Gene variants in the FTO gene are associated with adiponectin and TNF-alpha levels in gestational diabetes mellitus.

BACKGROUND: Obesity may have a role in the development of gestational diabetes mellitus (GDM). Single-nucleotide-polymorphisms (SNPs) of the FTO (fat mass and obesity associated) gene have been associated with obesity. The aim of this study was to investigate SNPs rs8050136, rs9939609, and rs1421085 of the FTO gene in women with GDM and their associations with maternal pre-pregnancy weight and body mass index, gestational weight gain and mediators of insulin resistance in GDM like leptin, adiponectin, ghrelin and tumor necrosis factor-alpha (TNF-alpha), compared with healthy pregnant controls. METHODS: 80 women with GDM and 80 women with normal pregnancy were considered for the present study. Genotyping of selected SNPs in all study subjects was done using the Taq-Man assay and the adipokines and ghrelin were measured by immunoassays. Chi square test, odds ratios (OR) and their respective 95% confidence intervals were used to measure the strength of association between FTO SNPs and GDM. RESULTS: There was no association among FTO SNPs and GDM. Interestingly, in GDM group, women carrying the risk alleles of the three SNPs had increased TNF-alpha, and decreased adiponectin levels; these associations remained significant after adjusting for pre-gestational body weight and age. Moreover, the risk allele of rs1421085 was also associated with increased weight gain during pregnancy. CONCLUSIONS: The FTP SNPs rs8050136, rs9939609, and rs1421085 are not a major genetic regulator in the etiology of GDM in the studied ethnic group. However, these SNPs were associated with adiponectin and TNF-alpha concentrations in GDM subjects.

Transforming growth factor beta and platelets in allergic rhinitis and sinusitis.

OBJECTIVE: To determine the TGF-? concentration in plasma and platelets in patients with allergic rhinitis or rhinosinusitis. METHODS: The study group included 36 adult females, 6 with clinical and laboratory diagnoses of allergic rhinitis, 18 with allergic rhinitis and sinusitis (rhino-sinusitis) and 12 clinically healthy controls. The samples were obtained from venous blood. TGF-? was measured in plasma and in the supernatant fluid of platelets by a solid phase Enzymo-immun assay, and IL-11 was quantified using a commercial enzyme-linked immunosorbent assay kit. RESULTS: In both patient groups platelet numbers (106/mL) were greater than in controls. Plasma concentration (pg/ml) of TGF-? in the allergic rhinitis group (276 ± 16) was lower than in control group (932 ± 99) (p <0.005), whereas in patients with rhino-sinusitis was higher (2606 ± 612) (p <0.005). In both patients groups, the intra-platelet TGF-? concentration was smaller than in control, but only significant (p <0.005), in allergic rhinitis patients. However, in all groups, an inverse correlation (p <0.0001) was found between the platelet number and intraplatelet TGF-? levels. CONCLUSIONS: The inverse correlation between intra-platelet TGF-? and circulating platelets number found in all individuals studied suggests that platelets do not alter the regulating mechanism of TGF-? production in allergy or infection.

Cytokine expression in CD4(+) cells exposed to the monocyte locomotion inhibitory factor produced by Entamoeba histolytica.

Entamoeba histolytica produces monocyte locomotion inhibitory factor (MLIF), a pentapeptide with in vitro and in vivo anti-inflammatory properties. MLIF may interfere with leukocyte migration, disturbing the balance of pro- and anti-inflammatory cytokines secreted by CD4(+) T lymphocytes. We evaluated the effect of MLIF on expression of pro- and anti-inflammatory cytokines in human CD4(+) T lymphocytes. Regulatory cytokines [interleukin-1 beta (IL-1beta), IL-2, interferon gamma (IFN-gamma), IL-5, IL-6, and IL-10] were studied by enzyme-linked immunosorbent assay method in CD4(+)-cell supernatant fluids. Proinflammatory cytokines were produced per se by MLIF (IL-1beta, IL-2, and IFN-gamma) and also anti-inflammatory cytokines (IL-5, IL-6, and IL-10) with 1-phorbol-12 myristate-13 acetate + MLIF; the IL-1beta, IFN-gamma, IL-5 and IL-6 production was inhibited but not that of IL-10 which disclosed increase in its expression. MLIF disturbs the pro- and anti-inflammatory balance, and it induces inhibition of IL-1beta (principal proinflammatory cytokine) and increases IL-10 (prototype of an anti-inflammatory cytokine).

Effect of zinc-treated Entamoeba histolytica on the human polymorphonuclear respiratory burst.

One of the mechanisms that Entamoeba histolytica uses to evade host immune response is inhibition of the polymorphonuclear (PMN) leukocyte respiratory burst. In studies previously conducted in a model used in our laboratory, we observed that when treating trophozoites with different zinc concentrations certain amebic functions are inhibited while significantly limiting development of hepatic abscess in golden hamsters (Mesocricetus aureatus). We carried out an in vitro study using a chemoluminescent method to assess the effect zinc-treated amebic trophozoites exercise on respiratory burst in human PMNs. We measured response of PMNs incubated with E. histolytica trophozoites from cultures with TYI-S33 medium alone and with zinc. Zinc concentrations between 0.1 and 1.0 mM did not affect amebic trophozoite viability, and PMNs in contact with these in a zinc-free medium had an oxidative response similar to that obtained with zymosan and significantly greater (p <0.05) than that generated by cells co-incubated with amebas cultured in TYI-S33 medium alone. These results suggest that zinc alters the amebic mechanism that inhibits the oxidative function of human polymorphonuclear leukocyte.

Immunization with a tetramer derivative of an anti-inflammatory pentapeptide produced by Entamoeba histolytica protects gerbils (Meriones unguiculatus) against experimental amoebic abscess of the liver.

Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with several anti-inflammatory properties, including the inhibition of human monocyte locomotion (Monocyte Locomotion Inhibitory Factor (MLIF)). A construct displays the same effects as the native material. It remains to be seen if MLIF is used, or even produced in vivo by the tissue-invading parasite. If MLIF were to be relevant in invasive amoebiasis, immunizing against it could diminish this parasite advantage and prevent lesions. KLH-linked MLIF mixed with Freund's adjuvant was too aggressive an immunizing material to answer this question. However, immunization with a tetramer of MLIF (but not a scrambled version of MLIF) around a lysine core (MLIF-MAPS), that displays increased antigenicity, yet lacks excessive innate immunity activation, completely protects gerbils against amoebic abscess of the liver caused by the intraportal injection of virulent E. histolytica. Liver abscesses caused by Listeria monocytogenes were not prevented. Invasive E. histolytica may produce the parent protein of MLIF in vivo, and if appropriately cleaved, it may play a role in invasive amoebiasis. MLIF may join new vaccination strategies against amoebiasis.

[Progressive motility increase caused by L-arginine and polyamines in sperm from patients with idiopathic and diabetic asthenozoospermia]. / Aumento de movilidad progresiva por L-arginina y poliaminas en espermatozoides de pacientes con astenozoospermia idiopática y diabética.

This study was designed to investigate the in vitro effect of L-arginine and polyamines putrescine, spermidine, and spermine on sperm motility of asthenozoospermic idiopathic and diabetic patients. 10 semen samples were obtained from healthy male volunteers. Other 10 samples were from men with idiopathic asthenozoospermia and 13 samples were from men with diabetes mellitus type 1. In vitro effect of L-arginine and polyamines on sperm motility type a was studied. In addition, concentration of L-arginine and polyamine levels was measured in seminal plasma. Addition of L-arginine or polyamines to sperm cells suspensions resulted in significant differences in motility type a. L-arginine concentrations in seminal plasma were similar in the three groups. Putrescine and spermidine levels in seminal plasma of diabetic patients were lower than those of healthy patients (p < or = 0.003 and p < or = 0.004, respectively). In asthenozoospermic patients, only spermidine was lower (p < or = 0.009). We can conclude that under the conditions of this study, the addition of L-arginine and polyamines to human sperm cells obtained from idiopathic or diabetic asthenozoospermic patients showed a beneficial effect on sperm motility.

An anti-inflammatory oligopeptide produced by Entamoeba histolytica down-regulates the expression of pro-inflammatory chemokines.

Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with anti-inflammatory properties that, among others, inhibits the in vitro and in vivo locomotion of human monocytes, sparing polymorphonuclear leucocytes from this effect [hence the name originally given. Monocyte Locomotion Inhibitory Factor (MLIF)]. A synthetic construct of this peptide displays the same effects as the native material. We now added MLIF to resting and PMA-stimulated cells of a human monocyte cell line and measured the effect upon mRNA and protein expression of pro-inflammatory chemokines (RANTES, IP-10, MIP-1alpha, MIP-1beta, MCP-1, IL-8, I-309 and lymphotactin) and the shared CC receptor repertoire. The constitutive expression of these chemokines and the CC receptors was unaffected, whereas induced expression of MIP-1alpha, MIP-1beta, and I-309, and that of the CCR1 receptor--all involved in monocyte chemotaxis--was significantly inhibited by MLIF. This suggests that the inhibition of monocyte functions by MLIF may not only be exerted directly on these cells, but also--and perhaps foremost--through a conglomerate down-regulation of endogenous pro-inflammatory chemokines.

Transdermal estradiol in menopausal women depresses interleukin-6 without affecting other markers of immune response.

OBJECTIVE: The aim of this study was to analyze the effect of transdermal estradiol replacement therapy (HRT) on immune function in menopausal women. STUDY DESIGN: A prospective comparative study was carried out in 30 women, aged 48-55 years, who were divided into two groups; 20 of them received transdermal estradiol 50 microg/day during 3 months and 10 who refused to receive HRT served as controls. Serum interleukins were quantified by specific immunoenzymatic assays; in addition, hormones of somatotropin axis and prolactin (PRL) were quantified by IRMA and RIA. RESULTS: Baseline elevated interleukin (IL)-6 levels decreased significantly (p < 0.001) after transdermal HRT as compared with the nontreated group. Contrarily, IL-2 and IL-10 levels as well as mitogenic induced T-cell proliferation were unchanged under HRT. Insulin-like growth factor-I, growth hormone and PRL levels were unaltered by transdermal HRT. CONCLUSION: Decrement of IL-6 in parallel with absent effect on some indices of immune activity suggests a beneficial action of transdermal HRT. These findings contrast with those demonstrating an increment of immune response in women taking oral HRT. Thus, the route of administra tion determines the effect of HRT on immune function.

Defective production of reactive oxygen intermediates (ROI) in a patient with recurrent amebic liver abscess.

Previously, we reported the case of a man in the fourth decade of life afflicted with three independent episodes of amebic liver abscesses over a period of 4 years. Previous evidence has indicated that the cellular immune response is involved in protection against recurrent invasive amebic infection, and macrophage-mediated effector mechanisms appear important for host resistance to Entamoeba histolytica infection. The aim of the present work was to investigate locomotor activity and oxidative burst function of peripheral mononuclear cells of this individual after healing of the third amebic liver abscess. A locomotion assay using Boyden chemotaxis chambers and the respiratory burst evaluated by chemiluminescence were performed in both mononuclear phagocytes (MPs) and polymorphonuclear (PMN) leukocytes. Levels of salivary IgA and serum IgG anti-amebic antibodies were followed during 48 months after the second amebic liver abscess. Results obtained showed a deficiency in MP but not in PMN leukocyte respiratory burst. Respiratory burst is a major microbicidal mechanism in MP leukocytes; this also has been considered as a host resistance strategy against E. histolytica. It may be at least one risk factor in our patient that was responsible for recurrence of amebic liver abscess.

Calreticulin-like molecule in trophozoites of Entamoeba histolytica HM1:IMSS (Swissprot: accession P83003).

In this work, we report the partial sequence of a 51 kDa protein of Entamoeba histolytica that is highly immunogenic in humans. Partial sequencing of the N-terminal end showed that 18 of the first 20 amino acid residues of the protein were identified uniquely, indicating that the final product was a homogeneous protein preparation. The N-terminal sequence that was found was: KVYFEETFENGWKXIWSKW. Comparing the 19-amino acid sequence of the protein in automated databases shows significant similarity with amino acid sequences of the calreticulin-like protein of spinach leaves (77%) and of the calreticulin precursor of Dictyostelium discoideum (60%).

Síndrome de hiper IgE con tratamiento de interferón alfa 2 beta. Reporte de un caso / Syndrome of hiper IgE with interferon processing alpha 2 beta. Report of a case

El síndrome de hiper IgE (SHIE) se caracteriza por abscesos recurrentes en la piel y las vías respiratorias. Se acompaña, además, de dermatitis pruriginosa. Los datos encontrados en el laboratorio son: hipergammaglobulinemia E, eosinofilia en sangre, esputo y tejidos, además de defectos en la quimiotaxis y fagocitosis. Hasta 1972 se habían reportado 150 casos en todo el mundo; no hay diferencias geográficas y predomina en el sexo masculino en relación de 2:1. Las modalidades terapéuticas son aún controversiales. Con el uso de gammaglobulina se han reportado efectos benéficos pero no contundentes. La terapia con interferón alfa 2 beta es una alternativa de tratamiento importante de la inflamación de la dermis y de la cantidad de IgE sérica. Se presenta el caso de un paciente con síndrome de hiper IgE, que no reaccionó favorablemente a la terapéutica habitual, por lo que se inició el manejo con interferón alfa 2 beta a dosis de 3 millones de unidades dos veces por semana. Con este esquema terapéutico se indujo la remisión de las lesiones dérmicas en más del 80 por ciento de la superficie corporal, así como la ausencia de síntomas respiratorios. Los exámenes de laboratorio mostraron una reducción en la concentración de IgE sérica de 12,000 a 679 Ul/mL, se normalizó la función fagocitaria y la actividad quimiotáctica de los eosinófilos, todo lo anterior sin efectos secundarios en el paciente.

The ultrastructure of Entamoeba histolytica locomotion

This quantitative ultrastructural survery of E. histolytica locomotion in Boyden chambers supports the concept that this parasitis is capable of random, chemokinetic and chemotactic motility. An E. histolytica committed to chemotaxis will flatten over the filter, accumulate smaller vacuoles at the front of the cell, and will also project pseudopods and its polarized body towards and alongside the chemoattractant axis, respectively. Other cell features such as cell polarization, membrane ruffling, hyaline, total number of pseudopods and caudal displacement of the nucleus appear to be associated with the locomotion efforts as such, perhaps reflecting speed (chemokinesis) but irrespective of orientation (chemotaxis). Finally, only on of the 11 features that were analyzed (i.e., number of vacuoles) failed to be distinctly associated with any of the movement forms studied. E. histolytica appears to possess the full repertoire of locomotion modalities observed in free moving eukaryots, and its motility translates into ultrastructural landmarks that could be useful indicators of subcellular events related to locomotion