[Maniac episode associated with stage C3 HIV infection].
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AIDS Dementia Complex↗
Biomedical subjects
E Ortega
Publications and source records attributed to E Ortega.
7-Azetidinylquinolones as antibacterial agents. 3. Synthesis, properties and structure-activity relationships of the stereoisomers containing a 7-(3-amino-2-methyl-1-azetidinyl) moiety.
A series of stereochemically pure 7-(3-amino-2-methyl-1-azetidinyl)-1,4- dihydro-6-fluoro-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to determine the effects of chirality on potency and in vivo efficacy relative to the racemic mixtures (for part 2, see: J. Med. Chem. 1994, 37, 4195-4210). A series of chiral 9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-(substituted-1- azetidinyl)-7H-pyrido[1,2,3- de]-1,4-benzoxazine-6-carboxylic acids was synthesized to study the effect of the azetidine moiety on tricyclic quinolone antibacterial agents. A series of amino acid prodrugs of chiral naphthyridines 24a and 24b and quinolone 33a (cetefloxacin) was prepared and evaluated for antibacterial activity, solubility, and pharmacokinetic behavior. The absolute configuration of the new azetidinylquinolones was established by X-ray analysis of one of the diastereomeric salts of the resolved azetidinols (15) and of compound 25a (E-4767), which showed the best in vitro and in vivo overall profile. Structure-activity relationship studies indicated that the absolute stereochemistry at the asymmetric centers of both the azetidine and the oxazine rings was critical to increase in vitro activity and oral efficacy. The 3S configuration in the pyridobenzoxazine series and the (2S,3R) configuration of the 3-amino-2-methylazetidine moiety for all new compounds conferred the best antibacterial activity.
Animals↗
Effects of physical exercise and aging on ascorbic acid and superoxide anion levels in peritoneal macrophages from mice and guinea pigs.
The relationship of physical activity and aging, two processes with a high production of oxygen-free radicals to the ascorbate and superoxide anion (O2-) contents of peritoneal macrophages was studied in two animals species: guinea-pig (in which ascorbic acid is a vitamin) and mouse (in which ascorbic acid is not a vitamin). The effects of exhaustive exercise were examined in young and old animals. The results show that macrophages from old animals have a lower ascorbate content than those from young ones, whereas with exercise the ascorbate content increased in both old and young animals. This increase was higher in young than in old animals, and more evident in mice than in guinea-pigs. Aging also resulted in an increase in the O2- levels of macrophages. With exercise these levels decreased in young mice but increased in young guinea-pigs. In old animals the exhaustive exercise did not change the O2- levels. The results suggest in general a lack of correlation between the intracellular ascorbate and O2- levels in relation to both physical exercise and aging.
Aging↗
Influence of the temperature upon the proliferative response of lymphocytes of tench (Tinca tinca) during winter and summer.
The influence of incubation temperature upon proliferation of Tinca tinca lymphocytes induced by phytohemagglutinin (PHA) and E. coli lipopolisaccharide (LPS) mitogens was studied during the summer and the winter. The cultures were performed in vitro at 22 degrees C in both summer and winter, and at 12 and 30 degrees C in winter and summer respectively. The proliferative response at 22 degrees C was higher than that at 12 degrees C during the winter, and a small increase was observed at 30 degrees C respective to 22 degrees C in summer. These results indicate that in vitro lymphocyte proliferation requires temperatures higher than those in the fish environment.
Animals↗
Seasonal variations in the immune system of the cyprinid Tinca tinca. Phagocytic function.
Seasonal variations in the in vitro phagocytic process of blood granulocytes from the tench Tinca tinca were examined. Different stages of the phagocytic process: mobility rate, attachment, ingestion and killing of Candida albicans were evaluated. Tench were kept in natural ponds in ambient water temperature, and the in vitro assays were performed at both 22 degrees C and the relative ambient temperature. Results between the seasonal samples were then compared. In vitro induced mobility, attachment, ingestion and killing of C. albicans showed strong seasonal variations, furthermore, the phagocytic process at 22 degrees C varied significantly according to season. Phagocytic activity from samples taken during the spring demonstrated the highest activity at 22 degrees C, whilst greatest activity at seasonal temperature, in terms of mobility rate, phagocytic index and microbicide capacity, occurred during the winter. These results are consistent with the hypothesis that phagocytosis in fish is resistant to low temperatures.
Animals↗
Effect of high summer temperatures upon granulocyte phagocytic function of the tench (Tinca tinca, L.).
Phagocytic activity and NBT reduction by blood granulocytes was evaluated in tench during the summer, when water temperature was high (30 degrees C). In vitro assays were performed at two temperatures, 30 degrees C, the temperature of the natural habitat in summer, and 22 degrees C, a commonly used temperature within the optimum range of warm-water fish. The results indicate that blood granulocytes from tench possess a lower capacity to ingest inert particles at 30 degrees C than at 22 degrees C, particularly during long periods of incubation (60 min). The lower capacity for ingesting inert particles at 30 degrees C is due to a decreased effectiveness of phagocytosis at this temperature, but not to a lower number of granulocytes with phagocytic capacity. The decline in inert particle ingestion capacity does not correspond to a lower production of superoxide anion at 30 degrees C, which is similar at both temperatures during phagocytosis, thus indicating a similar capacity for destruction of the antigen at 30 and 22 degrees C.
Animals↗
How do multichain immune recognition receptors signal? A structural hypothesis.
Several cell surface receptors involved in cellular activation by antigen, such as the B-cell and T-cell antigen receptors, and receptors for IgE and IgG (Fc epsilon RI and Fc gamma RIII) show substantial similarities in structure and signaling pathways. An essential step in the activation of immune cells through these receptors is the phosphorylation of specific tyrosine residues within certain consensus sequences found in the cytoplasmic tails of different chains belonging to each of these receptors. The mechanism by which aggregation of the receptors triggers these phosphorylation is still unknown. In this paper, a mechanistic model for this key event is proposed. This model assumes that the kinase(s) responsible for catalysing these phosphorylations do exist associated with the receptors, but for steric reasons they cannot phosphorylate tyrosine residues on chains of the same receptor complex. Upon aggregation, these kinases phosphorylate the tyrosines of a distinct receptor complex (cross-phosphorylation), thus starting the signaling cascade.
Animals↗
Monoclonal antibodies against acetylcholinesterase of Schistosoma mansoni: production and characterization.
Monoclonal antibodies (MAbs) were raised in mice against acetylcholinesterase (AChE, EC 3.1.1.7) of the parasite Schistosoma mansoni. Specific tests were used, in which the hybridoma culture supernatants were screened for MAbs capable of recognizing AChE. The MAbs were characterized by their recognition of different stages of the parasite life cycle, by their binding to epitopes of protein or of carbohydrate, and by their capability of blocking AChE activity of the intact parasites. Furthermore, the MAbs were tested for their cross-reaction with AChE derived from various species. One of the MAbs, termed SA31, showed strong cross-reactivity with invertebrate and vertebrate species, indicating some similarity of cross-reaction between schistosome and mammalian AChE. However, most of the schistosome AChE epitopes are not shared with vertebrate AChE. The specific interaction of three other MAbs with intact schistosomula resulted in a marked complement (C)-dependent cytotoxicity. Specific schistosome AChE epitopes might be suitable candidates for drug design and vaccine preparation.
Acetylcholinesterase↗
Core needle aspiration biopsy of palpable breast masses.
The purpose of the present study was to determine the usefulness of core needle aspiration biopsy (CNAB) with an 18-gauge modified menghini needle in the preoperative evaluation of 145 palpable breast masses as the major indicator for definitive treatment by surgery. Of the 145 lesions histologically verified by surgery, 126 were diagnosed as carcinoma, of which 117 were correctly diagnosed by the needle biopsy (93%). CNAB showed a sensitivity of 90% in the diagnosis of breast malignancy and a specificity of 100%. The overall diagnostic accuracy was 91%. There were no false-positive results and after definitive diagnosis with the Menghini needle, a one-stage procedure without frozen sections could be performed for definitive treatment of breast carcinoma.
Adult↗
Kinetics of Fc epsilon RI dimer formation by specific monoclonal antibodies on mast cells.
Clustering of the type I receptor for Fc epsilon domains constitutes the signal initiation leading to mast cell secretory response. In order to characterize the relationship between the lifetime of clustered Fc epsilon receptors and the cellular response we have studied the rates of association and dissociation of monoclonal, IgG class antibodies (mAbs) specific for the alpha-subunit of type 1 receptor for IgE (Fc epsilon RI) (designated as F4, J17, and H10) to and from this receptor on live rat mucosa-type mast cells (line RBL-2H3) were measured at three different temperatures (25, 15, and 4 degrees C). These antibodies dimerize the Fc epsilon RI on these cells and induce their secretion, thus providing clear evidence that Fc epsilon receptor dimers are sufficient for the stimulus [Ortega et al. (1988), EMBO J. 7, 4101]. Marked differences in the response to the different mAbs have been explained in terms of possible orientational constraints imposed by them on the Fc epsilon receptor dimers. Interaction kinetics between the Fab fragments of these mAbs and the Fc epsilon RI have previously been measured and found to be best fitted by a two-reaction-step model involving a conformational transition from a low-affinity (l) to a high-affinity (h) state of the receptor-ligand complex [Ortega et al. (1991) Biochemistry 30, 3473]. Analysis of the interaction kinetics between the corresponding intact mAbs and the Fc epsilon RI therefore requires consideration of this 1-->h transition for both complexes involved, namely, the monomeric Fc epsilon RI-mAb and the dimeric Fc epsilon RI-mAb-Fc epsilon RI complexes. This was done by assuming the involvement of the following Fc epsilon RI dimer species: all 1- or h-state dimers Dll and Dhh and a hybrid Dlh with one receptor in the l state and the other in the h state. A self-consistent set of rate constants was derived by fitting the experimental results to this model. At 25 degrees C the all-h-state dimers Dhh turned out to be preferentially stabilized, probably by interaction with other cellular components. Different dimer formation rates were observed for each of the three mAbs, indicating that the dimer distribution among different states is determined by the individual epitope-binding site combination and also by the geometry of the respective complexes.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Pharmacokinetics of ketoprofen enantiomers in monkeys following single and multiple oral administration.
Pharmacokinetic studies are reported after single oral administration of 3 mg/kg of stereochemically pure (S)-ketoprofen [(S)-KP] and (R)-ketoprofen [(R)-KP] to three male Cynomolgus monkeys and after repeated administration for 6 months of 3, 15 and 75 mg/kg/day of (S)-KP to both male and female monkeys. A high-performance liquid chromatographic (HPLC) analysis was performed without derivatization of the samples, using a chiral column. The pharmacokinetic parameters for (S)-KP after administration of (S)-KP and for (R)-KP after administration of (R)-KP were, respectively, elimination half-life 2.32 +/- 0.36 and 1.64 +/- 0.40 h; oral clearance 3.50 +/- 0.66 and 7.50 +/- 3.20 ml/min/kg; apparent volume of distribution 0.74 +/- 0.24 and 1.16 +/- 0.76 liter/kg; mean residence time 1.79 +/- 0.77 and 1.41 +/- 0.65 h; area under the concentration/time curve 14.16 +/- 2.93 and 7.31 +/- 2.98 micrograms.h/ml. Forty-nine percent unidirectional bioinversion of (R)-KP to (S)-KP was observed in this species and the pharmacokinetic parameters for the (S)-KP resulting from this inversion were also calculated. In the study of 6-month repeated administration of (S)-KP, linear pharmacokinetic behavior and no evidence of drug accumulation were observed at the three dose levels.
Administration, Oral↗
Lead concentration in farmlands in southern Spain: influence of the use of sewage sludge as fertilizer.
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Agriculture↗
Effect of corticotropin releasing factor (CRF) in the median eminence on gonadotropins in ovariectomized rats with or without steroid priming: dose-response study.
We determined the dose-response relationship and examined the time related effect of CRF (corticotropin releasing factor) injected directly into the median eminence (ME) on LH and FSH secretion in conscious female rats of different steroid status. Doses of 0.25, 0.75, 1, and 1.5 nM CRF dissolved in 1 microliter of water were injected into the ME in 5 experimental groups of rats: Short-term (2 days) ovariectomized (sOVX); long-term (3-4 weeks) ovariectomized (lOVX); lOVX primed by estradiol benzoate (EB) 4 h before the experiment (lOVX+E); lOVX primed by EB 36 h before the experiment (lOVXE) and lOVX primed by EB 72 h and progesterone 6 h before experiment (lOVXP). Blood was collected at 30, 60, 90, and 120 min postinjection to determine LH and FSH by RIA. CRF at the doses of 0.75, 1, and 1.5 nM significantly decreased serum LH levels in all groups. The dose of 0.25 nM CRF was ineffective. The highest dose (1.5 nM) of CRF had no effect on serum FSH levels. The results suggest that CRF inhibits LH secretion, at least in part, by a central action of GnRH release in the ME, and that this effect is independent of the estrogen/progesterone status of the animal.
Animals↗
Increased phagocytic activity of polymorphonuclear leukocytes during pregnancy.
Many immunological parameters are depressed during pregnancy. For this reason, an evaluation was made of the phagocytic activity, representing non-specific immunity, of polymorphonuclear leukocytes from pregnant women. The cells were isolated from heparinized venous human blood of pregnant women of 10 or more weeks' gestation and non-pregnant women (controls), 20-30 years old. The results indicate that the phagocytosis of inert particles (latex beads) does not significantly change in pregnancy. However, the attachment, ingestion and digestion of Candida albicans significantly increased in pregnancy, with the greatest difference from controls being in the second trimester. These findings suggest that the phagocytic activity in pregnant women is enhanced and that this increased non-specific immunity may compensate in part for weakened specific immunity of the maternal host.
Adult↗
Effect of age on adherence and chemotaxis capacities of peritoneal macrophages. Influence of physical activity stress.
The aim of the present research was to study the effects of age on the adherence and chemotaxis capacities of macrophages. Macrophages were obtained from the peritoneum of young and old mice (young, 12 +/- 4 weeks; old, 68 +/- 6 weeks) and young and mature guinea pigs (young, 12 +/- 1 weeks; mature, 108 +/- 2 weeks). Adherence of macrophages was evaluated with a plastic adherence technique, and chemotaxis in a Boyden chamber. The macrophages from old animals showed a higher adherence capacity (studied at 10, 40 and 60 min of incubation), and lower chemotaxis capacity in both mice and guinea pigs. The effect of physical activity stress (swimming until exhaustion) was also studied, both with and without a previous training program, on the adherence and chemotaxis of macrophages from young and old mice. While the physical activity stress (detected by the increase of the serum corticosterone concentration) did not induce changes in adherence or chemotaxis of peritoneal macrophages from young mice, in the old mice, there was a decrease in adherence and an increase in chemotaxis.
Aging↗
Decline in the phagocytic function of alveolar macrophages from mice exposed to cigarette smoke.
An investigation was made of the effects of a short and acute exposure to cigarette smoke on the capacity of alveolar macrophages from mice to carry out all stages of the phagocytic process. Cigarettes were commercial 80 mm filter cigarettes that contained 17 mg of tar and 1.1 mg of nicotine per cigarette. The acute exposure of each animal was with one cigarette for 15 min (until the complete consumption of the cigarette) in a box-shaped plastic chamber, 7732 cm3 vol and 450 cm2 floor surface, with a 3 cm dia airhole. Animals were sacrificed immediately after the exposure to the smoke. The results showed no differences either in the adherence or in the chemotaxis capacities between alveolar macrophages from control mice and from mice exposed to cigarette smoke. However, there was a significant decline both in attachment capacity and in ingestion capacity for Candida albicans. The reason for this was a decline in the number of macrophages with phagocytic capacity (percent of phagocytosis) and in the number of C. albicans phagocytized per cell (phagocytic efficiency). The conclusion is that a short, acute exposure to a smoke-filled atmosphere induced a decrease in the phagocytic function of alveolar macrophages.
Animals↗
Analysis of hepatitis B precore region in serum and liver of chronic hepatitis B virus carriers.
Using an oligonucleotide hybridization assay we studied the prevalence of wild-type and the predominant pre-core mutant hepatitis B virus in serum and liver of 49 antibody to hepatitis B e antigen carriers and three hepatitis B e antigen positive patients. Of the 45 serum samples from the anti-HBe carriers analyzed (no serum sample was available in four patients), 36 (80%) had hepatitis B virus DNA. In 26 of these 36 patients (72%) a mixed population was detected, wild-type genome alone was found in six patients (16%), the single mutant (nucleotide position 1896), in three cases (8%) and in one patient (2%) the viral DNA had the two nucleotide mutation (1896 and 1899). Of the liver biopsies from the 36 anti-HBe patients studied (no liver biopsy was available in 13 patients), 33 (92%) had hepatitis B virus DNA. A mixed viral population was detected in 23 patients (69%), only wild-type virus or a single mutation was found in eight (34%) and two patients (8%), respectively. In all cases, wild-type was the predominant genome. In serum and liver samples from the same patient, we found a concordance of the presence of wild-type HBV and the pre-core mutants studied in 23/26 (88%) of the patients. Alanine aminotransferase levels were higher (p < 0.01) and the duration of hepatitis B surface antigen carrier lower (p < 0.02) in patients with a predominance of precore mutant in comparison to wild-type.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Inflammatory and phagocytic response to experimental Campylobacter jejuni infection in mice.
After intraperitoneal inoculation with Campylobacter jejuni BALB/c, Swiss and DBA mice show a peritoneal inflammatory response of different intensity. Only BALB/c mice have a strong peritoneal response. Simultaneous intraperitoneal inoculation of C. jejuni plus FeCl3 increase both inflammatory response and phagocytic activity in Swiss mice, without production of diarrhea. Some thermostable compounds of C. jejuni have a very strong chemotactic activity against peritoneal cells of mice, whereas a diffusible, thermolabile and glutaraldehyde-resistant factor has an inhibitory effect over murine peritoneal cell phagocytosis. Bactericidal activity of peritoneal cells increased after in vitro re-challenge with C. jejuni. Bacteremia is present in all the mice strains tested, but the clearance is quick in DBA and slow in BALB/c and Swiss mice. These experiments confirm that in mice, peritoneal non-specific mechanisms of defense, such as macrophages, play an important role in order to control C. jejuni infection.
Animals↗