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Biomedical subjects

J M Huerta

Publications and source records attributed to J M Huerta.

9 recordsLinked to original sources

Diet score is associated with plasma homocysteine in a healthy institutionalised elderly population.

BACKGROUND AND AIM: Total plasma homocysteine (tHcy) is an independent risk factor for cardiovascular diseases. Among other dietary and non-dietary factors, B vitamins, such as folate, riboflavin and cobalamin, are primary determinants of tHcy in the general population. However, research has concentrated on the relationship of these nutrients with tHcy, and little is known about overall eating patterns and tHcy. METHODS AND RESULTS: In this study, we analysed whether a diet score based on the consumption of folate-, riboflavin- and cobalamin-rich food groups was associated with tHcy in a sample of 140 institutionalised elderly subjects (59 men and 81 women aged 60-80 years) from Northern Spain. The food groups identified as the major contributors to the intake of the three vitamins were vegetables, fruit, fish, meat and milk and dairy products. The mean tHcy level was 13.3+/-5.1 micromol/L (range: 3.9-30.7 micromol/L). None of the food groups predicted tHcy levels individually, but the overall diet score was inversely associated with tHcy in a multiple linear regression analysis. High tHcy levels (>16 micromol/L) were almost twice as prevalent in the groups scoring less than 7 than in those scoring 7 or more (37.5 vs 19.6%, p=0.021). CONCLUSIONS: These data suggest that a dietary pattern characterised by high intakes of B vitamin-rich foods is associated with a lower tHcy concentration and a reduced percentage of high tHcy levels in elderly subjects. They also support the use of dietary pattern approaches to evaluate the relationships between diet and health outcomes that go beyond single nutrient analyses.

Aged↗

Synthesis and biological evaluation of 3,4-diaryloxazolones: A new class of orally active cyclooxygenase-2 inhibitors.

A series of 3,4-diaryloxazolones were prepared and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). Extensive structure-activity relationship work was carried out within this series, and a number of potent and selective COX-2 inhibitors were identified. The replacement of the methyl sulfone group on the 4-phenyl ring by a sulfonamide moiety resulted in compounds with superior in vivo antiinflammatory properties. In the sulfonamide series, the introduction of a methyl group at the 5-position of the oxazolone ring gave rise to very COX-2-selective compounds but with decreased in vivo activity. Selected 3,4-diaryloxazolones exhibited excellent activities in experimental models of arthritis and hyperalgesia. The in vivo activity of these compounds was confirmed with the evaluation of their antipyretic effectiveness and their ability to inhibit migration of proinflammatory cells. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 4-day treatment of 100 mg/kg/day. Within this novel series, sulfonamides 9-11 have been selected for further preclinical evaluation.

Animals↗

Inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion but not IL-6 from activated human peripheral blood monocytes by a new synthetic demethylpodophyllotoxin derivative.

A newly synthesized demethylpodophyllotoxin derivative, 4-O-butanoyl-4'-demethylpodophyllotoxin (BDPT) or BN58705, has recently been shown to exert a potent cytotoxic activity in vitro against a variety of drug-resistant human tumor cell lines. The effect of this agent on effector cells of the immune system, however, has not been examined. The present study investigated the effect of BDPT on the response of activated human peripheral blood derived monocytes (PBM) to secrete cytokines. Activation of PBM overnight with LPS, IFN-gamma, or PMA resulted in secretion into the supernatant of TNF-alpha, IL-1 beta, IL-6, and IL-8 as assessed by ELISA. The addition of BDPT to the stimulated cultures resulted in significant inhibition of TNF-alpha and IL-1 beta secretion, whereas the secretion of IL-6 and IL-8 was not affected. The selective inhibition of TNF-alpha and IL-1 beta secretion by BDPT-treated PBM was observed with all three stimuli tested. The inhibitory effect mediated by BDPT was concentration dependent and was optimal at 6-20 microM. Time kinetic analysis indicated that the inhibition of secretion was rapid and detected as soon as 2 hr following stimulation of the PBM and lasted for as long as 24 hr. A comparison was made between BDPT and pentoxyfilline, a xanthine-derived phosphodisterase inhibitor that was reported to inhibit TNF-alpha and IL-1 beta secretion by PBM. Both BDPT and PTX showed similar time kinetics and patterns of inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Maturation of human myelomonocytic leukemia cells following ligation of the low affinity receptor for IgE (Fc epsilon RII/CD23).

The regulation of the low affinity receptor for IgE (Fc epsilon RII/CD23) expression and its role were investigated in U937 cell line and in leukemic cells from a patient (Amb) with acute myeloblastic leukemia. Both cell populations were CD23- but could acquire CD23 expression following treatment with IL-4. CD23+ cells, however, remained blastic and did not show any significant phenotypical and functional modifications. Following ligation of the CD23 on U937 and Amb cells by anti-CD23 mAb, these leukemic cells differentiated into mature monocyte/macrophage-like cells. CD23 ligation promoted the expression of the monocyte marker, CD14, increased the expression of the common beta chain of the LFA-1 family (CD18), and down-regulated the expression of the promonocytic marker CD33. Morphological and phenotypical changes were associated with functional modifications as CD23 ligation allowed the acquisition of the oxidative metabolism in leukemic cells as revealed by luminol-dependent chemiluminescence. As in mature monocytes, CD23 ligation induced an accumulation of intracellular cAMP in leukemic cells. These data indicate that ligation of CD23 may induce the maturation of myelomonocytic cells into monocytic-like cells.

Cyclic AMP↗

Role of platelet-activating factor in the ovine heparin-protamine reaction.

Platelet-activating factor (PAF) infusion into sheep, as well as protamine reversal of heparin anticoagulation, causes thromboxane release into plasma, pulmonary hypertension, hypoxemia, and leukopenia. We investigated the possible role of PAF in the heparin-protamine reaction. Intravenous protamine was administered to neutralize heparin anticoagulation in five awake sheep and caused an increase of mean pulmonary arterial pressure from 16.6 +/- 1 (SE) mmHg at base-line to 47 +/- 9 mmHg at 1 min after protamine injection (P < 0.01) because of a 4.5-fold increase of pulmonary vascular resistance. This neutralization reaction induced a 25% reduction of circulating leukocyte count and arterial PO2. Undetectable blood levels of PAF were measured by bioassay and high-performance liquid chromatography during these heparin-protamine reactions. Infusion of BN 52021 (20 mg/kg), a PAF receptor antagonist, before rechallenging the same sheep with heparin and then protamine did not reduce the level of peak pulmonary hypertension or the degree of hypoxemia and leukopenia. We conclude that the leukopenia and thromboxane-mediated pulmonary vasoconstriction occurring after rapid intravascular formation of heparin-protamine complexes in sheep are not due to the release of PAF.

Animals↗

Defective IFN-gamma production in the human neonate. II. Role of increased sensitivity to the suppressive effects of prostaglandin E.

Analysis of endogenous production and effects of exogenous addition of interleukin 2 (IL 2), leukotrienes (LT), and prostaglandin E (PGE) has been used to investigate the dysregulation responsible for impaired PHA-induced IFN-gamma secretion by cord blood leukocytes (CBL). The addition of LT or IL 2 could not reverse the IFN defect of CBL. The production of these two mediators was found to be normal in CBL cultures. CBL and control leukocytes from adult donors produced comparable amounts of PGE2. In contrast, sensitivity to the suppressive effects of PGE2 on IFN-gamma secretion was much higher with CBL than with control leukocytes. Treatment with indomethacin reversed the IFN-gamma defect with most CBL tested, and the addition of physiologic amounts of PGE2 to indomethacin-treated cultures resulted in a profound impairment of IFN-gamma production similar to that of untreated CBL cultures. Preincubation of CBL for 24 hr before PHA stimulation resulted in restoration of a normal sensitivity to exogenous PGE2, in parallel with correction of the IFN-gamma defect. Our observations suggest that the impairment of IFN-gamma secretion in neonates is not due to deficient amplification circuits, but is the consequence of an exaggerated cellular sensitivity to the suppressive effects of PGE produced endogenously in normal amounts.

Adult↗

In vitro inhibition of marginal caries-like lesions with fluoride-containing amalgam.

Carious lesions surrounding restorations represent one of the main causes of restoration failure. The addition of fluoride compounds to dental restorative materials prevents or reduces recurrent caries. The purpose of this study was to compare the capacity of three restorative materials to inhibit the development of recurrent caries in vitro. Thirty unrestored, noncarious premolars that were being extracted for orthodontic reasons were sectioned in half buccolingually and divided into three groups. One of the groups was restored with conventional amalgam. The second group was restored with a fluoride-containing amalgam, and the third group was restored with a glass-ionomer cement. All the samples were submitted to a medium containing Streptococcus mutans (Ingbritt strain) for 8 weeks. At the end of the 8-week incubation period, the samples were cut into 100 microns sections, soaked in Quinoline (IR = 1.62), and observed with light transmission and polarized light microscopy. The development of artificial caries in the cavity walls was measured in microns. The results show that conventional amalgam had an average caries penetration of 160 microns, fluoride-containing amalgam 46 microns, and glass-ionomer cement 11 microns. Glass-ionomer cement gave the best protection against recurrent caries.

Adolescent↗