vs. 203.4 +/- 69.0 microg/L, P = 0.04; and free PRL: 107.0 +/- 75.9 vs. 173.3 +/- 67.6 microg/L, P = 0.002). On the other hand, there was no difference between women with macroprolactinemia not related to anti-PRL autoantibodies and women with macroprolactinemia caused by anti-PRL autoantibodies, nor was there a difference between women with macroprolactinemia not related to anti-PRL autoantibodies and women without macroprolactinemia. There was a positive correlation between titers of the anti-PRL autoantibody and serum PRL levels (r = 0.82, P = 0.09). The presence of the anti-PRL autoantibody had no relation to the patient's age, stage of gestation, or number of previous pregnancies. We concluded that the frequency of macroprolactinemia was 3.8% among healthy, pregnant women, which was caused by a anti-PRL autoantibodies in 62.5% of the cases. The autoantibodies were found in the bloodstream, forming a PRL-IgG complex, in accordance with the following observations: 1) immunoreactive PRL on gel filtration was eluted in the fractions corresponding to the molecular mass of IgG (150 kDa); 2) a significantly high proportion of immunoreactive PRL was retained on an affinity gel for IgG (proteins A and G); and 3) a significantly high proportion of serum PRL bound to IgG was precipitated by protein A. There was a positive correlation between titers of anti-PRL autoantibodies and serum PRL levels. Serum levels of total PRL were higher, and serum levels of free PRL were lower, in pregnant women with anti-PRL autoantibodies than in pregnant women without macroprolactinemia.

Development of a diagnostic test for Entamoeba histolytica using idiotype expression in human.

The protozoan parasite Entamoeba histolytica is the etiological agent of human amebiasis. The pathology of the disease starts with the cytolysis of the host target cells by amoebae. It is initiated by the adhesion of trophozoites to the host cells, through surface lectin via specific receptors. These adherence lectins have been demonstrated to be highly conserved, and can be recognised by serum antibodies from patients with invasive amebiasis. Some of these molecules have been used as antigens in serologic studies, which has been very helpful in the diagnosis of invasive intestinal amebiasis. However, false-positive serologic reactivity can occur using E. histolytica extracts and purified antigens. Additional problems are because the extracts display a great enzymatic activity. Several diagnostic methods, using different molecules and techniques, have been described. However, the problem still remains since these tests are not capable of differentiating between amoebic liver abscess (ALA) and intestinal amebiasis.Here, the research has been addressed to the 66-kDa antigen, which is a part of the outer membrane proteins from the E. histolytica strain HM1-IMSS trophozoites. First of all, we characterized the 66-kDa antigen in order to prove the relevance. We found that the 66-kDa antigen is a part of the plasma membranes and is distributed rather homogeneously on the cell surface of trophozoites. Apparently, the 66-kDa antigen is a glycoprotein. Using a monoclonal antibody (MAb), we found 25% of inhibition in the erythrophagocytosis by the trophozoites. Starting form one monoclonal antibody, we prepared an anti-idiotype (anti-Id) antibody reagent, with the purpose of searching for the different expressions of the idiotype between the sera from ALA and the intestinal amebiasis patients. Moreover, we produced the antibody Ab3 that is capable of recognising the 66-kDa antigen; it means that the Ab2 displays the internal image of the antigen. We found that 91.6% of the serum from ALA patients displayed the expression of the Id. In contrast, 15.7% of the E. histolytica asymtomatic cyst carriers displayed the Id expression, 6.6% of the patients with another parasite infection, and 11% of the negative controls (serum from umbilical cords of newborn babies). Our results showed that the expression of the Id could be differentiated among the AHA patients from the other groups with a 91.6% sensibility and 88.3% specificity.

Satisfaction related factors of attendants to a medical research meeting.

OBJECTIVE: To assess satisfaction of attendants to a National Meeting on Medical Research in relation with the scientific quality and level of discussion of the research work. MATERIAL AND METHODS: An anonymous self-applied questionnaire was handed out to gather opinions about the scientific quality, level of discussion of the research work, and overall satisfaction with the meeting. The studied population included 400 physicians, all of them authors or collaborators of the research work presented. RESULTS: The rate of response was 62% (n = 249). Two hundred and twenty-four approved the scientific quality (90%), and 203 were satisfied with the level of discussion of research (88%); 239 were satisfied with the meeting as a whole (96%). The factors associated with dissatisfaction regarding the quality of the scientific meeting were the masculine gender (OR = 2.7, CI 95% = 0.8-9.l, p = 0.06), having an M.Sc. or Ph.D. degree (OR = 2.3, CI 95% = 0.9-5.5, p = 0.03), and having attending prior meetings more than twice (OR = 5.0, CI 95% = 1.5-18.4, p = 0.001). CONCLUSIONS: Most of the attendants were satisfied with the scientific quality and discussions of the research work. The masculine gender, having an M.Sc. or Ph.D. degree, and prior assistance were the factors associated with dissatisfaction of the scientific quality of the Meeting.

[Antibodies against prolactin in patients with systemic lupus erythematosus and hyperprolactinemia]. / Autoanticuerpos dirigidos contra prolactina en pacientes con lupus eritematoso sistémico e hiperprolactinemia.

We investigated patients with lupus erythematosus to detect the presence of hyperprolactinemia and to determine it's origin. From the seric specimens obtained in 225 patients with LES, we found 37 (14.5%) with hyperprolactinemia and they were trated with polyethylenglicol, in 11 of 37 patients (29.7%) had a high significance of prolactin precipitation (PRL). The test in gel filtration shown the big-big PRL (Molecular weight > 100 kDa) was the predominant form from PRL seric in these patients and no woman had clinic effects of hyperprolactinemia as galactorrhea and/or amenorrhea. The big-big PRL essence was due to an antibody, with it was found like a immune complex (Ig-PRL). This evidence suggest the patients with LES and hyperprolactinemia have a very high incidence of macroprolactinemia relationated to antibodies anti-PRL, and in spite of the hyperprolactinemia not have clinical effects like amenorrhea and/or galactorrhea, and it is other cause to explain the high incidence of hyperprolactinemia in patients with LES.

[Bibliometric analysis of publications by the Mexican Social Security Institute staff]. / Análisis bibliométrico de las publicaciones realizadas por el personal del IMSS.

OBJECTIVE: To describe and analyze the general characteristics and methodology of indexed publications by the health staff of the Mexican Social Security Institute in 1997. MATERIAL AND METHODS: Original articles were evaluated. The primary sources included Index Medicus, Current Contents and the Mexican National Council of Science and Technology (CONACYT) index. The following information was gathered for each article: affiliation and chief activity of the first author; impact factor of the journal; research type; field of study; topic of study, and methodological conduction. This latter point included congruence between design and objective, reproducibility of methods, applicability of the analysis, and pertinence of the conclusions. RESULTS: A total of 300 original articles was published of which 212 (71%) were available for the present study: full-time investigators (FTI) generated 109 articles and investigators with clinical activities (CAI) wrote 103 articles. The median impact factor of the journals in which FTI published was 1.337 (0.341 to 37.297) and for CAI publications, 0.707 (0.400 to 4.237). Biomedical research predominated in the first group (41%) and clinical investigation in the second (66%). Statistically significant differences were identified for the methodological conduction between groups of investigators. CONCLUSIONS: Descriptive studies and publications in journals without impact factor predominated. The FTI group had the highest bibliographic production of original articles in indexed journals with an impact factor.

Prolactin down-regulates CD4+CD25hiCD127low/- regulatory T cell function in humans.

Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (T(reg)) cells are still unknown. Our goal was to determine whether PRL plays a role in T(reg) function. We measured the expression of PRL and its receptor in T(reg) and effector T (T(eff)) cells from 15 healthy individuals. We also evaluated the functional activity of T(reg) cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T(reg) cells constitutively expressed PRL receptor, whereas T(eff) cells required stimulation with anti-CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by T(reg) cells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of T(reg) and T(eff) cells (P<0.05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNγ. We report for the first time that PRL receptor expression was constitutive in T(reg) cells but not in T(eff) cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T(reg) cells, apparently through the induced secretion of Th1 cytokines.

Beneficial effects of the n-3 long-chain polyunsaturated fatty acids in surgical patients: updating the evidence.

The use of n-3 polyunsaturated fatty acids in surgical patients has risen by the fact that this may attenuate systemic and acute inflammatory responses secondary to surgical trauma through modulation of inflammatory mediators and cell membrane interactions. Moreover, the inclusion of n-3 fatty acids in clinical trials as part of the therapy in patients, who expect to undergo a surgical stress, suggests benefits on clinical progress. Therefore, the objective of this article is to review data from n-3 polyunsaturated fatty acid effects on biochemical parameters and on reduced length of hospitalization, number of infections, and mortality as main clinical outcomes in human surgical patients.

Activation of TLR2 and TLR4 by minimally modified low-density lipoprotein in human macrophages and monocytes triggers the inflammatory response.

Oxidized low-density lipoproteins and Toll-like receptors (TLR) 2 and 4 are involved in the development of atherosclerosis. The TLR are important in the pro-inflammatory response. The aim of this research was to analyze the activation of CD14, TLR4, and TLR2 in response to minimally modified low-density lipoprotein (mmLDL). Human monocytes and macrophages secreted tumor necrosis factor (TNF)-alpha in response to mmLDL, and blocking CD14 or TLR4 resulted in a approximately 60% decrease in mmLDL-induced TNF-alpha secretion. We also observed similar inhibition of TNF-alpha synthesis in human monocytes ( approximately 65%) and macrophages ( approximately 70%) when both receptors were blocked simultaneously. When TLR2 was blocked, TNF-alpha synthesis was inhibited by approximately 70% in both cell types. Moreover mmLDL induced redistribution of CD14, TLR4, and TLR2 on the cell surface. This is the first evidence that TLR2 and TLR4 are upregulated in response to mmLDL. Our results suggest that mmLDL activates CD14, TLR4, and TLR2, inducing the production of TNF-alpha and increasing the expression of TLR2 and TLR4.

The effect of an anti-inflammatory pentapeptide produced by Entamoeba histolytica on gene expression in the U-937 monocytic cell line.

OBJECTIVE: Evaluate the Monocyte Locomotion Inhibitory Factor (MLIF) effect upon the expression of genes encoding human cytokines, receptors and related factors in the human cell line U-937. MLIF (Met-Gln-Cys-Asn-Ser) is an anti-inflammatory pentapeptide produced by Entamoeba histolytica that inhibits many human monocyte functions. MATERIAL AND METHODS: U-937 cell line cultured (24 hrs/RPMI). RNA extracted by Trizol method. 385 genes were analyzed on microarray membranes, complement by real-time RT-PCR and protein expression of some affected genes. RESULTS: MLIF had a preferentially inhibitory effect on gene expression; four genes were over-expressed and 13 underexpressed in MILF vs. simple medium - constitutive expression. Three genes are over-expressed and 19 under-expressed in MLIF/PMA vs. PMA - induced expression. CONCLUSIONS: Many modified genes are products regulated by the Nuclear Factor-kappaB and Mitogen Activated Protein Kinase pathways, suggesting MLIF involvement with these two major pathways for the modulation of the inflammation and immune responses.

[Eosinophils]. / Eosinófilos.

Although we still do not fully understand many aspects of eosinophil function, they are certainly active participants in important physiological and pathophysiological events. Eosinophils kill many species of helmints and other parasites and probably play a role in defence against infection; they also probably play a role in inflammatory responses in the lung, skin and heart. The following discussion will review finding that support such conclusions.

[Prolactin as an immunomodulator]. / Prolactina como inmunomodulador.

The aim of this revision is to explore the possible role of the prolactin in the immune response. The prolactin is a hormone secreted by the pituitary. However, it has a trophic function in the proliferation of the lymphocytes. The cell of the immune system show outer membrane receptor for the prolactin. Moreover, the lymphocytes are capable to produce and secret prolactin. In cell culture, different levels of prolactin show different immune responses- low levels of prolactin awake a weak immune response. In contrast, high levels of prolactin show a strong immune response. Alteration in the sera levels of prolactin has been describes in severe autoimmune disease like systemic lupus erythematosus. Reiter syndrome, adjuvant arthritis, uveitis etc. Until now many evidences has been reported about the roles of the prolactin in the immune response acting like an immunomodulator, but the relevance of this phenomena in the clinical practice is still unclear.

Association between prolactin and disease activity in systemic lupus erythematosus. Influence of statistical power.

OBJECTIVE: To analyze the statistical power of studies in the medical literature on the relationship between prolactin (PRL) and systemic lupus erythematosus (SLE) activity. METHODS: Published studies that were identified through MEDLINE search, as well as references from these articles, were reviewed. RESULTS: We identified 5 articles that sought to establish a relationship between PRL and SLE activity. In 4 of them, the frequency of hyperprolactinemia in SLE (>20 ng/ml) was 2.2-47.2%, and in one article, there was a relationship between PRL and SLE activity. A power analysis of individual studies could be carried out in only 2 of the 5; there were no significant effects; the 2 articles cited differences in the frequency of hyperprolactinemia in patients with and without lupus activity (1.6 and 12.3%, respectively), but because of a low power of the studies (> or =30.8%), it could not be determined whether the differences in the frequency of hyperprolactinemia were significant. On the other hand, joint analysis of 3 articles showed a significant association between hyperprolactinemia and lupus activity. CONCLUSION: Published clinical results concerning the relationship between PRL and Jupus activity are contradictory, due in part to the statistical power of the studies. Our analysis of these studies showed that PRL is related to lupus activity, without establishing a formal causal relationship.

Anti-prolactin autoantibodies in systemic lupus erythematosus patients with associated hyperprolactinemia.

Hyperprolactinemia has been found in a subset of systemic lupus erythematosus (SLE) patients. In order to explore whether antibodies to prolactin (PRL) play a role in SLE patients with associated hyperprolactinemia, we performed a cross-sectional study in which 259 consecutive SLE patients were tested for hyperprolactinemia and anti-prolactin autoantibodies. Forty-one (15.8%) had prolactin levels above the norm. The frequency of anti-PRL autoantibodies in hyperprolactinemia was 2/14 (14.3%). In the SLE patients with 'idiopathic hyperprolactinemia', 11/27 (40.7 %) had anti-PRL antibodies. The levels of serum PRL were significantly higher in patients with idiopathic hyperprolactinemia and anti-PRL autoantibody compared to the patients with idiopathic hyperprolactinemia who were anti-PRL autoantibody-negative. Patients with idiopathic hyperprolactinemia and anti-PRL autoantibody had relatively low SLE disease activity index (SLEDAI) scores and significantly different laboratory parameters compared to those with idiopathic hyperprolactinemia and no anti-PRL antibody. There was a significant correlation between titers of the anti-PRL autoantibody and serum PRL levels (rs = 0.98, P = 0.0001). These data suggest that anti-PRL antibodies could be the cause of hyperprolactinemia in a subset of SLE patients, especially those with particularly high serum prolactin levels with a diagnosis of 'idiopathic hyperprolactinemia'. The patients with anti-PRL antibody had fewer clinical manifestations and less serological activity, indicating that biological activity of PRL was attenuated by the autoantibody.

Analysis of anti-prolactin autoantibodies in systemic lupus erythematosus.

Evidence has shown that prolactin is an essential component of an effective immune response. In systemic lupus erythematosus, clinical trials have produced controversial information about the role of PRL. Some results find association between serum PRL levels and disease activity. In contrast, other authors did not find this. Recently, autoantibodies against prolactin in SLE patients have been described. One hundred percent of SLE patients with anti-PRL autoantibodies had hyperprolactinemia (hPRL) and 31.7% of the SLE patients classified with idiopathic hPRL had anti-prolactin antibodies. A similar result was found in 103 pediatric SLE patients. The patients with idiopathic hyperprolactinemia and anti-PRL autoantibodies had less clinical and serological lupus activity than the SLE patients with idiopathic hyperprolactinemia, but without anti-PRL autoantibodies. This evidence suggests that anti-PRL autoantibodies or the complex with any other molecule, like macroprolactinemia (big-big PRL) could have attenuated biological activity and this could explain why some clinical studies did not find any association between serum PRL levels and disease activity in SLE patients. However, studies in vitro have shown normal or elevated biological activity in Nb2 cell lines using PRL from serum with anti-PRL autoantibodies from patients with or without autoimmune diseases. Several conclusions could be drawn. One is that while a set of hyperprolactinemic SLE patients display autoantibodies against PRL, it is not clear what role these autoantibodies play in the whole system. However, until now, we knew that the patients with antibodies to PRL lacked the clinical symptoms of hyperprolactinemia such as menstrual disturbances and/or galactorrhea and show less clinical and serological lupus activity.