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Biomedical subjects

E Ortega

Publications and source records attributed to E Ortega.

At least 55 records · Page 3Linked to original sources

Dehydroepiandrosterone sulfate and growth axis hormones in patients with ischemic heart disease.

BACKGROUND: The present study aimed to determine whether decreases in dehydroepiandrosterone sulfate (DHEA-S) and growth axis components precede cardiovascular disease or are a consequence of it. METHODS: We measured the concentrations in serum of DHEA-S, ACTH, cortisol, growth hormone, insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in 30 male controls and also in 37 male patients on days 0, 2, 5, 7 and 9 after suffering a myocardial infarction (MI). RESULTS: There was no significant variation in any of these parameters between the controls and the patients on day 0. However, we found a significant (p < 0.001) reduction in the DHEA-S concentrations of the patients between day 0 and subsequent days (days 2, 5, 7 and 9). CONCLUSION: We conclude that the decrease in DHEA-S in patients with MI is a consequence and not a cause of the disease.

Adrenocorticotropic Hormone↗

[Evolution of perinatal Escherichia coli disease in the era of group B Streptococcus prophylaxis].

BACKGROUND: The aim of this study was to characterize perinatal Escherichia coli disease, and to analyze its possible correlation with the employment of prophylaxis for group B streptococcal (GBS)disease. PATIENTS AND METHOD: Between 1994 and 2000, 24 neonates born in our hospital were diagnosed of early-onset E. coli disease: 12 born to mothers who received prenatal care in our center and 12 born to mothers who were referred from other hospitals shortly before labor. Three further neonates born in other centers were also referred with the same diagnosis. RESULTS: The annual rate did not change significantly (RR:1.065; confidence interval [CI] 95% -0.873-1.301; p = 0.533):from 0.6 per 1,000 live births in 1994 to 1.7 per 1,000 in 1997 and 0.5 in 2000. Among mothers, 92% presented obstetric risk factors including 68% with prematurity (mean 32.9 gestation weeks, median 32), 64% with prolonged rupture of membranes (mean 184 hours,median 44), and 56% with intrapartum fever. Twelve percent of mothers received intrapartum ampicillin as prophylaxis against GBS and 80% received antibiotics: prophylaxis for rupture of membranes in 6 cases, treatment of urinary tract infection in 6 cases and treatment of probable chorioamnionitis in 8 cases. Ampicillin-resistant E. coli was isolated in 81% of neonates. No significant correlation was found between ampicillin resistance and prematurity(p = 0.57), rupture of membranes (p = 0.63), intrapartum fever(p = 0.24) or death (p = 0.53). CONCLUSIONS: Our results suggest that perinatal E. coli disease is not related with the employment of prophylaxis against GBS disease. Instead, it seems to be related with prematurity, prolonged gestation in premature rupture of membranes and exposure to antibiotics.

Bacteremia↗

Overcoming the signaling defect of Lyn-sequestering, signal-curtailing FcepsilonRI dimers: aggregated dimers can dissociate from Lyn and form signaling complexes with Syk.

Clustering the tetrameric (alphabetagamma(2)) IgE receptor, FcepsilonRI, on basophils and mast cells activates the Src-family tyrosine kinase, Lyn, which phosphorylates FcepsilonRI beta and gamma subunit tyrosines, creating binding sites for the recruitment and activation of Syk. We reported previously that FcepsilonRI dimers formed by a particular anti-FcepsilonRI alpha mAb (H10) initiate signaling through Lyn activation and FcepsilonRI subunit phosphorylation, but cause only modest activation of Syk and little Ca(2+) mobilization and secretion. Curtailed signaling was linked to the formation of unusual, detergent-resistant complexes between Lyn and phosphorylated receptor subunits. Here, we show that H10-FcepsilonRI multimers, induced by adding F(ab')(2) of goat anti-mouse IgG to H10-treated cells, support strong Ca(2+) mobilization and secretion. Accompanying the recovery of signaling, H10-FcepsilonRI multimers do not form stable complexes with Lyn and do support the phosphorylation of Syk and phospholipase Cgamma2. Immunogold electron microscopy showed that H10-FcepsilonRI dimers colocalize preferentially with Lyn and are rarely within the osmiophilic "signaling domains" that accumulate FcepsilonRI and Syk in Ag-treated cells. In contrast, H10-FcepsilonRI multimers frequently colocalize with Syk within osmiophilic patches. In sucrose gradient centrifugation analyses of detergent-extracted cells, H10-treated cells show a more complete redistribution of FcepsilonRI beta from heavy (detergent-soluble) to light (Lyn-enriched, detergent-resistant) fractions than cells activated with FcepsilonRI multimers. We hypothesize that restraints imposed by the particular orientation of H10-FcepsilonRI dimers traps them in signal-initiating Lyn microdomains, and that converting the dimers to multimers permits receptors to dissociate from Lyn and redistribute to separate membrane domains that support Syk-dependent signal propagation.

Animals↗

Involvement of pp125FAK and p60SRC in the signaling through Fc gamma RII-Fc gamma RIII in murine macrophages.

Cross-linking the FcgammaRs can activate a wide variety of biological responses in macrophages. Receptor stimulation induces activation of protein tyrosine kinase cascades that result in phagocytosis, a process known to involve cytoskeletal rearrangements. Therefore, an involvement of non-receptor tyrosine kinases such as pp125FAK, in FcgammaR signaling is likely. Using the murine macrophage cell line J774, we demonstrate that FcgammaRII-RIII cross-linking induces a time- and dose-dependent increase in tyrosine phosphorylation of the focal adhesion kinase pp125FAK that correlates with an increase in its catalytic activity. Interestingly enough, pp125FAK activation results in its association both to the FcgammaRII-III and to p60Src. The results presented here define a novel-signaling pathway likely to be important in low affinity FcgammaRII-III mediated phagocytosis.

Animals↗

The use of 7-amino-actinomycin D in the analysis of Candida albicans phagocytosis and opsonization.

We describe the use of 7-amino-actinomycin D (7AAD) to measure phagocytosis and the opsonizing capacity of serum. Heat-inactivated Candida albicans was previously stained with 7AAD and incubated with resident peritoneal macrophages. The samples were analyzed by flow cytometry and phagocytic cells were identified by their bright red fluorescence. This is a rapid, reproducible and reliable one-step procedure and provides a means of evaluating low levels of phagocytosis.

Animals↗

Phyllodes tumor of the breast with actin inclusions in stromal cells: diagnosis by fine-needle aspiration cytology.

The occurrence of hyaline inclusions in stromal cells in fibroepithelial tumors of the breast is very uncommon. These inclusions, characteristic of infantile digital fibromatosis, are comprised of actin filaments. This report illustrates a case of a benign phyllodes tumor of the breast with inclusion bodies, identified by fine-needle aspiration. Histologically, many of the stromal cells contained round intracytoplasmic inclusions, with positivity for smooth muscle actin.

Adult↗

Potential intervention of Campylobacter jejuni in the modulation of murine immune response.

Campylobacter jejuni has been reported to produce different toxins that may modulate the immune response in both animals and humans. The effect of C. jejuni enterotoxin on the immune response was investigated in two groups of Balb/c mice. One of them was inoculated intraperitoneally with 1010 colony forming units (CFU) of an enterotoxigenic strain (CCUG 7580), and the second one with a non-enterotoxigenic strain (CCUG 7440). The number of polymorphonuclear (PMN) cells from spleen increased in both enterotoxigenic and non-enterotoxigenic strains as a consequence of C. jejuni infection. Notwithstanding, lymphocyte proliferation stimulated by lipopolysaccharide (LPS) was increased by both enterotoxigenic and non-enterotoxigenic strains. Interleukin-2 (IL-2) production from splenic cells was increased significantly by infection with the enterotoxigenic strain. Both enterotoxigenic and non-enterotoxigenic strains reduced the splenic response to sheep erythrocytes; the response was significantly suppressed for immunoglobulin M (Ig M) and for immunoglobulin G (Ig G) synthesis. These results suggest that C. jejuni is able to modify some components of the immune response in mice, and also that the enterotoxigenic strain has more immunomodulating activity than the non-enterotoxigenic strain.

Animals↗

Effects of CRH and ACTH administration on plasma and brain neurosteroid levels.

The 3alpha-hydroxy ring A-reduced metabolite of progesterone, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) is among the most potent known ligands of the gamma aminobutyric acid (GABA) receptor, designated GABA-A, in the central nervous system. We determined by RIA serum levels of progesterone (PROG), 5-alpha-dihidroprogesterone (DHP) and allopregnanolone in male and female rats after corticotropin releasing hormone (CRH) and adrenocorticotropin hormone (ACTH) administration. Allopregnanolone was undetectable in plasma and brain of control males but detectable in plasma and brain of males injected with CRH and ACTH and of control and similarly treated females. Allopregnanolone increased in the plasma and brain after CRH and ACTH administration in all cases. The data demonstrate that the administration of CRH plus ACTH results in a rapid increase of the neuroactive steroid allopregnanolone in the brain of males and females to levels known to modulate GABA-A receptor function. Thus, stress could regulate neurosteroid biosynthesis via the hormones ACTH and CRH.

20-alpha-Dihydroprogesterone↗

Decreased insulin requirements after LAR-octreotide but not after lanreotide in an acromegalic patient.

A diabetic acromegalic man, not cured after surgery and radiosurgery, received lanreotide i.m. with great clinical and biochemical improvement. He required NPH insulin (76 to 84 units/day) to control his diabetes mellitus. Thirty-six hours after changing to LAR-octreotide (20 mg i.m/month) he presented symptomatic hypoglycemia, repeated at 48 and 72 h (50 mg/dL), despite reducing insulin to 26 Units/day. Thereafter, he reduced insulin by 30 to 50% for the first week after each LAR-octreotide injection, and gradually increased it again over the next 3 weeks. This situation persists after every injection 3 years later; this consistent behavior supports a specific effect of LAR-octreotide, and not a by chance phenomenon. No marked changes in circulating GH, IGF-1, immunoreative insulin, C-peptide, testosterone and glucose were observed prior to, and 3, 7, 14, 21, and 28 days after LAR-octreotide; however, there was 28% fall in plasma glucagon after 7 days, which rose thereafter. C-peptide (< 1.8 ng/mL) was indicative of decreased beta-cell function. To our knowledge, this is the first report of such a distinct differential behaviour of blood glucose and insulin requirements with different somatostatin analogs, and is worth recalling when starting an insulin-treated diabetic patient on this treatment. It may be related to a preferential binding of LAR-octreotide to subtype 2 somatostatin receptors in the pancreas, while lanreotide preferentially binds to subtype 5, not expressed in this tissue; this would explain the fall in glucagon, in parallel to the decrease in insulin requirements after LAR-octreotide; however, a contribution of differences in the effect of both somatostatin analogues on postreceptor signalling systems and/or intestinal carbohydrate absorption cannot be entirely ruled out.

Acromegaly↗

Circadian rhythm of melatonin, corticosterone and phagocytosis: effect of stress.

Melatonin has a functional connection with the immune system. Phagocyte function is altered by extirpation of the pineal gland, one source of melatonin, or by in vitro incubation of phagocytes with pharmacological concentrations of melatonin. Given that its synthesis by pinealocytes is under the control of the noradrenaline released by the sympathetic postganglionaric nerve endings, the present work was aimed at evaluating the circadian rhythm of melatonin, corticosterone, and phagocytosis in BALB/c mice in basal and stress situations. Peritoneal macrophages were used as phagocytes, latex beads as the particles to be ingested, and forced swimming to exhaustion as the stress situation. Radioimmunoassay was used to determine the animals' serum hormone levels. Samples were taken every 3 hr in the period from 04:00 to 22:00 hr, and every 30 min during the remaining period from 22:00 to 04:00 hr. Control mice presented a short-term melatonin peak at 23:30 hr, while the maximum inert-particle ingestion capacity of the peritoneal macrophages also occurred during the night but at 03:30 hr. The corticosterone levels in control mice presented a circadian rhythm with a day-time maximum peak (16:00 hr). Compared with the controls, the animals subjected to stress maintained, although at lower values, the melatonin peak at 23:30 hr, but they presented a loss of the rhythm of serum corticosterone levels, and the corticosterone levels and the macrophage phagocytic capacity were greater at all hours of the day.

Animals↗

Physiological concentrations of melatonin and corticosterone affect phagocytosis and oxidative metabolism of ring dove heterophils.

A functional connection between the neuroendocrine and the immune systems has been established. Of particular interest is the finding that hormones such as melatonin and corticosterone are able to exert modulating effects on the immune function. Therefore, after determining the circadian rhythms of melatonin and corticosterone, we evaluated the in vitro effect of physiological concentrations of melatonin and corticosterone, separately and together, on the phagocytic function and superoxide anion levels of heterophils in ring dove (Streptopelia risoria). Trials were performed with concentrations corresponding to the nocturnal and diurnal levels reached by each of the hormones (50:300 pg/mL and 100:10 ng/mL for melatonin and corticosterone, diurnal:nocturnal, respectively). The phagocytes were incubated with the hormones both alone and concurrently. At the highest (nocturnal) concentration, melatonin augmented phagocytic function and at the same time inducing a fall in superoxide anion levels. At the highest (diurnal) concentration, corticosterone also enhanced phagocytic function, but without modifying the phagocyte oxidative metabolism. In the presence of both hormones, however, whether with nocturnal or diurnal concentrations, there was a greater increase in phagocytic function and a decrease in superoxide anion levels than was produced by either of the hormones alone. In conclusion, our findings suggest that melatonin and corticosterone may have an additive effect in the modulation of phagocytic function.

Animals↗

Persistence of respiratory syncytial virus in macrophages alters phagocytosis and pro-inflammatory cytokine production.

Functions of macrophage are known to be altered by acute infection with respiratory syncytial virus (RSV). However, it is unknown whether the persistent presence and expression of the RSV genome have any effect on the functions of these cells. We used a murine macrophage-like cell line (P388D1) persistently infected with RSV to determine: (i) phagocytic activity mediated by Fcgamma receptors, (ii) expression of Fcgamma receptors, and (iii) production of IL-1beta, IL-6 and TNF-alpha. Viral persistence was found to increase phagocytosis, expression of Fcgamma receptors and the production of IL-1beta and IL-6. In contrast the biological activity of secreted TNF-alpha decreased. In this study we give novel evidence that RSV persistence alters the biological activities of macrophages.

Animals↗

Mechanistic aspects of the induction of apoptosis by lauryl gallate in the murine B-cell lymphoma line Wehi 231.

The effect of lauryl gallate (antioxidant E-312) has been studied on the mouse B-cell lymphoma line Wehi 231. This compound is able to inhibit protein tyrosine kinases (PTKs) in whole cells and in crude extracts with a better efficiency than other well-known PTK inhibitors such as herbimycin or genistein. Initial events triggered upon the incubation of cells with lauryl gallate in phosphate-buffered saline (up to 1 h) include the inhibition of tyrosine phosphorylation, discharge of the mitochondrial transmembrane potential, and induction of mRNA for Bcl-2. Long-term cultures in complete medium supplemented with fetal calf serum (up to 24 h) in the presence of this compound exhibit clear apoptotic features such as increase in phosphatidylserine in the cell surface, decrease in the functionality of mitochondria, cytochrome c release to the cytosol, activation of caspases, hypodiploidy, and oligonucleosomal breakdown of DNA. Comparison between Wehi cells overexpressing Bcl-2 (Wehi-bcl-2) with Wehi-neo cells shows a delay in the manifestations of the apoptotic signs, indicating that Bcl-2 has a partial protective effect on the apoptosis induced by lauryl gallate. The proapoptotic effect of lauryl gallate is not dependent on DNA or protein synthesis, is not blocked by the chelation of calcium, and is not reverted by N-acetylcysteine.

Acetylcysteine↗

Effects of acute alcohol intoxication on growth axis in human adolescents of both sexes.

We previously reported the deleterious effects of acute alcohol intoxication (AAI) on pituitary-gonadal and pituitary-adrenal axes hormones in human adolescents. In the present paper we studied the effects of AAI on the growth axis hormones, and the possible contribution of the insulin-glucose axis to the alcohol-induced dysfunction of the growth axis in human adolescents. Blood samples were drawn from adolescents that arrived at the emergency department with evident behavioural symptoms of drunkenness (AAI) or with nil consumption of alcohol (controls [C]). AAI produced in the adolescents of both sexes in our series: a decrease in growth hormone (GH) levels, without significant alteration of either insulin-like growth factor-I (IGF-I) or insulin-like growth factor binding protein-3 (IGFBP3); an increase in plasma glucose and a decrease in insulin in the female adolescents but not in the males. Males and females undergo a significant period of bone growth during adolescence. Growth axis hormones play an important role in the pubertal spurt. Thus, ethanol consumption during adolescence could have long-lasting deleterious effects on this aspect of development. In industrialised countries, around 35% of alcohol drinkers are under 16 years old, therefore the result of this study should be made known to adolescents and the appropriate authorities.

Adolescent↗

Changes with aging in the modulation of macrophages by norepinephrine.

The effect of aging on the norepinephrine (NE)-induced modulation of phagocytic and oxygen-dependent microbicidal processes of mouse peritoneal macrophages was studied. Phagocytosis of latex beads on culture plates and superoxide anion production was evaluated in young (12 weeks), adult (22 weeks), mature (48 weeks) and old (72 weeks) BALB/c mice after in vitro incubation with 10(-12), 10(-9), 10(-7), 10(-5) or 10(-3) M concentrations of NE. The results indicate that the phagocytic response to NE is quite similar in young and mature mice, with increased phagocytosis after incubation with 10(-7) and 10(-3) M, and decreased phagocytosis with 10(-5) M. Macrophages from adult mice increased their phagocytic capacity after incubation with the highest concentrations of NE (10(-5) and 10(-3) M) and macrophages from old animals only were stimulated with 10(-3) M. In addition, it was found that usually NE increased the extracellular superoxide anion production in the absence of phagocytosis in adult mice. No statistically significant changes were found in intracellular superoxide anion levels, but an increase was seen after phagocytosis in macrophages from adult, mature and old animals, especially after incubation with 10(-5) M. In conclusion, the results obtained indicate that the modulation of macrophages by NE does not only depend on the concentration of this neurotransmitter, but also on age.

Aging↗

Immunologically mediated signaling in basophils and mast cells: finding therapeutic targets for allergic diseases in the human FcvarepsilonR1 signaling pathway.

The high affinity IgE receptor, FcvarepsilonRI, plays key roles in an array of acute and chronic human allergic reactions including asthma, allergic rhinitis, atopic dermatitis, urticaria and anaphylaxis. In humans and rodents, this receptor is found at high levels on basophils and mast cells where its activation by IgE and multivalent antigen produces mediators and cytokines responsible for FcvarepsilonRI-dependent acute inflammation. Mast cells can additionally contribute to sustained inflammatory responses by internalizing antigen bound to IgE-FcvarepsilonRI complexes for processing to peptides and presentation to T cells. In humans, the FcvarepsilonRI is also expressed, at lower density, on monocytes, macrophages and dendritic cells (DC) where its likely functions again include both signaling to mediator and cytokine production and antigen presentation. Our laboratories have focused on defining the earliest steps in the FcvarepsilonRI signaling cascade in basophils and mast cells and on developing new routes to control allergic inflammation based on inhibiting these events. Here, we describe novel strategies to limit antigen-stimulated FcvarepsilonRI signaling by: (1) sequestering the FcvarepsilonRI-associated protein-tyrosine kinase, Lyn, that initiates FcvarepsilonRI signaling; (2) eliminating; or (3) inactivating the protein-tyrosine kinase, Syk, that propagates FcvarepsilonRI signaling; and (4) establishing inhibitory crosstalk between FcvarepsilonRI and a co-expressed receptor, FcgammaRII, that again limits FcvarepsilonRI-mediated Syk activation. These strategies may form the basis for new therapies for allergic inflammation.

Animals↗

Effects of acute alcohol intoxication on pituitary-gonadal axis hormones, pituitary-adrenal axis hormones, beta-endorphin and prolactin in human adolescents of both sexes.

Teenage drinking continues to be a major problem in industrialized countries, where almost 35% of alcohol drinkers are under 16 years old. In the present paper we studied the effects of acute alcohol intoxication (AAI) on the pituitary-gonadal (PG) axis hormones, and the possible contribution of pituitary-adrenal (PA) axis hormones, beta-endorphin (BEND), and prolactin (PRL) to the alcohol-induced dysfunction of PG axis hormones. Blood samples were drawn from adolescents that arrived at the emergency department with evident behavioral symptoms of drunkenness (AAI) or with nil consumption of alcohol (controls [C]). Our results demonstrated that AAI produces in adolescents a high increase in plasma PRL, ACTH, and cortisol (F), and a contradictory behavior of testosterone (T) according to gender: plasma T was increased in females and decreased in males. ACTH and PRL correlated positively with F, dehydroepiandrosterone-sulphate (DHEAS) and T in females, which suggests that PRL and ACTH could synergistically stimulate adrenal androgen production. In contrast, the decrease in T and increase in BEND in males suggests that AAI could have an inhibitory effect on testicular T, perhaps mediated by BEND. The hormones studied are involved in the development of secondary sexual characteristics and the growth axis during adolescence. The deleterious effects of alcohol abuse should be made known to adolescents and the appropriate authorities.

Acute Disease↗

Modification of acquired immunity in BALB/c mice by aztreonam.

Recent studies have suggested that antibiotics may act as biological response modifiers. In this study we investigated the effect of aztreonam, a monobactam antibiotic, on different parameters of acquired immunity in BALB/c mice. Different dosages of aztreonam injected into mice induced an increase in the lymphoproliferative response to specific mitogens and in the production of interleukin-2 by splenic cells, as well as a decreased response of this immune population to sheep erythrocytes lower total blood cell counts and a lower percentage of monocytes than in untreated mice. These results show a modulatory action of aztreonam on different immune parameters, which is independent of its antimicrobial activity and that could be of interest in human therapy.

Animals↗