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Biomedical subjects

A Ubeda

Publications and source records attributed to A Ubeda.

At least 37 records · Page 2Linked to original sources

Anti-inflammatory activity in mice of extracts from Mediterranean marine invertebrates.

The effects of dichloromethane and methanol extracts from the marine invertebrates Leptogorgia ceratophyta, Holothuria tubulosa, Coscinasterias tenuispina and Phallusia fumigata on carrageenan-induced paw oedema in mice were investigated. The dichloromethane extract of Coscinasterias tenuispina and the methanol extract of Holothuria tubulosa administered p.o. at 50, 100 and 150 mg/kg, inhibited oedema in a dose-dependent manner 3 h after administration of carrageenan. Both extracts partially decreased elastase activity and PGE2 levels measured in homogenates from inflamed paws, without affecting the levels of this prostanoid present in stomach homogenates. As observed with the selective inhibitor NS398, both extracts can decrease cyclo-oxygenase activity in inflamed tissues but do not modify the constitutive cyclo-oxygenase enzyme. Therefore, these extracts represent new marine resources for the isolation of novel agents active on inflammatory conditions.

Animals↗

Hematological changes in rats exposed to weak electromagnetic fields.

A number of experimental studies report that biological systems can be affected by in vivo exposure to low frequency and extremely low frequency electromagnetic fields. However, attempts to independently replicate some of these studies have shown the reported effects to be elusive. The difficulty in replicating results could be due to unidentified physical and/or biological parameters which may affect the response of a sample to electromagnetic fields. The present paper reports a failure to independently replicate a study showing that in vivo exposure to a pulsed magnetic field of 1.5 mT caused significant changes on plasma proteins in rats. Although the possibility has to be considered that the results from the seminal work were artifactual, substantial differences in levels of plasma proteins were observed between the control groups of the two studies indicating that the animals in the first study had an infectious illness. This observation supports the hypothesis that the state of physiological equilibrium of a biological system is crucial to its response to a potentially effective electromagnetic field.

Animals↗

Transvaginal sonographic appearance of functional ovarian cysts.

Knowledge of the nature of ovarian lesions is important in order to establish the correct treatment and, especially, to detect ovarian cysts that do not require surgical treatment. With the purpose of demonstrating the utility of transvaginal sonography with colour Doppler of ovarian functional ovarian cysts, 378 ovarian tumours were studied, comparing sonographic diagnosis with pathological findings. Sensitivity and specificity of colour Doppler transvaginal sonography to detect functional ovarian cysts were 84.6 and 99.2% respectively. Positive and negative predictive values were 98 and 93.5% respectively. In our experience, transvaginal sonography with colour Doppler is a useful technique in the diagnosis of ovarian pathology.

Adult↗

Variabilin: a dual inhibitor of human secretory and cytosolic phospholipase A2 with anti-inflammatory activity.

The marine product variabilin was identified as a novel inhibitor of phospholipase A2 (PLA2), which exhibited IC50 values of 6.9 microM and 7.9 microM for human synovial secretory PLA2 and U937 cells cytosolic PLA2 activities, respectively. This compound was less potent on bee venom or zymosan-injected rat air pouch enzymes and failed to affect Naja naja venom PLA2. The production of leukotriene B4 by human neutrophils stimulated with calcium ionophore A23187 was also inhibited by variabilin, which was without effect on 5-lipoxygenase, cyclo-oxygenase 1 and cyclo-oxygenase 2 activities in cell-free assays. Other functions of human neutrophils, such as degranulation and superoxide generation, were also significantly reduced in vitro. Variabilin administered topically suppressed the mouse ear edema induced by 12-O-tetradecanoylphorbol 13-acetate, whereas the ear edema induced by arachidonic acid was unaffected; this suggests an action previous to arachidonic acid metabolism. This compound administered p.o. at 30 mg/kg and 45 mg/kg significantly inhibited mouse paw edema induced by carrageenan and, at 0.01 to 1.0 micromol/pouch in the mouse air pouch injected with zymosan, exerted a marked inhibition on PGE2 and leukotriene B4 levels in exudates (ID50 values of approximately 0.028-0.029 micromol/pouch), without affecting cell migration. Our results indicate that variabilin is an inhibitor of human secretory and cytosolic PLA2 activities that controls eicosanoid production in vitro and in vivo, inhibits neutrophil degranulation and superoxide generation in vitro and shows anti-inflammatory activity after topical or p.o. administration to mice.

Animals↗

Magnetic fields at resonant conditions for the hydrogen ion affect neurite outgrowth in PC-12 cells: a test of the ion parametric resonance model.

PC-12 cells primed with nerve growth factor (NGF) were exposed to sinusoidal extremely-low-frequency (ELF) magnetic fields (MFs) selected to test the predictions of the ion parametric resonance (IPR) model under resonance conditions for a single ion (hydrogen). We examined the field effects on the neurite outgrowth (NO) induced by NGF using three different combinations of flux densities of the parallel components of the AC MF (Bac) and the static MF (Bdc). The first test examined the NO response in cells exposed to 45 Hz at a Bdc of 2.96 microT with resonant conditions for H+ according to the model. The Bac values ranged from 0.29 to 4.11 microT root-mean-square (rms). In the second test, the MF effects at off-resonance conditions (i.e., no biologically significant ion at resonance) were examined using the frequency of 45 Hz with a Bdc of 1.97 microT and covering a Bac range between 0.79 and 2.05 microT rms. In the third test, the AC frequency was changed to 30 Hz with the subsequent change in Bdc to 1.97 microT to tune for H+ as in the first test. The Bac values ranged from 0.79 to 2.05 microT rms. After a 23 h incubation and exposure to the MF in the presence of NGF (5 ng/ml), the NO was analyzed using a stereoscopic microscope. The results showed that the NGF stimulation of neurite outgrowth (NSNO) was affected by MF combinations over most of the Bac exposure range generally consistent with the predictions of the IPR model. However, for a distinct range of Bac where the IPR model predicted maximal ionic influence, the observed pattern of NSNO contrasted sharply with those predictions. The symmetry of this response suggests that values of Bac within this distinct range may trigger alternate or additional cellular mechanisms that lead to an apparent lack of response to the MF stimulus.

Animals↗

Effect of bakuchiol on leukocyte functions and some inflammatory responses in mice.

The effects of bakuchiol, a meroterpenoid isolated from the leaves of Psoralea glandulosa L., on phospholipase A2 (PLA2) activity from different sources, human neutrophil responses, zymosan air pouch and topical inflammation in mice, were investigated. This natural product was a weak inhibitor of secretory and intracellular PLA2 but dose-dependently reduced the formation of LTB4 and TXB2 by human neutrophils and platelet microsomes, respectively. In addition, bakuchiol inhibited degranulation in human neutrophils, whereas superoxide generation was not affected. In mice, bakuchiol decreased cell migration, myeloperoxidase activity and eicosanoid levels in the air pouch inflammation induced by zymosan. After topical administration, this compound was effective as an inhibitor of oedema and myeloperoxidase activity in the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear oedema and significantly reduced the PGE2 content and ear oedema in the arachidonic acid-induced response. Bakuchiol is a natural anti-inflammatory agent able to control leukocytic functions such as eicosanoid production, migration and degranulation in the inflammatory site.

Animals↗

Synthesis and pharmacological evaluation of 2'-hydroxychalcones and flavones as inhibitors of inflammatory mediators generation.

2'-Hydroxy-3,4-dimethoxy-3',4'-dimethylchalcone (3a), 2'-hydroxy-3',4',3,4-tetramethoxychalcone (3b), and their corresponding flavones, 3',4'-dimethoxy-7,8-dimethylflavone (4a) and 3',4',7,8-tetramethoxyflavone (4b), were prepared from 3,4-dimethoxycinnamic acid and the respective phenol. The four compounds inhibited enzymic lipid peroxidation and showed weak peroxyl scavenging activity. They also reduced LTB4 release from human neutrophils stimulated by A23187. The chalcone 3b was the only compound able to inhibit in a concentration-dependent way, synovial human recombinant phospholipase A2 activity, human platelet TXB2 generation, and human neutrophil degranulation. This chalcone exerted topical antiinflammatory effects in mice.

Animals↗

Melatonin enhances junctional transfer in normal C3H/10T1/2 cells.

Gap junctional intercellular communication is known to be involved in controlling cell proliferation and differentiation, and seems to play a crucial role in suppression of tumor promotion. The pineal gland and its hormone, melatonin, are believed to intervene in the control of neoplastic processes. Several possible mechanisms have been suggested to be potentially responsible for melatonin's oncostatic action; however, the actual mechanisms involved in melatonin's effects at the cellular level remain unidentified. In the present study low-density cultures of C3H/10T1/2 mouse embryo fibroblasts were incubated until relatively quiescent monolayers were established (17-18 days). Gap junctional intercellular communication in control samples and in cells treated with 10(-12) to 10(-8) M melatonin was determined by the scrape-loading assay using the fluorescent dye Lucifer yellow. The results showed that concentrations of melatonin considered physiological (10(-11) and 10(-10) M) induced a significant increase in the transfer of the dye to adjacent cells through gap junctions; both higher and lower concentrations were ineffective. These results suggest that melatonin could exert its putative oncostatic action, in part, by modulating the levels of gap junctional intercellular communication.

Animals↗

Inhibition of inflammatory responses by epitaondiol and other marine natural products.

The marine metabolites pacifenol, stypotriol triacetate and epitaondiol were tested for their effects on a number of inflammatory responses. Epitaondiol exhibited a potent topical anti-inflammatory activity related to inhibition of leukocyte accumulation. The other compounds showed a lower potency, similar to that of indomethacin. None of the compounds affected superoxide generation by human neutrophils but pacifenol effectively inhibited the degranulation response. This compound and epitaondiol decreased the release of eicosanoids with a higher potency on the cyclo-oxygenase pathway. Only epitaondiol inhibited human recombinant synovial phospholipase A2 activity in a concentration-dependent manner.

Animals↗

A 50 Hz magnetic field blocks melatonin-induced enhancement of junctional transfer in normal C3H/10T1/2 cells.

There is strong evidence that pineal melatonin is involved in controlling neoplastic processes. We have reported that physiological, but not pharmacological or sub physiological, concentrations of melatonin enhance intercellular communication in normal C3H/10T/2 fibroblasts. Gap junctional intercellular communication intervenes in the control of cell proliferation and differentiation, and seems to play a crucial role in suppression of tumor promotion. A number of in vivo studies have shown that extremely low frequency (ELF) magnetic fields (MF) can act as cancer promoters or co-promoters. In vitro, 60 Hz MF have been reported to block melatonin-induced inhibition of cell proliferation in human breast cancer cells. The mechanisms responsible for the observed interactions of MF at the cellular level remain unknown. In the present study melatonin was added to confluent fibroblasts at a concentration of 10(-10) M. Twenty-seven hours later, a fluorescent dye was scrape-loaded into groups of cells and the transfer of the dye to adjacent cells through gap junctions was quantified. Under these conditions melatonin induced a significant increase of dye transfer; this increase was not observed when the cultures were exposed to the MF for 30 min before the previously reported results suggesting that the in vivo oncostatic action of melatonin could be exerted, in part, through modulation of the levels of gap junctional intercellular communication. Also, the data indicate that ELF-MF could counteract the melatonin-induced enhancement of junctional transfer.

Animals↗

Chick embryo development can be irreversibly altered by early exposure to weak extremely-low-frequency magnetic fields.

Several reports have shown that weak, extremely-low-frequency (ELF), pulsed magnetic fields (PMFs) can adversely affect the early embryonic development of the chick. In this study, freshly fertilized chicken eggs were exposed during the first 48 h of postlaying incubation to PMFs with 100 Hz repetition rate, 1.0 microT peak-to-peak amplitude, and 500 microseconds pulse duration. Two different pulse waveforms were used, having rise and fall times of 85 microseconds (PMF-A) or 2.1 microseconds (PMF-B). It has been reported that, with 2 day exposure, these fields significantly increase the proportion of developmental abnormalities. In the present study, following exposure, the eggs were allowed to incubate for an additional 9 days in the absence of the PMFs. The embryos were taken out of the eggs and studied blind. Each of the two PMF-exposed groups showed an excess in the percentage of developmental anomalies compared with the respective sham-exposed samples. This excess of anomalies was not significant for the PMF-A-treated embryos (P = 0.173), whereas it was significant for the PMF-B-exposed group (P = 0.007), which showed a particularly high rate of early embryonic death. These results reveal that PMFs can induce irreversible developmental alterations and confirm that the pulse waveform can be a determinant factor in the embryonic response to ELF magnetic fields. The data also validate previous work based on the study of PMFs' effects at day 2 of embryonic development under field exposure.

Abnormalities, Radiation-Induced↗

Hysteroscopic incision of the septate uterus: scissors versus resectoscope.

Out of a total of 81 women who underwent hysteroscopic incision of symptomatic septate uteri during a 5-year period, 70 were analysed with respect to reproductive outcome. Division of the septum was performed with hysteroscopic scissors in 17 patients and by means of the resectoscope in 53. Pre-operative indications included infertility, repetitive pregnancy losses, abnormal uterine bleeding and intractable dysmenorrhoea. There were a total of 51 pregnancies after a mean period of 9.3 months following hysteroscopic metroplasty, of which 29 (56.8%) were carried to term, 12 (23.5%) were spontaneous abortions, and 10 (19.6%) are in progress. The post-treatment pregnancy success rate was 73%. The number of spontaneous abortions, pregnancies to term and mean time between surgery and conception was similar in both groups. There were three cases of perforation in the group of excision with hysteroscopic scissors and a case of pulmonary oedema in the group of the resectoscope. Although different advantages are provided by each technique, and more pregnancies were established using scissors, it seems that operator experience is a major consideration in performing these therapeutic hysteroscopic operations.

Adult↗

Influence of a series of natural flavonoids on free radical generating systems and oxidative stress.

1. A series of flavonoids isolated from Indian medicinal plants: kaempferol-3-O-galactoside, hispidulin, nepetin, scutellarein, scutellarein-7-O-glucuronide, hibifolin and morelloflavone were studied for their activity as inhibitors of microsomal lipid peroxidation and scavengers of oxygen free radicals in vitro as well as in a model of xenobiotic toxicity in mouse. 2. All compounds inhibited lipid peroxidation in vitro. The most potent compounds were nepetin (non-enzymic lipid peroxidation) and morelloflavone (enzymic lipid peroxidation) with IC50's in the micromolar range. Some of the compounds behaved as scavengers of hydroxyl radical in the deoxyribose degradation assay, with a calculated rate constant for kaempferol-3-O-galactoside of 1.55 x 10(10) M-1 s-1. 3. Scutellarein and nepetin were found to be inhibitors of xanthine oxidase activity, whereas morelloflavone acted as a scavenger of superoxide generated by hypoxanthine/xanthine oxidase. 4. Treatment of mice with scutellarein, hispidulin, nepetin and kaempferol-3-O-galactoside after bromobenzene intoxication decreased serum glumate-pyruvate transaminase activity, although only the last flavonoid was able to significantly reduce hepatic lipid peroxidation products and to increase the reduced glutathione level. In contrast, morelloflavone increased bromobenzene toxicity.

Animals↗

Iron-reducing and free-radical-scavenging properties of apomorphine and some related benzylisoquinolines.

The scavenging and iron-reducing properties of a series of benzylisoquinolines of natural and synthetic origin have been studied. Bulbocapnine, boldine, glaucine, and stepholidine acted as scavengers of hydroxyl radical in the deoxyribose degradation by Fe(3+)-EDTA + H2O2. On the contrary, laudanosoline, apomorphine, protopapaverine, anonaine, and tetrahydroberberine increased deoxyribose degradation by a mechanism related to generation of superoxide anion. Only apomorphine had a stimulating effect in the system using citrate instead of ethylenediaminetetraacetic acid (EDTA) as well as in the absence of chelator. Apomorphine also stimulated DNA damage by Cu2+. The iron-ion reducing ability of apomorphine and laudanosoline was confirmed using cytochrome c. Both compounds scavenged peroxyl radicals in an aqueous medium, while in Fe(3+)-induced microsomal lipid peroxidation apomorphine acted as an inhibitor and laudanosoline stimulated the process. It is suggested that in microsomes the chain-breaking antioxidant properties of apomorphine overcome its possible influence on redox cycling of iron, or prooxidant properties.

Animals↗

Antioxidant action of benzylisoquinoline alkaloids.

The antioxidant action of a series of benzylisoquinoline alkaloids has been investigated. Laudanosoline, protopapaverine, anonaine, apomorphine, glaucine, boldine, bulbocapnine, tetrahydroberberine and stepholidine produced a dose-dependent inhibition of microsomal lipid peroxidation induced by Fe2+/ascorbate, CCl4/NADPH or by Fe3+ ADP/NADPH. Apomorphine exerted the highest inhibitory effects in the three systems of induction used, with a potency higher than propyl gallate. Laudanosoline was particularly effective in the first system, while bulbocapnine and anonaine were more potent when CCl4/NADPH or Fe3(+)-ADP/NADPH were used as inducers. Laudanosoline, protopapaverine, apomorphine, tetrahydroberberine and stepholidine were also potent inhibitors of nitroblue tetrazolium (NBT) reduction. The presence of a free hydroxyl group or preferably of a catechol group is a feature relevant for inhibition of lipid peroxidation and NBT reduction, nevertheless the antioxidant activity of benzylisoquinoline alkaloids cannot be only ascribed to the formation of phenoxy radicals and other free radical species may be formed during aporphine and tetrahydroprotoberberine oxidation. The influence of this series of compounds on the time course of lipid peroxidation suggests that some of them, like apomorphine and boldine act as chain-breaking antioxidants.

Alkaloids↗

Effects of coumarin derivatives on superoxide anion generation.

A number of simple coumarins with different patterns of substitution were tested on activated polymorphonuclear leukocyte superoxide generation and superoxide scavenging using the reduction of nitroblue tetrazolium. The most effective compound was fraxetin, which showed a better potency as an inhibitor of superoxide radical generation than as a scavenger. From the structure-activity study it can be deduced the importance of an ortho-dihydroxyl function, especially at the position 7, 8. Blockade of active hydroxyl groups by methylation or glycosylation decreases the activity. None of the coumarins were cytotoxic on leukocytes as assessed by lactic dehydrogenase activity release. Inhibition of superoxide generation in activated neutrophils may play a role in the vasoprotective effects of simple coumarins.

Animals↗

Effects of khellin on contractile responses and 45Ca2+ movements in rat isolated aorta.

The effects of khellin on contractile responses and 45Ca2+ flux have been studied in rat isolated aortae. Khellin (10(-5)-3.2 x 10(-4) M) produced a concentration-dependent inhibition of noradrenaline (10(-6) M) and high K+ (80 mM)-induced contractions. At 3.2 x 10(-4) M, khellin increased cAMP levels and reduced 45Ca2+ influx in resting tissues and in tissues stimulated by noradrenaline (10(-5) M) and high K+ without affecting basal 45Ca2+ efflux or noradrenaline induced 45Ca2+ efflux. It is concluded that in rat isolated aorta, khellin caused a non-specific inhibition of Ca2+ influx but may also exhibit intracellular actions, thus decreasing the availability of Ca2+ required for activation. One or more of these mechanisms may be related to an increase in intracellular cAMP levels.

Animals↗